1,721,152 research outputs found
FABP1 in wonderland
No full textCannabinoid receptors hold a core position in the brain and control memory, cognition, movement, and pain sensitivity. sn-2 arachidonoylglycerol (2-AG) activates neuronal cannabinoid receptors as a full agonist. The brain may rely on circulating arachidonic acid to synthesize endogenous cannabinoids. This Editorial highlights a study by Martin and coworkers in the current issue of the Journal of Neurochemistry in which the authors describe, for the first time, that liver acts as a pool of arachidonic acid that under certain conditions feeds the brain to produce endocannabinoids. Therapeutics affecting liver FABP1 levels should take into account that FABP1 represents a fatty acid reservoirs for the brain. Read the highlighted article "FABP-1 gene ablation impacts brain endocannabinoid system in male mice" on doi: 10.1111/jnc.13664
Lipid-activated nuclear receptors: from gene transcription to the control of cellular metabolism
No full textCellular homeostasis is maintained through a complicated network of signaling, transport and enzymatic events that take place in different compartments of the cell. The result of this composite network determines the cellular behavior in response to environmental challenges. Within this network, many cellular functions are regulated at the transcriptional level and consequently the comprehension of the molecular mechanisms of gene regulation is fundamental to fully understand how the cell reacts to environmental changes. Moreover, it offers an opportunity to find novel targets for the design of better strategies to improve healthy human nutrition and to treat metabolic diseases. In this framework, nuclear receptors have emerged as key regulators of many cellular functions in response to lipid action. In this review, we will discuss the new concepts on the biology of the recently "adopted" nuclear receptors sensing oxysterols (LXR), bile acids (FXR) and fatty acids (PPARs) and their function in the integrated regulation of lipid and glucose metabolism. We will also address the role played by other orphan nuclear receptors, such as FTF, SHP and HNF-4, acting in concert with these lipid-sensing nuclear receptors in the regulation of cellular metabolism
Inhibition of histone deacetylases for the treatment of hyperlipidemias and prevention of atherosclerosis and cardiovascular diseases
No full textThe present invention relates to the use of inhibitors of the histone deacetylases for the preparation of a medicament for the treatment of pathologies caused by increased levels of plasma cholesterol and plasma and hepatic triglycerides. Particularly, the invention relates to the use of said inhibitors for the preparation of a medicament for the treatment of diseases such as hyperlipidaemia, particularly, hypercholesterolaemia, hypertriglyceridaemia, atherosclerosis, cardiovascular and cerebrovascular pathologies, obesity, diabetes metabolic syndromes
Non-insulin anti-diabetic drugs : an update on pharmacological interactions
No full textNowadays, the goal in the management of type 2 diabetes mellitus (T2DM) remains personalized control of glucose. Since less than 50% of patients with T2DM achieve glycemic treatment goal and most of them take medications for comorbidities associated to T2DM, drug interactions, namely pharmacokinetic and pharmacodynamic interactions, may enhance or reduce the effect of compounds involved in hyperglycemia. Hence, clinicians should be aware of the severe complications in T2DM patients in case of a concomitant use of these medications. It is within this context that this review aims to evaluate the effect of a second drug on the pharmacokinetic of these compounds which may lead, along with several pharmacodynamic interactions, to severe clinical complications, i.e., hypoglycemia. Available drugs already approved in Europe, USA and Japan have been included
Fluorescence Resonance Energy Transfer Techniques to Study Ligand-Mediated Interactions of PPARs with Coregulators
No full textThe capacity to induce the association of peroxisome proliferator-activated receptors (PPARs) with different transcriptional coregulators is determined by the peculiar 3D-structure that the receptors adopt when bound with a specific ligand. The fluorescence resonance energy transfer assay is a technique widely used to evaluate coregulator recruitment to nuclear receptors induced by ligands. With this assay it is possible to quantitatively determine the interaction and the affinity of coregulators with PPARs when these receptors are complexed with ligands. Here, we describe the use of this technique to assess the preferential interaction and the affinity of PPARγ with coregulators as a function of the chemical structure of the bound ligan
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
Site-Directed Mutagenesis to Study the Role of Specific Amino Acids in the Ligand Binding Domain of PPARs
No full textThe role of certain amino acids in the interactions of ligands with their cognate nuclear receptors is usually achieved by the resolution of the crystal structure of the receptor complexed with the ligand. As a complementary functional approach, site-directed mutagenesis, a technique broadly used in molecular biology, allows the assessment of the role of a specific amino acid in determining the interaction with a specific ligand. This method makes it possible to evaluate several mutations of a key amino acid for ligand binding and to determine the relationship between protein structure and ligand interaction. Here, we describe an application of this technique to evaluate different point mutations on the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) in the absence or presence of chemically different ligand
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