648 research outputs found

    Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin

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    The role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 mu M. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.NIT-Rourkela; DST, Government of Indi

    Epigenetic Signatures of Genes and Their Correlations with Various Signaling Pathways During Tumorigenesis

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    During the past 15 years the epigenetic regulation of gene has been studied extensively. The genesis of cancer and epigenetic regulation of genes are deeply interconnected. DNA methylation, histone tail modification, nucleosome remodelling, and non-coding RNA regulate many biological processes that are elementary to the cancer development. This thesis evaluates the expression profile and epigenetic regulation (especially, DNA methylation and histone H3 modifications) of various genes, such as caveolin 1 (CAV1), clusterin (CLU), beta 1 integrin (β1 integrin), histone H3.3 and chromatin modifying enzymes like DNA methyltransferases (DNMTs), histone methyltransferases (HMTs) and histone acetyltransferases (HATs) in colon and breast cancers. Additionally, lipid raft, RAS/MEK/ERK and FAK signaling pathway mediated regulation of histone modifications in colon cancer is also examined. mRNA and protein level analysis of respective gene products in cancer tissue samples and cell lines demonstrated that CAV1 is expressed in a stage-specific manner whereas nuclear CLU (nCLU) is down-regulated; whereas, secretory CLU (sCLU), β1 integrin and H3.3 genes are up-regulated in both the cancers. Inhibition of cell growth in breast and colon cancer cell lines after treatment with epigenetic modulators is associated with up-regulation of CAV1 and nCLU; ultimately resulting in down-regulation of β1 integrin. On investigating the epigenetic regulatory mechanisms of CAV1 gene, it is observed that histone modifications (H3K4me3, H3K9me3, H3K9AcS10p) predominantly regulate CAV1 expression in both cancers whereas promoter DNA methylation is partially responsible in case of only breast cancer. Moreover, expression of CLU is associated with global histone marks in case of breast cancer. In colon cancer, promoter H3K4me, H3K9me3 and H3K9AcS10p enrichment is the predominant regulator of CLU gene expression. Along with expression pattern and epigenetic regulation this thesis also evaluated the involvement of different signaling responsible for histone modifications. The modulation of global and gene specific histone marks in colon cancer is demonstrated to be regulated by lipid raft, RAS/MEK/ERK and FAK signaling pathways. These pathways influence global H3K4me3, H3K9me3, H3K9AcS10p levels and in turn differentially regulate gene specific expression, such as that of CAV1

    Lesbian Radio, August 15 2012

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    Host Deb Gallagher talks again with Leela Sinha, author of You’re Not Too Much: Intensive Lies in an Expansive World, about the fundamentals of good communication.https://digitalcommons.usm.maine.edu/wmpg_lesbianradio/1002/thumbnail.jp

    Lesbian Radio, June 20 2012

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    Host Deb Gallagher talks with Leela Sinha, author of You’re Not Too Much: Intensive Lies in an Expansive World, about the fundamentals of good communication.https://digitalcommons.usm.maine.edu/wmpg_lesbianradio/1001/thumbnail.jp

    Herbalist Deb Soule, author of The Roots of Healing: A Woman\u27s Book of Herbs,

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    Herbalist Deb Soule, author of The Roots of Healing: A Woman\u27s Book of Herbs, founded Avena Botanicals of Rockland ten years ago. Avena Botanicals, perhaps the largest herbal apothecary in the Northeast, grows or gathers around 60 percent of the raw plant materials used in producing herbal extracts, oils, salves and teas. The Shaker Community of Sabbath Day Lake has an herbal tradition that is 200 years old, and the herb department is the Shakers\u27 largest industry. Pol Hermes of Dayton, Gail Edwards of Athens and Betty Chase of Falmouth are other Mainers who use herbs. Details

    Increasing fuel resilience to survive Cascadia

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    prepared by Oregon Seismic Safety Policy Advisory Commission, Working Group on CEI Hub Mitigation Strategies ; production writer: Laura Hall ; production assistant: Deb Schueller.Title from PDF cover (viewed on January 15, 2020)."OSSPAC Publication Number 19-01."This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (pages 31-32).Mode of access: Internet from the Oregon Government Publications Collection.Text in English

    Graduate medical education in 2030 (Podcast)

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    In the June issue of the Journal of Graduate Medical Education, an editorial explores what graduate medical education will look like in 2030. In this episode, JGME deputy editor, Deb Simpson, speaks with physician, educator, and author, James Woolliscroft, about the future of graduate medical education, especially in the wake of the COVID-19 pandemic. They discuss the roles of the DIO, program director, and faculty as well as the impact of technology on the medical education system

    Graduate medical education in 2030 (Podcast)

    No full text
    In the June issue of the Journal of Graduate Medical Education, an editorial explores what graduate medical education will look like in 2030. In this episode, JGME deputy editor, Deb Simpson, speaks with physician, educator, and author, James Woolliscroft, about the future of graduate medical education, especially in the wake of the COVID-19 pandemic. They discuss the roles of the DIO, program director, and faculty as well as the impact of technology on the medical education system

    Micro-machinability of A-286 Steel with and without Laser Assist

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    AbstractMachinability of high nickel content steels (e.g. stainless) is known to be challenging. This paper presents an experimental study of the micro-machinability of A-286 (∼43 HRC), a precipitation-hardened high nickel content steel. Micro milling experiments are carried out under dry, wet, and laser-assisted conditions, and the resulting surface morphology, burr, part feature depth, tool wear, and cutting forces are analyzed. It is found that laser-assist consistently yields the best results characterized by minimal chip adhesion to the workpiece surface, low cutting forces, good feature depth accuracy, low tool wear, and acceptable burrs
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