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  • 1
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    B cell homeostasis and plasma cell homing controlled by Kruppel-like factor 2 [Immunology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-01-12
    Description: Krüppel-like factor 2 (KLF2) controls T lymphocyte egress from lymphoid organs by regulating sphingosin-1 phosphate receptor 1 (S1Pr1). Here we show that this is not the case for B cells. Instead, KLF2 controls homeostasis of B cells in peripheral lymphatic organs and homing of plasma cells to the bone marrow, presumably by controlling the expression of β7-integrin. In mice with a B cell-specific deletion of KLF2, S1Pr1 expression on B cells was only slightly affected. Accordingly, all splenic B cell subsets including B1 cells were present, but their numbers were increased with a clear bias for marginal zone (MZ) B cells. In contrast, fewer peyers patches harboring fewer B cells were found, and fewer B1 cells in the peritoneal cavity as well as recirculating B cells in the bone marrow were detected. Upon thymus-dependent immunization, IgG titers were diminished, and antigen-specific plasma cells were absent in the bone marrow, although numbers of antigen-specific splenic plasmablasts were normal. KLF2 plays also a role in determining the identity of follicular B cells, as KLF2-deficient follicular B cells showed calcium responses similar to those of MZ B cells and failed to down-regulate MZ B cell signature genes, such as CD21 and CXCR7.
    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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  • 2
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    Broadband electro-optic frequency comb generation in a lithium niobate microring resonator (2019)
    Springer Nature
    In: Nature
    Details
    Publication Date: 2019
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 3
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    Measuring sexual selection [Evolution] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-01-21
    Description: Sexual selection is a cornerstone of evolutionary theory, but measuring it has proved surprisingly difficult and controversial. Various proxy measures—e.g., the Bateman gradient and the opportunity for sexual selection—are widely used in empirical studies. However, we do not know how reliably these measures predict the strength of sexual selection across...
    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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    Cold activates human brown adipose tissue [Medical Sciences] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-06-20
    Description: As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by 18F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.
    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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    Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production [Medical Sciences] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-08-31
    Description: Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle.
    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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  • 6
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    Design and synthesis of a mimetic from an antibody complementarity-determining region (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-16
    Description: A technique for producing non-peptide compounds (mimetics) of designed specificities was developed that permitted the synthesis of a conformationally restricted molecule that mimicked the binding and functional properties of monoclonal antibody (MAb) 87.92.6, which recognizes the reovirus type 3 cellular receptor. Binding of either MAb 87.92.6, peptide analogs, or 87.1-mimetic to the cellular receptor inhibited cellular proliferation. The mimetic was a synthetic beta-loop structure that mimics the second complementarity-determining region of the MAb. These studies may lead to strategies for the synthetic design of antibody complementarity regions, ligands, and other pharmacologically active agents that are water soluble, resistant to proteolysis, and nonimmunogenic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saragovi, H U -- Fitzpatrick, D -- Raktabutr, A -- Nakanishi, H -- Kahn, M -- Greene, M I -- New York, N.Y. -- Science. 1991 Aug 16;253(5021):792-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1876837" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/*chemistry ; Cell Division/drug effects ; Drug Design ; Endopeptidases/pharmacology ; Mammalian orthoreovirus 3 ; Models, Molecular ; Molecular Conformation ; Peptides/metabolism ; Piperidines/chemical synthesis/*chemistry/pharmacology ; Receptors, Virus/drug effects/*immunology/metabolism ; Structure-Activity Relationship
    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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  • 7
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    Laboratory simulation of charge exchange-produced X-ray emission from comets (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-06-07
    Description: In laboratory experiments using the engineering spare microcalorimeter detector from the ASTRO-E satellite mission, we recorded the x-ray emission of highly charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange reactions between heavy ions in the solar wind and neutral gases in cometary comae. The spectra are complex and do not readily match predictions. We developed a charge exchange emission model that successfully reproduces the soft x-ray spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beiersdorfer, P -- Boyce, K R -- Brown, G V -- Chen, H -- Kahn, S M -- Kelley, R L -- May, M -- Olson, R E -- Porter, F S -- Stahle, C K -- Tillotson, W A -- New York, N.Y. -- Science. 2003 Jun 6;300(5625):1558-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lawrence Livermore National Laboratory, 7000 East Avenue, L-260, Livermore, CA 94550, USA. beiersdorfer@llnl.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12791989" target="_blank"〉PubMed〈/a〉
    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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  • 8
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    An unexpectedly low oscillator strength as the origin of the Fe XVII emission problem (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-12-14
    Description: Highly charged iron (Fe(16+), here referred to as Fe XVII) produces some of the brightest X-ray emission lines from hot astrophysical objects, including galaxy clusters and stellar coronae, and it dominates the emission of the Sun at wavelengths near 15 angstroms. The Fe XVII spectrum is, however, poorly fitted by even the best astrophysical models. A particular problem has been that the intensity of the strongest Fe XVII line is generally weaker than predicted. This has affected the interpretation of observations by the Chandra and XMM-Newton orbiting X-ray missions, fuelling a continuing controversy over whether this discrepancy is caused by incomplete modelling of the plasma environment in these objects or by shortcomings in the treatment of the underlying atomic physics. Here we report the results of an experiment in which a target of iron ions was induced to fluoresce by subjecting it to femtosecond X-ray pulses from a free-electron laser; our aim was to isolate a key aspect of the quantum mechanical description of the line emission. Surprisingly, we find a relative oscillator strength that is unexpectedly low, differing by 3.6sigma from the best quantum mechanical calculations. Our measurements suggest that the poor agreement is rooted in the quality of the underlying atomic wavefunctions rather than in insufficient modelling of collisional processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernitt, S -- Brown, G V -- Rudolph, J K -- Steinbrugge, R -- Graf, A -- Leutenegger, M -- Epp, S W -- Eberle, S -- Kubicek, K -- Mackel, V -- Simon, M C -- Trabert, E -- Magee, E W -- Beilmann, C -- Hell, N -- Schippers, S -- Muller, A -- Kahn, S M -- Surzhykov, A -- Harman, Z -- Keitel, C H -- Clementson, J -- Porter, F S -- Schlotter, W -- Turner, J J -- Ullrich, J -- Beiersdorfer, P -- Lopez-Urrutia, J R Crespo -- England -- Nature. 2012 Dec 13;492(7428):225-8. doi: 10.1038/nature11627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Kernphysik, 69117 Heidelberg, Germany. sven.bernitt@mpi-hd.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235875" target="_blank"〉PubMed〈/a〉
    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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  • 9
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    An epigenetic blockade of cognitive functions in the neurodegenerating brain (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-06
    Description: Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer's disease. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer's-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer's disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498952/" 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/PMC3498952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graff, Johannes -- Rei, Damien -- Guan, Ji-Song -- Wang, Wen-Yuan -- Seo, Jinsoo -- Hennig, Krista M -- Nieland, Thomas J F -- Fass, Daniel M -- Kao, Patricia F -- Kahn, Martin -- Su, Susan C -- Samiei, Alireza -- Joseph, Nadine -- Haggarty, Stephen J -- Delalle, Ivana -- Tsai, Li-Huei -- R01 DA028301/DA/NIDA NIH HHS/ -- R01 MH095088/MH/NIMH NIH HHS/ -- R01 NS078839/NS/NINDS NIH HHS/ -- R01DA028301/DA/NIDA NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 29;483(7388):222-6. doi: 10.1038/nature10849.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22388814" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation/drug effects ; Alzheimer Disease/complications/genetics/physiopathology ; Amyloid beta-Peptides/toxicity ; Animals ; Brain/drug effects/metabolism/*physiopathology ; Disease Models, Animal ; *Epigenesis, Genetic/drug effects ; Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; Hippocampus/drug effects/metabolism ; Histone Deacetylase 2/deficiency/*genetics/metabolism ; Histones/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Memory Disorders/complications/*genetics/*physiopathology ; Mice ; Neurodegenerative Diseases/complications/*genetics/*physiopathology ; Neuronal Plasticity/drug effects/genetics ; Peptide Fragments/toxicity ; Phosphorylation/drug effects ; Promoter Regions, Genetic/drug effects/genetics ; RNA Polymerase II/metabolism ; Receptors, Glucocorticoid/metabolism
    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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  • 10
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    Shox2 and adipose depots [Cell Biology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-07-10
    Description: Visceral and s.c. fat exhibit different intrinsic properties, including rates of lipolysis, and are associated with differential risk for the development of type 2 diabetes. These effects are in part related to cell autonomous differences in gene expression. In the present study, we show that expression of Shox2 (Short stature...
    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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