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  • 1
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    Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-13
    Description: The orphan G protein-coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is highly expressed in central nervous system (CNS) endothelium. Here, we show that complete null or endothelial-specific GPR124 deletion resulted in embryonic lethality from CNS-specific angiogenesis arrest in forebrain and neural tube. Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS-specific hyperproliferative vascular malformations. In vivo, GPR124 functioned cell-autonomously in endothelium to regulate sprouting, migration, and developmental expression of the blood-brain barrier marker Glut1, whereas in vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain-derived, vascular endothelial growth factor-independent cues. Our results demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and illuminate functions of the poorly understood adhesion GPCR subfamily. Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099479/" 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/PMC3099479/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuhnert, Frank -- Mancuso, Michael R -- Shamloo, Amir -- Wang, Hsiao-Ting -- Choksi, Vir -- Florek, Mareike -- Su, Hua -- Fruttiger, Marcus -- Young, William L -- Heilshorn, Sarah C -- Kuo, Calvin J -- 1DP2 OD006477/OD/NIH HHS/ -- 1R01HL074267/HL/NHLBI NIH HHS/ -- 1R01NS052830/NS/NINDS NIH HHS/ -- 1R01NS064517/NS/NINDS NIH HHS/ -- 1R21 NS058600/NS/NINDS NIH HHS/ -- G0501711/Medical Research Council/United Kingdom -- GM07365/GM/NIGMS NIH HHS/ -- P01NS44155/NS/NINDS NIH HHS/ -- R01 CA095654/CA/NCI NIH HHS/ -- R01 CA095654-01/CA/NCI NIH HHS/ -- R01 HL074267/HL/NHLBI NIH HHS/ -- R01 HL074267-02/HL/NHLBI NIH HHS/ -- R01 NS052830/NS/NINDS NIH HHS/ -- R01 NS052830-01/NS/NINDS NIH HHS/ -- R01 NS064517/NS/NINDS NIH HHS/ -- R01 NS064517-02/NS/NINDS NIH HHS/ -- R01NS27713/NS/NINDS NIH HHS/ -- R21 NS070153/NS/NINDS NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 12;330(6006):985-9. doi: 10.1126/science.1196554.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Hematology Division, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21071672" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/abnormalities ; Blood-Brain Barrier/metabolism ; Cell Movement ; Embryonic Development ; Endothelial Cells/physiology ; Endothelium, Vascular/embryology/metabolism ; Gene Deletion ; Glucose Transporter Type 1/metabolism ; Mesencephalon/blood supply/embryology/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; *Neovascularization, Physiologic ; Neural Tube/*blood supply/embryology/metabolism ; Prosencephalon/*blood supply/embryology/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rhombencephalon/blood supply/embryology/metabolism ; Telencephalon/blood supply/embryology/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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    Local and long-range reciprocal regulation of cAMP and cGMP in axon/dendrite formation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-30
    Description: Cytosolic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) often mediate antagonistic cellular actions of extracellular factors, from the regulation of ion channels to cell volume control and axon guidance. We found that localized cAMP and cGMP activities in undifferentiated neurites of cultured hippocampal neurons promote and suppress axon formation, respectively, and exert opposite effects on dendrite formation. Fluorescence resonance energy transfer imaging showed that alterations of the amount of cAMP resulted in opposite changes in the amount of cGMP, and vice versa, through the activation of specific phosphodiesterases and protein kinases. Local elevation of cAMP in one neurite resulted in cAMP reduction in all other neurites of the same neuron. Thus, local and long-range reciprocal regulation of cAMP and cGMP together ensures coordinated development of one axon and multiple dendrites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shelly, Maya -- Lim, Byung Kook -- Cancedda, Laura -- Heilshorn, Sarah C -- Gao, Hongfeng -- Poo, Mu-ming -- NS-22764/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 29;327(5965):547-52. doi: 10.1126/science.1179735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110498" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/metabolism ; Animals ; Axons/metabolism/*physiology ; Cell Differentiation ; Cell Line ; Cell Polarity ; Cells, Cultured ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Cyclic GMP/*metabolism ; Dendrites/metabolism/*physiology ; Enzyme Inhibitors/pharmacology ; Fluorescence Resonance Energy Transfer ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; Hippocampus/*cytology ; Humans ; Neurites/metabolism/physiology ; Neurons/cytology/*physiology ; Phosphodiesterase Inhibitors/pharmacology ; Phosphoric Diester Hydrolases/metabolism ; Phosphorylation ; Rats ; Signal Transduction ; Transfection
    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
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    The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-21
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations [Cell Biology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-01-12
    Description: The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1+ ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1+ ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5+ ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    A definition of bioinks and their distinction from biomaterial inks (2018)
    Institute of Physics
    Details
    Publication Date: 2018-11-23
    Print ISSN: 1758-5082
    Electronic ISSN: 1758-5090
    Topics: Biology
    Published by Institute of Physics
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