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  • 1
    Publication Date: 2013-02-01
    Description: The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788641/" 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/PMC3788641/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shoji-Kawata, Sanae -- Sumpter, Rhea -- Leveno, Matthew -- Campbell, Grant R -- Zou, Zhongju -- Kinch, Lisa -- Wilkins, Angela D -- Sun, Qihua -- Pallauf, Kathrin -- MacDuff, Donna -- Huerta, Carlos -- Virgin, Herbert W -- Helms, J Bernd -- Eerland, Ruud -- Tooze, Sharon A -- Xavier, Ramnik -- Lenschow, Deborah J -- Yamamoto, Ai -- King, David -- Lichtarge, Olivier -- Grishin, Nick V -- Spector, Stephen A -- Kaloyanova, Dora V -- Levine, Beth -- K08 AI099150/AI/NIAID NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- R01 GM066099/GM/NIGMS NIH HHS/ -- R01 GM079656/GM/NIGMS NIH HHS/ -- R01 GM094575/GM/NIGMS NIH HHS/ -- R01 NS050199/NS/NINDS NIH HHS/ -- R01 NS077111/NS/NINDS NIH HHS/ -- R01 NS084912/NS/NINDS NIH HHS/ -- R0I DK083756/DK/NIDDK NIH HHS/ -- R0I DK086502/DK/NIDDK NIH HHS/ -- R0I GM066099/GM/NIGMS NIH HHS/ -- R0I GM079656/GM/NIGMS NIH HHS/ -- R0I NS063973/NS/NINDS NIH HHS/ -- R0I NS077874/NS/NINDS NIH HHS/ -- RC1 DK086502/DK/NIDDK NIH HHS/ -- T32 GM008297/GM/NIGMS NIH HHS/ -- U54 AI057156/AI/NIAID NIH HHS/ -- U54AI057156/AI/NIAID NIH HHS/ -- U54AI057160/AI/NIAID NIH HHS/ -- Cancer Research UK/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Feb 14;494(7436):201-6. doi: 10.1038/nature11866. Epub 2013 Jan 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23364696" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis Regulatory Proteins/*chemistry/metabolism/pharmacology/*therapeutic use ; Autophagy/*drug effects ; Cell Membrane Permeability ; Cells, Cultured ; Chikungunya virus/drug effects ; HIV-1/drug effects/metabolism/physiology ; HeLa Cells ; Humans ; Macrophages/cytology ; Membrane Proteins/*chemistry/metabolism/pharmacology/*therapeutic use ; Mice ; Molecular Sequence Data ; Peptide Fragments/*chemistry/metabolism/*pharmacology ; Recombinant Fusion Proteins/chemistry/metabolism/pharmacology ; Virus Replication/drug effects ; West Nile virus/drug effects ; nef Gene Products, Human Immunodeficiency Virus/metabolism ; tat Gene Products, Human Immunodeficiency Virus/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1979-12-07
    Description: Monomeric DNA lengths from Physarum nuclear chromatin occur in two subunit forms which differ from each other and from higher oligomers of nucleosomes in content of transcribed ribosomal DNA sequences. Labeled DNA restriction fragments from ribosomal RNA coding regions reanneal most rapidly with DNA from a monomeric subunit fraction. A particles, isolated from growing plasmodia and containing 144 base pairs of DNA in an extended conformation. Higher oligomers of nucleosomes are depleted in sequences from transcribing gene regions but are enriched in sequences from the nontranscribed central spacer of the ribosomal DNA palindrome. Nucleosome configuration on two 26S gene intervening sequences resembles that on adjacent coding regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, E M -- Campbell, G R -- Allfrey, V G -- New York, N.Y. -- Science. 1979 Dec 7;206(4423):1192-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/505006" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Nucleolus/ultrastructure ; Chromatin/ultrastructure ; Genes ; Genetic Linkage ; Nucleosomes/*ultrastructure ; Physarum ; RNA, Ribosomal/*genetics ; *Transcription, Genetic
    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
    Publication Date: 1990-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 4
    Publication Date: 1989-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 5
    Publication Date: 1988-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 6
    Publication Date: 1987-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 156 (1975), S. 201-216 
    ISSN: 1432-0878
    Keywords: Smooth muscle ; Myofilaments ; Vas deferens ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Smooth muscle cells of the mouse vas deferens fixed with 5% glutaraldehyde contained three types of filaments, namely, thin (50–80 Å) filaments, intermediate (100 Å) filaments and thick (120–180 Å) filaments. However, in 2 out of 16 experiments, under identical conditions, the cells did not contain thick filaments. With OsO4 fixation, thin filaments were not prominent, the most obvious being thick (120–250 Å) and intermediate (100 Å) filaments. After soaking in a modified Ringer solution under no applied tension for one hour, thick filaments (120–180 Å) appeared prominently in smooth muscle cells of the mouse vas deferens and thin filaments were in ordered bundles. By 4 hours, thick filaments had increased in size and density, with thin filaments distributed randomly around them. After 8 hours in Ringer, thin filaments were diffuse and difficult to discern, while thick filaments were large (up to 300 Å) and electron-dense. Intermediate (100 Å) filaments were present in association with dark bodies. Physiological experiments indicated that the intracellular components responsible for the development of a mechanical response were still functional at this time. The presence of “thick filaments” is also reported in degenerating smooth muscle cells of the guinea-pig vas deferens in tissue culture.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0878
    Keywords: Sympathetic nerves ; Cardiac muscle cells ; Long-lasting associations ; Receptor blockers ; Tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Sympathetic nerves in vitro form long-lasting, intimate, functional relationships with cardiac muscle cells, but not with fibroblasts. In the presence of an adrenergic β-blocker and a cholinergic muscarinic blocker, long-lasting relationships still take place. It was concluded that neurotransmitter ‘receptors’ are not involved in the mechanism of ‘recognition’ of cardiac muscle cells by sympathetic nerves.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0878
    Keywords: Endothelium ; Microvilli ; Heart ; Coronary vessels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Examination of cardiac vascular endothelium with scanning electron microscopy, and transmission electron microscopy of previously scanned tissue, revealed several regions of the coronary venous system that contained ‘cluster’ microvilli. These consisted of 2–15 microvillous projections that emanated radially from a common base or were grouped into a fan-like arrangement. Although rare, these clusters, when present, were widely distributed over the endothelial cell surface.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cultured bovine endothelial cells were seeded onto the intimal surface of endothelium-denuded rings of canine coronary artery. These rings did not previously relax to acetylcholine, substance P, bradykinin, and A23187. After seeding, the same rings relaxed to bradykinin and A23187, but not to acetycholine or substance P. Indomethacin pretreatment did not affect these responses. Cells from the same source were then grown to confluence on microcarrier beads, poured into small columns, and perfused with Krebs+ solution. The perfusate from the columns was bioassayed on endothelium-denuded rings of coronary artery from either the dog or pig. Challenge of the column in the presence of indomethacin with either bradykinin or A23187 as well as acetylcholine or substance P caused release of a substance that relaxed both types of artery. Its activity half-life was 6.4 ± 0.4 sec at 37°C and it was hydrophilic and negatively charged. Prostacyclin (PGI2) as a candidate for EDRF was ruled out because (1) indomethacin failed to block its release and (2) the pig coronary artery, although insensitive to PGI2, relaxed to the endothelium-derived substance. These results show that, in response to a number of dilator drugs, cultured endothelial cells release a vascular relaxing substance (EDRF) that has characteristics similar to the EDRF of normal endothelium. The chemical nature of EDRF awaits clarification.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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