1,159 research outputs found
Giulia Veronica Varisco
No full textThe headword explains the biography and the contribution of the author Giulia Varisco to the children's literatur
Structural and biophysical studies on the lectin domain of GalNAc-T6 for therapeutic applications
No full textThe expression of glycoproteins containing immature truncated O-glycans such as the Thomsen-Friedenreich antigen (Ser/Thr-O-Galβ1–3GalNAc; T-antigen) and the Lewis antigen (sialyl-T-antigen) is a characteristic feature observed on almost all malignant epithelial cells. Therefore, there is a particular interest in their application not only as prognostic markers but also as therapeutic targets [1]. These antigens can be recognized by lectins, a group of highly specific carbohydrate-binding proteins that have been proposed as useful tools for antitumor drug-targeting [2].The three-dimensional structure of several lectins with antitumor properties has been determined in our laboratory by X-ray crystallography. N-α-acetylgalactosaminyltransferase-6 (GalNAc-T6) is an enzyme present also in humans which contains a catalytic domain and a lectin domain with a binding site for N-acetylgalactosamine (GalNAc), one of the saccharides exposed by cancer cells (Tn-antigen). Unlike other lectins with these properties, the lectin domain of GalNAc-T6 presents a structural fold found also in other human proteins, unlocking the opportunity to use protein engineering tools to design new anticancer therapeutics [3]. The three-dimensional structure of GalNAc-T6 has not been determined so far, neither has been its substrate specificity. Therefore, the production of a recombinant form containing only the lectin domain can contribute to these two critical points that need to be considered to evaluate its possible use in cancer therapies. The lectin domain of this enzyme was expressed by cloning the C-terminal portion of the DNA coding sequence and introducing it into Pichia pastoris for its recombinant production. Biophysical methods such as spectrofluorimetry and isothermal titration calorimetry were used to analyze the ability of the engineered protein to bind the T-antigen monosaccharides. The binding dissociation constant (Kd) of the protein-carbohydrate interaction was determined. The stability of the protein was also studied through its thermodynamic parameters of unfolding using differential scanning calorimetry. Crystallization screenings were set up using a broad variety of precipitants in order to produce crystals to be used to study the three-dimensional structure of the engineered protein using X-ray diffraction. The crystals that were grown were taken to the European Synchrotron Radiation Facility (ESRF) in Grenoble (France) to carry out the diffraction experiments. Although we were able to collect data up to a resolution of 2.8 Å (854,648 reflections) all the crystals we have examined so far were found to be twinned making the assignment of a definitive space group uncertain. We are currently working on correcting this problem using both the appropriate software and attempting to grow better crystals. Our goal is to produce an engineered human protein that specifically recognizes cancer specific carbohydrates and is thus suitable for protein therapeutics applied in drug-delivery methods for cancer treatment. The present structural and biophysical data are the prerequisite for future studies regarding the biological and clinical properties of the lectin. [1] Stowell, S. R. Tongzhong J. and Cummings R. D. Protein Glycosylation in Cancer. Annu Rev Pathol 2015. 10: 473–510. [2] Sharon, N., and Lis, H. Lectins: from hemagglutinins to biological recognition molecules. A historical overview. Glycobiology. 2004. 14: 53–62. [3] Berois, N., Mazal, D. et al. UDP-N-Acetyl-D-Galactosamine: N-acetylgalactosaminyltransferase-6 as a New Immunohistochemical Breast Cancer Marker. Journal of Histochemistry & Cytochemistry. 2006. 54(3): 317–328
Ytterbium Disilicate/Monosilicate Multilayer Environmental Barrier Coatings: Influence of Atmospheric Plasma Spray Parameters on Composition and Microstructure
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Ytterbium Disilicate/Monosilicate Multilayer Environmental Barrier Coatings: Influence of Atmospheric Plasma Spray Parameters on Composition and Microstructure
by Giulia Di Iorio,Laura Paglia *ORCID,Giulia PedrizzettiORCID,Virgilio GenovaORCID,Francesco MarraORCID,Cecilia BartuliORCID andGiovanni PulciORCID
INSTM Reference Laboratory for Materials and Surface Engineering, Sapienza University of Rome, Eudossiana 18, 00184 Rome, Italy
*
Author to whom correspondence should be addressed.
Coatings 2023, 13(9), 1602; https://doi.org/10.3390/coatings13091602
Original submission received: 10 August 2023 / Revised: 31 August 2023 / Accepted: 11 September 2023 / Published: 13 September 2023
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Abstract
SiC/SiC ceramic matrix composites (SiCf/SiC CMCs) are regarded as the new materials for the hot-section components of aircraft gas turbine engines, since they have one-third of the density of metallic superalloys, a higher temperature capability, good mechanical strength, and excellent thermal shock resistance. However, high-temperature water-vapor-rich combustion gases can induce severe surface recession phenomena in SiC/SiC leading to component failure. For this reason, it is necessary to design protective coatings, i.e., environmental barrier coatings (EBCs), able to protect the SiC/SiC surface in combustion environments. In the present work, ytterbium monosilicate (Yb2SiO5), stable when exposed to water vapor at high temperatures, and ytterbium disilicate (Yb2Si2O7), characterized by a thermal expansion coefficient closer to that of the substrate, were selected for a multilayer EBC system. EBCs were processed using the atmospheric plasma spray (APS) technique. A set of deposition parameters were tested, varying the power of the torch, and the composition and microstructure of the deposited coatings were studied in terms of porosity, crack density, and post-deposition phase retention by performing SEM, EDS, and XRD analysis. The results allow for the definition of the influence of deposition parameters on the final properties of multilayer EBC coatings
Un unico Stato israelo-palestinese: l'inseguimento di un'utopia? Oltre la soluzione "a due Stati"
No full textCorrection to: Safety and Psychological Outcomes of Tandem t:Slim X2 Insulin Pump with Control-IQ Technology in Children, Adolescents, and Young Adults with Type 1 Diabetes: A Systematic Review
No full textThe second author name was incorrectly published as Giula Maria Smylie. The correct name is Giulia Marie Smylie. The original article has been corrected
Scrivere senza anestesia. La chiarezza di Giulia Niccolai
No full textIl saggio colloca storicamente la narratrice e poetessa Giulia Niccolai nel canone del Novecento letterario italiano discutendone poetica e cifre stilistiche. L'ampia analisi proposta tocca tutte le opere dell'autrice evidenziandone i legami intertestuali, anche tra poesia e narrativa, e i progressivi sviluppi in un arco cronologico esteso, tra anni Sessanta e primi anni Duemila. Lo studio coglie anche l'importanza dei riferimenti alle arti visive, in particolare alla fotografia, che Giulia Niccolai ha praticato in prima persona negli anni della Neoavanguardia, e alla pittura americana.The essay places the narrator and poet Giulia Niccolai in the canonical twentieth century Italian literary discussing her poetics and stylistic figures. The wide analysis proposed touches all the works of the author highlighting the intertextual links, also between poetry and narrative, and the progressive developments in an extended chronological period, between the Sixties and early Twenties. The study also captures the importance of references to the visual arts, especially photography, which Giulia Niccolai has practiced in the years of the Neo-avant-garde, and to American painting
Structural insights into the bifunctional enzyme human FAD synthase
No full textHuman flavin adenine dinucleotide synthase (hFADS) is a bifunctional, multi-domain enzyme that exhibits both flavin mononucleotide adenylyltransferase and pyrophosphatase activities. Here we report the crystal structure of full-length hFADS2 and its C-terminal PAPS domain in complex with flavin adenine dinucleotide (FAD), and dissect the structural determinants underlying the contribution of each individual domain, within isoforms 1 and 2, to each of the two enzymatic activities. Structural and functional characterization performed on complete or truncated constructs confirmed that the C-terminal domain tightly binds FAD and catalyzes its synthesis, while the combination of the N-terminal molybdopterin-binding and KH domains is the minimal essential substructure required for the hydrolysis of FAD and other ADP-containing dinucleotides. hFADS2 associates in a stable C2-symmetric dimer, in which the packing of the KH domain of one protomer against the N-terminal domain of the other creates the adenosine-specific active site responsible for the hydrolytic activity
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L'afrofuturismo tra Stati Uniti e Italia. Dalla memoria storica ai viaggi intergalattici per re-immaginare futuri postumani
No full textIn this article the author explores the cultural movement called Afrofuturism, tracing its origins, features, simbology, and its historical and political meanings. Starting from the (supposed) discoursive gap between African and African American people on one side and technology and science fiction on the other, this paradigm addresses themes related to the intersection of African Diaspora and African cultures with technology and science fiction, with the aim to recover the history of slavery and racism through the projections into alternative space-time contexts. In particular, the author explores the feminist afrofuturism perspective in order to examine the specific oppression and cultural production of African and African American women. In doing so, the author analyzes the development of afrofuturism in Italy, focusing on the work of the singer and beatmaker Karima 2G
Multiple and Alternative Sites Make Tau Protein an Adaptable Sticky Surface for the SH3 Domain of Fyn Kinase
No full text: The interaction between the microtubule associated protein Tau and the tyrosine kinase Fyn is believed to play a pivotal role in the early stage of Alzheimer's disease. Previous studies have identified the SRC Homology 3 (SH3) domain of Fyn as the binding receptor of several proline-rich motifs in Tau. However, the role of each proline-rich motif and their interplay in molecular recognition are still unclear. In this work, we investigated the mechanism of Fyn-SH3 recognition by the multiple PxxP sites inserted within the full-length Tau protein by using nuclear magnetic resonance (NMR) spectroscopy combined with computational, calorimetric and in-cell FRET (Förster resonance energy transfer) methods. Both in vitro and in-cell experiments revealed no single binding site strictly necessary for the binding. Instead, Fyn-SH3 contacts full-length Tau on multiple hot spot regions, located over a distance of 85 residues, through global moderate-to-low affinity interactions. Beyond two principal regions containing classical PxxP motifs, we identified a novel non-canonical binding site at the beginning of the microtubule binding domain. Our study indicates that multiple binding sites in Tau are involved in the interaction, making Tau an adaptable recognition surface that can function when single consensus motifs are deleted
BDC-Decomposition for global influence analysis
No full textIn biochemical networks, the steady-state input-output influence is the sign of the output steady-state variation due to a persistent positive input perturbation; if the sign does not depend on the value of the strictly positive system parameters, the influence is structural. As recently shown for small perturbations, when the linearized system approximation is valid, steady-state input-output influences can be structurally assessed, for biochemical networks with m unknown parameters, by means of a vertex algorithm with complexity 2m. This letter shows that the structural input-output influence of a biochemical network is a global property, which does not require any small-perturbation assumption. It also shows that, using a new algorithm, the complexity can be reduced down to 2m-n , where n is the system order, thus drastically reducing the computation time. Finally, when the uncertain parameters belong to known intervals, non-conservative bounds are given for the steady-state ratio between output and input, allowing for sensitivity analysis.Accepted Author ManuscriptTeam Tamas Keviczk
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