1,721,112 research outputs found
Ivano Eberini. Spillover
No full textLa review recensisce il podcast "Spillover" condotto dal prof. Ivano Eberini dell'Università degli Studi di Milano
Ivano Eberini, Spillover
No full textIvano Eberini, Spillover (CTU - Centro per l’innovazione didattica e le tecnologie multimediali, Università degli Studi di Milano, Podcast, 2020)
di Carlotta Fiammengh
DISC867317_SupplementalMaterial – Supplemental material for SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure
No full textSupplemental material, DISC867317_SupplementalMaterial for SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure by Luca Palazzolo, Chiara Paravicini, Tommaso Laurenzi, Sara Adobati, Simona Saporiti, Uliano Guerrini, Elisabetta Gianazza, Cesare Indiveri, Catriona M. H. Anderson, David T. Thwaites and Ivano Eberini in SLAS Discovery</p
Recombinant S. cerevisiae expressing Old Yellow Enzymes from non-conventional yeasts: an easy system for selective reduction of activated alkenes
No full textBackground: Old Yellow Enzymes (OYEs) are flavin-dependent enoate reductases (EC 1.6.99.1) that catalyze the stereoselective hydrogenation of electron-poor alkenes. Their ability to generate up to two stereocenters by the trans-hydrogenation of the C = C double bond is highly demanded in asymmetric synthesis. Isolated redox enzymes utilization require the addition of cofactors and systems for their regeneration. Microbial whole-cells may represent a valid alternative combining desired enzymatic activity and efficient cofactor regeneration. Considerable efforts were addressed at developing novel whole-cell OYE biocatalysts, based on recombinant Saccharomyces cerevisiae expressing OYE genes.Results: Recombinant S. cerevisiae BY4741{increment}Oye2 strains, lacking endogenous OYE and expressing nine separate OYE genes from non-conventional yeasts, were used as whole-cell biocatalysts to reduce substrates with an electron-poor double bond activated by different electron-withdrawing groups. Ketoisophorone, α-methyl-trans-cinnamaldehyde, and trans-β-methyl-β-nitrostyrene were successfully reduced with high rates and selectivity. A series of four alkyl-substituted cyclohex-2-enones was tested to check the versatility and efficiency of the biocatalysts. Reduction of double bond occurred with high rates and enantioselectivity, except for 3,5,5-trimethyl-2-cyclohexenone. DFT (density functional theory) computational studies were performed to investigate whether the steric hindrance and/or the electronic properties of the substrates were crucial for reactivity. The three-dimensional structure of enoate reductases from Kluyveromyces lodderae and Candida castellii, predicted through comparative modeling, resulted similar to that of S. cerevisiae OYE2 and revealed the key role of Trp116 both in substrate specificity and stereocontrol. All the modeling studies indicate that steric hindrance was a major determinant in the enzyme reactivity.Conclusions: The OYE biocatalysts, based on recombinant S. cerevisiae expressing OYE genes from non-conventional yeasts, were able to differently reduce the activated double bond of enones, enals and nitro-olefins, exhibiting a wide range of substrate specificity. Moreover whole-cells biocatalysts bypassed the necessity of the cofactor recycling and, tuning reaction parameters, allowed the synthetic exploitation of endogenous carbonyl reductases. Molecular modeling studies highlighted key structural features for further improvement of catalytic properties of OYE enzymes
Computational biochemistry: a link between base and applied research
No full textComputational biochemistry is mainly based on molecular modelling and informatics tools, combined to try addressing structural, dynamics and functional features of biomolecules, with focus on biopolymers. Its applications include comparative modelling, molecular dynamics simulations, and several other techniques, such as ab initio calculations based on the density functional theory.
Computations and simulations are frequently used to manage biochemical problems not easily addressed by wet experimental approaches, such as deciphering the three-dimensional structure of a biopolymer, inferring its in vivo activity, characterizing at a molecular level its catalytic function or its signal transduction mechanism, or studying the impact of mutations on the structure-function relationship in proteins and eventually their effects on carriers’ phenotypes.
Besides these purposes, mainly focused on basic research, computational biochemistry is becoming one of the most relevant tools of the drug discovery pipeline. It is useful for identifying putative targets, for solving their structure via computational methods, for better understanding their pathophysiological functions, and for identifying and deploying pharmacological strategies, primarily based on the development of novel compounds with specific target-modifying activities. Not only pharmacology, but also toxicology is benefitting from computational biochemistry to clarify the mechanism of action of xenobiotics or to prioritize large datasets of compounds in risk evaluation tasks.
In my talk, I am going to report some typical applications of computational biochemistry: an investigation about the dynamic behaviour of a model protein, some application to pharmacology towards the development of novel enzymatic inhibitors for atherosclerosis and of GPCR agonists for demyelinating neurodegenerative diseases, and an example of toxicological prioritization among environmental xenobiotics involved either in teratogenic or in endocrine disrupting outcomes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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