16 research outputs found

    Person

    No full text
    This record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/5971

    Concert al Palais Chaillot de París

    No full text
    Excursió artística de l'Orfeó Català a París (del 2 a l'11 de juny de 1952). Al verso: "Bajo la batuta maestra de Luis Maria Millet se interpretó en el Palacio Chaillot de París, la Gran Misa de J.S. Bach cuya ejecución [entusia]smó a los parisienses

    Concert al Palais Chaillot de París

    No full text
    Excursió artística de l'Orfeó Català a París (del 2 a l'11 de juny de 1952

    Stolz (geb. Ulrich), Yvonne Louise (01.05.1912-18.01.2004); 1946.08

    No full text
    http://scopeq.cc.univie.ac.at/Query/detail.aspx?id=6271

    Promotional headshot of French harpsichordist Robert Veyron-Lacroix wearing a dark suit and tie

    No full text
    This record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/431638Two inscriptions on front: Teddy Piaz, 122 Champs-Elysées Paris, and a signed message: à Madame Hanson-Dyer. Respectueusement, Affectueusement… et avec un sourire en plus ! R. Veyron-Lacroix, Novembre 54.311439 Sub-item: [2016.0035.00396] "Promotional headshot of French harpsichordist Robert Veyron-Lacroix wearing a dark suit and tie

    Proteomic investigation of the impact of Cannabidiolic acid on Eukaryotic Translation complex in glioblastoma

    No full text
    2021 - 2022Phytocannabinoids, the major secondary metabolites of cannabis plants, exert a wide range of biological activities. The present work was focused on investigating the mechanism of action of cannabidiolic acid (CBDA) in U87MG glioblastoma cell line, exploiting the efficacy of chemical-proteomics based approaches in identifying target proteins of uncharacterized drugs. DARTS experiments showed Eukaryotic Initiation Translation Factor 2A (EIF2A) as a putative target of CBDA. This interaction was further validated by western blot and CETSA, thus showing a thermal stabilization of Eukaryotic Translation Complex conferred by CBDA. Moreover, Limited Proteolysis showed that the EIF2A C-terminal portion 460-480 could play a critical role in the molecular recognition of CBDA by the protein. This result was also confirmed by Molecular Dynamics (MD) calculations, which revealed that CBDA interacts with a stretch of residues in the 460-480 portion and in the adjacent C-terminal helix, acting as a bridge between these regions. Hence, since EIF2A is the initiator factor of translation process, the impact of CBDA-EIF2A interaction on proteins synthesis was investigated by p-SILAC and enrichment via click-chemistry. Comparing CBDA and EIF2A-silencing treatments, a similar remodeling of nascent proteome was detected in the two conditions in terms of protein expression reduction and biological effect. Particularly, CBDA appeared to induce an UPR response, triggering as a balancing effect between the ER-stress response and the attempt to restore cellular homeostasis. Moreover, EIF2A revealed to interact not only with eukaryotic translation proteins but also with the proteins involved in triggering of UPR response and the CBDA-induced reorganization of eukaryotic translation machinery. Interestingly, these proteins seem to be involved in several pathways already highlighted by nascent proteome investigation. In order to evaluate the protein-CBDA interaction in a cell model closer to the tumor in vivo, a 3D cell culture was set up using a classic-sandwich model. Based on the observation that in 2D- and 3D- cell model U87MG cells grow differently since in 3D they show a natural shape and more cellular interactions, a global proteome comparative analysis was firstly carried out. Interestingly, the obtained results highlighted a higher-amount of proteins involved in invasion cellular processes and cell-ECM interaction expressed by 3D-U87MG, compared to 2D-cultured cells. These findings prompted us to further study the effects of CBDA in 2D and 3D cellular models. In 3D cultured cells, CBDA showed a different cytotoxicity depending on the concentration of FBS in the upper and lower- gels and in the culture medium as well. DARTS assay performed in this cell system also suggested a direct correlation between the percentage of FBS used in cell culture conditions and the ability of CBDA to interact with EIF2A, thus confirming the critical role played by the molecule-FBS interaction on its availability. Furthermore, comparing the results of DARTS assays performed on 2D and 3D, a difference of the EIF2A interactome with respect to the entire translational complex was revealed in the two conditions. In contrast to 2D-cellular model, EIF2A was highly resistant to proteolysis in untreated 3D cultured cells, but was more digested after CBDA treatment. This result suggested that EIF2A in 3D-U87MG could be likely associated with the other protein partners more strongly than in the 2D model. In closing of this study, it is possible to state that the use of a multi-proteomic approach allowed us to highlight the potential impact of CBDA on the eukaryotic translation machinery, also suggesting the importance of investigating the interactome differences that exist between innovative three-dimensional and conventional cellular models. [edited by Author]XXXV cicl

    Proteomic profiles of cultured cells stimulated with VEGFs dimers and search for natural compounds angiogenesis inhibitors

    No full text
    2010 - 2011Some members of the vascular endothelial growth factor (VEGF) family, such as VEGF and PlGF, and related receptors (KDR and Flt-1) play a key role in the modulation of angiogenesis, both physiological and pathological. For this reason they are considered valid therapeutic targets. Anti-angiogenesis therapy, despite the scientific efforts and promising results, is still suffering of some limitations. In the attempt to produce a research that can facilitate the future development of new antiangiogenic therapy strategies, we realized these goals: 1) carry out an expression proteomic study of cell coltures, after their treatment with some dimers of VEGF family; 2) identify new natural compounds able to inhibit the axis of interaction VEGF/Flt-1 and PlGF/Flt-1. We used gel-based proteomics to detect the differentially expressed proteins by VEGF, PlGF and VEGF/PlGF, in HUVECs and HEK-293-hFlt-1. Gels variability was also determined by principal component analysis (PCA)... [edited by Author]X n.s

    Study of the mechanism of action of bioactive plants tarpenoids

    No full text
    2014-2015Natural products are small-molecule secondary metabolites displaying considerable structural complexity and “privileged scaffolds”. They are able to bind several endogenous targets eliciting biological effects as chemical weapons or to convey information from one organism to another. Nowadays, medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets. Therefore, the primary purpose of this PhD thesis has been a comprehensive characterization of the interactome profile and then the molecular mechanism of action of bioactive natural molecules. Achieving this in an effective, unbiased and efficient manner subsists as a significant challenge for the new era in drug discovery and optimization. Indeed, the full understanding of the mechanism of action of natural molecules could lead to a number of advantages: first of all, exploit their full therapeutic potential, the identification of side effects or toxicity, or the ability to set up target-based assays and to allow structure activity relationships studies to guide medicinal chemistry efforts towards lead optimization. In my research project, the attention was paid on ent-kaurane diterpenes, a class of natural terpenoids with a great structural variability and a wide spectrum of biological activities. Firstly, I focused on the determination of the interactome of a semi synthetic compound 15-ketoatractyligenin methyl ester. This compound has been previously reported to possess high antiproliferative activity against several solid tumor-derived cell lines. In this regard, I decided to investigate the mechanism of action of this actratylignin derivative researching first of all its molecular targets, responsible for the biological activity. In order to achieve this goal, I used a chemical proteomic approach first. This study led to the identification of PPARγ as the main cellular partner of this compound; achieved results were supported and validated through different biological assays. Subsequently, I studied another diterpene: oridonin. This molecule has been shown to have multiple biological activities. Among them, the anticancer activity has been repeatedly reported by many research groups. With the aim of expanding and validate our knowledge about this molecule, also seen the limitations of the fishing for partners method, I decided to use two orthogonal compound-centric proteomics approaches to define the possible protein target(s) of oridonin. Using this strategy HSP70 and nucleolin were identified. Therefore, several in vitro and in cell tests have been performed to validate the interaction of oridonin with these proteins, and to evaluate its effect on their activity. Some of these tests were developed and optimized during my period of research abroad at the Massachusset General Hospital- Center for System Biology -Harvard Medical School; in that twelve months period I expanded my knowledge into the techniques useful for the study of the mechanism of action of a small molecule, also applying experimental methods complementary to proteomics and focusing on the use of high-resolution intravital microscopy imaging for drug pharmacology. [edited by Author]XIV n.s

    A chemical-toxicological study of animal models exposed to organohalogen environmental contaminants

    No full text
    2011 - 2012Sensitive effect determination, the understanding of molecular toxicity mechanisms and the discovery of novel biochemical biomarkers are some of the major challenges in ecotoxicology in dealing with chemicals in the environment. Among several ‘omics’ tools, proteomic approaches are used to study the whole proteome of organisms and may provide novel insights into the functional molecular state of a biological system and for discovery of new sensitive biomarkers indicating exposure or effects at low toxicant concentrations. In this study, a proteomic approach has been used in Mytilus galloprovincialis as a screening of changes in protein expression caused by a mixture of polychlorinated biphenyls (PCBs), in order to characterize the effects of these environmental contaminants on protein profile and to develop new molecular biomarkers through identification of more drastically altered proteins. To achieve this objective, 100 mussels were exposed to PCB 138, 153 and 180 for 3 weeks under controlled conditions at the concentration of 30μg/l. An equal number of mussels was kept under the same conditions, but not treated, as control. The edible parts were homogenized and lyophilized. Extracted proteins were quantified and separated by two-dimensional electrophoresis (2-DE). It has been made a comparative study of two-dimensional electrophoresis gels obtained from proteomic analysis and the changes in protein expression were assessed by image analysis. Image analysis included spot detection, quantification, normalization and matching. On average more than 1000 spots were resolved and altered expression was qualitatively detected. Stained protein spots of interest were excised from preparative gels and their tryptic digests were subjected to protein identification by mass spectrometry. It was used Matrix Science Mascot search engine, database NCBI and for a homology search the program BLAST. .. [edited by Author]XI n.s
    corecore