108 research outputs found

    Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death

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    BACKGROUND: Glycogen Synthase Kinase-3 (GSK-3) \u3b1 and \u3b2 are two serine-threonine kinases controlling insulin, Wnt/\u3b2-catenin, NF-\u3baB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3\u3b1 and GSK-3\u3b2 function in multiple myeloma (MM). METHODS: GSK-3 \u3b1 and \u3b2 expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 \u3b1 and \u3b2 isoforms. Survival signaling pathways were studied with WB analysis. RESULTS: GSK-3\u3b1 and GSK-3\u3b2 were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3\u3b2 knock down decreased MM cell viability, while GSK-3\u3b1 knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of \u3b2-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3\u3b1 knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. CONCLUSIONS: These data suggest that in MM cells GSK-3\u3b1 and \u3b2 i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors

    Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

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    Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defense responses. In this review, we summarize the latest findings on plant factors that are activated by pathogen effectors to suppress plant immunity. By looking from a different point of view into host and nonhost resistance, we propose a novel breeding strategy: disabling plant disease susceptibility genes (S-genes) to achieve durable and broad-spectrum resistance

    Development of 100^{100}Mo-containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search

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    We report recent achievements in the development of scintillating bolometers to search for neutrinoless double-beta decay of 100^{100}Mo. The presented results have been obtained in the framework of the LUMINEU, LUCIFER and EDELWEISS collaborations, and are now part of the R\&D activities towards CUPID (CUORE Update with Particle IDentification), a proposed next-generation double-beta decay experiment based on the CUORE experience. We have developed a technology for the production of large mass (\sim1 kg), high optical quality, radiopure zinc and lithium molybdate crystal scintillators (ZnMoO4_4 and Li2_2MoO4_4, respectively) from deeply purified natural and 100^{100}Mo-enriched molybdenum. The procedure is applied for a routine production of enriched crystals. Furthermore, the technology of a single detector module consisting of a large-volume (100\sim 100~cm3^3) Zn100^{100}MoO4_4 and Li2_2100^{100}MoO4_4 scintillating bolometer has been established, demonstrating performance and radiopurity that are close to satisfy the demands of CUPID. In particular, the FWHM energy resolution of the detectors at 2615 keV --- near the QQ-value of the double-beta transition of 100^{100}Mo (3034~keV) --- is \approx 4--10~keV. The achieved rejection of α\alpha-induced dominant background above 2.6~MeV is at the level of more than 99.9\%. The bulk activity of 232^{232}Th (228^{228}Th) and 226^{226}Ra in the crystals is below 10 μ\muBq/kg. Both crystallization and detector technologies favor Li2_2MoO4_4, which was selected as a main element for the realization of a CUPID demonstrator (CUPID-0/Mo) with \sim7 kg of 100^{100}Mo

    The triatominae species of French Guiana (Heteroptera: Reduviidae)

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    An annotated list of the triatomine species present in French Guiana is given. It is based on field collections carried out between 1993-2008, museum collections and a literature review. Fourteen species, representing four tribes and six genera, are now known in this country and are illustrated (habitus). Three species are recorded from French Guiana for the first time: Cavernicola pilosa, Microtriatoma trinidadensis and Rhodnius paraensis. The two most common and widely distributed species are Panstrongylus geniculatus and Rhodnius pictipes. The presence of two species (Panstrongylus megistus and Triatoma maculata) could be fortuitous and requires confirmation. Also, the presence of Rhodnius prolixus is doubtful; while it was previously recorded in French Guiana, it was probably mistaken for R. robustus. A key for French Guiana's triatomine species is provided

    Congo red immobilized on a silica/aniline xerogel: Preparation and application as an amperometric sensor for ascorbic acid

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    Congo red (CR) was immobilized on a silica/aniline xerogel through electrostatic interaction. The dye is strongly retained and is not easily leached from the xerogel matrix. The material containing the adsorbed dye was used to prepare a carbon paste electrode and the electrochemical properties of the hybrid material were investigated using cyclic voltammetry and amperometry. The modified electrode was used to study the electrochemical oxidation of ascorbic acid. The adsorbed dye mediates ascorbic acid oxidation at the solid electrode surface-solution interface at an anodic potential of 0.18 V at pH 7, in a 0.5 cool L-1 KCl solution. This novel modified carbon paste electrode shows good analytical performance for the determination of ascorbic acid in commercial Vitamin C tablets.17762562

    A sol-gel synthesis for thermally stable aniline/silica material

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    Aniline/silica sol-gel material was obtained. The aniline was immobilized on the silica surface using chloropropyltrimethoxysilane as bridge reagent. The base activator NaH was used to produce a fast SN2 reaction between the base and the alkylorganosilane. The resulting modified silica was characterized by elemental analysis and infrared spectroscopy using an oven cell. The organic coverage on the surface was proportional to the organic precursor concentration. The aniline/silica materials are thermally stable up to 300degreesC, in high vacuum.23212913
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