4,463 research outputs found
Structural flexibility of hyaluronan oligomers as probed by molecular modeling
No full textIn the last few years, molecular modeling studies have been published that are devoted to a better understanding of the structural flexibility of hyaluronan (HA). Further conformational investigations, however, are needed on this polysaccharide, such as the application of statistical methods to perform enhanced one-step conformational analyses of its subunits. Moreover, the adjustment of assisted model building and energy refinement (AMBER) force field could provide the appropriate computational tool to study the interactions of HA and its derivatives with proteins. The present paper reports a combined Monte Carlo (MC) and molecular dynamics (MD) approach applied to the conformational study of HA, using an adjusted version of AMBER force field and the generalized Born solvent-accessible surface area (GB/SA) continuum solvation model. The MC approach turned out to be extremely effective to outline a conformational survey of the disaccharides constituting HA. Complete sets of conformations of the monomers were provided for the first time, some of which had never been predicted. MD technique, integrating the MC results, correctly reproduced the unusual stiffness of HA and predicted the existence of a minor skew-boat conformation of the β-D-glucuronic moiety. The computational approach, as a whole, improved the comprehension of the dynamic behavior of HA and offered a clear causal explanation of the relative dynamics of the glycosidic linkages
Peptides as autoimmune diseases antigenic probes - A peptide-based reverse approach to detect biomarkers of autoimmune diseases
No full textAbstract not availabl
Feline immunodeficiency virus plasma load reduction by a retroinverso octapeptide reproducing the Trp-rich motif of the transmembrane glycoprotein
No full textThe Trp-rich motif (TrpM) of the transmembrane glycoprotein (TM) of lentiviruses is an attractive domain on which to design new potential cell entry peptide inhibitors. We recently demonstrated that an octapeptide reproducing the TrpM of feline immunodeficiency virus (FIV), designated C8, broadly inhibited this virus in vitro and that the retroinverso analogue of this peptide (riC8) was almost as inhibitory and exhibited features suggestive of a much increased stability. Here, we demonstrated that riC8 is indeed highly stable, maintaining its concentration unchanged for at least 24 In in cat serum in vitro. Furthermore, once inoculated into cats, riC8 produced no major acute toxic effects and exhibited satisfactory pharmacolkinetic properties. Finally, we report the results of a short-term monotherapy experiment in chronically FIV-infected cats showing that riC8 is well tolerated and also has substantial antiviral activity in vivo. In particular, the mean viral load of riC8-treated animals declined progressively with increasing time of treatment, whereas that of control animals given C8 or solvent alone did not. These results provide the first evidence that clinically useful inhibition of virus replication with a small peptide derived from a functional domain of the TM of a lentivirus can be achieved in vivo
New insights into the biological properties of Crocus sativus L.: chemical modifications, human monoamine oxidases inhibition and molecular modeling studies
No full textAlthough there are clinical trials and in vivo studies in literature regarding the anxiolytic and antidepressant activities of the components of Crocus sativus L., their effects on the human monoamine oxidases (hMAO-A and hMAO-B), enzymes which are involved in mental disorders and neurodegenerative diseases, have not yet been investigated. We have thus examined the hMAO inhibitory activities of crocin and safranal (the most important active principles in saffron) and, subsequently, designed a series of safranal derivatives to evaluate which chemical modifications confer enhanced inhibition of the hMAO isoforms. Docking simulations were performed in order to identify key molecular recognitions of these inhibitors with both isoforms of hMAO. In this regard, different mechanisms of action were revealed. This study concludes that safranal and crocin represent useful leads for the discovery of novel hMAO inhibitors for the clinical management of psychiatric and neurodegenerative disorders
Interactively using Semantic Web knowledge: Creating scalable abstractions with FacetOntology
No full textThe amount of knowledge accessible on the Semantic Web is growing, and there is a need for a scalable solution to facilitate exploring that data. Currently approaches to exploring Semantic Web data either focus on exploring resources individually, following links during exploration, and making little use of collated data, or take the approach of collating and aligning multiple sources into one store for one purpose, and hand-crafting a specific browsing interface onto it. We present an approach that provides a scalable browsing interface, which can browse knowledge from the Semantic Web at will. Our approach creates abstractions of knowledge, collated into facets, which are described using FacetOntology. FacetOntology facilitates describing facets from RDF data, suitable for use in creating datasets for faceted browsing
Growth Morphologies and Mechanisms of Non-Equilibrium Solidified MC Carbide
No full textGrowth morphologies and mechanisms of the carbide of group IVB and VB elements (MC carbide), a typical faceted crystal, were studied with an estimated cooling rate from 102 to 105 K/s. Results showed that although the growth morphologies of the MC carbide vary remarkably with solidification cooling rate, the solid/liquid interface is always atomically smooth, and the growth mechanisms are always lateral growth. The growth mechanism transition from lateral to continuous growth mode, which was predicted by the classic crystal growth theory, was not observed for the TiC type MC carbide within the estimated cooling rate range of 102?105 K/s
Ruth Klüger: la creatività per non “smarrirsi strada facendo”
No full textR. Klüger, a jewish viennese, a US citizen and a germanist, is the Author of two autobiographies “weiter leben”and “unterwegs versore”. Written in a style which alternates between essay and poetry, account and recollection, they are the occasion for the Author to establish a dialogue with the women having as a focus the exchange of experiences and reflections over the status of the feminine emancipation
Eutectic MC Carbide Growth Morphologies of a Laser Clad TiC/FeAl Composite Coating
No full textIn this paper, eutectic MC carbide growth morphology and its evolution with laser scanning speed were studied comprehensively of a laser clad MC carbide reinforced FeAl intermetallic matrix composite coating. As the laser scanning speed increased, the growth morphology of eutectic MC carbide was found to be needle-aligned annulation, butterfly-like and well-developed dendrite
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