305,134 research outputs found

    Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry

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    Background: Pharmacogenetics is the study of genetic variations that cause alterations in drug level, drug response and adverse drug reactions. SNPs found in CYP450 genes have the greatest genetic influences on interindividual variability in drug bioavailability. The polymorphic nature of these genes may modulate several enzyme levels that affect individual responses to pharmacological treatment. Among them, CYP3A4, CYP3A5, CYP2C9 and CYP2C19 isoforms of CYP450 enzymes are involved in the metabolism of many commonly prescribed drugs. Aims: In this study, we would like to develop a CYP450 genotyping platform that could lead a complete definition of a patient’s metabolic genotype in order to improve the clinical outcome of some drug treatments. Materials & methods: We used matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Sequenom®) to develop a SNP genotyping method. Results: This MALDI-TOF-based multiplexing system allows the simultaneous and efficient genotyping of a set of CYP450 gene polymorphisms. Conclusion: The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Five mutations in the GABAA α6 gene 5′ flanking region are associated with a reduced basal and ethanol-induced α6 upregulation in mutated Sardinian alcohol non-preferring rats

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    The presence of four nucleotide changes and a three base-pair deletion in the GABAA α6-subunit promoter is described in Sardinian alcohol non-preferring rats, selectively bred for their ethanol aversion. These mutations are associated with the R100Q α6 intragenic mutation that was previously characterized in the same animals. The possibility that these mutated nucleotides alter the ethanol-induced upregulation of the α6 gene was investigated by measuring cerebellar α6 mRNA levels after a chronic ethanol liquid diet in sNP rat. Real-time quantitative PCR showed an increased α6 gene expression after ethanol ingestion in normal and mutated rats. However, lower amounts of α6 mRNA levels were detected both in control and in ethanol-treated sNP rats carrying the five promoter and the intragenic mutations in a homozygous state. Using the electromobility shift assay, specific DNA binding sites were found in cerebellar extracts of the α6 regions comprising the five mutations. These results suggest that one or more of the mutated binding sites that were found in the 5′ flanking α6 region may be a consensus sequence for regulatory factors which are responsible for both basal and ethanol-induced α6 gene expression. © 2005 Elsevier B.V. All rights reserved

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author, publisher and bookseller : a tripartite synergy in Nigerian book industry

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    This work is about the roles of Author, Publisher and Bookseller in Book development in Nigeria. The paper started by delving into the history of Book Publishing in Nigeria after which it proceeded by defining who an author, a publisher, and a bookseller is and expatiated on the indispensable roles of these key actors in Nigerian Book Industry and in the emerging Information Society. Furthermore, the various constraints to book development were identified while the paper advised on how the Book Industry can be further promoted in Nigeria. However, the paper concluded and made recommendations on how the Book sector can help in enhancing scholarship in the country
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