140 research outputs found
Invecchiamento e risposta ai fitomitogeni: analisi della sottopopolazione linfocitaria T attiva (T-Ea)
No full textBenign idiopathic partial seizures in the velocardiofacial syndrome: report of two cases.
No full textSTATO DI MALE ELETTRICO IN SONNO, DISPLASIA CORTICALE E SINDROME DI COHEN: PRESENTAZIONE DI UN CASO
No full textTheoretical Evaluation of Sulfur-Based Reactions as a Model for Biological Antioxidant Defense
Get PDFSulfur-containing amino acids, Methionine (Met) and Cysteine (Cys), are very susceptible to Reactive Oxygen Species (ROS). Therefore, sulfur-based reactions regulate many biological processes, playing a key role in maintaining cellular redox homeostasis and modulating intracellular signaling cascades. In oxidative conditions, Met acts as a ROS scavenger, through Met sulfoxide formation, while thiol/disulfide interchange reactions take place between Cys residues as a response to many environmental stimuli. In this work, we apply a QM/MM theoretical–computational approach, which combines quantum–mechanical calculations with classical molecular dynamics simulations to estimate the free energy profile for the above-mentioned reactions in solution. The results obtained, in good agreement with experimental data, show the validity of our approach in modeling sulfur-based reactions, enabling us to study these mechanisms in more complex biological systems
On the use of time windows for the determination of sound strength parameter G from uncalibrated room impulse responses measurements
No full textThe sound strength parameter G is one of the most important objective parameters related to the acoustical quality of concert halls, opera houses, and chamber music halls. G at mid frequencies is highly correlated with the acoustic quality reported by music conductors and subjects with musical training. Measuring this parameter requires a calibrated sound source or the direct sound isolated using a suitable time window as in [B. Katz, In situ calibration of the sound strength parameter G, JASA 138 (2) (2015) EL167–EL173]. In this article, the performance of several window functions and lengths used to isolate the direct sound is investigated. Although the errors obtained for low frequencies are large, an error in the order of a just-noticeable-difference at mid frequencies is obtained for a 30 ms Flat-Top window centered around arrival time of direct sound.Fil: Accolti Mostazo, Ernesto Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Instituto de Automática. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Automática; ArgentinaFil: di Sciscio, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Instituto de Automática. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Automática; Argentin
In silico and in vitro analysis of major cannabis-derived compounds as fatty acid amide hydrolase inhibitors
Get PDFAccumulated evidence suggests that enhancing the endocannabinoid (eCB) tone, in partic-ular of anandamide (N-arachidonoylethanolamine, AEA), has therapeutic potential in many human diseases. Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme principally responsible for the degradation of AEA, and thus it represents a relevant target to increase signaling thereof. In recent years, different synthetic and natural compounds have been developed and tested on rat FAAH, but little is known of their effect on the human enzyme. Here, we sought to investigate six major cannabis-derived compounds to compare their action on rat and human FAAHs. To this aim, we combined an in silico analysis of their binding mode and affinity, with in vitro assays of their effect on enzyme activity. This integrated approach allowed to disclose differences in efficacy towards rat and human FAAHs, and to highlight the role of key residues involved in the inhibition of both enzymes. This study suggests that the therapeutic efficacy of compounds targeted towards FAAH should be always tested in vitro on both rat and human enzymes
Fatty acid amide hydrolase, anandamide, and neurological diseases
No full texthe endocannabinoid anandamide (N-arachidonoylethanolamine, AEA) is a bioactive lipid that has been shown to regulate a number of important pathophysiological conditions in humans, including several neurological disorders. AEA acts on cannabinoid receptors, and many studies reported that it may also interact with other targets, such as vanilloid and peroxisome proliferator-activated receptors. AEA, together with 2-arachidonoylglycerol (2-AG), their molecular targets, biosynthetic and degradative enzymes form the endocannabinoid system (ECS).
The biological activity of AEA depends on a “metabolic control” that modulates the effects of this substance by finely tuning its in vivo concentration. In particular, the major molecular player involved in AEA metabolism is fatty acid amide hydrolase (FAAH). As such, this enzyme is the subject of numerous studies and clinical trials to investigate about its potential therapeutic role and how it impacts various disease processes that present significant unmet medical needs
- …
