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  • 1
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    Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-06-22
    Description: Although the oncogene product of CT10 virus, P47gag-crk, does not itself phosphorylate proteins at tyrosine residues, it elevates phosphotyrosine in transformed cells. The P47gag-crk oncoprotein contains SH2 and SH3 domains, which are conserved in several proteins involved in signal transduction, including nonreceptor tyrosine kinases. P47gag-crk bound in vitro to phosphotyrosine-containing proteins from crk-transformed cells and from cells transformed by oncogenic tyrosine kinases. The association between P47gag-crk and p60v-src, a phosphotyrosine-containing protein, was abolished by dephosphorylation of p60v-src. This suggests that the SH2 and SH3 regions function to regulate protein interactions in a phosphotyrosine-dependent manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuda, M -- Mayer, B J -- Fukui, Y -- Hanafusa, H -- AI 07233/AI/NIAID NIH HHS/ -- CA44356/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 22;248(4962):1537-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1694307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Transformed ; Cell Transformation, Viral ; Oncogene Protein v-crk ; Phosphorylation ; Phosphotyrosine ; Precipitin Tests ; Protein Binding ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Retroviridae Proteins/*metabolism ; *Signal Transduction ; Tyrosine/*analogs & derivatives/metabolism
    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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    Neutrophils scan for activated platelets to initiate inflammation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-12-06
    Description: Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280847/" 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/PMC4280847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sreeramkumar, Vinatha -- Adrover, Jose M -- Ballesteros, Ivan -- Cuartero, Maria Isabel -- Rossaint, Jan -- Bilbao, Izaskun -- Nacher, Maria -- Pitaval, Christophe -- Radovanovic, Irena -- Fukui, Yoshinori -- McEver, Rodger P -- Filippi, Marie-Dominique -- Lizasoain, Ignacio -- Ruiz-Cabello, Jesus -- Zarbock, Alexander -- Moro, Maria A -- Hidalgo, Andres -- HL03463/HL/NHLBI NIH HHS/ -- HL085607/HL/NHLBI NIH HHS/ -- HL090676/HL/NHLBI NIH HHS/ -- P01 HL085607/HL/NHLBI NIH HHS/ -- R01 HL034363/HL/NHLBI NIH HHS/ -- R01 HL090676/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1234-8. doi: 10.1126/science.1256478. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. ; Unidad de Investigacion Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain. ; Department of Anesthesiology and Critical Care Medicine, University of Munster and Max Planck Institute Munster, Munster, Germany. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia. ; Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan. ; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. ; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. ahidalgo@cnic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477463" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Circulation ; Blood Platelets/*immunology ; Cell Movement ; Cell Polarity ; Endothelium, Vascular/immunology ; Inflammation/blood/*immunology ; Male ; Membrane Glycoproteins ; Mice ; Mice, Inbred C57BL ; Neutrophils/*immunology ; *Platelet Activation ; Signal Transduction ; Thrombosis/*immunology ; Venules/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-28
    Description: During chemotaxis, activation of the small guanosine triphosphatase Rac is spatially regulated to organize the extension of membrane protrusions in the direction of migration. In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor. Upon stimulation, we found that DOCK2 rapidly translocated to the plasma membrane in a phosphatidylinositol 3,4,5-trisphosphate-dependent manner. However, subsequent accumulation of DOCK2 at the leading edge required phospholipase D-mediated synthesis of phosphatidic acid, which stabilized DOCK2 there by means of interaction with a polybasic amino acid cluster, resulting in increased local actin polymerization. When this interaction was blocked, neutrophils failed to form leading edges properly and exhibited defects in chemotaxis. Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761877/" 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/PMC3761877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishikimi, Akihiko -- Fukuhara, Hideo -- Su, Wenjuan -- Hongu, Tsunaki -- Takasuga, Shunsuke -- Mihara, Hisashi -- Cao, Qinhong -- Sanematsu, Fumiyuki -- Kanai, Motomu -- Hasegawa, Hiroshi -- Tanaka, Yoshihiko -- Shibasaki, Masakatsu -- Kanaho, Yasunori -- Sasaki, Takehiko -- Frohman, Michael A -- Fukui, Yoshinori -- R01 GM084251/GM/NIGMS NIH HHS/ -- R01GM71520/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):384-7. doi: 10.1126/science.1170179. Epub 2009 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325080" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Butanol/pharmacology ; Actins/metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Cell Polarity ; *Chemotaxis, Leukocyte ; Enzyme Inhibitors/pharmacology ; GTPase-Activating Proteins/chemistry/genetics/*metabolism ; Humans ; Mice ; Neutrophils/cytology/drug effects/*physiology ; Phosphatidic Acids/*metabolism/pharmacology ; Phosphatidylinositol Phosphates/*metabolism ; Phospholipase D/genetics/metabolism ; Protein Binding ; Pseudopodia/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; rac GTP-Binding Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Electronic Resource
    Electronic Resource
    Role of the MT-MTOC complex in determination of the cellular locomotory unit inDictyostelium (1985)
    Springer
    Protoplasma 127 (1985), S. 133-146 
    Details
    ISSN: 1615-6102
    Keywords: Cytokinesis ; Dictyostelium ; Locomotion microtubule ; Motility ; Microtubule organizing center
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The microtubule inhibitors, ethyl-N-phenylcarbamate (EPC) and thiabendazole (TB), which disrupt cytoplasmic microtubules and induce giant cells inDictyostelium (Kitanishi et al. 1984), were found to induce the occurrence of multiple microtubule organizing centers (MTOCs) in these giant cells. Probing was done by indirect immunofluorescence using monoclonal anti-α-tubulin. The nuclear DNA content of the giant cells increased in parallel with an increase in the number of MTOCs, as shown by microspectrophotometory of cells stained with the fluorescent DNA stain DAPI (4′,6-diamidino-2-phenylindole). Shortly after the inhibitors were removed, the MTOCs of the giant cell formed multiple mitotic spindles or synchronously reconstituted numerous cytoplasmic MT-networks. These events apparently reflected the cell-cycle dependent activities of the MTOCs at the time the inhibitors were removed. When multiple spindles were formed, numerous cytoplasmic MT-networks became organized subsequent to the breakdown of the spindles. In either case, reconstitution of the cytoplasmic MT-networks was followed by apparently normal cytokinesis resulting in the production of many daughter cells each containing a single MT-MTOC complex. The evidence suggested the possible mechanism of the induction of multiple MTOCs, and implied that the MT-MTOC complex is significant in the cytokinesis ofDictyostelium by determining the cell locomotory unit.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01273710
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  • 5
    Electronic Resource
    Electronic Resource
    Dictyostelium MTOC: Structure and linkage to the nucleus (1985)
    Springer
    Protoplasma 127 (1985), S. 212-221 
    Details
    ISSN: 1615-6102
    Keywords: Dictyostelium ; Microtubule(s) ; Microtubule organizing center ; Saltatory movement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The microtubule organizing center (MTOC) was isolated fromDictyostelium discoideum to investigate the fine structure of the components as the first step in clarifying its molecular organization and function. The isolation protocol was designed to preserve microtubules bound to the MTOC by using indirect immunofluorescence employing anti-α-tubulin. After cell lysis with Triton X-100, the MTOCs were isolated in association with the nucleus by centrifugation in a microtubule-stabilizing buffer. The MTOC was found to be bound to the nucleus via an electron-dense fibrous structure, and this linkage could not be destroyed by KI, KCl, or sonication. We named this complex composed of microtubules, MTOC, and the anchor the MTOC-complex. Negative staining of the isolated MTOC-complex revealed that distinct vesicles decorated with 11-nm tacks were associated with microtubules radiating from the MTOC. Fine filaments, 4–5 nm wide, were also present close to the MTOC, aligned parallel to the microtubules. The three-dimensional profile of the central core of the MTOC, examined by transmission electron microscopy of serial thin sections of the isolated MTOC fraction supplemented by a microcomputer analysis, was concluded to be a matchbox-like cuboid (180 × 210 × 370 nm) of 15 layers. We propose that theDictyostelium MTOC is the structural domain of a more complicated unit composed of 1. MTOC, 2. microtubules, and 3. a firm fibrous linkage connecting the MTOC to the nucleus, with the MTOC core being a multilayered cuboid, associated with nodules and surrounded by amorphous electron-dense material including peculiar vesicles with 11 nm-tacks. The possible functions of these domains are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01276265
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  • 6
    Electronic Resource
    Electronic Resource
    Disruption of microtubules and retardation of development ofDictyostelium with ethylN-phenylcarbamate and thiabendazole (1984)
    Springer
    Protoplasma 120 (1984), S. 185-196 
    Details
    ISSN: 1615-6102
    Keywords: Dictyostelium ; EthylN-phenylcarbamate ; Lysosomophagy ; Microtubule(s) ; Microtubule inhibitor(s) ; Thiabendazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effects of ethylN-phenylcarbamate (EPC) and thiabendazole (TB) onDictyostelium discoideum andD. mucoroides cells were examined as a step toward purifying tubulin and clarifying the function of microtubules in cellular slime molds. EPC (1.5 × 10−3M) or TB (5 × 10−5M) inhibited the development ofDictyostelium, inducing the formation of aberrant fruiting bodies with stalks irregular in shape and sori containing spores of various sizes and shapes. EPC and TB inhibited cell division but not cell growth, resulting in the production of giant cells up to ten times larger than untreated cells. The giant cells either had a single huge nucleus of irregular shape or contained multiple nuclei. The effects of the inhibitors were reversible. After the removal of the inhibitors, the giant cells underwent successive cell divisions producing many daughter cells. Interestingly, most of the giant cells induced by EPC treatment contained gigantic secondary lysosomes probably produced by extensive lysosomophagy. Light microscopy using Nomarski optics revealed that these inhibitors caused the round-up of the cells resulting in the inhibition of cell locomotion, whereas non-Brownian movement of the cytoplasmic granules was not affected. Indirect immunofluorescence using anti-α-tubulin revealed that networks of microtubules were apparently destroyed by the EPC or TB treatment. These results show both EPC and TB are potent inhibitors of microtubules inDictyostelium and are effective tools for studying the function of microtubules either in cellular or multicellular organization throughout its life cycle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01282599
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  • 7
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    The HERschel Inventory of the Agents of Galaxy Evolution in the Magellanic Clouds, a HERschel Open Time Key Program (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: We present an overview or the HERschel Inventory of The Agents of Galaxy Evolution (HERITAGE) in the Magellanic Clouds project, which is a Herschel Space Observatory open time key program. We mapped the Large Magellanic Cloud (LMC) and Small Magellanic Cloud (SMC) at 100, 160, 250, 350, and 500 micron with the Spectral and Photometric Imaging Receiver (SPIRE) and Photodetector Array Camera and Spectrometer (PACS) instruments on board Herschel using the SPIRE/PACS parallel mode. The overriding science goal of HERITAGE is to study the life cycle of matter as traced by dust in the LMC and SMC. The far-infrared and submillimeter emission is an effective tracer of the interstellar medium (ISM) dust, the most deeply embedded young stellar objects (YSOs), and the dust ejected by the most massive stars. We describe in detail the data processing, particularly for the PACS data, which required some custom steps because of the large angular extent of a single observational unit and overall the large amount of data to be processed as an ensemble. We report total global fluxes for LMC and SMC and demonstrate their agreement with measurements by prior missions. The HERITAGE maps of the LMC and SMC are dominated by the ISM dust emission and bear most resemblance to the tracers of ISM gas rather than the stellar content of the galaxies. We describe the point source extraction processing and the critetia used to establish a catalog for each waveband for the HERITAGE program. The 250 micron band is the most sensitive and the source catalogs for this band have approx. 25,000 objects for the LMC and approx. 5500 objects for the SMC. These data enable studies of ISM dust properties, submillimeter excess dust emission, dust-to-gas ratio, Class 0 YSO candidates, dusty massive evolved stars, supemova remnants (including SN1987A), H II regions, and dust evolution in the LMC and SMC. All images and catalogs are delivered to the Herschel Science Center as part of the conummity support aspects of the project. These HERITAGE images and catalogs provide an excellent basis for future research and follow up with other facilities.
    Keywords: Astrophysics
    Type: GSFC-E-DAA-TN19482 , The Astrophysical Journal; 146; 3; 62
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  • 8
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    Detailed Investigation of the Gamma-Ray Emission in the Vicinity of SNR W28 with FERMI-LAT (2014)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: We present a detailed investigation of the Gamma-ray emission in the vicinity of the supernova remnant (SNR) W28 (G6.40.1) observed by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. We detected significant -ray emission spatially coincident with TeV sources HESS J1800240A, B, and C, located outside the radio boundary of the SNR. Their spectra in the 2-100 GeV band are consistent with the extrapolation of the power-law spectra of the TeV sources. We also identified a new source of GeV emission, dubbed Source W, which lies outside the boundary of TeV sources and coincides with radio emission from the western part of W28. All of the GeV Gamma-ray sources overlap with molecular clouds in the velocity range from 0 to 20 km s (exp1). Under the assumption that the Gamma-ray emission toward HESS J1800240A, B, and C comes from 3.14(exp0) decay due to the interaction between the molecular clouds and cosmic rays (CRs) escaping from W28, they can be naturally explained by a single model in which the CR diffusion coefficient is smaller than the theoretical expectation in the interstellar space. The total energy of the CRs escaping from W28 is constrained through the same modeling to be larger than is approximately 2 10(exp49) erg. The emission from Source W can also be explained with the same CR escape scenario.
    Keywords: Astrophysics
    Type: GSFC-E-DAA-TN15818 , The Astrophysical Journal; 786; 2; 145
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