1,720,955 research outputs found
Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells
No full textApoptosis (or programmed cell death) is a genetically controlled “cell suicide” pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule
Distinct promoters mediate constitutive and inducible Bcl-X-L expression in malignant lymphocytes
No full textBcl-X-L is a Bcl-2-related survival protein that is essential for normal development. Bcl-X-L expression is rapidly induced by a wide range of survival signals and many cancer cells constitutively express high levels. The Bcl-X gene has a complex organization with multiple promoters giving rise to RNAs with alternate 5' non-codingexons. Here we have investigated the mechanisms that control basal and induced expression of Bcl-X-L in B-lymphoma cells. Antisense experiments demonstrated that Bcl-X-L was essential for survival of Akata6 B-lymphoma cells. The levels of RNAs containing the IB Bcl-X non-coding exon, derived from the distal 1B promoter, correlated with basal expression of Bcl-X-L in primary malignant B cells and this promoter was highly active in B-cell lines. The activity of this promoter was largely dependent on a single Ets binding site and Ets family proteins were bound at this promoter in intact cells. CD40 ligand (CD40L)-induced cell survival was associated with increased Bcl-X-L expression and accumulation of exon IA-containing RNAs, derived from the proximal 1A promoter. Nuclear factor-kappaB (NF-kappa B) inhibition prevented induction of Bcl-X-L protein and exon IA-containingRNAs by CD40L. Therefore, the distal Bcl-X 1B promoter plays a critical role in driving constitutive expression-mediated via Ets family proteins in malignant B cells, whereas NF-kappa B plays a central role in the induction of Bcl-X-L in response to CD40 signalling via the proximal 1A promoter
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
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
Pharmacological inhibitors of NF-kappa B accelerate apoptosis in chronic lymphocytic leukaemia cells
No full textNuclear factor-kappaB NF-kappa B) is a transcription factor that plays a critical role in the inappropriate survival of various types of malignant cells. Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world. Although overexpression and regulation of NF-kappa B has been described in CLL, its function remains unclear. Exposure of CLL cells to BAY117082 or Kamebakaurin, potent pharmacological inhibitors of the NF-kappa B pathway, accelerated apoptosis in approximately 70% of cases. Sensitivity to NF-kappa B pathway inhibitors was not related to the prognostic markers VH status, CD38 or Zap70 expression, or to the levels of nuclear NF-kappa B. Normal peripheral B cells were resistant to the apoptosis-inducing effects of these compounds. Cell death induced by the inhibitors was associated with activation of caspase-9 and -3, and loss of mitochondrial membrane polarization, but did not involve changes in the expression of Bcl-2 or Mcl-1. Inhibitors caused an increase in c-jun NH2-terminal kinase activity in CLL, but this did not appear to be important for apoptosis. Microarray analysis identified some potential novel NF-kappa B target genes, including interleukin-16- and the Bcl-2- related survival protein Bcl-w. These results demonstrate that a substantial proportion of CLL are dependent on NF-kappa B for enhanced survival and suggest that inhibition of NF-kappa B may have therapeutic potential
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
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