1,721,397 research outputs found
The regulation of catalase activity by PPAR gamma is affected by alpha-synuclein
Get PDFObjective: While evidence for oxidative injury is frequently detected in brains of humans affected by Parkinson's disease (PD) and in relevant animal models, there is uncertainty regarding its cause. We tested the potential role of catalase in the oxidative injury that characterizes PD. Methods: Utilizing brains of A53T alpha-Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites. Results: Lower catalase expression and lower activity levels were detected in A53T alpha-Syn brains and alpha-Syn-expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and alpha-Syn mutation, suggesting a potential physiological function for alpha-Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that alpha-Syn expression downregulate the peroxisome proliferator-activated receptor (PPAR)gamma, which controls catalase transcription. Importantly, activation of either PPAR gamma 2, PPAR alpha or retinoic X receptor eliminated the inhibiting effect of alpha-Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble alpha-Syn oligomers, resulting in a positive association between the degree of soluble alpha-Syn oligomers and catalase activity. Of note, a comprehensive biochemical analysis of specific peroxisomal metabolites indicated no signs of dysfunction in specific peroxisomal activities in brains of A53T alpha-Syn mice. Interpretation: Our results suggest that alpha-Syn expression may interfere with the complex and overlapping network of nuclear receptors transcription activation. In result, catalase activity is affected through mechanisms involved in the regulation of soluble alpha-Syn oligomer
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
The role of KDAC inhibitors in nitrogen metabolism: the therapeutic challenges for liver disease and hepatocelular carcinoma
No full textTese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2015Lysine deacetylases inhibitors (KDACi) are compounds that interfere with the activity of Lysine deacetylases, enzymes that mediate removal of acetyl groups from protein lysine residues. Modulation of acetylation status may alter the activity of many proteins of intermediary metabolism. KDACi became promising drugs for cancer therapy, where valproic acid (VPA) is one example. VPA is associated with mitochondrial dysfunction, although its multifactorial effects still need further research, especially regarding its properties as KDACi. It was our aim to unveil the potential benefit of VPA as part of a therapeutic strategy for hepatocellular carcinoma (HCC), a disease without effective pharmacological options.
In this study, we characterized part of the nitrogen and bioenergetic exometabolome of in vitro HCC-derived cell line, HepaRG, after exposure to acute or repeated treatment with VPA or in combination with N-Carbamoyl Glutamate (CG).
For that purpose we developed an analytical method for urea cycle and amino acids intermediates using LC-MS/MS. The analysis of organic acids from TCA cycle and related metabolites using GC-MS was also optimized. Both methods showed to be reliable for metabolites quantification with acceptable reproducibility and specificity. Analysis of AST, GLDH, urea and ammonia were performed in cell supernatant, whereas GLDH and SIRT3 protein levels were obtained in cells.
Results showed that the major hallmarks on (exo)metabolites profiling associated with VPA exposure include: i) a decreased consumption of ornithine; ii) a clear accumulation of ammonia regardless of ureagenesis capacity; iii) the accumulation of pyruvate and lactate; iv) a significant decrease on α-ketoglutarate export or production whereas levels of glutamate are increased. These changes demonstrate a link between urea cycle and Krebs cycle metabolic dysfunction during VPA treatment.
This work adds novel information for potential HCC therapeutic strategies involving the use of VPA as KDACi and also for the understanding of cancer cell rewiring of metabolism
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
The role of KDAC inhibitors in nitrogen metabolism: the therapeutic challenges for liver disease and hepatocelular carcinoma
No full textTese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2015Lysine deacetylases inhibitors (KDACi) are compounds that interfere with the activity of Lysine deacetylases, enzymes that mediate removal of acetyl groups from protein lysine residues. Modulation of acetylation status may alter the activity of many proteins of intermediary metabolism. KDACi became promising drugs for cancer therapy, where valproic acid (VPA) is one example. VPA is associated with mitochondrial dysfunction, although its multifactorial effects still need further research, especially regarding its properties as KDACi. It was our aim to unveil the potential benefit of VPA as part of a therapeutic strategy for hepatocellular carcinoma (HCC), a disease without effective pharmacological options.
In this study, we characterized part of the nitrogen and bioenergetic exometabolome of in vitro HCC-derived cell line, HepaRG, after exposure to acute or repeated treatment with VPA or in combination with N-Carbamoyl Glutamate (CG).
For that purpose we developed an analytical method for urea cycle and amino acids intermediates using LC-MS/MS. The analysis of organic acids from TCA cycle and related metabolites using GC-MS was also optimized. Both methods showed to be reliable for metabolites quantification with acceptable reproducibility and specificity. Analysis of AST, GLDH, urea and ammonia were performed in cell supernatant, whereas GLDH and SIRT3 protein levels were obtained in cells.
Results showed that the major hallmarks on (exo)metabolites profiling associated with VPA exposure include: i) a decreased consumption of ornithine; ii) a clear accumulation of ammonia regardless of ureagenesis capacity; iii) the accumulation of pyruvate and lactate; iv) a significant decrease on α-ketoglutarate export or production whereas levels of glutamate are increased. These changes demonstrate a link between urea cycle and Krebs cycle metabolic dysfunction during VPA treatment.
This work adds novel information for potential HCC therapeutic strategies involving the use of VPA as KDACi and also for the understanding of cancer cell rewiring of metabolism
The role of KDAC inhibitors in nitrogen metabolism: the therapeutic challenges for liver disease and hepatocelular carcinoma
No full textTese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2015Lysine deacetylases inhibitors (KDACi) are compounds that interfere with the activity of Lysine deacetylases, enzymes that mediate removal of acetyl groups from protein lysine residues. Modulation of acetylation status may alter the activity of many proteins of intermediary metabolism. KDACi became promising drugs for cancer therapy, where valproic acid (VPA) is one example. VPA is associated with mitochondrial dysfunction, although its multifactorial effects still need further research, especially regarding its properties as KDACi. It was our aim to unveil the potential benefit of VPA as part of a therapeutic strategy for hepatocellular carcinoma (HCC), a disease without effective pharmacological options.
In this study, we characterized part of the nitrogen and bioenergetic exometabolome of in vitro HCC-derived cell line, HepaRG, after exposure to acute or repeated treatment with VPA or in combination with N-Carbamoyl Glutamate (CG).
For that purpose we developed an analytical method for urea cycle and amino acids intermediates using LC-MS/MS. The analysis of organic acids from TCA cycle and related metabolites using GC-MS was also optimized. Both methods showed to be reliable for metabolites quantification with acceptable reproducibility and specificity. Analysis of AST, GLDH, urea and ammonia were performed in cell supernatant, whereas GLDH and SIRT3 protein levels were obtained in cells.
Results showed that the major hallmarks on (exo)metabolites profiling associated with VPA exposure include: i) a decreased consumption of ornithine; ii) a clear accumulation of ammonia regardless of ureagenesis capacity; iii) the accumulation of pyruvate and lactate; iv) a significant decrease on α-ketoglutarate export or production whereas levels of glutamate are increased. These changes demonstrate a link between urea cycle and Krebs cycle metabolic dysfunction during VPA treatment.
This work adds novel information for potential HCC therapeutic strategies involving the use of VPA as KDACi and also for the understanding of cancer cell rewiring of metabolism
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