The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.

Abstract Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation. (Cancer Res 2006; 66(12): 6280-7

Treatment of Secondary Raw Materials by Innovative Processes

This paper presents an overview of the various innovative methodologies used in the recovery of valuable metals and critical raw materials from secondary sources. The review also highlights the used varieties of application on large scale in real situations and hopes to provide insights into valorization of spent sources

Rat protein tyrosine phosphatase η physically interacts with the PDZ domains of syntenin

AbstractThe tyrosine phosphatase r-PTPη is able to suppress the malignant phenotype of rat thyroid tumorigenic cell lines. To identify r-PTPη interacting proteins, a yeast two-hybrid screening was performed and an insert corresponding to the full-length syntenin cDNA was isolated. It encodes a protein containing two PDZ domains that mediates the binding of syntenin to proteins such as syndecan, proTGF-α, β-ephrins and neurofascin. We show that r-PTPη is able to interact with syntenin also in mammalian cells, and although syntenin is a tyrosine-phosphorylated protein it is not a substrate of r-PTPη. The integrity of both PDZ domains of syntenin and the carboxy-terminal region of r-PTPη are required for the interaction between syntenin and r-PTPη

Sustainable recovery of secondary and critical raw materials from classified mining residues using mycorrhizal-assisted phytoextraction

In this work, mycorrhizal-assisted phytoextraction (MAP, Helianthus annuus–arbuscular mycorrhizal fungus Rhizophagus intraradices–Zn-volcanic ashes) was applied for the recovery of secondary and critical raw materials (SRMs and CRMs, respectively) from Joda West (Odisha, India) mine residues, within a novel multidisciplinary management strategy. Mine residues were preliminarily characterized by using advanced analytical techniques, and subsequently mapped, classified and selected using multispectral satellite Sentinel-2A images and cluster analysis. Selected mine residues were treated by MAP at laboratory scale, and the fate of several SRMs (e.g., Zn, Cr, As, Ni, Cu, Ca, Al, K, S, Rb, Fe, Mn) and CRMs (such as Ga, Ti, P, Ba and Sr) was investigated. Bioconcentration factors in shoots (BCS) and roots (BCR) and translocation factors (TF) were: 5.34(P) > BCS > 0.00(Al); 15.0(S) > BCR > 0.038(Ba); 9.28(Rb) > TF > 0.02(Ti). Results were used to predict MAP performance at larger scale, simulating a Vegetable Depuration Module (VDM) containing mine residues (1 m3). Estimated bio-extracting potential (BP) was in the range 2417 g/m3 (K) > BP> 0.14 g/m3 (As), suggesting the eventual subsequent recovery of SRMs and CRMs by hydrometallurgical techniques, with final purification by selective electrodeposition, as a viable and cost-effective option. The results are promising for MAP application at larger scale, within a circular economy-based approach.Fil: Scotti, Adalgisa. Comisión Nacional de Energía Atómica; ArgentinaFil: Stefano, Milia. Consiglio Nazionale delle Ricerche; ItaliaFil: Silvani, Vanesa Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Giovanna, Cappai. Consiglio Nazionale delle Ricerche; ItaliaFil: Guglietta, Daniela. Consiglio Nazionale delle Ricerche; ItaliaFil: Francesca, Trapasso. Consiglio Nazionale delle Ricerche; ItaliaFil: Emanuela, Tempesta. Consiglio Nazionale delle Ricerche; ItaliaFil: Daniele, Passeri. Consiglio Nazionale delle Ricerche; ItaliaFil: Godeas, Alicia Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Gomez, Martin. Comisión Nacional de Energía Atómica; ArgentinaFil: Stefano, Ubaldini. Consiglio Nazionale delle Ricerche; Itali

Dialkyl carbonates: scale-up synthesis and application as green solvents for PVDF membranes preparation

Dialkyl carbonates (DACs) are well-known green solvents and reagents that have been extensively investigated as safe alternatives to chlorine-based compounds. In fact, they can replace alkyl halides and dimethyl sulfate in alkylation and carbonylation reactions as well as phosgene and its derivatives in alkoxycarbonylation ones. Recently we have developed a high yielding scale-up synthesis of non-commercially available or expensive DACs via transcarbonylation reactions of an alcohol with dimethyl carbonate (DMC) promoted by the nitrogen-based organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene TBD. Compared to previously published works, the proposed procedure has been customized for DACs large scale production (up to 100 mL of product obtained). Purification of these compounds has been achieved by fractional distillation and the exceeding reagents have been recovered and recycled. Selected DACs for this study include both symmetrical and unsymmetrical compounds, incorporating several alkyl, alkoxyalkyl, alkylamino and alkylthio functional groups. Chemical-physical properties of the new DACs have been also evaluated, as well as their water solubility. Furthermore, biodegradability and cytotoxicity tests have been carried out to investigate the effects of the different substituents on the greenness of these potential solvents and reagents. DACs application as green solvents for membrane preparation was next investigated, using non-solvent induced phase separation (NIPS) and vapor induced phase separation (VIPS) techniques, achieving both porous and plain membranes [4]. Morphology, additives effect, physical-chemical and mechanical proprieties as well as their performances in terms of water permeability and rejection were evaluated and compared to membranes obtained using commercially available cyclic carbonates (namely ethylene carbonate – EC and propylene carbonate – PC)

Application of Innovative Processes for Gold Recovery from Romanian Mining Wastes

The application of a new hydrometallurgical process for gold extraction by thiosulphate leaching from Romanian mining wastes, coming from Balan and Deva deposits, was studied. There was obtained 85% of Au extraction after leaching; moreover, an integrated flow-sheet, including recycling of process solution and carbon, was outlined, based on results obtained at a laboratory scale, using a schematic chemical circuit of treatment. Global recovery of the process (leaching-adsorption-desorption-electrodeposition) of about 75-80% of Au was achieved. The developed integrated flow-sheet, allows to recycle the reagents during the process, with a loss of only 5-10%, in particular thiosulphate and alcohol, for each complete circuit of treatment

SI113, a Specific Inhibitor of the Sgk1 Kinase Activity that Counteracts Cancer Cell Proliferation

Background/Aims: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this kinase as a central player in colon carcinogenesis and in resistance to taxanes. Methods: By in vitro kinase activity inhibition assays, cell cycle and viability analysis in human cancer model systems, we describe the biologic effects of a recently identified kinase inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. Results: SI113 was able to inhibit in vitro cell growth in cancer cells derived from tumors with different origins. In RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated the effects of paclitaxel on cell viability. Conclusion: Since SI113 appears to be effective in inducing cell death in RKO cells, potentiating paclitaxel sensitivity, we believe that this new molecule could be efficiently employed, alone or in combination with paclitaxel, in colon cancer chemotherapy

Toward a Multidisciplinary Strategy for the Classification and Reuse of Iron and Manganese Mining Wastes

The aim of this paper is to evaluate an integrated multidisciplinary strategy for the characterization of mining waste, their possible recycling and reuse. The use of Fe-Mn rich wastes in arsenic removal and phosphorus recovery from water and the phytoextraction potential of metals and their possible recovery from biomass are evaluated

Mechanical activation of alkaline residues in view of the application of accelerated carbonation

Mineral carbonation is a permanent and safe way for the sequestration of anthropogenic CO2. Carbonation reactions of metal oxides- and hydroxides-bearing alkaline solid waste occur spontaneously at atmospheric temperature and pressure, but proceed slowly to obtain an industrial viable process. In order to enhance mineral carbonation it is necessary a careful selection of the process routes and the process conditions and to use pre-treatments that increase the material reactivity. Mechanical activation is a pre-treatment method that increases mineral dissolution rates due to particle size reduction, specific surface increase and structural disorder production. Many experiments were conducted by increasing the grinding time and the carbonation time of the selected materials (steelmaking slag, incinerator ashes and track ballast) to evaluate how increasing grinding time influences the carbonation rate. The two key factors for the selection of the materials for the laboratory tests were the presence of alkali metals and alkaline earth metals and the time of mechanical activation. A jaw crusher and a continuous ring mill were used to reduce the samples size and / or to obtain homogeneous samples, while a disc mill and a vario-planetary mill were used for mechanical activation. The chemical composition of the samples was determined with X-ray fluorescence, a simultaneous DSC / TGA analyzer was utilized to define the carbonate content, the CO2 uptake and the calcium conversion efficiency and X-ray diffraction was used to determine the mineralogical composition of the materials and the changes in the crystal structure after the experiments. X-ray diffraction and thermogravimetric analyses of mechanically activated alkaline residues show respectively that with increasing the grinding time the crystallinity of the materials decreases and the carbonate content, the CO2 uptake and the calcium conversion efficiency generally increase

Il Processo degli Acquisti in Sogin Spa: il Business Intelligence per la valutazione della performance aziendale

In questa Tesi si presenta il tema del Business Intelligence, per la realizzazione di cruscotti e report di monitoraggio e controllo della Performance Aziendali applicata al caso della Sogin Spa. La progettazione e realizzazione di tale cruscotti e report è del tutto nuova poiché applicata ad un contesto aziendale, l’Azienda Sogin Spa, molto complesso e delicato per il settore, il decommissioning nucleare, in cui essa è inserita. Prima di tutto si è effettuata un’analisi minuziosa sul processo degli Acquisti, in concomitanza alla presenza dello strumento aziendale di eProcurement, da cui sono emerse delle criticità. Da qui è iniziato la fase di progettazione dei Cruscotti e Report, nel mondo del Business Intelligence, studiando le applicazioni servite dal SAP BI. Infine, si sono realizzati rispettivamente, cruscotti gestionali per il monitoraggio e controllo delle Richieste di Acquisto (RDA) e cruscotti gestionali per il monitoraggio e controllo degli Ordini di Acquisto (ODA)