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  • 1
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    A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial infection (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-05-10
    Description: Immune interferon gamma (IFN-gamma) is essential for mammalian host defense against intracellular pathogens. IFN-gamma induces nearly 2000 host genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-gamma-inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, and Gbp10--conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps solicited host defense proteins, including the phagocyte oxidase, antimicrobial peptides, and autophagy effectors, to kill intracellular bacteria. Thus, specific 65-kD Gbps coordinate a potent oxidative and vesicular trafficking program to protect the host from infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Bae-Hoon -- Shenoy, Avinash R -- Kumar, Pradeep -- Das, Rituparna -- Tiwari, Sangeeta -- MacMicking, John D -- R01 AI068041-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2011 May 6;332(6030):717-21. doi: 10.1126/science.1201711.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21551061" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy ; Cell Line ; GTP-Binding Proteins/chemistry/genetics/*metabolism ; Humans ; Immunity, Innate ; Interferon-gamma/*immunology ; Listeria monocytogenes/growth & development/immunology/pathogenicity ; Listeriosis/*immunology/metabolism/microbiology ; Lysosomes/metabolism ; Macrophages/*immunology/metabolism/*microbiology ; Mice ; Mycobacterium bovis/growth & development/immunology/pathogenicity ; NADPH Oxidase/metabolism ; Oxidation-Reduction ; Peptides/metabolism ; Phagocytosis ; Phagosomes/metabolism ; RNA Interference ; Tuberculosis/*immunology/metabolism/microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-03-31
    Description: Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1beta/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed pronounced caspase-1 and IL-1beta/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shenoy, Avinash R -- Wellington, David A -- Kumar, Pradeep -- Kassa, Hilina -- Booth, Carmen J -- Cresswell, Peter -- MacMicking, John D -- R01 AI068041-06/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Apr 27;336(6080):481-5. doi: 10.1126/science.1217141. Epub 2012 Mar 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22461501" target="_blank"〉PubMed〈/a〉
    Keywords: Alum Compounds ; Animals ; Apoptosis Regulatory Proteins ; Carrier Proteins/genetics/*metabolism ; Caspase 1/metabolism ; Cell Line ; Cytoskeletal Proteins/metabolism ; GTP-Binding Proteins/chemistry/genetics/*metabolism ; Humans ; Inflammasomes/*metabolism ; Interferon-gamma/immunology ; Interleukin-1beta/secretion ; Lipopolysaccharides/immunology ; Listeria monocytogenes ; Listeriosis/immunology ; Macrophages/immunology/*metabolism ; Mice ; Protein Multimerization ; RNA Interference ; Salmonella typhimurium/immunology ; Uric Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
    Electronic Resource
    Electronic Resource
    An Optimal Control Problem for Flows with Discontinuities (1997)
    Springer
    Journal of optimization theory and applications 94 (1997), S. 273-309 
    Details
    ISSN: 1573-2878
    Keywords: Optimal control ; Euler flow equations ; sequential quadratic programming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this paper, we study a design problem for a duct flow with a shock. The presence of the shock causes numerical difficulties. Good shock-capturing schemes with low continuity properties often cannot be combined successfully with efficient optimization methods requiring smooth functions. A remedy studied in this paper is to introduce the shock location as an explicit variable. This allows one to fit the shock and yields a problem with sufficiently smooth functions. We prove the existence of optimal solutions, Fréchet differentiability, and the existence of Lagrange multipliers. In the second part, we introduce and investigate the discrete problem and study the relations between the optimality conditions for the infinite-dimensional problem and the discretized one. This reveals important information for the numerical solution of the problem. Numerical examples are given to demonstrate the theoretical findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1022616327742
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  • 4
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    An Optimal Control Problem for Flows with Discontinuities (1997)
    Springer
    Details
    Publication Date: 1997-08-01
    Print ISSN: 0022-3239
    Electronic ISSN: 1573-2878
    Topics: Mathematics
    Published by Springer
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  • 5
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    Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing (2018)
    The American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in 〈i〉SQSTM1〈/i〉, which encodes p62, are linked to hereditary inflammatory conditions such as Paget’s disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62〈sup〉TRM〈/sup〉. We found that p62〈sup〉TRM〈/sup〉, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapamycin complex 1 (mTORC1). The kinase RIPK1 and caspase-8 controlled p62〈sup〉TRM〈/sup〉 production and thus promoted mTORC1 signaling. An FTD-linked p62 D329G polymorphism and a rare D329H variant could not be proteolyzed by caspase-8, and these noncleavable variants failed to activate mTORC1, thereby revealing the detrimental effect of these mutations. These findings on the role of p62〈sup〉TRM〈/sup〉 provide new insights into 〈i〉SQSTM1〈/i〉-linked diseases and mTORC1 signaling.〈/p〉
    Print ISSN: 1945-0877
    Electronic ISSN: 1937-9145
    Topics: Biology , Medicine
    Published by The American Association for the Advancement of Science (AAAS)
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  • 6
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    Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis (2019)
    Springer Nature
    Details
    Publication Date: 2019
    Description: 〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉 〈p〉GBP1 targets 〈i〉Toxoplasma〈/i〉 and 〈i〉Salmonella〈/i〉 in macrophages and regulates host cell death. GBP1 promotes 〈i〉Toxoplasma 〈/i〉DNA detection by AIM2-ASC-caspase-8 leading to apoptosis and targeting of 〈i〉Salmonella〈/i〉 by caspase-4 leading to pyroptosis.〈/p〉 〈p〉 〈l type="unord"〉〈li〉〈p〉IFN-induced GBP1 translocates to 〈i〉Toxoplasma gondii-〈/i〉 and 〈i〉Salmonella〈/i〉 Typhimurium-containing vacuoles in a lipidation and GTPase dependent manner.〈/p〉〈/li〉 〈li〉〈p〉GBP1 induces AIM2-, ASC- and caspase-8-dependent atypical apoptosis in 〈i〉Toxoplasma gondii〈/i〉-infected macrophages.〈/p〉〈/li〉 〈li〉〈p〉〈i〉Toxoplasma gondii〈/i〉 induces degradation of NLRP1, NLRP3, NLRC4 and pro-caspase-1, switching cell death type from pyroptosis to apoptosis.〈/p〉〈/li〉 〈li〉〈p〉GBP1 is essential for targeting of 〈i〉Salmonella〈/i〉 by caspase-4, its activation and increased pyroptosis.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
    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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  • 7
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    Rv0805: cyclic nucleotide phosphodiesterase fromM. tuberculosis (2005)
    International Union of Crystallography
    Details
    Publication Date: 2005-08-23
    Print ISSN: 0108-7673
    Electronic ISSN: 2053-2733
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by International Union of Crystallography
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  • 8
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    Flow over a thin circular disk at low to moderate Reynolds numbers (2008)
    Cambridge University Press
    Details
    Publication Date: 2008-05-23
    Description: Computation of viscous flow over a circular disk of aspect ratio 10 (thickness/diameter) in the Reynolds number (Re) range of 10 to 300 was performed. The following flow regimes were observed: (I) steady axisymmetric flow when Re 〈 135, with the presence of a toroidal vortex behind the disk; (II) regular bifurcation with loss of azimuthal symmetry but with planar symmetry and a double-threaded wake, for 135 ≤ Re 〈 155; (III) three-dimensional flow with periodic shedding of double-sided hairpin-shaped vortex structures and periodic motion of the separation region for 155 ≤ Re 〈 172; (IV) regular shedding of double-sided hairpin-shaped vortex structures with planar and spatio-temporal symmetry for 172 ≤ Re 〈 280; (V) periodic three-dimensional flow with irregular rotation of the separation region when Re = 280-300. This transition process for the disk differs from that for the sphere as we observe a loss of the symmetry plane in Regime III due to a twisting motion of the axial vorticity strands in the wake of the disk. The periodic flow was characterized by double-sided hairpin structures, unlike the one-sided vortex loops observed for the sphere. This resulted in the drag coefficient oscillating at twice the frequency of the axial velocity. In Regime IV, the vortex loops were shed from diametrically opposite locations and with equal strength, resulting in the lift coefficient oscillating symmetrically about a zero mean. These results imply the presence of spatio-temporal symmetry. © 2008 Cambridge University Press.
    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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  • 9
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    Influence of aspect ratio on the dynamics of a freely moving circular disk (2010)
    Cambridge University Press
    Details
    Publication Date: 2010-06-02
    Description: The influence of aspect ratio (X =diameter/thickness) on the vortex shedding behaviour of fixed, and freely moving, circular disk has been investigated numerically. The aspect ratio significantly changes the structure of the vortices shed from the disk, thus altering the fluid induced forces. Disks of X =2 and 4 were selected, and by choosing Re=240 periodic behaviour was observed for both the 'fixed' and 'freely' moving disks. First, the vortex structures shed from a 'fixed' circular disk of X =2 and 4 were computed for Re=240. This was followed by a computation of their trajectories falling 'freely' under the action of gravity at Re=240. For the 'fixed' disk of X =2, periodic shedding of one-sided hairpin-shaped vortex loops was observed. The flow field had a spatial planar symmetry and the vortices were shed from the same location, resulting in an asymmetric lateral force on the disk. The Strouhal number (St), calculated using the fluctuation in the axial velocity in the far-wake, was 0.122. This vortex shedding behaviour is referred to as the 'single-sided' vortex shedding mode. For the 'fixed' disk of X =4, periodic shedding of hairpin-shaped vortex loops was observed from the diametrically opposite location of the disk. The flow field had a spatial planar symmetry, and also a spatio-temporal one, with respect to a plane orthogonal to the spatial symmetry plane. The shed vortices induced a symmetric lateral force on the disk with a zero mean. The computed Strouhal number, was equal 0.122, same as that for X =2. This vortex shedding behaviour is referred as the 'double-sided' vortex shedding mode. For the 'freely falling' disk of X =2, an oscillatory motion was observed in a plane with a 83. phase lag between the lateral and angular velocity. The Strouhal number (Stb), calculated using the oscillation frequency of the 'freely' falling disk was equal to 0.116, which is comparable to the St of the fixed disk. For a 'freely falling' disk of X =4, oscillatory motion was observed in a plane with a 21. phase lag between the lateral and angular velocity. The Strouhal number (Stb) was equal to 0.171, which differs from the St observed in the wake of the fixed disk. © 2010 Cambridge University Press.
    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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