1,720,954 research outputs found
Targeting Epigenetic ‘Readers’ with Natural Compounds for Cancer Interception
No full textNatural compounds from diverse sources, including botanicals and commonly consumed foods and beverages, exert beneficial health effects via mechanisms that impact the epigenome and gene expression during disease pathogenesis. By targeting the so-called epigenetic ‘readers’, ‘writers’, and ‘erasers’, dietary phytochemicals can reverse abnormal epigenome signatures in cancer cells and preneoplastic stages. Thus, such agents provide avenues for cancer interception via prevention or treatment/therapeutic strategies. To date, much of the focus on dietary agents has been directed towards writers (e.g., histone acetyltransferases) and erasers (e.g., histone deacetylases), with less attention given to epigenetic readers (e.g., BRD proteins). The drug JQ1 was developed as a prototype epigenetic reader inhibitor, selectively targeting members of the bromodomain and extraterminal domain (BET) family, such as BRD4. Clinical trials with JQ1 as a single agent, or in combination with standard of care therapy, revealed antitumor efficacy but not without toxicity or resistance. In pursuit of second-generation epigenetic reader inhibitors, attention has shifted to natural sources, including dietary agents that might be repurposed as ‘JQ1-like’ bioactives. This review summarizes the current status of nascent research activity focused on natural compounds as inhibitors of BET and other epigenetic ‘reader’ proteins, with a perspective on future directions and opportunities
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
The BAZ Family of Chromatin Remodelers in Colorectal Cancer: Insights into Oncogenesis, Alternative Splicing and Chemosensitization
No full textColorectal cancer (CRC) poses a significant healthcare challenge worldwide, necessitating a deeper understanding of the molecular mechanisms underlying its pathogenesis for improved therapeutic interventions. This thesis investigates the BAZ (Bromodomain Adjacent to Zinc finger) family of chromatin remodelers and their intricate involvement in CRC. The BAZ family members, including BAZ1A, BAZ1B, BAZ2A, and BAZ2B, exert critical regulatory functions in chromatin architecture and transcription, impacting various cellular processes from development to disease.
In colorectal cancer, BAZ1A is overexpressed, and its depletion resulted in diminished cell viability, increased apoptosis, augmented DNA damage, and cellular senescence, concomitant with the downregulation of components within the Wnt/��-catenin signaling pathway. In vivo studies corroborated these findings, revealing that knockdown of BAZ1A leads to diminished tumor growth and alterations in chromatin regulation. Interestingly, BAZ1A undergoes alternative splicing, which is promoted by treatment with histone deacetylase inhibitors, thereby highlighting its therapeutic potential. Remarkably, the full-length form of BAZ1A is implicated in DNA repair mechanisms, while its alternatively spliced counterpart is susceptible to increased DNA damage and sensitivity to DNA-damaging agents. These observations underscored the oncogenic role of BAZ1A in colorectal cancer and the importance of considering an oncogene���s alternative splicing patterns.
Similar to BAZ1A, BAZ2A is also upregulated in CRC and associated with reduced patient survival. Functional studies demonstrated their roles in inhibiting cell viability, colony formation, and modulating Wnt/��-catenin signaling. Inhibition of BAZ2A led to reduced tumor growth rates in mouse models, where it also affected histone modification patterns, favoring a less repressive chromatin state, and influencing major histocompatibility complex (MHC) regulation.
In contrast to BAZ1A and BAZ2A, BAZ1B knockdown enhanced cell viability, colony formation, and altered cell cycle progression, suggesting a tumor-suppressive role in metastatic CRC. BAZ1B impacted c-MYC expression independently of the Wnt/��-catenin pathway, and influenced p53 and p21 levels, implicating its involvement in tumor suppressive pathways.
Overall, the study underscores the potential of BAZ family members as therapeutic targets in CRC. Future research should focus on elucidating their molecular mechanisms, translating findings into clinical applications, and exploring combination therapies to improve treatment outcomes for CRC patients, thus advancing more personalized therapeutic approaches for CRC
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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