8,922 research outputs found
Identification of “on-off residues” in rat Cav1.2 α1C subunit channel using in silico analysis and docking simulation
No full textIntroduction
Voltage-dependent calcium channels (VSCC) is involved in important biological function as calcium ion transmembrane transport and cardiac contraction. VSCC is a multi-pass membrane protein, made up from α-1, α-2, β and δ subunits. α-1 subunit regulates the entry of ion calcium. Voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2 α1C subunit channel) is an isoform of VSCC, and is characterized from an high-voltage activation. Previous study have shown that class of molecules as benzothiazepines (Tikhonov D. et al, 2008), are able to block the alpha-1C subunit. Recent works have demonstrated that molecules belonged at the flavonoid class are able to inhibit or to raise channel activity (Saponara S. et al, 2011). In this work, we reported the sensing- residues that could play a key role in Cav1.2 α1C activity. Furthermore, we proposed a potential mechanism of action inside Cav1.2 α1C binding-site with differences between inhibitors and stimulants. Our work has clarifiedas the ligands operate on Cav1.2 α1C, this information could be useful in order to improve their usefulness.
Methods
The 3D structure of Cav1.2 α1C subunit channel was obtained on basis of previous work (Saponara S. et al, 2015). The structure of flavons were downloaded from Pubchem(Kim S. et al, 2015). Docking simulation was carried out through Autodock/Vina v.1.1.2 (O.Trott et al, 2010). PDBePISAwas used in order to evaluate buried surface area values (B.S.A). Protein-ligand interactions were obtained using protein–ligand interaction profiler (P.L.I.P)(Salentin S. et al, 2015). Pymol was used as molecular graphics system (The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.).
Results and discussion
In vitro analysis on rat Cav1.2 L-type channel of 20 flavonoids have shown stimulatory and inhibitory activities (Saponara S. et al, 2015).The 11 inhibitors and 8 stimulators derivatives are positioned in their corresponding binding-sites with peculiar sensing-residues interactions (shown in figure 1). Analyzing the network of interactions among the two classes of flavonoids we have observed hydrogen bonds, hydrophobic interactions and π–π stacking bonds characterizing their activities that could differently promote pore open/closed conformation and decreasing voltage-sensitive calcium channel activity (Tikhonov D. et al, 2009). Furthermore, on the basis of the selectivity filters model, we have evaluated B.S.A residues values present in the binding-sites, we have observed that B.S.A of some residues dramatically decrease, showing that these residues play a key role in the pore stabilization. The different mechanism of action of these molecules can be attributed to their chemical-physical proprieties as steric hindrance and different positions of hydroxyl groups.</jats:p
Identification of Inhibitors Binding Site of Ebola L Polymerase Based on its Homology Model
No full textModeling specific phobias and post-traumatic stress disorder in rodents: the challenge to convey both cognitive and emotional features
No full textAberrant emotional memory processing is a core, disabling feature of both specific phobias and posttraumatic stress disorder (PTSD), two psychiatric diseases of significant prevalence and morbidity whose cognitive symptoms cannot be adequately treated by current psychopharmacological tools. Elucidating the neurobiological mechanisms involved in the etiology of these diseases is of great interest for the identification of new therapeutics that improve not only the symptomatology but also the full recovery from the pathology. To this aim, several animal models have been proposed based on substantial resemblance between the behavioral alterations seen in animals and the human pathology. The purpose of this review is to describe and comment on the most commonly used rodent models of specific phobias and PTSD. A particular focus will be reserved to the cued version of fear conditioning, as the highly specific stimulus-bound conditioned fear response seems to fit well with clinical descriptions of phobic fear. Moreover, animal models of PTSD will be evaluated by referring to three elements that are considered essential in a valid model of this disease: stressor exposure, memory for the stressor, and anxiety-related behaviors. Finally, current therapeutic directions, with a focus on cannabinoid and glucocorticoid compounds, will be briefly outlined
Andrea Bacová
No full textAndrea Bacová focuses on research and teaching in the field of residential architecture. Her work includes systematic research on residential buildings and their urban context. She actively participates in promoting Slovak architecture and is the author of several publications and exhibitions
A preclinical model of Post-Traumatic Stress Disorder (PTSD) capturing both the emotional and cognitive features of the disease: behavioral validation
No full text
Viewer-, Author-, and Ownership in the Work of Andrea Zittel
No full textAndrea Zittel invites others to collapse the distinctions between artist, viewer, and collaborator by interacting with her usable works. This thesis explores the process of interacting with Zittel\u27s works, and how it affects viewer-, author- and ownership
The Lettere of Andrea Calmo: authorial artifices and historical reality
No full textopenNonostante l’edizione di Vittorio Rossi del 1888, la raccolta di "ingegnosi cheribizzi" e di "fantastiche fantasie" di Andrea Calmo è ancora avvolta da un certo mistero. L’autore, dissimulando la propria identità dietro alla “maschera” dell’umile pescatore veneziano, è stato in grado di offrire uno spaccato della cultura e della società nella Venezia cinquecentesca.
In particolare, è il quarto libro delle Lettere ad aver suscitato maggiore interesse tra gli studiosi ed i lettori: pubblicato nel 1566, a diversi anni di distanza dai primi tre, questo libro si distingue per il fatto che tutte le epistole sono indirizzate a delle donne immaginarie o realmente esistite.
In questa sede si propone, in primo luogo, uno studio della biografia del Calmo accompagnata da un’analisi del contesto storico-culturale della Venezia cinquecentesca; in secondo luogo, invece, viene proposto un commento di alcune lettere dell’ultimo libro dell’opera calmiana, che cerchi di far luce principalmente sull’aspetto linguistico e contenutistico del testo.Despite Vittorio Rossi's 1888 edition, Andrea Calmo's collection of "ingegnosi cheribizzi" and "fantastiche fantasie" is still shrouded in a certain mystery. The author, dissimulating his own identity behind the "mask" of the humble Venetian fisherman, was able to offer a cross-section of culture and society in sixteenth-century Venice.
In particular, it is the fourth book of the Letters that has aroused greater interest among scholars and readers: published in 1566, several years after the first three, this book stands out for the fact that all the epistles are addressed to women imaginary or actually existed.
Here we propose, first of all, a study of Calmo's biography accompanied by an analysis of the historical-cultural context of sixteenth-century Venice; secondly, however, a commentary on some letters from the last book of Calmo's work is proposed, which seeks to shed light mainly on the linguistic and content aspect of the text
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