1,720,988 research outputs found
Regulation of gamma-aminobutyric acidA receptor subunit expression by activation of N-methyl-D-aspartate-selective glutamate receptors.
No full textDistinct developmental patterns of expression of rat alpha 1, alpha 5, gamma 2S, and gamma 2L gamma-aminobutyric acidA receptor subunit mRNAs in vivo and in vitro.
No full textEndocrine disruptors present in food packages do act as lipid metabolism modulators.
No full textEndocrine-disrupting chemicals (EDCs) may cause several noxious problems to both humans and wildlife and their modulations on energy balance and lipid metabolism are nowadays of great concern. Among environmental EDCs, plasticizers employed in food wrapping materials are very relevant due to their widespread distribution and persistence in the food chain. In the present work we first identify by in silico screening compounds, among the permitted plasticizers for food packaging (EU Regulation, 10/2011), with high predicted affinity for nuclear receptors known to mediate obesogenic effects, such as PPARs, LXR and RXR. The following molecules were therefore chosen for the subsequent studies: the well-known, bisphenol-A, three phthalates (di-isononylphpthalate, DiNP; Di-isodecyl phthalate, DiDP; diethylene glycol dibenzoate, DiGD) and one organophosphorus (tri-m-cresyl phosphate,TmCP).The predicted affinity for the nuclear receptors was then verified in vitro with a luciferase assay: DiNP, DiDP and DiGD were shown to have activity on PPAR α/γ at 10-5-10-7M and to induce the expression of downstream target genes (FABP4, PDK4, FGF21, CPT2). The potential obesogenic effects of the selected compounds were then tested on 3T3-L1 murine preadipocytes cells, a widely used model for adipogenesis in vitro. All the molecules, when used in a range of 10-8-10-6M, were able to significantly enhance lipid droplets deposition, both when administered during the two-days differentiation induction, as well as when maintained for all the eight-days post-differentiation period. Food plastic packages are mostly composed by a mixture of plasticizers so that many molecules at the same time may migrate and contaminate food. We consequently treated 3T3-L1 cells with mixtures of the selected plasticizers (10-8M each), coherently with some commercial plastics (pvc, polypropylene, polyethylene teraphthalate), and we observed in all the cases a significant positive modulation on lipid deposition. The obesogenic effects of the compounds were also investigated by performing qRT-PCR on target genes such as PPARs, LXR, RXR and their downstream effectors. Taken together, our data enforce the emerging awareness on energy balance and lipid metabolism modifications following environmental exposure that could be of concern in vulnerable periods, such as early postnatal life
Combined in silico and in vitro studies of phthalates and organophosphorus compounds: effects on peroxisome proliferator activated receptors (PPARs) signalling pathways
No full textIncreasing evidence suggests that some environmental contaminants, including known endocrine disrupting chemicals (EDCs), are able to interfere with metabolic pathways by interacting with nuclear receptors. Recently, it has been demonstrated that phthalates and organometallic compounds bind to peroxisome proliferator activated receptors (PPARs) resulting in modulation of lipid metabolism at both the systemic and peripheral level. However, little is known about the metabolic impact of these pollutants on fish. In this context, we performed an in silico docking screen of an EDCs database to identify a set of ligands with conveniently high affinity for the PPARs. Kd values in the nanomolar to micromolar range, generated by the in silico model, suggest that piscine PPARs may be activated by phthalates (e.g. di-isononylphpthalate -DiNP; Di-isodecyl phthalate-DiDP) and some organophosphorus compounds (e.g. tri-m-cresyl phosphate-TmCP) at concentrations similar to those activating the homologous mammalian receptors. Because natural endogenous ligands for PPARs are involved in lipid homeostasis, we assessed the effects of compounds identified using in silico screening on Sparus aurata hepatocytes primary cultures. Generally, exposure of hepatocytes to 0.1, 1 or 10 microM of DiNP, DiDP or TmCP consistently increased both PPAR and its heterodimeric partner Retinoid X Receptor (RXR) mRNA levels at 48 h. In addition, all compounds investigated produced significant increases in the expression of the PPAR target genes, carnitine palmitoyltransferase (CPT) isoforms. In general our data show that phthalates and TmCP modulated PPAR signaling in the seabream in vitro system. The results also suggest the potential involvement of these pollutants in the modulation of mitochondrial fatty acid oxidation
Elevata presenza di cellule dopaminergiche nello striato neonatale: possibile parallelismo con lo striato parkinsoniano.
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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
Endocrine disruptors and nuclear receptors in the control of neural progenitors proliferation
No full textEndocrine-disrupting chemicals (EDCs), in particular plasticizers present in food wrapping materials, are very relevant to human health. Several studies have shown that EDCs may pose the greatest risk during prenatal and early postnatal development, especially when binding to members of the nuclear receptor (NR) superfamily. EDCs can mimic/suppress estrogen actions in the developing brain by binding to estrogen receptors (ERs), and also interfere with neural progenitors (NPs) homeostasis through activation of peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs). We used the ST14A immortalized neural progenitor cell line to simulate the effects of prenatal NPs exposure to EDCs. We found by RT-PCR that the following NRs were expressed: ERα, ERβ, PPARα, PPARβ, PPARγ, RXR. Plasticizers were chosen based on their computational affinity for these receptors. NPs were exposed for 24-48 hours to endogenous and synthetic estrogens (17-β-estradiol and ethinyl estradiol) and to the following plasticizers: Bisphenol A, Diisononyl phthalate, Diisodecyl phthalate, Diethileneglicol benzoate. Both estrogens were able to increase cell proliferation by about 30% at 24hrs. Bisphenol-A (10nM) had an estrogen-like behavior in enhancing cell number, but its action was still significant at 48hrs. At 200nM concentration, all plasticizers determined an early increase in proliferation, however only DiDP and DGB were able to sustain this positive modulation for 48hrs. Ongoing studies in our lab will determine the cellular pathways activated by these EDCs in NPs, in order to earn greater insight into how these molecules may influence and perturb the neurogenic process
Plasticizers present in food packaging significantly affect lipid metabolism
No full textRecent data suggest that endocrine-disrupting chemicals (EDCs) may alter lipid metabolism and energy balance. Among environmental EDCs, plasticizers employed in food packaging are of great concern due to their widespread distribution and high persistency in the food chain. We first selected by in silico screening several compounds from a list of plasticizers approved for food packaging (EU Regulation 10/2011) showing high affinity for lipogenic nuclear receptors (PPARs, LXR and RXR). The following plasticizers were chosen: the well-known bisphenol-A, three phthalates (diisononylphpthalate, DiNP; Di-isodecyl phthalate, DiDP; diethylene glycol dibenzoate, DiGD) and one organophosphorus compound (tri-m-cresylphosphate,TmCP).Their binding capacity to nuclear receptors was verified on HEPG2 cells transfected with receptor-luciferase reporter constructs; all phtalates (10-5-10-7 M) were shown to activate PPAR and to induce the expression of downstream target genes (FABP4, PDK4, FGF21, CPT2). The potential obesogenic effects of these compounds were then tested on differentiating 3T3-L1 preadipocyte cells. All molecules (10-8-10-6 M) were able to significantly enhance lipid droplet deposition when administered both in the two-days differentiation induction, or in the eight-days post differentiation period. Food plastic packaging is mostly composed by mixtures of plasticizers, so multiple molecules may migrate simultaneously into food. We therefore treated 3T3-L1 cells with mixtures of plasticizers (10-8 M each), mimicking commercial plastics (pvc, polypropylene, polyethylene teraphthalate); in all cases we observed a significant positive modulation of lipid deposition. The obesogenic effects of all compounds were also investigated at the molecular level by performing qRT-PCR on target genes such as PPARs, LXR, RXR and their downstream effectors. Taken together, our data enforce the emerging awareness on alteration of lipid metabolism following environmental exposure to plasticizers. This effect could be of special concern in vulnerable periods such as pregnancy and early postnatal life
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
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