1,720,965 research outputs found
Role of cytochrome P450 against toxic insult in neuroblastoma SH-SY5Y cells
No full textCytochrome P450 (CYP) is one of the main metabolic systems involved in xenobiotic clearance in live organisms. Its activity is mainly carried out at hepatic level, but in the last two decades, its function has been also reported to be important in other extrahepatic tissues, especially in the central nervous system. In brain, CYP isoenzymes vary their expression depending on the brain area and the cell type. However, the role of the different isoforms is not yet well characterized. Some of them have been involved in detoxification and/or toxic activation of xenobiotics; while other have been related with production of oxidative stress through the metabolism of endogenous compounds. Therefore, the presence and the function of the CYP in the brain has been related with neurodegenerative diseases such as Parkinson’s Disease (PD).
On the other hand, the study of the degeneration of dopaminergic neurons in vitro has been carried out by the use of several toxins that promote apoptosis and similar pathological features that the observed in PD. Among these xenobiotics, 1-methyl-4-phenylpyridinium (MPP+), rotenone, and paraquat are the most used because they are able to promote neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria.
Recently, it has been reported that some CYP isoforms, such as CYP 2D6, can be involved in the development of this neurodegenerative disease. To better characterize this role, we have studied the induction of some isoforms in an in vitro system. Undifferentiated SH-SY5Y cells were treated with well-known inducers of CYP for 48 hours, namely β-naphtoflavone (β-NF), ethanol (EtOH), and cyclophosphamide (CPA); and qRT-PCR, Western Blot (WB) and confocal microscopy analysis were performed. CPA increased the mRNA levels of CYP 1A1, 2D6 and 2E1, while the other inducers promoted a slight increase on these isoforms compared to CPA. WB analysis confirmed the induction promoted by CPA in CYP 1A1 and 2D6, and revealed that CYP 2D6 was also inducible by EtOH. Moreover, CYP 2E1 was increased by β-NF and EtOH treatments. In differentiated SH-SY5Y cells, a preliminary WB analysis of CYP 2D6 and 2E1 was also performed. The results suggested a change in the regulation of the expression of CYP 2D6 when treated with β-NF, and also of CYP 2E1 levels when treated with β-NF and CPA. Immunohistochemistry analysis confirmed the inducibility of CYPs and showed a co-localization of CYP 2D6 with mitochondria. These data indicate that CYP can be induced in both undifferentiated and differentiated neuroblastoma cells, and underline the possibility to use this in vitro system for studying the role of CYPs in neurodegeneration.
Moreover, as showed by our group and others, β-naphtoflavone and ethanol have the ability to induce the expression of some CYP isoforms. In order to study the possible role of CYP induction in neurodegeneration, we have use the same in vitro model than before, where undifferentiated neuroblastoma SH-SY5Y cells have been treated with these inducers separately previous and during exposure of MPP+. In both experimental conditions, the toxic effect of MPP+ was partially reverted. MTT assays showed an increase in cell viability of approximately 17% in β-NF treatment, while EtOH showed an increase between 13-15%. The analysis of apoptotic population by flow cytometry showed that both treatments were able to restore the populations to control values compared to the toxic effect of MPP+. The mitochondrial fission-fusion kinetics revealed that both treatments were able to avoid the impairment of this mitochondrial motility after exposure to the toxin. Finally, this neuroprotection was confirmed by a lowest effect of MPP+ upon complex I activity when cells were preincubated with the inducers. These results bring new insights about the possible role of CYPs, specially CYP 2D6, in neuroprotection and possible development of therapeutic drugs
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
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
Recommended from our members
The ClC Cl– channel CLH-1 mediates HCO3– efflux from the amphid sheath glia in C. elegans
No full textCellular function is regulated by the concentration of intracellular and extracellular ions, including pH. Ion channels and transporters that mediate the flux/transport of protons and bicarbonate (HCO
3
–
) are the chief regulators of pH. In the nervous system, due to their high electrical activity, neurons tend to produce and excrete large amounts of acids. On the contrary, glial cells have been proposed to be key contributors of pH buffering. We published that the Cl
–
/HCO
3
–
permeable channel CLH-1 mediates intracellular pH buffering of
C. elegans
Amphid sheath (AMsh) glia at baseline. We show here that, under physiological conditions,
clh-1
knock out worms show reduced HCO
3
–
extrusion from AMsh glia, suggesting that CLH-1 may help prevent cellular alkalinization. This function becomes even more apparent when animals are grown on plates enriched with HCO
3
–
. We speculate that CLH-1 might function as a regulator of extracellular pH
Recommended from our members
A protocol for imaging calcium and chloride in C. elegans glia upon touch stimulation
No full textGlia are important for the function of touch receptors. Here, we present a protocol in Caenorhabditis elegans for calcium and chloride imaging in worm glia upon nose touch stimulation. We describe aspects of the procedure that are essential for data reproducibility, including worm immobilization, poking angle, and applied force. We then detail data processing and analysis of calcium and chloride transients in glia. This protocol can be used for other types of mechanical stimulations or for stimulation using odorants.
For complete details on the use and execution of this protocol, please refer to Fernandez-Abascal et al., 2022.
[Display omitted]
•Fluorescence imaging in C. elegans upon nose touch stimulation•Gluing worms for in vivo recordings•Processing and analysis of calcium and chloride transients in glia•Useful for other types of mechanical stimulations or for stimulation using odorants
Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Glia are important for the function of touch receptors. Here, we present a protocol in Caenorhabditis elegans for calcium and chloride imaging in worm glia upon nose touch stimulation. We describe aspects of the procedure that are essential for data reproducibility, including worm immobilization, poking angle, and applied force. We then detail data processing and analysis of calcium and chloride transients in glia. This protocol can be used for other types of mechanical stimulations or for stimulation using odorants
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
