1,720,974 research outputs found
Role of Protein-Protein Interactions in Metabolism: Genetics, Structure, Function
No full textGenetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks
A Study of Cytochrome P450's Level and Method of Response to the Common Environmental Compound Ethylbenzene
No full textiv, 33 p.Cytochrome P450 is a super family of enzymes that metabolize a wide variety of
endogenous and exogenous compounds. These enzymes are involved in the bioactivation of xenobiotics and drug metabolism, which may cause P450 to either increase or decrease its own enzyme levels as well as the substrate's. In the current study, three specific cytochrome enzymes levels were investigated 2B1, 3A2 and 2C 11. Previous studies demonstrated the responses of these enzymes to a barbiturate, phenobarbital (PB). However, a direct evaluation of the responses of PB to ethylbenzene (EB), an aromatic hydrocarbon found in the environment, will help to yield a better understanding of how the environment may influence P450 drug metabolizing enzymes. Hormones are also known to regulate the expression of various P450 isozymes, therefore this study removed the pituitary gland in order to consider this endogenous factor. The evaluation of P450 2B 1 showed no significant difference in enzyme levels when treated by either PB or EB over a twenty-four hour period. The removal of the pituitary gland, hypophysectomy, demonstrated that PB increases 2B 1 levels even in the absence of endogenous hormones. Ethylbenzene (EB), however, does not increase the enzyme levels in the absence of pituitary gland. Therefore indicating that the similar induction levels of 2B1 caused by PB and EB may occur through two different mechanisms. In the evaluation of P450 3A2 no significant difference existed between the enzyme levels of the EB and PB responses
in both intact and hypophysectomized (hypox) rats. This indicates that similar
mechanisms may be involved in the enzyme's response to both EB and PB. Cytochrome
P450 2C11 also demonstrated no overall significant difference between EB and PB
induced responses in both intact and hypox rats. Therefore, a similar mechanism may be involved in the mediation of 2CII by both the drug PB and the environmental factor EB.Department of Pharmacology. Louisiana State University Health Science Center. Louisiana State University. Baton Rouge, Louisiana
Ethylbenzene Exposure to Cytochrome P450: Does Ethylbenzene Produce Transient Changes in P450 2B Messenger RNA Levels?
No full textvi, 30 p.The introduction of aromatic hydrocarbons to an organism has been
shown to cause the induction of certain cytochrome P450 (P450) isozymes that
function to detoxify xenobiotics from the body (Backes, 1993). A past study
demonstrated the induction of P450 2B1 and 2B2 (2B1/2) proteins by
ethylbenzene (Bergeron, 1995). Bergeron's study showed an unusual pattern
of induction with ethylbenzene treatment. Although P450 2B1/2 mRNA and
protein levels both initially increased, the protein levels remained elevated
thereafter, but the mRNA returned to control levels for the rest of the
treatment period. Considering that the t l/2 of 2B1/2 protein has been
reported to be 20 hours (Shiraki et al., 1984), protein degradation should
ordinarily be expected. To derive a possible mechanism for this pattern of
induction, male Holtzman rats were treated daily with ethylbenzene for 4
days, and killed at various times thereafter. The 2B1/2-dependent catalytic
activity, protein levels, and mRNA levels of liver samples from these rats
were then measured. The catalytic activity, estimated by
spectrophotometrically measuring the dealkylation of pentoxyresorufin by
P450 2B1/2 protein, showed significantly higher levels for all ethylbenzene-treated
rats relative to the control rats which were treated with corn oil.
Protein levels were measured by Western blotting, using P450 2B1/2 specific
antibodies to identify and quantitate the levels of these isozymes. They
showed similar results as the catalytic activity, with the protein levels in all
ethylbenzene treated rats being significantly higher than in the control rats.
The changes in mRNA were measured using Northern blotting, where RNA
samples isolated from liver were separated electrophoretically and reacted
with radioactively-labeled P450 2B1 or 2B2 oligonucleotide probes. These
showed significantly elevated mRNA levels between 5 and 12 hours after administration of ethylbenzene. Thus it was conclusively shown that in rats
chronically treated with ethylbenzene, protein levels are maintained at
elevated levels by transient increases in mRNA.Department of Pharmacology. Louisiana State University Health Science Center. Louisiana State University. Baton Rouge, Louisiana
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
Changes in Cytochrome P450-Dependent Activities and Isozyme Levels Following Cerebral Ischemia
No full textvii, 38 p.Cerebral ischemia has been shown to cause a number of metabolic changes
including an accumulation of free fatty acids (Bazan, 1970; Kogure and Nakano, 1992).
In extrahepatic tissues such as kidney and cornea, cytochrome P450 has been implicated
in the production of biologically active compounds from the metabolism of free fatty
acids such as arachidonate (McGiff, 1991; Davis et al., 1992). In the present study,
cytochrome P450 enzyme activity in rat brain was measured through the analysis of
P450-dependent metabolism of testosterone following 10 minute periods of global
cerebral ischemia. Western Blotting was also performed using polyclonal antibodies
specific for purified hepatic microsomal P450 2E1 and P450 1A1 to examine levels of
these isozymes. Preliminary fin~gs suggested that there is differential regulation of
cytochrome P450-dependent testosterone hydroxylation in brain microsomes and
mitochondria following the induction of stroke. In these experiments, levels of 16 -,
2α-, and possibly 2-hydroxytestosterone increased in rat brain microsomes following
stroke treatment; whereas levels of 6-hydroxytestosterone decreased. The levels of
16α-hydroxytestosterone were unchanged. Western Blot analysis of rat brain microsomes
revealed a protein similar in molecular weight and antigenic specificity to hepatic P450
2E1. A smaller weight protein which reacted with antibodies to P450 2E1 was found in
all stroke-treated animals and one control animal. Western Blot analysis of rat brain
mitochondria revealed a protein similar in molecular weight and antigenic specificity to
hepatic P450 1A1, suggesting elevated levels of P450 1A1 in stroke-treated animals.Department of Pharmacology. Louisiana State University Medical Center. Louisiana State University. New Orleans, Louisiana
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
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