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  • 1
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    IDH3{alpha} regulates one-carbon metabolism in glioblastoma (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉Mutation or transcriptional up-regulation of isocitrate dehydrogenases 1 and 2 (〈i〉IDH1〈/i〉 and 〈i〉IDH2〈/i〉) promotes cancer progression through metabolic reprogramming and epigenetic deregulation of gene expression. Here, we demonstrate that IDH3α, a subunit of the IDH3 heterotetramer, is elevated in glioblastoma (GBM) patient samples compared to normal brain tissue and promotes GBM progression in orthotopic glioma mouse models. IDH3α loss of function reduces tricarboxylic acid (TCA) cycle turnover and inhibits oxidative phosphorylation. In addition to its impact on mitochondrial energy metabolism, IDH3α binds to cytosolic serine hydroxymethyltransferase (cSHMT). This interaction enhances nucleotide availability during DNA replication, while the absence of IDH3α promotes methionine cycle activity, 〈i〉S〈/i〉-adenosyl methionine generation, and DNA methylation. Thus, the regulation of one-carbon metabolism via an IDH3α-cSHMT signaling axis represents a novel mechanism of metabolic adaptation in GBM.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    PRC2 recruitment and H3K27me3 deposition at FLC require FCA binding of COOLAIR (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉The cold-induced antisense transcript 〈i〉COOLAIR〈/i〉 represses 〈i〉FLOWERING LOCUS C〈/i〉 (〈i〉FLC〈/i〉) transcription with increased H3K27me3 and decreased H3K36me3 levels in response to cold temperatures. However, the molecular connection between 〈i〉COOLAIR〈/i〉 and histone modification factors in the absence of cold treatment remains unclear. We report that the RNA binding protein FCA interacts with the PRC2 subunit CURLY LEAF (CLF) and binds nascent 〈i〉COOLAIR〈/i〉 transcripts to allow deposition of H3K27me3 at 〈i〉FLC〈/i〉. Loss of 〈i〉COOLAIR〈/i〉 function results in a reduction in FCA and CLF enrichment, which, in turn, decreases H3K27me3 levels at 〈i〉FLC〈/i〉. The 〈i〉Arabidopsis〈/i〉 protein phosphatase SSU72 physically interacts with the RRM1 motif of FCA to antagonize FCA binding with 〈i〉COOLAIR〈/i〉. Mutations in 〈i〉SSU72〈/i〉 caused early flowering, reduced 〈i〉FLC〈/i〉 transcription, increased CLF enrichment and H3K27me3, and enhanced affinity between FCA and 〈i〉COOLAIR〈/i〉. Our results suggest that FCA binding of 〈i〉COOLAIR〈/i〉 and SSU72 is critical for PRC2 enrichment and H3K27me3 deposition in 〈i〉Arabidopsis〈/i〉.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    String patterns in the doped Hubbard model (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉Understanding strongly correlated quantum many-body states is one of the most difficult challenges in modern physics. For example, there remain fundamental open questions on the phase diagram of the Hubbard model, which describes strongly correlated electrons in solids. In this work, we realize the Hubbard Hamiltonian and search for specific patterns within the individual images of many realizations of strongly correlated ultracold fermions in an optical lattice. Upon doping a cold-atom antiferromagnet, we find consistency with geometric strings, entities that may explain the relationship between hole motion and spin order, in both pattern-based and conventional observables. Our results demonstrate the potential for pattern recognition to provide key insights into cold-atom quantum many-body systems.〈/p〉
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉About 257 million people with chronic infection of hepatitis B virus (HBV) worldwide are at high risk of developing terminal liver diseases. Reactivation of virus replication has been frequently reported in those patient populations receiving imatinib (an Abl kinase inhibitor) or bortezomib (a proteasome inhibitor) to treat concurrent diseases, but the underlying mechanism for this reactivation is unknown. We report that the HBV polymerase protein is recruited by Cdt2 to the cullin-RING ligase 4 (CRL4) for ubiquitination and proteasome degradation and that this process is stimulated by the c-Abl nonreceptor tyrosine kinase. Genetic ablation of the Abl-CRL4〈sup〉Cdt2〈/sup〉 axis or pharmaceutical inhibition of this process stabilizes HBV polymerase protein and increases viral loads in HBV-infected liver cancer cell lines. Our study reveals a kinase-dependent activation of CRL4 ubiquitin ligase that can be targeted for blocking HBV replication.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Experimental observation of the quantum anomalous Hall effect in a magnetic topological insulator (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2013-03-16
    Beschreibung: The quantized version of the anomalous Hall effect has been predicted to occur in magnetic topological insulators, but the experimental realization has been challenging. Here, we report the observation of the quantum anomalous Hall (QAH) effect in thin films of chromium-doped (Bi,Sb)2Te3, a magnetic topological insulator. At zero magnetic field, the gate-tuned anomalous Hall resistance reaches the predicted quantized value of h/e(2), accompanied by a considerable drop in the longitudinal resistance. Under a strong magnetic field, the longitudinal resistance vanishes, whereas the Hall resistance remains at the quantized value. The realization of the QAH effect may lead to the development of low-power-consumption electronics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Cui-Zu -- Zhang, Jinsong -- Feng, Xiao -- Shen, Jie -- Zhang, Zuocheng -- Guo, Minghua -- Li, Kang -- Ou, Yunbo -- Wei, Pang -- Wang, Li-Li -- Ji, Zhong-Qing -- Feng, Yang -- Ji, Shuaihua -- Chen, Xi -- Jia, Jinfeng -- Dai, Xi -- Fang, Zhong -- Zhang, Shou-Cheng -- He, Ke -- Wang, Yayu -- Lu, Li -- Ma, Xu-Cun -- Xue, Qi-Kun -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):167-70. doi: 10.1126/science.1234414. Epub 2013 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493424" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Centrilobular injury following hypoxia in isolated, perfused rat liver (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 1981-08-07
    Beschreibung: Hypoxia was produced in isolated, hemoglobin-free, perfused rat liver by reducing the flow rate of oxygen-carrying fluid entering the organ. The procedure caused anoxia in centrilobular regions. In these anoxic areas, structural derangements developed rapidly, characterized by bleb-like protrusions of hepatocyte plasma membrane through fenestrations in the sinusoidal endothelium. Periportal tissue remained normoxic and was completely spared. Cellular injury resulting from localized anoxia may play an important role in the pathogenesis of centrilobular liver disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lemasters, J J -- Ji, S -- Thurman, R G -- AA-00033/AA/NIAAA NIH HHS/ -- AA-03624/AA/NIAAA NIH HHS/ -- AA-04853/AA/NIAAA NIH HHS/ -- New York, N.Y. -- Science. 1981 Aug 7;213(4508):661-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7256265" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Anoxia/*complications ; Cell Membrane/pathology ; Female ; Liver/*blood supply ; Liver Diseases/*etiology/pathology ; NAD/metabolism ; NADP/metabolism ; Oxidation-Reduction ; Rats ; Regional Blood Flow
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA library (2017)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2017-10-19
    Beschreibung: Cell cycle progression is a tightly controlled fundamental process in living cells, with any defects being closely linked to various abnormalities. The tumor suppressor p53/p21 axis is a core pathway controlling cell cycle progression; however, its regulatory mechanism has not been fully elucidated. In an effort to unravel this crucial network, we screened a short hairpin RNA expression vector library and identified unspliced X-box binding protein 1 (XBP1-u) as a novel and critical regulator of the p53/p21 axis. Specifically, XBP1-u negatively regulates the p53/p21 axis by enhancing p53 ubiquitination, which in turn down-regulates p21 expression. We show that XBP1-u suppression induces G 0 -G 1 phase arrest and represses cell proliferation. We further report that the carboxyl terminus of XBP1-u, which differs from that of its spliced form (XBP1-s) due to a codon shift, binds and stabilizes mouse double minute homolog 2 (MDM2) protein, a negative regulator of p53, by inhibiting its self-ubiquitination. Concomitantly, XBP-u overexpression enhances tumorigenesis by positively regulating MDM2. Together, our findings suggest that XBP1-u functions far beyond being merely a precursor of XBP1-s and, instead, is involved in fundamental biological processes. Furthermore, this study provides new insights regarding the regulation of the MDM2/p53/p21 axis.
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    SPO16 binds SHOC1 to promote homologous recombination and crossing-over in meiotic prophase I (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉Segregation of homologous chromosomes in meiosis I is tightly regulated by their physical links, or crossovers (COs), generated from DNA double-strand breaks (DSBs) through meiotic homologous recombination. In budding yeast, three ZMM (Zip1/2/3/4, Mer3, Msh4/5) proteins, Zip2, Zip4, and Spo16, form a "ZZS" complex, functioning to promote meiotic recombination via a DSB repair pathway. Here, we identified the mammalian ortholog of Spo16, termed SPO16, which interacts with the mammalian ortholog of Zip2 (SHOC1/MZIP2), and whose functions are evolutionarily conserved to promote the formation of COs. SPO16 localizes to the recombination nodules, as SHOC1 and TEX11 do. SPO16 is required for stabilization of SHOC1 and proper localization of other ZMM proteins. The DSBs formed in SPO16-deleted meiocytes were repaired without COs formation, although synapsis is less affected. Therefore, formation of SPO16-SHOC1 complex–associated recombination intermediates is a key step facilitating meiotic recombination that produces COs from yeast to mammals.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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