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  • 1
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    Linear ubiquitination prevents inflammation and regulates immune signalling (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-04-02
    Description: Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKgamma or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1beta was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerlach, Bjorn -- Cordier, Stefanie M -- Schmukle, Anna C -- Emmerich, Christoph H -- Rieser, Eva -- Haas, Tobias L -- Webb, Andrew I -- Rickard, James A -- Anderton, Holly -- Wong, Wendy W-L -- Nachbur, Ueli -- Gangoda, Lahiru -- Warnken, Uwe -- Purcell, Anthony W -- Silke, John -- Walczak, Henning -- 10950/Cancer Research UK/United Kingdom -- England -- Nature. 2011 Mar 31;471(7340):591-6. doi: 10.1038/nature09816.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tumour Immunology Unit, Department of Medicine, Imperial College London, W12 0NN London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21455173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD40 Ligand/metabolism ; Carrier Proteins/chemistry/metabolism ; Cell Line ; Humans ; I-kappa B Kinase/metabolism ; Immunity/*immunology ; Inflammation/*metabolism/pathology/prevention & control ; Interleukin-1beta/metabolism ; Mice ; Multiprotein Complexes/chemistry/metabolism ; NF-kappa B/metabolism ; Nerve Tissue Proteins/chemistry/genetics/metabolism ; Phenotype ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Receptors, Tumor Necrosis Factor/deficiency/genetics/metabolism ; *Signal Transduction ; Skin/cytology/immunology/metabolism/pathology ; Tumor Necrosis Factor-alpha/deficiency/genetics ; Ubiquitin/chemistry/metabolism ; Ubiquitin-Protein Ligase Complexes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; *Ubiquitination
    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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  • 2
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    Pathological oscillations of a rotating fluid (1969)
    Cambridge University Press
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    Publication Date: 1969-03-10
    Description: A theoretical study is made of the free periods of oscillation of an incompressible inviscid fluid, bounded by two rigid concentric spheres of radii a, b (a 〉 b), and rotating with angular velocity Ω about a common diameter. An attempt is made to use the Longuet-Higgins solution of the Laplace tidal equation as the first term of an expansion in powers of the parameter ε = (a − b)/(a + b), of the solution to the full equations governing oscillations in a spherical shell. This leads to a singularity in the second-order terms at the two critical circles where the characteristic cones of the governing equation touch the shell boundaries.A boundary-layer type of argument is used to examine the apparent non-uniformity in the neighbourhood of these critical circles, and it is found that, in order to remove the singularity in the pressure, an integrable singularity in the velocity components must be introduced on the characteristic cone which touches the inner spherical boundary. Further integrable singularities are introduced by repeated reflexion at the shell boundaries, and so, even outside the critical region the velocity terms contain what may reasonably be described as a pathological term, generally of order ε½ compared to that found by Longuet-Higgins, periodic with wavelength O(εa) in the radial and latitudinal directions.Some consequences of this result are discussed.
    Print ISSN: 0022-1120
    Electronic ISSN: 1469-7645
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Published by Cambridge University Press
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