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  • 1
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    Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-24
    Description: Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following alphaSyn expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1983366/" 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/PMC1983366/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, Antony A -- Gitler, Aaron D -- Cashikar, Anil -- Haynes, Cole M -- Hill, Kathryn J -- Bhullar, Bhupinder -- Liu, Kangning -- Xu, Kexiang -- Strathearn, Katherine E -- Liu, Fang -- Cao, Songsong -- Caldwell, Kim A -- Caldwell, Guy A -- Marsischky, Gerald -- Kolodner, Richard D -- Labaer, Joshua -- Rochet, Jean-Christophe -- Bonini, Nancy M -- Lindquist, Susan -- P50 NS038372/NS/NINDS NIH HHS/ -- R01-HG002923/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 21;313(5785):324-8. Epub 2006 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16794039" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Dopamine/physiology ; Drosophila ; Endoplasmic Reticulum/*metabolism ; Gene Expression ; Gene Library ; Golgi Apparatus/*metabolism ; Humans ; Mice ; Nerve Degeneration ; Neurons/cytology/*physiology ; Parkinsonian Disorders/metabolism/pathology/*physiopathology ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; *Protein Transport ; Proteins/chemistry/metabolism ; Rats ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; alpha-Synuclein/chemistry/genetics/*metabolism ; rab GTP-Binding Proteins/genetics/metabolism ; rab1 GTP-Binding Proteins/genetics/*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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    Functional links between Abeta toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-10-29
    Description: Abeta (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Abeta toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Abeta was previously unknown. The factors identified in yeast modified Abeta toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Abeta impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Abeta, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281757/" 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/PMC3281757/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Treusch, Sebastian -- Hamamichi, Shusei -- Goodman, Jessica L -- Matlack, Kent E S -- Chung, Chee Yeun -- Baru, Valeriya -- Shulman, Joshua M -- Parrado, Antonio -- Bevis, Brooke J -- Valastyan, Julie S -- Han, Haesun -- Lindhagen-Persson, Malin -- Reiman, Eric M -- Evans, Denis A -- Bennett, David A -- Olofsson, Anders -- DeJager, Philip L -- Tanzi, Rudolph E -- Caldwell, Kim A -- Caldwell, Guy A -- Lindquist, Susan -- F32 NS067782-02/NS/NINDS NIH HHS/ -- K08 AG034290/AG/NIA NIH HHS/ -- K08AG034290/AG/NIA NIH HHS/ -- P30 AG019610/AG/NIA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Dec 2;334(6060):1241-5. doi: 10.1126/science.1213210. Epub 2011 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22033521" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*genetics/*metabolism ; Amyloid beta-Peptides/chemistry/genetics/*metabolism ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/metabolism ; Cell Membrane/metabolism ; Cells, Cultured ; Clathrin/metabolism ; Cytoskeleton/metabolism ; Disease Susceptibility ; *Endocytosis ; Genetic Association Studies ; Genetic Testing ; Glutamates/metabolism ; Humans ; Monomeric Clathrin Assembly Proteins/genetics/metabolism ; Neurons/physiology ; Peptide Fragments/chemistry/genetics/*metabolism ; Protein Multimerization ; Protein Transport ; Rats ; Risk Factors ; *Saccharomyces cerevisiae/cytology/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Secretory Pathway
    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
    Electronic Resource
    Electronic Resource
    Variant cDNAs encoding proteins similar to the α subunit of chicken CapZ (1991)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 18 (1991), S. 204-214 
    Details
    ISSN: 0886-1544
    Keywords: actin-binding ; muscle ; Z-line ; capping ; isoform ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Chicken adult muscle and liver cDNA libraries were screened with a cDNA, α1, previously isolated from a chicken embryo library by screening with antibodies against the α subunit of chicken CapZ. cDNAs with a new coding region, called α2, were found in addition to ones with the α1 coding region. α2 predicts a protein sequence that matches exactly the N-terminal sequence of 5 peptides prepared from CapZ α purified from chicken muscle, while the protein sequence predicted by α1 matches the peptides well, but not exactly. The predicted protein sequences of α1 and α2 are very similar to each other, and they are similar to those of the α subunit of capping protein from Dictyostelium [Hartmann et al., J. Biol. Chem. 163:5254-5254, 1989] and an actin-binding protein from Xenopus [Ankenbauer et al., Nature 342:822-824, 1989]. Other conserved features of the predicted primary and secondary structures are noted. Chicken α1 and α2 are transcribed in all of 7 adult chicken muscle and non-muscle tissues in comparable amounts by Northern analysis. α2 has four poly(A)+ RNA transcripts, one of which is rare in liver. α1 has two transcripts. α1 and α2 are encoded by different single-copy genes by Southern analysis of chicken genomic DNA.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970180306
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  • 4
    Electronic Resource
    Electronic Resource
    Biochemical and morphological properties of bovine erythrocyte membrane glycoproteins (1982)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 19 (1982), S. 157-170 
    Details
    ISSN: 0730-2312
    Keywords: erythrocyte ; membranes ; glycoproteins ; electronmicroscope ; gel electrophoresis ; bovine ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The major and minor sialoglycoproteins of the bovine erythrocyte have been solubilized and extensively purified. A comparison of composition revealed that the major glycoprotein had 77% carbohydrate and 23% peptide, and the minor one had 27% carbohydrate and 73% peptide. Molar ratios of sugars were related, however, the major glycoprotein had twice as much galactose and sialic acid as did the minor glycoprotein. Molecular weights, estimated from retardation coefficients of mobility in sodium dodecyl sulfate gel electrophoresis, were 55,000 for the major glycoprotein and 34,000 for the minor glycoprotein. The glycoproteins were studied by electron microscopy before and after delipidation and after ultracentrifugation. The major glycoprotein, prior to delipidation, formed large micelles. After delipidation, the major glycoprotein could not be visualized suggesting that it did not form aggregates in aqueous solution. The minor glycoprotein was visualized as rather uniform spherical aggregates (62 Å average diameter) which tended to form short chains and small clumps. These characteristic aggregates were seen both before and after delipidation. After ultracentrifugation, fixation and sectioning both glycoproteins appeared to have formed microcrystalline arrays with average periodicity of 49 Å.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240190206
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  • 5
    Electronic Resource
    Electronic Resource
    Distribution of lysosomal enzymes in animal tissuesThis research was supported by grant RG-5759 from the National Institutes of Health and project WM-33 of the U. S. Department of Agriculture. (1963)
    Philadelphia : Wiley-Blackwell
    Journal of Cellular and Comparative Physiology 61 (1963), S. 85-92 
    Details
    ISSN: 0095-9898
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Additional Material: 5 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1030610109
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  • 6
    Electronic Resource
    Electronic Resource
    Culture perfusion schedules influence the metabolic activity and granulocyte-macrophage colony-stimulating factor production rates of human bone marrow stromal cells (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 147 (1991), S. 344-353 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The metabolic function and GM-CSF production rates of adherent human bone marrow stromal cells were investigated as functions of medium and serum feeding rates. A range of medium exchange schedules was studied, ranging from a typical Dexter culture protocol of one weekly medium exchange to a full media exchange daily, which more closely approximates what bone marrow cells experience in situ. Glucose consumption was found to be significantly higher at full daily exchange rate than at any other exchange schedule examined. However, the lactate yield on glucose was a constant, at 1.8 mol/mol, under all conditions considered. Differential serum vs. medium exchange experiment showed that both serum supply and medium nutrients were responsible for the altered behavior at high exchange rates. Glutamine consumption was found to be insignificant under all culture conditions examined. A change in exchange schedule from 50% daily medium exchange to full daily medium exchange after 14 days of culture was found to result in a transient production of GM-CSF and a change in metabolic behavior to resemble that of cultures which had full daily exchange from day one. These results suggest that both stromal cell metabolism and GM-CSF production are sensitive to medium exchange schedules. Taken together, the data presented indicate that attempts to model the function of human bone marrow in vitro may be well served by beginning with medium exchange schedules that more closely mimic the in vivo physiologic state of bone marrow.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041470221
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  • 7
    Electronic Resource
    Electronic Resource
    IL-1α and TNFα act synergistically to stimulate production of myeloid colony-stimulating factors by cultured human bone marrow stromal cells and cloned stromal cell strains (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 159 (1994), S. 221-228 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human bone marrow stromal cells repond to stimulation by the monokines IL-1 and TNF by producing colony-stimulating factors such as GM-CSF and G-CSF. In this study we show that IL-1α and TNFα act synergistically to stimulate GM-CSF and G-CSF production by cultured marrow stromal cells. We further show that IL-1α and TNFα synergistically stimulate production of GM-CSF and G-CSF by a clonal stroma-derived cell strain. Although IL-1 and TNF share many of the same biological activities, we show that IL-1α and TNFα have an unequal ability to induce myeloid-CSF production by both cultures, with IL-1α being the more potent inducer. We found that induction by IL-1α and TNFα was independent of cell proliferation. The effect of IL-1α and TNFα on production of the two myeloid-CSFs by the clonal cells was significantly greater than the unfractionated passaged stromal cultures, having the greater effect on G-CSF production. The clonally derived stromal cells constitutively produced colony-stimulating activity, in particular GM-CSF, at levels easily detected by ELISA. These findings show that, in addition to the overlapping and additive activities of IL-1α and TNFα, they can interact synergistically. Our findings further suggest that a small subpopulation of stroma cells may be the major producer of G-CSF in the marrow microenvironment during immune response. © 1994 wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041590205
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  • 8
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    Careers in behavioral science. Neuromarketing careers (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-05-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caldwell, Mark -- New York, N.Y. -- Science. 2007 May 18;316(5827):1060-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17510369" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/*physiology ; *Career Choice ; Economics ; Humans ; Interdisciplinary Communication ; Magnetic Resonance Imaging ; *Marketing ; *Neurosciences
    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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  • 9
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    Diverse fisheries require diverse solutions (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ban, Natalie C -- Caldwell, Iain R -- Green, Thomas L -- Morgan, Sian K -- O'Donnell, Kerrie -- Selgrath, Jennifer C -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):338-9. doi: 10.1126/science.323.5912.338.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ecosystem ; *Fisheries/economics/methods ; Fishes ; Humans ; *Motivation
    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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  • 10
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    Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-23
    Description: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998180/" 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/PMC2998180/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olive, Kenneth P -- Jacobetz, Michael A -- Davidson, Christian J -- Gopinathan, Aarthi -- McIntyre, Dominick -- Honess, Davina -- Madhu, Basetti -- Goldgraben, Mae A -- Caldwell, Meredith E -- Allard, David -- Frese, Kristopher K -- Denicola, Gina -- Feig, Christine -- Combs, Chelsea -- Winter, Stephen P -- Ireland-Zecchini, Heather -- Reichelt, Stefanie -- Howat, William J -- Chang, Alex -- Dhara, Mousumi -- Wang, Lifu -- Ruckert, Felix -- Grutzmann, Robert -- Pilarsky, Christian -- Izeradjene, Kamel -- Hingorani, Sunil R -- Huang, Pearl -- Davies, Susan E -- Plunkett, William -- Egorin, Merrill -- Hruban, Ralph H -- Whitebread, Nigel -- McGovern, Karen -- Adams, Julian -- Iacobuzio-Donahue, Christine -- Griffiths, John -- Tuveson, David A -- CA084291/CA/NCI NIH HHS/ -- CA101973/CA/NCI NIH HHS/ -- CA105490/CA/NCI NIH HHS/ -- CA111292/CA/NCI NIH HHS/ -- CA114028/CA/NCI NIH HHS/ -- CA15704/CA/NCI NIH HHS/ -- F32 CA123939/CA/NCI NIH HHS/ -- F32 CA123939-03X1/CA/NCI NIH HHS/ -- F32CA123887-01/CA/NCI NIH HHS/ -- F32CA123939-02/CA/NCI NIH HHS/ -- K08 CA106610/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 12;324(5933):1457-61. doi: 10.1126/science.1171362. Epub 2009 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460966" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*administration & dosage/metabolism/therapeutic use ; *Antineoplastic Combined Chemotherapy Protocols ; Apoptosis/drug effects ; Carcinoma, Pancreatic Ductal/blood supply/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Deoxycytidine/administration & dosage/*analogs & ; derivatives/metabolism/therapeutic use ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/*metabolism ; Humans ; Kruppel-Like Transcription Factors/metabolism ; Mice ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Pancreatic Neoplasms/blood supply/*drug therapy/metabolism/pathology ; Receptors, G-Protein-Coupled/antagonists & inhibitors/metabolism ; Signal Transduction/drug effects ; Stromal Cells/drug effects/pathology ; Veratrum Alkaloids/*administration & dosage/pharmacokinetics/therapeutic use
    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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