131,217 research outputs found
A Transgenic Mouse Model of Merkel Cell Virus Small Tumor Antigen
No full textMerkel cell carcinoma (MCC), a primary cutaneous neoplasm, originates in the mechanoreceptor Merkel cells in the basal layer of the epidermis. Risk factors include UV exposure, advanced age and immunosuppression, suggesting an infectious etiology. MCC
incidence in the US is rising, with approximately 1500 cases per year. The non-enveloped, double-stranded DNA Merkel cell polyomavirus (MCV) is responsible for approximately 80% of MCC cases. The virus was discovered by subjecting MCC tissue samples to digital transcriptome subtraction, in which mRNA is isolated, the human transcripts subtracted in silico and the remaining transcripts compared to viral sequences.
MCV expresses differentially spliced Large (LT), Small (sT) and 57 kT tumor antigens from the T antigen early locus, similar to other polyomaviruses such as SV40. Both LT and sT are critical for transformation. LT is a helicase responsible for replication of the viral genome, however in integrated viral genomes it is either truncated or mutated to eliminate its replicative functions. sT contributes to transformation via hyperphosphorylation and inhibition of the cap-dependent translation inhibitor 4E-BP1. The function of 57 kT remains unknown. Knockdown of LT induces necroptosis of MCVpositive MCC cells, whereas sT expression in rodent Rat-1 cells is transformative.
Being that sT is the transformative agent in rodent cells, it would be of interest to develop a mouse model expressing sT in a tissue-specific manner to determine whether tumor formation occurs. Indeed, several mouse models of SV40 T antigen have been developed over the past decades, each resulting in tissue-specific tumor formation. We developed a MCV sT transgenic mouse model, in which a lox-stop-lox sT is expressed via an ER-inducible Cre gene under the control of the ubiquitin promoter. Upon tamoxifen induced MCV sT expression, ER-Cre-positive mice demonstrate severe weight loss, ruffled fur and a hunched posture, necessitating euthanasia. Western blotting reveals sT expression in several tissues, whereas TUNEL staining shows significant cell death. While
we were unable to observe transformation, we believe this drastic phenotype demonstrates the validity of our MCV sT transgenic mouse model and warrants further investigation into the mechanism of death
Comparative Evaluation of Milk Oligosaccharides Isolated and Fractionated from Indigenous Rathi Cow Milk for Anti-Oxidant and Anti-Adhesive Properties
No full textMilk, a cornerstone of neonatal nutrition and human health, harbors various components with antioxidant capabilities, including oligosaccharides. In this study, we explored the antioxidant potential of acetylated milk oligosaccharides (A-MOs) and deacetylated oligosaccharides (D-MOs) sourced from Rathi cow milk through assays, with a focus on their comparative efficacy. Concurrently, we evaluated the antioxidant activity of Ascorbic Acid (AA) for comparison. Results revealed significant dynamics within the antioxidant profiles of A-MOs and D-MOs. A-MOs demonstrated concentration-dependent antioxidant activity, with higher concentrations correlating with increased efficacy, while D-MOs displayed a distinct pattern, with varying antioxidant potential across concentrations. Notably, both A-MOs and D-MOs exhibited promising antioxidant activity, suggesting their potential as natural antioxidants. In contrast, AA exhibited a decline in antioxidant activity with increasing concentration, indicating a differing pattern from oligosaccharides. These findings underscore the significance of acetylation in modulating the antioxidant properties of milk oligosaccharides. Further investigation is warranted to elucidate the mechanisms underlying these observations and to explore the practical implications of A-MOs and D-MOs as functional food components or potential therapeutic agents. Overall, our study contributes to the understanding of milk oligosaccharides’ antioxidant properties and highlights the potential of acetylated and deacetylated oligosaccharides from Rathi cow milk as valuable sources of natural antioxidants with diverse applications in nutrition and healthcare
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
sj-docx-1-aor-10.1177_00034894231179016 – Supplemental material for Rates of Antidepressant, Anxiolytic, and ADHD Medication Use Among Patients Undergoing ESS
No full textSupplemental material, sj-docx-1-aor-10.1177_00034894231179016 for Rates of Antidepressant, Anxiolytic, and ADHD Medication Use Among Patients Undergoing ESS by Alan D. Workman, Lillian W. Dattilo, Margaret B. Mitchell, Vinay K. Rathi and Neil Bhattacharyya in Annals of Otology, Rhinology & Laryngology</p
ROLE OF MULTIPLE DOMAINS OF T ANTIGEN IN GENE REGULATION AND TRANSFORMATION
No full textSV40 large T antigen (TAg) is a dominant acting oncoprotein that elicits transformation of many cell types and induces tumors in rodents. TAg induces transformation, in part, by disabling the functions of tumor suppressors such as pRb and p53. This dissertation is aimed to determine if inactivation of Rb and p53 are the major TAg activities required for transformation or if additional activities contribute.To determine whether Rb-family protein inactivation by the J domain of TAg is required for induction of intestinal hyperplasia, we have generated transgenic mice that express a J domain mutant (D44N) in villus enterocytes. In contrast to wild-type T antigen, the D44N mutant is unable to induce enterocyte proliferation. Unlike mice expressing wild-type TAg, mice expressing D44N do not reduce the protein levels of p130 and are also unable to dissociate p130-E2F DNA binding complexes. To determine if Rb inactivation is sufficient for the induction of hyperplasia or if progression to dysplasia requires some activity in the C-terminus of TAg (independent of p53), I have screened several transgenic lines expressing an amino-terminal mutant of TAg (N136) in villus enterocytes. I found that these mice develop intestinal hyperplasia, although not as early as wild-type TAg does, suggesting that the inactivation of Rb family members is sufficient to induce this phenotype. Furthermore, the appearance of signs of dysplasia was significantly delayed. I performed global analysis of gene regulation in MEFs and in mouse intestinal epithelium expressing TAg or various mutants. In mouse intestine most of the gene regulation is dependent on binding and inactivation of Rb-proteins by the LXCXE motif and J domain. Regulated genes are involved in cell cycle and proliferation. In MEFs genes belonging to cell cycle, apoptosis and growth factors are differentially regulated by TAg and its mutants. Additionally, we found upregulation of immune response genes by TAg requires the LXCXE motif and some activity mapping to the C-terminus of TAg for their regulation. Significant numbers of genes were found to be regulated independently of the LXCXE motif, J domain and p53 binding domain. This suggests activity independent of these functions
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund
No full textAt the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far
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