196,065 research outputs found
In silico and in vitro analysis of major cannabis-derived compounds as fatty acid amide hydrolase inhibitors
No full textAccumulated 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
Fatty acid amide hydrolase, anandamide, and neurological diseases
No full textThe 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
Reply to discussion of “Permian—Triassic vertebrate footprints from South Africa: Ichnotaxonomy, producers and biostratigraphy through two major faunal crises” by Marchetti, L., Klein, H., Buchwitz, M., Ronchi, A., Smith, R.M.H., DeKlerk, W.J., Sciscio, L., and Groenewald, G.H. (2019)
No full textOur recent comprehensive review of the Permian-Early Triassic tetrapod tracksites from South Africa includes a revision of the ichnotaxonomy and the incorporation of a large quantity of new material. The paper also discusses, in light of the revised ichnotaxonomy and palaeontology of several sites, trackmaker attribution and the biostratigraphy of Permian-Early Triassic tetrapod tracks. Precise information about the fossiliferous localities was provided where possible and when sites were relocated. Three footprint associations were described (FA I-III) and highlight their potential stratigraphic value. The youngest (FA III) was recognized at four different localities and is likely Induan in age. A recent comment by Gastaldo and Neveling (2019) regarded one of these FA III localities, the Bethel tracksite, which received criticism for its unclear geographic placement and its stratigraphic position. Further comments included a discussion of the possible palaeoecological interpretation of this tracksite. In replying to these queries, we provided more precise geographic and stratigraphic information, confirming the occurrence of this tracksite ~15 m above the faunal transition which we consider to be currently coinciding with the Permian-Triassic boundary (PTB). Palaeoecological inferences are herein further clarified
Fabrication of nanostructured targets for improved laser-driven proton acceleration
No full textn this work, we present a novel realization of nanostructured targets suitable forimproving laser-driven proton acceleration experiments, in particular with regard to theTarget-Normal-Sheath Acceleration (TNSA) acceleration mechanism. The nanostructuredtargets, produced asfilms, are realized by a simpler and cheaper method than usingconventional lithographic techniques. The growth process includes a two step approach forthe production of the gold nanoparticle layers: 1) Laser Ablation in Solution and 2) spray-dry technique using a colloidal solution on target surfaces (Aluminum, Mylar and MultiWalled Carbon Nanotube). The obtained nanostructuredfilms appear, at morphologicaland chemical analysis, uniformly nanostructured and the nanostructure distributed on thetarget surfaces without presence of oxides or external contaminants. The obtained targetsshow a broad optical absorption in all the visible region and a surface roughness that istwo times greater than non-nanostructured targets, enabling a greater laser energy ab-sorption during the laser-matter interaction experiments producing the laser-drivenproton acceleratio
Laser-Accelerated proton beams as diagnostics for cultural heritage
No full textThis paper introduces the first use of laser-generated proton beams as diagnostic for materials of interest in the domain of Cultural Heritage. Using laser-accelerated protons, as generated by interaction of a high-power short-pulse laser with a solid target, we can produce proton-induced X-ray emission spectroscopies (PIXE). By correctly tuning the proton flux on the sample, we are able to perform the PIXE in a single shot without provoking more damage to the sample than conventional methodologies. We verify this by experimentally irradiating materials of interest in the Cultural Heritage with laser-accelerated protons and measuring the PIXE emission. The morphological and chemical analysis of the sample before and after irradiation are compared in order to assess the damage provoked to the artifact. Montecarlo simulations confirm that the temperature in the sample stays safely below the melting point. Compared to conventional diagnostic methodologies, laser-driven PIXE has the advantage of being potentially quicker and more efficien
Ultra-Fast High-Precision Metallic Nanoparticle Synthesis using Laser-Accelerated Protons
No full textLaser-driven proton acceleration, as produced during the interaction of a high-intensity (I > 1 × 1018 W/cm2), short pulse (<1 ps) laser with a solid target, is a prosperous field of endeavor for manifold applications in different domains, including astrophysics, biomedicine and materials science. These emerging applications benefit from the unique features of the laser-accelerated particles such as short duration, intense flux and energy versatility, which allow obtaining unprecedented temperature and pressure conditions. In this paper, we show that laser-driven protons are perfectly suited for producing, in a single sub-ns laser pulse, metallic nanocrystals with tunable diameter ranging from tens to hundreds of nm and very high precision. Our method relies on the intense and very quick proton energy deposition, which induces in a bulk material an explosive boiling and produces nanocrystals that aggregate in a plasma plume composed by atoms detached from the proton-irradiated surface. The properties of the obtained particles depend on the deposited proton energy and on the duration of the thermodynamical process. Suitably controlling the irradiated dose allows fabricating nanocrystals of a specific size with low polydispersity that can easily be isolated in order to obtain a monodisperse nanocrystal solution. Molecular Dynamics simulations confirm our experimental results
Progression of diastolic dysfunction in type II diabetes is associated with blood pressure, weight gain and increasing LV mass
No full textY.Y. Chirkov, M. De Sciscio, A.L. Sverdlov, S. Leslie, J.D. Horowit
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
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