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  • 1
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    Genome-wide profiles of H2AX and {gamma}-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells (2012)
    Oxford University Press
    Details
    Publication Date: 2012-07-22
    Description: Phosphorylation of the histone variant H2AX forms -H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and -H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on -H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. -H2AX-enriched regions of endogenous origin in replicating cells included sub-telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with -H2AX of endogenous origin. -H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous -H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Sub-telomeres were less responsive to external DNA damage than to endogenous stress. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉Although polycrystalline hexagonal boron nitride (PC-hBN) has been realized, defects and grain boundaries still cause charge scatterings and trap sites, impeding high-performance electronics. Here, we report a method of synthesizing wafer-scale single-crystalline hBN (SC-hBN) monolayer films by chemical vapor deposition. The limited solubility of boron (B) and nitrogen (N) atoms in liquid gold promotes high diffusion of adatoms on the surface of liquid at high temperature to provoke the circular hBN grains. These further evolve into closely packed unimodal grains by means of self-collimation of B and N edges inherited by electrostatic interaction between grains, eventually forming an SC-hBN film on a wafer scale. This SC-hBN film also allows for the synthesis of wafer-scale graphene/hBN heterostructure and single-crystalline tungsten disulfide.〈/p〉
    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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    Pathway for the Production of Neutron-Rich Isotopes around the N=126 Shell Closure (2015)
    American Physical Society (APS)
    Details
    Publication Date: 2015-10-24
    Description: Author(s): Y. X. Watanabe, Y. H. Kim, S. C. Jeong, Y. Hirayama, N. Imai, H. Ishiyama, H. S. Jung, H. Miyatake, S. Choi, J. S. Song, E. Clement, G. de France, A. Navin, M. Rejmund, C. Schmitt, G. Pollarolo, L. Corradi, E. Fioretto, D. Montanari, M. Niikura, D. Suzuki, H. Nishibata, and J. Takatsu Absolute cross sections for isotopically identified products formed in multinucleon transfer in the Xe 136 + Pt 198 system at ∼ 8     MeV / nucleon are reported. The isotopic distributions obtained using a large acceptance spectrometer demonstrated the production of the “hard-to-reach” neutron-rich isotopes f… [Phys. Rev. Lett. 115, 172503] Published Fri Oct 23, 2015
    Keywords: Nuclear Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 4
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    Autophagy in Inflammatory Diseases (2012)
    Hindawi
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    Publication Date: 2012-06-21
    Description: Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. During starvation, autophagy exerts a homeostatic function that promotes cell survival by recycling metabolic precursors. Additionally, autophagy can interact with other vital processes such as programmed cell death, inflammation, and adaptive immune mechanisms, and thereby potentially influence disease pathogenesis. Macrophages deficient in autophagic proteins display enhanced caspase-1-dependent proinflammatory cytokine production and the activation of the inflammasome. Autophagy provides a functional role in infectious diseases and sepsis by promoting intracellular bacterial clearance. Mutations in autophagy-related genes, leading to loss of autophagic function, have been implicated in the pathogenesis of Crohn's disease. Furthermore, autophagy-dependent mechanisms have been proposed in the pathogenesis of several pulmonary diseases that involve inflammation, including cystic fibrosis and pulmonary hypertension. Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases associated with inflammation.
    Print ISSN: 1687-8876
    Electronic ISSN: 1687-8884
    Topics: Biology
    Published by Hindawi
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  • 5
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    An E3 ligase complex regulates SET-domain polycomb group protein activity in Arabidopsis thaliana [Plant Biology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-05-11
    Description: Transcriptional repression via methylation of histone H3 lysine 27 (H3K27) by the polycomb repressive complex 2 (PRC2) is conserved in higher eukaryotes. The Arabidopsis PRC2 controls homeotic gene expression, flowering time, and gene imprinting. Although downstream target genes and the regulatory mechanism of PRC2 are well understood, much less is known about the significance of posttranslational regulation of PRC2 protein activity. Here, we show the posttranslational regulation of CURLY LEAF (CLF) SET-domain polycomb group (PcG) protein by the F-box protein, UPWARD CURLY LEAF1 (UCL1). Overexpression of UCL1 generates mutant phenotypes similar to those observed in plants with a loss-of-function mutation in the CLF gene. Leaf curling and early flowering phenotypes of UCL1 overexpression mutants, like clf mutants, are rescued by mutations in the AGAMOUS and FLOWERING LOCUS T genes, which is consistent with UCL1 and CLF functioning in the same genetic pathway. Overexpression of UCL1 reduces the level of CLF protein and alters expression and H3K27 methylation of CLF-target genes in transgenic plants, suggesting that UCL1 negatively regulates CLF. Interaction of UCL1 with CLF was detected in plant nuclei and in the yeast two-hybrid system. The UCL1 F-box binds in vivo to components of the E3 ligase complex, which ubiquitylate proteins that are subsequently degraded via the ubiquitin-26S proteasome pathway. Taken together, these results demonstrate the posttranslational regulation of the CLF SET-domain PcG activity by the UCL1 F-box protein in the E3 ligase complex.
    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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    Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation (2014)
    Oxford University Press
    Details
    Publication Date: 2014-04-15
    Description: ALKBH5 is a 2-oxoglutarate (2OG) and ferrous iron-dependent nucleic acid oxygenase (NAOX) that catalyzes the demethylation of N 6 -methyladenine in RNA. ALKBH5 is upregulated under hypoxia and plays a role in spermatogenesis. We describe a crystal structure of human ALKBH5 (residues 66–292) to 2.0 Å resolution. ALKBH5 66–292 has a double-stranded β-helix core fold as observed in other 2OG and iron-dependent oxygenase family members. The active site metal is octahedrally coordinated by an HXD...H motif (comprising residues His204, Asp206 and His266) and three water molecules. ALKBH5 shares a nucleotide recognition lid and conserved active site residues with other NAOXs. A large loop (βIV–V) in ALKBH5 occupies a similar region as the L1 loop of the fat mass and obesity-associated protein that is proposed to confer single-stranded RNA selectivity. Unexpectedly, a small molecule inhibitor, IOX3, was observed covalently attached to the side chain of Cys200 located outside of the active site. Modelling substrate into the active site based on other NAOX–nucleic acid complexes reveals conserved residues important for recognition and demethylation mechanisms. The structural insights will aid in the development of inhibitors selective for NAOXs, for use as functional probes and for therapeutic benefit.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Friction anisotropy-driven domain imaging on exfoliated monolayer graphene (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-02
    Description: Graphene produced by exfoliation has not been able to provide an ideal graphene with performance comparable to that predicted by theory, and structural and/or electronic defects have been proposed as one cause of reduced performance. We report the observation of domains on exfoliated monolayer graphene that differ by their friction characteristics, as measured by friction force microscopy. Angle-dependent scanning revealed friction anisotropy with a periodicity of 180 degrees on each friction domain. The friction anisotropy decreased as the applied load increased. We propose that the domains arise from ripple distortions that give rise to anisotropic friction in each domain as a result of the anisotropic puckering of the graphene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jin Sik -- Kim, Jin-Soo -- Byun, Ik-Su -- Lee, Duk Hyun -- Lee, Mi Jung -- Park, Bae Ho -- Lee, Changgu -- Yoon, Duhee -- Cheong, Hyeonsik -- Lee, Ki Ho -- Son, Young-Woo -- Park, Jeong Young -- Salmeron, Miquel -- New York, N.Y. -- Science. 2011 Jul 29;333(6042):607-10. doi: 10.1126/science.1207110. Epub 2011 Jun 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Quantum Phases and Devices, Department of Physics, Konkuk University, Seoul 143-701, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21719640" 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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    Trophic cascades in a formerly cod-dominated ecosystem (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-06-11
    Description: Removal of top predators from ecosystems can result in cascading effects through the trophic levels below, completely restructuring the food web. Cascades have been observed in small-scale or simple food webs, but not in large, complex, open-ocean ecosystems. Using data spanning many decades from a once cod-dominated northwest Atlantic ecosystem, we demonstrate a trophic cascade in a large marine ecosystem. Several cod stocks in other geographic areas have also collapsed without recovery, suggesting the existence of trophic cascades in these systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, Kenneth T -- Petrie, Brian -- Choi, Jae S -- Leggett, William C -- New York, N.Y. -- Science. 2005 Jun 10;308(5728):1621-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Fisheries and Oceans, Bedford Institute of Oceanography, Ocean Sciences Division, Post Office Box 1006, Dartmouth, Nova Scotia, B2Y 4A2, Canada. frankk@mar.dfo-mpo.gc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15947186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Biodiversity ; Biomass ; *Ecosystem ; Fisheries ; *Fishes ; *Food Chain ; Gadus morhua ; *Invertebrates ; *Phytoplankton ; Population Density ; Population Dynamics ; Predatory Behavior ; Principal Component Analysis ; Seals, Earless ; *Seawater ; Time Factors ; *Zooplankton
    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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  • 9
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    Conformation and function of the N-linked glycan in the adhesion domain of human CD2 (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-09-01
    Description: The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)2-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wyss, D F -- Choi, J S -- Li, J -- Knoppers, M H -- Willis, K J -- Arulanandam, A R -- Smolyar, A -- Reinherz, E L -- Wagner, G -- New York, N.Y. -- Science. 1995 Sep 1;269(5228):1273-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7544493" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylglucosamine/chemistry ; Amino Acid Sequence ; Animals ; Antigens, CD/metabolism ; Antigens, CD2/*chemistry/metabolism ; Antigens, CD58 ; Binding Sites ; CHO Cells ; Carbohydrate Conformation ; Carbohydrate Sequence ; Cell Adhesion ; Cricetinae ; Glycosylation ; Humans ; Magnetic Resonance Spectroscopy ; Membrane Glycoproteins/metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligosaccharides/*chemistry ; *Protein Conformation
    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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  • 10
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    Response: CD2: An Exception to the Immunologlobulin Superfamily Concept? (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinherz, E L -- Li, J -- Smoylar, A -- Wyss, D F -- Knoppers, M H -- Willis, K J -- Arulanandam, A R -- Choi, J S -- Wagner, G -- New York, N.Y. -- Science. 1996 Aug 30;273(5279):1242.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17842602" 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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