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  • 1
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    CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling (2018)
    Springer Nature
    Details
    Publication Date: 2018
    Description: 〈p〉Multi-subunit cullin-RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 is required to disrupt the assembly and attenuate the ligase activity of human CRL5〈sup〉SOCS〈/sup〉〈sup〉3〈/sup〉 and HIV-1 CRL5〈sup〉VIF〈/sup〉 complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5〈sup〉SOCS〈/sup〉〈sup〉3〈/sup〉 and CRL5〈sup〉VIF〈/sup〉, respectively. Thus, by discovering a substrate of CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.〈/p〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 2
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    The Sound of William Barnes's Dialect Poems: 1. Poems of Rural Life in the Dorset Dialect, first collection (1844) (2021)
    University of Adelaide Press
    Details
    Publication Date: 2024-03-25
    Description: This series, developed from Tom Burton’s groundbreaking study, William Barnes’s Dialect Poems: A Pronunciation Guide (The Chaucer Studio Press, 2010), sets out to demonstrate for the first time what all of Barnes’s dialect poems would have sounded like in the pronunciation of his own time and place. Every poem is accompanied by a facing-page phonemic transcript and by an audio recording freely available from this website.
    Keywords: eclogues ; poem ; rural life ; dorset ; english literature ; eclogue ; dialect poems ; william barnes ; dorset dialect ; dialect ; Diphthong ; Drow ; Rhyme ; Vowel ; thema EDItEUR::D Biography, Literature and Literary studies::DC Poetry::DCF Poetry by individual poets
    Language: English
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  • 3
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    Six Eclogues from William Barnes's Poems of Rural Life in the Dorset Dialect (First Collection, 1844) (2021)
    University of Adelaide Press
    Details
    Publication Date: 2024-03-25
    Description: When William Barnes began publishing poems in the Dorset County Chronicle in the 1830s in the dialect of his native Blackmore Vale, the first poems that appeared were in the form of eclogues — dialogues between country people on country matters. Although an immediate success, the eclogues were in time overshadowed by the many lyric poems that Barnes published in the dialect. They are now perhaps the most undervalued works by this brilliant but neglected poet. Each eclogue is, effectively, a one-scene play, demanding performance for its potential to be realized. The phonemic transcripts in this book, based on the findings in T. L. Burton’s William Barnes’s Dialect Poems: A Pronunciation Guide (2010), show what the poems would have sounded like in Barnes’s own time; the accompanying audio recordings (made at the 2010 Adelaide Fringe) give living voice to the sounds noted in the transcripts.
    Keywords: tom burton ; dorset ; english literature ; poetry ; william barnes ; dorset dialect ; t l burton ; William Barnes ; thema EDItEUR::D Biography, Literature and Literary studies::DC Poetry::DCF Poetry by individual poets
    Language: English
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  • 4
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    Structure of HCV E2 antigenic region 412-423 [Immunology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-06-13
    Description: Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412–423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptide at 1.8-Å resolution reveal that the epitope is a β-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu413 and Trp420 on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn415 on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Ross Ice Shelf response to climate driven by the tectonic imprint on seafloor bathymetry (2019)
    Springer Nature
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    Publication Date: 2019
    Print ISSN: 1752-0894
    Electronic ISSN: 1752-0908
    Topics: Geosciences
    Published by Springer Nature
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  • 6
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    6.7-GHz methanol maser associated outflows: an evolutionary sequence (2015)
    Oxford University Press
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    Publication Date: 2015-03-20
    Description: We present a continuing study of a sample 44 molecular outflows, observed in 13 CO lines, closely associated with 6.7-GHz methanol masers, hence called methanol maser associated outflows (MMAOs). We compare MMAO properties with those of outflows from other surveys in the literature. In general, MMAOs follow similar trends, but show a deficit in number at low masses and momenta, with a corresponding higher fraction at the high end of the distributions. A similar trend is seen for the dynamical time-scales of MMAOs. We argue that the lack of relatively low mass and young flows in MMAOs is due to the inherent selection-bias in the sample, i.e. its direct association with 6.7-GHz methanol masers. This implies that methanol masers must switch on after the onset of outflows (hence accretion), and not before a sufficient abundance of methanol is liberated from icy dust mantles. Consequently the average dynamical age of MMAOs is older than for the general population of molecular outflows. We propose an adjusted evolutionary sequence of outflow and maser occurrence in the hot core phase, where methanol masers turn on after the onset of the outflow phase.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Methanol maser associated outflows: detection statistics and properties (2014)
    Oxford University Press
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    Publication Date: 2014-08-20
    Description: We have selected the positions of 54 6.7 GHz methanol masers from the Methanol Multibeam Survey catalogue, covering a range of longitudes between 20° and 34° of the Galactic plane. These positions were mapped in the J = 3-2 transition of both the 13 CO and C 18 O lines. A total of 58 13 CO emission peaks are found in the vicinity of these maser positions. We search for outflows around all 13 CO peaks, and find evidence for high-velocity gas in all cases, spatially resolving the red and blue outflow lobes in 55 cases. Of these sources, 44 have resolved kinematic distances, and are closely associated with the 6.7 GHz masers, a subset referred to as Methanol Maser Associated Outflows (MMAOs). We calculate the masses of the clumps associated with each peak using 870 μm continuum emission from the ATLASGAL survey. A strong correlation is seen between the clump mass and both outflow mass and mechanical force, lending support to models in which accretion is strongly linked to outflow. We find that the scaling law between outflow activity and clump masses observed for low-mass objects, is also followed by the MMAOs in this study, indicating a commonality in the formation processes of low-mass and high-mass stars.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-07-06
    Description: Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme-the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors-most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724525/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Timothy R -- Fridlyand, Jane -- Yan, Yibing -- Penuel, Elicia -- Burton, Luciana -- Chan, Emily -- Peng, Jing -- Lin, Eva -- Wang, Yulei -- Sosman, Jeff -- Ribas, Antoni -- Li, Jiang -- Moffat, John -- Sutherlin, Daniel P -- Koeppen, Hartmut -- Merchant, Mark -- Neve, Richard -- Settleman, Jeff -- K24 CA097588/CA/NCI NIH HHS/ -- England -- Nature. 2012 Jul 26;487(7408):505-9. doi: 10.1038/nature11249.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763448" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/*pharmacology ; Breast Neoplasms/*drug therapy/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; *Drug Resistance, Neoplasm/drug effects ; Female ; Hepatocyte Growth Factor/*metabolism/pharmacology ; Humans ; Indoles/*pharmacology ; Ligands ; Melanoma/*drug therapy/enzymology/genetics/pathology ; Mitogen-Activated Protein Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics ; Quinazolines/pharmacology ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, ErbB-2/genetics/metabolism ; Signal Transduction/drug effects ; Sulfonamides/*pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 9
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    The Q-Cycle Mechanism of the bc1 Complex: A Biologist’s Perspective on Atomistic Studies (2017)
    American Chemical Society (ACS)
    Details
    Publication Date: 2017-03-15
    Description: The Journal of Physical Chemistry B DOI: 10.1021/acs.jpcb.6b10524
    Electronic ISSN: 1520-5207
    Topics: Chemistry and Pharmacology , Physics
    Published by American Chemical Society (ACS)
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  • 10
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    EMAGE mouse embryo spatial gene expression database: 2014 update (2013)
    Oxford University Press
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    Publication Date: 2013-12-29
    Description: EMAGE ( http://www.emouseatlas.org/emage/ ) is a freely available database of in situ gene expression patterns that allows users to perform online queries of mouse developmental gene expression. EMAGE is unique in providing both text-based descriptions of gene expression plus spatial maps of gene expression patterns. This mapping allows spatial queries to be accomplished alongside more traditional text-based queries. Here, we describe our recent progress in spatial mapping and data integration. EMAGE has developed a method of spatially mapping 3D embryo images captured using optical projection tomography, and through the use of an IIP3D viewer allows users to view arbitrary sections of raw and mapped 3D image data in the context of a web browser. EMAGE now includes enhancer data, and we have spatially mapped images from a comprehensive screen of transgenic reporter mice that detail the expression of mouse non-coding genomic DNA fragments with enhancer activity. We have integrated the eMouseAtlas anatomical atlas and the EMAGE database so that a user of the atlas can query the EMAGE database easily. In addition, we have extended the atlas framework to enable EMAGE to spatially cross-index EMBRYS whole mount in situ hybridization data. We additionally report on recent developments to the EMAGE web interface, including new query and analysis capabilities.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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