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  • 1
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    Genetic analysis of digestive physiology using fluorescent phospholipid reporters (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-05-19
    Description: Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farber, S A -- Pack, M -- Ho, S Y -- Johnson, I D -- Wagner, D S -- Dosch, R -- Mullins, M C -- Hendrickson, H S -- Hendrickson, E K -- Halpern, M E -- DK 54942/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 May 18;292(5520):1385-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA. sfarber@lac.jci.tju.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11359013" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anticholesteremic Agents/pharmacology ; Atorvastatin Calcium ; Bile Acids and Salts/pharmacology ; Boron Compounds/metabolism ; Cholesterol/metabolism ; Digestive System/drug effects/*metabolism/pathology ; *Digestive System Physiological Phenomena/drug effects ; Fluorescent Dyes/*metabolism ; Gallbladder/drug effects/metabolism ; Heptanoic Acids/pharmacology ; Larva/drug effects/metabolism ; Lipase/metabolism ; Mice ; Microscopy, Fluorescence ; Microscopy, Video ; Mutation/genetics ; Phospholipids/*metabolism ; Pyrroles/pharmacology ; Signal Transduction/drug effects ; Zebrafish/embryology/genetics/*metabolism/physiology
    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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    Lethargus is a Caenorhabditis elegans sleep-like state (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-01-11
    Description: There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep-like states are evolutionarily ancient. The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults. Like sleep, lethargus maintains a constant temporal relationship with the expression of the C. elegans Period homologue LIN-42 (ref. 5). Here we show that quiescence associated with lethargus has the additional sleep-like properties of reversibility, reduced responsiveness and homeostasis. We identify the cGMP-dependent protein kinase (PKG) gene egl-4 as a regulator of sleep-like behaviour, and show that egl-4 functions in sensory neurons to promote the C. elegans sleep-like state. Conserved effects on sleep-like behaviour of homologous genes in C. elegans and Drosophila suggest a common genetic regulation of sleep-like states in arthropods and nematodes. Our results indicate that C. elegans is a suitable model system for the study of sleep regulation. The association of this C. elegans sleep-like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raizen, David M -- Zimmerman, John E -- Maycock, Matthew H -- Ta, Uyen D -- You, Young-jai -- Sundaram, Meera V -- Pack, Allan I -- England -- Nature. 2008 Jan 31;451(7178):569-72. doi: 10.1038/nature06535. Epub 2008 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. raizen@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18185515" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arousal/genetics/physiology ; Biological Evolution ; Caenorhabditis elegans/enzymology/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/metabolism ; Conserved Sequence/genetics ; Cyclic GMP-Dependent Protein Kinases/genetics/metabolism ; Drosophila melanogaster/genetics/physiology ; Homeostasis/physiology ; Larva/physiology ; Lethargy ; Molting/physiology ; Sleep/genetics/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-03-12
    Description: Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes systemically for purposes of tolerance and immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delamarre, Lelia -- Pack, Margit -- Chang, Henry -- Mellman, Ira -- Trombetta, E Sergio -- R37-AI34098/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 11;307(5715):1630-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Department of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520-8002, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15761154" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigen Presentation ; Antigen-Presenting Cells/*enzymology/*immunology/metabolism ; Antigens/*metabolism ; B-Lymphocytes/enzymology/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/*enzymology/immunology/metabolism ; Endocytosis ; Green Fluorescent Proteins/immunology/metabolism ; Histocompatibility Antigens Class II/immunology ; Horseradish Peroxidase/immunology/metabolism ; Lymphoid Tissue/cytology/enzymology/immunology ; Lysosome-Associated Membrane Glycoproteins ; Lysosomes/*enzymology/ultrastructure ; Macrophages/enzymology/immunology/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Inbred C3H ; Peptide Hydrolases/*metabolism ; Ribonuclease, Pancreatic/immunology/metabolism ; Ribonucleases/immunology/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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  • 4
    Electronic Resource
    Electronic Resource
    Molecular mechanics calculations of the noncovalent interaction of aflatoxin B1 and its ultimate carcinogen with various dna sequences (1990)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 38 (1990), S. 133-143 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular mechanics calculations have been used to study the external noncovalent complexes formed between DNA and the strong carcinogen, aflatoxin B1. Three different sequences of hexameric duplexes were used for the DNA. Both the aflatoxin B1 parent molecule and its ultimate carcinogenic form, a carbocation, were modeled. The results are compared with recent experimental data on sequence specificity of the covalent attachment of aflatoxin to sites on the nucleotide bases. The comparison is discussed in light of a recently proposed hypothesis suggesting that the locus of carbocation formation is in acidic domains near the surface of the macroion and this determines the site of covalent adduct formation.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560381715
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  • 5
    Electronic Resource
    Electronic Resource
    Molecular orbital studies of the hydrolysis reactions of benzo[a]pyrene diol epoxides (1992)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 44 (1992), S. 1-14 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Kinetic studies of the hydrolysis of benzo[a]pyrene diol epoxides have shown that hydrolysis proceeds through an acid-catalyzed SN1 mechanism and that the rate-determining step is the formation of a benzylic carbocation. The formation of this carbocation indicates that the diol epoxide can react with nucleophilic sites on DNA as an alkylating agent. Previous work has indicated that the kinetic data could be accurately fit to kobsd = kH [H+] + k0, in which kH [H+] is the pseudo first-order rate constant for acid-catalyzed hydrolysis and k0 is the rate constant for spontaneous hydrolysis. The observation made in several laboratories, that DNA catalyzes the hydrolysis of carcinogenic diol epoxides, is of direct interest in light of our recent calculation indicating that the local environment of DNA has a high concentration of hydrogen ions. The significance of acidic domains around nucleic acids is primarily in the ability of the protons to catalyze reactions. We have hypothesized that the high concentration of hydrogen ions at the DNA surface is responsible for the catalysis and that the generation of benzylic carbocations at the DNA surface can result in either nontoxic tetraols or in mutagenic nucleotide adducts, depending on the nucleophile with which the carbocation reacts. The calculations presented here are concerned with qualitatively understanding the rate constants in terms of the mechanisms of the acid-catalyzed and the spontaneous (H2O-catalyzed) hydrolyses. © 1992 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560440705
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  • 6
    Electronic Resource
    Electronic Resource
    Counterion condensation theory revisited: Limits on its applicability (1993)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 48 (1993), S. 213-230 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Metropolis Monte Carlo and Poisson-Boltzmann calculations were done to quantitatively assess the conditions under which counterion condensation (CC) theory could be considered valid. The fundamental prediction of condensation theory, that the number of counterions bound to a polyelectrolyte molecule can be predicted by a single parameter describing the linear charge density of the charged system, was shown to be quantitatively correct for a range of conditions. To define the number of counterions bound, it was necessary to use an energy-based criterion by which ions that interact with the polyion with an energy less than -kT were considered bound. Using this criterion, Monte Carlo calculations on systems consisting of charged cylinders and a neutralizing number of counterions in a dielectric continuum showed that the number of bound counterions was quantitatively predictable by the CC relation (1-1/ξ) for systems with a linear charge density and dimensions approaching those of duplex or triplex DNA. Poisson-Boltzmann (PB) calculations on cylinders with different linear charge densities and radii have been done to assess the limits of the CC prediction that the number of counterions bound is a constant even as the bulk concentration of electrolyte in the surrounding is increased. As in the case of the MC calculations, the validity of the CC prediction is seen to increase with increasing linear charge density of the charged cylinder. The agreement between PB and CC is seen to be very good for highly charged cylinders. The results described here provide justification for the use of CC theory for interpreting experimental data on polyelectrolytes of the approximate dimensions and linear charge density of duplex or triplex DNA. © 1993 John Wiley & Sons, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560480722
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  • 7
    Electronic Resource
    Electronic Resource
    Theoretical predictions of the functional interactions of DNA and mutagenic aziridines (1995)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 56 (1995), S. 29-37 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The aziridine analogues of the epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons have greater mutagenic potency than the epoxides. Like their well-studied analogues, the aziridines undergo a pH-dependent decomposition that leads to a reactive carbocation intermediate. In aqueous solution the nucleophile with which the carbocation generally reacts is water. The kinetics of this pH-dependent reaction have been experimentally characterized by others. Although the effect of DNA on this reaction has not been studied, we hypothesize that, like their epoxide analogues, the aziridine derivatives of polycyclic aromatic hydrocarbons undergo a DNA-catalyzed reaction leading through a carbocation to either a DNA-adduct or a hydrolysis product. Using Poisson-Boltzmann calculations in conjunction with Metropolis Monte Carlo simulations and energy-minimized conformations, we predict the DNA-dependence of the acidcatalyzed decomposition of the K-region aziridine, phenanthrene[9,10]imine. © 1995 John Wiley & Sons, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560560704
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  • 8
    Electronic Resource
    Electronic Resource
    New developments in computational polyelectrolyte theory (1984)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 26 (1984), S. 287-299 
    Details
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A computational methodology for calculating the spatial distribution of average electrolyte ion density in the presence of a polyelectrolyte macroion is presented. The method makes use of an iterative solution technique previously applied to solve the three-dimensional Poisson-Boltzmann equation. Criteria are developed for determining the regions in space at which the Poisson-Boltzmann approximation fails. In these regions the formal series of sums of products describing the local probability densities is constructed. Accurate approximations to the series are developed. The result is a computationally feasible method that avoids the inaccuracies of Poisson-Boltzmann theory.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/qua.560260730
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