106,879 research outputs found
Micheli, Murri e la prima Democrazia cristiana
No full textIl saggio analizza i contatti, durante il periodo giovanile, del cattolico parmigiano Giuseppe Micheli e la il gruppo della prima Democrazia cristiana di Romolo Murri, da cui emerge con evidenza l'influsso murriano su Micheli. Micheli avrebbe poi avuto un brillante futuro politico, prima nel Partito popolare e poi nella Democrazia cristiana degasperian
Le vite degli uomini illustri di Plutarco volgarizzate da Girolamo Pompei con varie note trascelte dal commento di Dacier edizione stereotipa ... volume 1. (-12.) - vol. 4
No full textCremona : dalla stamperia e fonderia stereotipa di Luigi De-Micheli e Bernardo Bellini, 1824
Incisioni in ovale di G. Maina
Segn.: [1]-15/8.
Mutilo di 1 c. di tav. Legatura in cartone rigido
Fondo Catellani
https://galileodiscovery.unipd.it/discovery/fulldisplay?context=L&vid=39UPD_INST:VU1&search_scope=MyInst_and_CI&tab=Everything&docid=alma99002563265020604
Echinodorus longipetalus Micheli
No full textEchinodorus longipetalus Micheli in A. DC. & C. DC., Monogr. Phan. 3: 60. 1881. Lectotypus (colección designada por RATAJ, 1969: 332; specimen in hoc loco rite designatum): PARAGUAY. Central: “ Patiño-Cue, dans les marais, fleurs blanches ”, 28.II.1875, Balansa, B. 570 (G-DC [G00488759]!; isolecto-: K [K000098939] foto). Syntypi: PARAGUAY. Cordillera: “ Cordillère de Peribebuy, dans les prairies marécageuses, fleurs blanches ”, 11.I.1877, Balansa, B. 570a (G-DC [G00488758]!; isosyn-: K [K000098938] foto). BRASIL: Gardner 5191 (BM); Riedel s.n. (LE); SaintHilaire 1395 (P); Saint-Hilaire 178 (P); Weddell 1973 (?). Notas. – La lectotipificación efectuada por RATAJ (1969) no tiene en cuenta la regla que establece, en la designación de un lectótipo, la obligación de elegir primero el síntipo y si éste no existiera un isosíntipo (Art. 9.12, McNEILL & al., 2012). Micheli en su descripción menciona que el espécimen Balansa 570 fue consultado en el herbario G-DC, lo que hace de este espécimen uno de los síntipos. La existencia de otro espécimen de Balansa 570 no está mencionada por Micheli en el protólogo, y por lo tanto el espécimen de K es un isosíntipo (duplicado del síntipo original). Efectuamos aquí la corrección de la lectotipificación errónea de RATAJ (1969) designando el síntipo del herbario G-DC como lectótipo.Published as part of Lehtonen, Samuli & Ramella, Lorenzo, 2017, Tipificaciones y sinónimos nuevos en Echinodorus Engelm. y Sagittaria L. (Alismataceae) de la Flora del Paraguay, pp. 405-407 in Candollea 72 (2) on page 406, DOI: 10.15553/c2017v722a17, http://zenodo.org/record/572208
Design, synthesis and biological characterization of PfGAPDH inhibitors
No full textMalaria has a tremendous health, social and economic impact on people living in tropical and subtropical regions of the world. WHO estimated 214 million cases and 438 000 deaths in 2015 and 3.2 billion people are globally at risk of infection1. Available treatments are becoming progressively less effective, mainly because parasites are constantly acquiring resistance toward the drug in use. Therefore, there is an urgent need of developing therapeutic agents acting on new targets.
Plasmodium parasites (P. falciparum is the most lethal), in their amastigote phase, produce energy only through glycolysis. In this pathway, GAPDH catalyses the first energy productive step and thus represent a valuable target for drug discovery. Known GAPDH inhibitors that bind to the active site are small nonselective molecules (iodoacetamide, 3-bromopyruvate), which irreversibly react with cysteine residues of the enzyme, including the catalytic one. We designed and synthesized the first series of inhibitors characterized by a 3-bromoisoxazoline warhead2, inspired by 3-bromoacivicin, a known inhibitor of reactive cysteine containing enzymes3. The compounds were assayed for the inhibitory activity on the P. falciparum isolated enzyme showing a biphasic irreversible inactivation. MS/MS studies of the digested protein demonstrated the mild reactivity of the exploited warhead, which only reacts with catalytic Cys (activated by a His residues). The human ortholog of GAPDH is only partially inhibited (up to 25%). We explained this through a negative cooperativity that prevents the alkylation of all the four monomers of hGAPDH, resulting in selectivity among the two isoforms of GAPDH4. Compounds were also assayed on cultures of the bloodstream form of P. falciparum and human cell lines in order to determine their in vitro antiparasitic activity and toxicity.
The goal of this project is to obtain compounds with improved potency and pharmacokinetic properties, suitable for in vivo studies on animal model of P. falciparum infections.
1. http://www.who.int/mediacentre/factsheets/fs094/en/
2. Bruno, S.; Pinto, A.; Paredi, G.; Tamborini, L.; De Micheli, C.; La Petra, V.; Marinelli, L.; Novellino, E.; Conti, P.; Mozzarelli, A. J. Med. Chem. 2014, 57(17), 7465-7471.
3. a) Conti, P.; Pinto, A.; Wong, P.E.; Major, L.L.; Tamborini, L.; Iannuzzi M.C.; De Micheli, C.; Barrett, M.P.; Smith, T.K. ChemMedChem 2011, 6(2), 329-333. b) Tamborini, L.; Pinto, A.; Smith, T.K.; Major, L.L.; Iannuzzi, M.C.; Cosconati, S.; Marinelli, L.; Novellino, E.; Lo Presti, L.; Wong, P.E.; Barrett, M.P.; De Micheli, C.; Conti, P. ChemMedChem 2012, 7(9), 1623-1634.
4. Bruno, S.; Margiotta, M.; Pinto, A.; Cullia, G.; Conti, P.; De Micheli, C.; Mozzarelli, A. Bioorg. Med. Chem. 2016, 24(12), 2654-2659
Vecchio G.-Truffelli M., Giuseppe Micheli nella storia d'Italia e nella storia di Parma, Carocci, Roma 2002
No full textRecensione al volume: Vecchio G.-Truffelli M., Giuseppe Micheli nella storia d'Italia e nella storia di Parma, Carocci, Roma 200
Joint co-clustering: co-clustering of genomic and clinical bioimaging data
No full textAbstractFor better understanding the genetic mechanisms underlying clinical observations, and better defining a group of potential candidates for protein-family-inhibiting therapy, it is interesting to determine the correlations between genomic, clinical data and data coming from high resolution and fluorescent microscopy. We introduce a computational method, called joint co-clustering, that can find co-clusters or groups of genes, bioimaging parameters and clinical traits that are believed to be closely related to each other based on the given empirical information. As bioimaging parameters, we quantify the expression of growth factor receptor EGFR/erb-B family in non-small cell lung carcinoma (NSCLC) through a fully-automated computer-aided analysis approach. This immunohistochemical analysis is usually performed by pathologists via visual inspection of tissue samples images. Our fully-automated techniques streamlines this error-prone and time-consuming process, thereby facilitating analysis and diagnosis. Experimental results for several real-life datasets demonstrate the high quantitative precision of our approach. The joint co-clustering method was tested with the receptor EGFR/erb-B family data on non-small cell lung carcinoma (NSCLC) tissue and identified statistically significant co-clusters of genes, receptor protein expression and clinical traits. The validation of our results with the literature suggest that the proposed method can provide biologically meaningful co-clusters of genes and traits and that it is a very promising approach to analyse large-scale biological data and to study multi-factorial genetic pathologies through their genetic alterations
Orthosteric and allosteric ligands selectively acting at cholinergic receptor subtypes
No full textThe presentation will focus on the results recently achieved by our research group in the design, synthesis and pharmacological evaluation of selective ligands which target cholinergic receptor subtypes, belonging to both the nicotinic (nAChR) and the muscarinic (mAChR) acetylcholine receptor families. A set of spirocyclic derivatives will be illustrated, in which the simultaneous presence of the quinuclidinyl and Delta2-isoxazolinyl moieties, coupled with suitable stereoelectronic features of the substituent at position 3 of the spirocyclic ring, engendered a selective agonist profile at the homomeric neuronal alpha7 nAChRs [1]. The most promising compound in the series has been further investigated in preclinical studies and in in vivo models of CNS disorders and neuropathic pain. A group of novel hybrid peptides structurally related to natural alpha-conotoxins MII and PIA will be also presented, which behave as competitive antagonists able to discriminate alpha6beta2* and alpha3beta2* nAChR subtypes [2]. The five mAChR subtypes bind their physiological transmitter in the highly conserved orthosteric site within the transmembrane domains of the receptors. Orthosteric muscarinic agonists have negligible binding selectivity and poor signaling specificity. A less conserved allosteric site has been also characterized at the extracellular entrance of the binding pocket of mAChRs. To gain subtypeselective M2 receptor activation, we designed a group of putative bitopic compounds, i. e. hybrid derivatives fusing highly potent, unselective oxotremorinelike orthosteric activators with M2-selective bis(ammonio)alkane-type allosteric fragments. The new ligands interacted simultaneously with both recognition areas of the receptor protein, thus allowing the exploitation of favorable features of the orthosteric and the allosteric site by a single ligand molecule. The orthosteric interaction provided high affinity binding and activation of M2 mAChRs. The allosteric interaction yielded receptor subtype-selectivity and, in addition, could modulate efficacy and activate pathway-specific intracellular signaling [3]. [1] C.Dallanoce, P.Magrone, C.Matera, F.Frigerio, G.Grazioso, M.De Amici, S.Fucile, V.Piccari, K.Frydenvang, L.Pucci, C.Gotti, F.Clementi, C.De Micheli, ChemMedChem, 6, 2011, 889-903. [2] M.De Amici, G.Grazioso, C.Dallanoce, C.De Micheli et al., submitted. [3] K.Mohr, C.Tränkle, E.Kostenis, E.Barocelli, M.De Amici, U.Holzgrabe, Br.J.Pharmacol., 159, 2010, 997-1008
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