60 research outputs found

    Interview with Rebecca Katzman

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    Becca Katzman talks about the Owl Creek Produce Auctionhttps://digital.kenyon.edu/ps_interviews/1047/thumbnail.jp

    Interview with Kenyon Professor Emeritus Roy T. Wortman

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    Roy T. Wortman talks about Public Life in Knox County and his involvement with the Masons.https://digital.kenyon.edu/ps_interviews/1018/thumbnail.jp

    The notch regulator MAML1 interacts with p53 and functions as a coactivator.

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    Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that binds to native p53-response elements within the promoter of the p53 target genes. Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. MAML1 increases the half-life of p53 protein and enhances its phosphorylation/acetylation upon DNA damage of cells. Finally, RNA interference-mediated knockdown of the single Caenorhabditis elegans MAML homolog, Lag-3, led to substantial abrogation of p53-mediated germ-cell apoptotic response to DNA damage and markedly reduced the expression of Ced-13 and Egl-1, downstream pro-apoptotic targets of the C. elegans p53 homolog Cep-1. Thus, we present evidence for a novel coactivator function of MAML1 for p53, independent of its function as a coactivator of Notch signaling pathway

    Sexual expression and cognitive function: gender-divergent associations in older adults

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    Prior research demonstrates a positive association between sexual activity and cognitive function in later life. However, the relationship between the type of sexual activity and cognitive function in older adulthood remains unclear. This study explores the associations between the frequency of engaging in different types of sexual activities (intercourse, masturbation, and kissing/petting/fondling) and cognitive function in older women and men. Using data from Wave 6 of the English Longitudinal Study of Ageing (ELSA), 1915 women and 2195 men (age range 50-89 years; n = 4110) reporting any type of sexual activity over the past 12 months, were included in the study. Multiple regression controlling for age, education, satisfaction with sex life, cohabiting, wealth, general health, physical activity, depression and loneliness, was used to explore the associations between the frequency of engagement in intercourse, masturbation and kissing/petting/fondling, and two measures of cognitive function; word recall and number sequencing. For women, masturbation was linked to better word recall (p = .008), whilst for men, kissing/petting/fondling was associated with better number sequencing (p = .035). In women (p = .016) and men (p = .018), dissatisfaction with sex life was associated with better number sequencing. The results point to gendered links between sexual activity and cognitive function. These gender-related divergences may reflect differences in biological/neurological mechanisms, or in cognitive lifestyle factors that could influence cognitive reserve in later life. This novel study underscores the need to delineate the underlying mechanisms of the association between sex and cognition in men and women

    Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

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    Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

    LMP2A Does Not Require Palmitoylation To Localize to Buoyant Complexes or for Function

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    Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed constitutively in lipid rafts in latently infected B lymphocytes. Lipid rafts are membrane microdomains enriched in cholesterol and sphingolipids selective for specific protein association. Lipid rafts have been shown to be necessary for B-cell receptor (BCR) signal transduction. LMP2A prevents BCR recruitment to lipid rafts, thereby abrogating BCR function. As LMP2A is palmitoylated, whether this fatty acid modification is necessary for LMP2A to localize to lipid rafts and for protein function was investigated. LMP2A palmitoylation was confirmed in latently infected B cells. LMP2A was found to be palmitoylated on multiple cysteines only by S acylation. An LMP2A mutant that was not palmitoylated was identified and functioned similar to wild-type LMP2A; unmodified LMP2A localized to lipid rafts, was tyrosine phosphorylated, was associated with LMP2A-associated proteins, was ubiquitinated, and was able to block calcium mobilization following BCR cross-linking. Therefore, palmitoylation of LMP2A is not required for LMP2A targeting to buoyant complexes or for function

    Fundamentals of Cell Biology

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    This textbook, a remix of other open educational resources, is developed through a Round 15 Textbook Transformation Grant. Chapters include: Cytoskeleton DNA Packaging and Chromosomes Transcription and mRNA Modification Translation Transcriptional Regulation Cell and Organelle Membrane Structure Transport Across Cellular Membranes The Electrochemical Gradient Protein Trafficking Vesicles in the Endomembrane System Principles of Cell Signaling GPCRs and RTKs Cell Cycle and its Regulation DNA Replication Cell Death and Cancer Stem Cellshttps://oer.galileo.usg.edu/biology-textbooks/1022/thumbnail.jp

    CORONA, a Member of the Class III Homeodomain Leucine Zipper Gene Family in Arabidopsis, Regulates Stem Cell Specification and Organogenesis

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    Organogenesis at the shoot meristem requires a delicate balance between stem cell specification and differentiation. In Arabidopsis thaliana, WUSCHEL (WUS) is a key factor promoting stem cell identity, whereas the CLAVATA (CLV1, CLV2, and CLV3) loci appear to promote differentiation by repressing WUS expression. In a screen for mutations modifying clv1 mutants, we have identified a novel regulator of meristem development we term CORONA (CNA). Whereas cna single mutant plants exhibit subtle defects in meristem development, clv cna double mutants develop massively enlarged apices that display early loss of organogenesis, misexpression of WUS and CLV3, and eventual differentiation of the entire apex. The CNA gene was isolated by positional cloning and found to encode a class III homeodomain Leu zipper protein. A missense mutation resulting in the dominant-negative cna-1 allele was identified in a conserved domain of unknown function, and a likely null allele was shown to display a similar but weaker phenotype. CNA is expressed in developing vascular tissue, diffusely through shoot and flower meristems, and within developing stamens and carpels. Our analysis of WUS expression in wild-type, clv, and clv cna plants revealed that, contrary to current models, WUS is neither necessary nor sufficient for stem cell specification and that neither WUS nor CLV3 is a marker for stem cell identity. We propose that CNA functions in parallel to the CLV loci to promote organ formation
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