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  • 1
    Keywords: INVASION ; PATHWAY ; GROWTH-FACTOR RECEPTOR ; endocytosis ; CELL-MIGRATION ; TUMOR-METASTASIS ; ACTIN ; SRC ; INVADOPODIA FORMATION ; PODOSOMES
    Abstract: Amplified HER2, which encodes a member of the epidermal growth factor receptor (EGFR) family, is a target of effective therapies against breast cancer. In search for similarly targetable genomic aberrations, we identified copy number gains in SYNJ2, which encodes the 5'-inositol lipid phosphatase synaptojanin 2, as well as overexpression in a small fraction of human breast tumors. Copy gain and overexpression correlated with shorter patient survival and a low abundance of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and invasion in culture and lung metastasis of breast tumor xenografts in mice. Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of cellular lamellipodia and invadopodia. Screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration but did not affect the related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable target to block cancer cell migration.
    Type of Publication: Journal article published
    PubMed ID: 25605973
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  • 2
    ISSN: 1435-1528
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Zusammenfassung In der Meßzelle eines Magneto-Rotationsrheometers wurden rheologische Untersuchungen an einer Reihe von Ferrosuspensionen in einem weiten Bereich von Konzentration und Temperatur, sowie Intensität und Orientierung des Magnetfeldes durchgeführt. Die gewonnenen Daten werden in Form einer universellen magnetorheologischen Charakteristik zusammengefaßt, die sowohl bezüglich des Typs und der Temperatur der Ferrosuspension als auch der Intensität und der Orientierung des äußeren Magnetfeldes invariant ist. Weiter wurde eine experimentelle Untersuchung der mechanischen Besonderheiten bei Ferrosuspensionen in der Scherströmung eines Couette-Viskosimeters infolge der dynamischen Veränderung ihrer inneren Struktur durch ein rotierendes Magnetfeld durchgeführt. Einige Abschätzungen der Impulsübertragung in Ferrosuspensionen als Funktion des Magnet- und des Scherfeldes sind angegeben.
    Notes: Summary In a measuring cell of a rotational magnetorheometer a rheological investigation of a number of ferrosuspensions is carried out over wide ranges of their concentration, temperature, intensity and orientation of the magnetic field. The obtained data are correlated by a new universal magnetorheological characteristic invariant for the ferrosuspension type and temperature, intensity and orientation of the external magnetic field. An experimental investigation is made of peculiarities of the mechanical behaviour of ferrosuspension shear flows in a coaxial cylinder system, with their internal structure dynamically controlled by a rotating magnetic field. Some estimates are made of the momentum transfer mechanism in ferrosuspensions affected by magnetic and shear fields.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1528
    Keywords: Electrorheological suspensions ; shear flow ; periodic deformations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Abstract Studies have been made of concentrated (up to 60%) diatomite suspensions in transformer oil, the structure and theological properties of which depend on an applied electric field. Studies have been conducted of steady-state and transient regimes of straining involving continuous and periodic shear. The structure in such suspensions is formed in the presence of an electric field of 10−3 −102 duration. The suspensions under continuous stationary strain behave as non-Newtonian fluids with a yield stress dependent on electric intensity. Under periodic deformation conditions the test suspensions exhibit elasticity which abruptly diminishes with increasing deformation amplitude.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2015-07-18
    Description: The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression, while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gitlin, Alexander D -- Mayer, Christian T -- Oliveira, Thiago Y -- Shulman, Ziv -- Jones, Mathew J K -- Koren, Amnon -- Nussenzweig, Michel C -- 1F30AI109903-01/AI/NIAID NIH HHS/ -- 1UM1 AI100663-01/AI/NIAID NIH HHS/ -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):643-6. doi: 10.1126/science.aac4919. Epub 2015 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute (HHMI), The Rockefeller University, New York, NY 10065, USA. nussen@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26184917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*cytology ; Cell Cycle/genetics/*immunology ; Cell Proliferation ; DNA Replication/genetics/*immunology ; Gene Expression Regulation ; Germinal Center/*cytology ; Immunity, Humoral/*genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; S Phase/genetics/immunology ; T-Lymphocytes/*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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  • 5
    Publication Date: 2013-07-28
    Description: T follicular helper (T(FH)) cells are a specialized subset of effector T cells that provide help to and thereby select high-affinity B cells in germinal centers (GCs). To examine the dynamic behavior of T(FH) cells in GCs in mice, we used two-photon microscopy in combination with a photoactivatable fluorescent reporter. Unlike GC B cells, which are clonally restricted, T(FH) cells distributed among all GCs in lymph nodes and continually emigrated into the follicle and neighboring GCs. Moreover, newly activated T(FH) cells invaded preexisting GCs, where they contributed to B cell selection and plasmablast differentiation. Our data suggest that the dynamic exchange of T(FH) cells between GCs ensures maximal diversification of T cell help and that their ability to enter ongoing GCs accommodates antigenic variation during the immune response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941467/" 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/PMC3941467/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shulman, Ziv -- Gitlin, Alexander D -- Targ, Sasha -- Jankovic, Mila -- Pasqual, Giulia -- Nussenzweig, Michel C -- Victora, Gabriel D -- 5DP5OD012146-02/OD/NIH HHS/ -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- AI100663-01/AI/NIAID NIH HHS/ -- DP5 OD012146/OD/NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- R37 AI037526/AI/NIAID NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):673-7. doi: 10.1126/science.1241680. Epub 2013 Jul 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23887872" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigenic Variation ; B-Lymphocytes/cytology/*immunology ; Clone Cells ; Germinal Center/cytology/*immunology ; Mice ; T-Lymphocytes, Helper-Inducer/cytology/*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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  • 6
    Publication Date: 2014-08-30
    Description: T follicular helper (T(FH)) cells select high-affinity, antibody-producing B cells for clonal expansion in germinal centers (GCs), but the nature of their interaction is not well defined. Using intravital imaging, we found that selection is mediated by large but transient contacts between T(FH) and GC B cells presenting the highest levels of cognate peptide bound to major histocompatibility complex II. These interactions elicited transient and sustained increases in T(FH) intracellular free calcium (Ca(2+)) that were associated with T(FH) cell coexpression of the cytokines interleukin-4 and -21. However, increased intracellular Ca(2+) did not arrest TFH cell migration. Instead, T(FH) cells remained motile and continually scanned the surface of many GC B cells, forming short-lived contacts that induced selection through further repeated transient elevations in intracellular Ca(2+).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519234/" 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/PMC4519234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shulman, Ziv -- Gitlin, Alexander D -- Weinstein, Jason S -- Lainez, Begona -- Esplugues, Enric -- Flavell, Richard A -- Craft, Joseph E -- Nussenzweig, Michel C -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- AI100663-02/AI/NIAID NIH HHS/ -- AR053495-08/AR/NIAMS NIH HHS/ -- AR40072-24/AR/NIAMS NIH HHS/ -- P30 AR053495/AR/NIAMS NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- R01 AR040072/AR/NIAMS NIH HHS/ -- R21 AR063942/AR/NIAMS NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1058-62. doi: 10.1126/science.1257861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA. ; Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA. ; Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA. Howard Hughes Medical Institute (HHMI). ; Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA. Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute (HHMI). nussen@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170154" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*immunology ; Calcium Signaling/*immunology ; Germinal Center/*immunology ; Green Fluorescent Proteins/metabolism ; Histocompatibility Antigens Class II/*immunology ; Interleukin-4/immunology ; Interleukins/immunology ; Mice ; Mice, Knockout ; Molecular Imaging ; T-Lymphocytes, Helper-Inducer/*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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  • 7
    Publication Date: 2014-05-09
    Description: During immune responses, B lymphocytes clonally expand and undergo secondary diversification of their immunoglobulin genes in germinal centres (GCs). High-affinity B cells are expanded through iterative interzonal cycles of division and hypermutation in the GC dark zone followed by migration to the GC light zone, where they are selected on the basis of affinity to return to the dark zone. Here we combine a transgenic strategy to measure cell division and a photoactivatable fluorescent reporter to examine whether the extent of clonal expansion and hypermutation are regulated during interzonal GC cycles. We find that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells to follicular helper T cells in the light zone. Our data explain how GC B cells with the highest affinity for antigen are selectively expanded and diversified.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271732/" 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/PMC4271732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gitlin, Alexander D -- Shulman, Ziv -- Nussenzweig, Michel C -- 1UM1 AI100663-01/AI/NIAID NIH HHS/ -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):637-40. doi: 10.1038/nature13300. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. ; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805232" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Affinity/immunology ; Antigen Presentation/immunology ; Antigens/immunology ; B-Lymphocytes/*cytology/immunology/*metabolism ; Cell Movement ; Cell Proliferation ; *Clonal Selection, Antigen-Mediated/immunology ; Clone Cells/cytology/immunology/metabolism ; Genes, Reporter/genetics ; Germinal Center/*cytology/*immunology ; Male ; Mice ; S Phase ; Somatic Hypermutation, Immunoglobulin/*genetics ; T-Lymphocytes, Helper-Inducer/cytology/immunology ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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