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  • 1
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    Bile acids: natural ligands for an orphan nuclear receptor (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-21
    Description: Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parks, D J -- Blanchard, S G -- Bledsoe, R K -- Chandra, G -- Consler, T G -- Kliewer, S A -- Stimmel, J B -- Willson, T M -- Zavacki, A M -- Moore, D D -- Lehmann, J M -- F32 DK09793/DK/NIDDK NIH HHS/ -- R01 DK53366/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1365-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334993" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bile Acids and Salts/chemistry/*metabolism/pharmacology ; Carrier Proteins/metabolism ; Cell Line ; Chenodeoxycholic Acid/*metabolism/pharmacology ; Cholesterol/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Deoxycholic Acid/metabolism/pharmacology ; Histone Acetyltransferases ; Homeostasis ; Humans ; Ligands ; Lithocholic Acid/metabolism/pharmacology ; Mice ; Nuclear Receptor Coactivator 1 ; *Organic Anion Transporters, Sodium-Dependent ; Protein Conformation ; Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Structure-Activity Relationship ; *Symporters ; Transcription Factors/chemistry/genetics/*metabolism ; 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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  • 2
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    Structural convergence in the active sites of a family of catalytic antibodies (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-02-21
    Description: The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. The high resolution structures account for catalysis by transition state stabilization, and in all three antibodies a tyrosine residue participates in the oxyanion hole. Despite significant conformational differences in their combining sites, the three antibodies, which are the most efficient among those elicited, achieve catalysis in essentially the same mode, suggesting that evolution for binding to a single TSA followed by screening for catalysis lead to antibodies with structural convergence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Charbonnier, J B -- Golinelli-Pimpaneau, B -- Gigant, B -- Tawfik, D S -- Chap, R -- Schindler, D G -- Kim, S H -- Green, B S -- Eshhar, Z -- Knossow, M -- New York, N.Y. -- Science. 1997 Feb 21;275(5303):1140-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Enzymologie et de Biochimie Structurales, CNRS, 91198 Gif sur Yvette Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9027317" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Catalytic/*chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Enzyme-Linked Immunosorbent Assay ; *Evolution, Molecular ; Haptens/chemistry/metabolism ; Hydrogen Bonding ; Immunoglobulin Fab Fragments/chemistry/metabolism ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Organophosphonates/chemistry/metabolism ; *Protein Conformation ; Tyrosine/chemistry
    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
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    Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-01-05
    Description: Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas aeruginosa lung infections. Cultured human airway epithelial cells expressing the delta F508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core oligosaccharide was identified as the bacterial ligand for epithelial cell ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may contribute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677515/" 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/PMC3677515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pier, G B -- Grout, M -- Zaidi, T S -- Olsen, J C -- Johnson, L G -- Yankaskas, J R -- Goldberg, J B -- AI22806/AI/NIAID NIH HHS/ -- AI35674/AI/NIAID NIH HHS/ -- HL42384/HL/NHLBI NIH HHS/ -- R01 HL058398/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Jan 5;271(5245):64-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115-5899, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8539601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Cell Line, Transformed ; Cystic Fibrosis/*complications/genetics/microbiology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/*physiology ; Disease Susceptibility ; Epithelium/microbiology ; Humans ; Lipopolysaccharides/pharmacology ; Lung/microbiology ; Mice ; Mice, Inbred BALB C ; Pseudomonas Infections/*etiology/microbiology ; Pseudomonas aeruginosa/*physiology ; Respiratory System/*microbiology ; Respiratory Tract Infections/*etiology/microbiology
    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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  • 4
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    Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-12-20
    Description: Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, E -- Kim, J B -- Sarraf, P -- Spiegelman, B M -- R37DK31405/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2100-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953045" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Adipocytes/*cytology/metabolism ; Animals ; Blood ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism ; Cell Differentiation ; Cell Line ; Enzyme Inhibitors/pharmacology ; Epidermal Growth Factor/pharmacology ; Flavonoids/pharmacology ; Insulin/pharmacology ; Ligands ; Mice ; Mitogens/pharmacology ; Mutation ; Phosphorylation ; Rats ; Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic/drug effects ; Transfection
    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
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    Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-02-03
    Description: To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉John, S W -- Krege, J H -- Oliver, P M -- Hagaman, J R -- Hodgin, J B -- Pang, S C -- Flynn, T G -- Smithies, O -- GM20069/GM/NIGMS NIH HHS/ -- HL49277/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 3;267(5198):679-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of North Carolina, Chapel Hill 27599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7839143" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atrial Natriuretic Factor/analysis/blood/*deficiency/*genetics ; *Blood Pressure ; Crosses, Genetic ; Female ; Gene Targeting ; Genotype ; Heart Atria/chemistry/ultrastructure ; Heterozygote ; Homozygote ; Hypertension/genetics/pathology/*physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Protein Precursors/*genetics ; Sodium, Dietary/*administration & dosage
    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
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    Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-02-17
    Description: Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Linton, M F -- Atkinson, J B -- Fazio, S -- DK-26657-15/DK/NIDDK NIH HHS/ -- HL-02925/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 17;267(5200):1034-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2250.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7863332" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aortic Diseases/prevention & control ; Apolipoproteins E/blood/*deficiency/genetics ; Arteriosclerosis/*prevention & control ; *Bone Marrow Transplantation ; Cholesterol/*blood ; Coronary Artery Disease/prevention & control ; Lipoproteins/*blood ; Lipoproteins, IDL ; Lipoproteins, LDL/blood ; Lipoproteins, VLDL/blood ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL
    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
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    The Physical Interpretation of X-Ray Phase Lags and Coherence: RXTE Observations of Cygnus X-1 as a Case Study (1998)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: There have been a number of recent spectral models that have been successful in reproducing the observed X-ray spectra of galactic black hole candidates (GBHC). However, there still exists controversy over such issues as: what are the sources of hard radiation, what is the system's geometry, is the accretion efficient or inefficient, etc. A potentially powerful tool for distinguishing among these possibilities, made possible by the Rossi X-ray Timing Explorer (RXTE), is the variability data, especially the observed phase lags and variability coherence. These data, in conjunction with spectral modeling, have the potential of determining physical sizes of the system, as well as placing strong constraints on both Compton corona and advection models. As an example, we present RXTE variability data of Cygnus X-1.
    Keywords: Astronomy
    Type: Nuclear Physics B (Proceedings Supplements) (ISSN 0920-5632); 69; 3-Jan; 302-307
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  • 8
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    Ammonia Observations of NGC 6334 I(N) (1995)
    In:  Other Sources
    Details
    Publication Date: 2019-08-15
    Description: Coincident with the far-infrared source NGC 6334 I(N) and water maser source E is a massive dense cloud which has the most intense ammonia (1, 1) emission of any known interstellar cloud. We have mapped the (3, 3) emission and find the cloud is extended 0.8 pc in the direction parallel to the Galactic plane, and 0.5 pc perpendicular to it. It has a velocity gradient of 1 km/s.pc perpendicular to the Galactic plane. The gas kinetic temperature is about 30 K and the density is greater than 10(exp 6)/cc. The mass of the cloud is about 3000 solar mass, 3 times greater than previously estimated. The para-ammonia column density is 6 - 8 x 10(exp 15)/sq cm. An ammonia abundance of 0.5 - 1.5 x 10(exp -8) is inferred, where the larger number assumes an early time ortho/para ratio. This suggests either a cloud age of less than approximately 10(exp 6) yr, or substantial depletion of ammonia.
    Keywords: Astronomy
    Type: Astrophysical Journal; 446; 692-698
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  • 9
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    RXTE Observation of Cygnus X-1 Spectral Analysis (1998)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: We present the results of the analysis of the broad-band spectrum of Cygnus X-1 from 3.0 to 200 keV, using data from a 10 ksec observation by the Rossi X-ray Timing Explorer. Although the spectrum can be well described phenomenologically by an exponentially cut-off power law (photon index Gamma = 1.45+0.01 -0.02 , e-folding energy e(sub f) = 162+9 -8 keV, plus a deviation from a power law that formally can be modeled as a thermal blackbody, with temperature kT(sub BB) = 1.2 +0.0 -0.1 keV), the inclusion of a reflection component does not improve the fit. As a physical description of this system, we apply the accretion disc corona (ADC) models. A slab-geometry ADC model is unable to describe the data. However, a spherical corona, with a total optical depth tau- = 1.6 + or - 0.1 and an average temperature kTc = 87 + or - 5 keV, surrounded by an exterior cold disc, does provide a good description of the data (X red (exp 2) = 1.55). These models deviate from the data bv up to 7% in the 5-10 keV range. However, considering how successfully the spherical corona reproduces the 10-200 keV data, such "photon-starved" coronal geometries seem very promising for explaining the accretion processes of Cygnus X-1.
    Keywords: Astronomy
    Type: Nuclear Physics B: Proceedings Supplements (ISSN 0920-5632); 69/1; 302-307
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  • 10
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    ASCA and Radio/RXTE Observations of GX 339-4 (1999)
    In:  CASI
    Details
    Publication Date: 2019-07-10
    Description: We have analyzed three separate archival Advanced Satellite for Cosmology and Astrophysics (ASCA) observations and eight separate Rossi X-ray Timing Explorer (RXTE) observations of the black hole candidate GX 339-4 in its low luminosity, spectrally hard state. Three of the RXTE observations were strictly simultaneous with 843 MHz and 8.3- 9.1 GHz radio observations. All data sets show evidence for an approximately 6.4 keV Fe line with equivalent widths approximately 20-100 eV. 'Reflection models' show a hardening of the RXTE spectra with decreasing X-ray flux; however, these models do not exhibit evidence of a correlation between the photon index of the incident power law flux and the solid angle subtended by the reflector. None of the models fit to the X-ray data, however, simultaneously explain the observed radio properties. We argue that the spatial extent of the observed radio emission is at least 0(10(exp 7 GM/c squared). Timing analysis reveals that all observations save one show evidence of a persistent f(qpo approximately equals 0.3 Hz quasi-periodic oscillations(quasi-periodic oscillations)). The broad band (10-3-102 Hz) power appears to be dominated by two independent processes that can be modeled as very broad Lorentzians with Q approximately less than 1. Similar to Cyg X-1, the hard photon variability is seen to lag the soft photon vaxiability with the lag time increasing with decreasing Fourier frequency. The magnitude of this time lag is seen to be positively correlated with the flux of GX 339-4.
    Keywords: Astronomy
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