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  • 1
    Publication Date: 2018-07-10
    Description: The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4 + T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4 + T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4 + T cells from UC patients. Naive CD4 + T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the Il4 promoter to enhance the expression of IL-4 in CD4 + T cells. CD4 + T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2012-01-31
    Description: Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (alpha-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartzentruber, Jeremy -- Korshunov, Andrey -- Liu, Xiao-Yang -- Jones, David T W -- Pfaff, Elke -- Jacob, Karine -- Sturm, Dominik -- Fontebasso, Adam M -- Quang, Dong-Anh Khuong -- Tonjes, Martje -- Hovestadt, Volker -- Albrecht, Steffen -- Kool, Marcel -- Nantel, Andre -- Konermann, Carolin -- Lindroth, Anders -- Jager, Natalie -- Rausch, Tobias -- Ryzhova, Marina -- Korbel, Jan O -- Hielscher, Thomas -- Hauser, Peter -- Garami, Miklos -- Klekner, Almos -- Bognar, Laszlo -- Ebinger, Martin -- Schuhmann, Martin U -- Scheurlen, Wolfram -- Pekrun, Arnulf -- Fruhwald, Michael C -- Roggendorf, Wolfgang -- Kramm, Christoph -- Durken, Matthias -- Atkinson, Jeffrey -- Lepage, Pierre -- Montpetit, Alexandre -- Zakrzewska, Magdalena -- Zakrzewski, Krzystof -- Liberski, Pawel P -- Dong, Zhifeng -- Siegel, Peter -- Kulozik, Andreas E -- Zapatka, Marc -- Guha, Abhijit -- Malkin, David -- Felsberg, Jorg -- Reifenberger, Guido -- von Deimling, Andreas -- Ichimura, Koichi -- Collins, V Peter -- Witt, Hendrik -- Milde, Till -- Witt, Olaf -- Zhang, Cindy -- Castelo-Branco, Pedro -- Lichter, Peter -- Faury, Damien -- Tabori, Uri -- Plass, Christoph -- Majewski, Jacek -- Pfister, Stefan M -- Jabado, Nada -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2012 Jan 29;482(7384):226-31. doi: 10.1038/nature10833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22286061" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics ; Base Sequence ; Child ; Chromatin/*genetics/metabolism ; Chromatin Assembly and Disassembly/*genetics ; DNA Helicases/genetics ; DNA Mutational Analysis ; Exome/genetics ; Gene Expression Profiling ; Glioblastoma/*genetics ; Histones/*genetics/metabolism ; Humans ; Molecular Sequence Data ; Mutation/*genetics ; Nuclear Proteins/genetics ; Telomere/genetics ; Tumor Suppressor Protein p53/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-02-02
    Description: Kaposiform hemangioendothelima (KHE) is a locally aggressive vascular tumor that mainly occurs during childhood and invades adjacent tissue and organ. It is commonly complicated by Kasabach-Merritt phenomenon (KMP) in about 50%-70% of the cases. KMP is most often associated with a rapidly growing, large solitary tumor that may result in severe hemorrhage and directly responsible for high mortality and morbidity. This article is protected by copyright. All rights reserved.
    Print ISSN: 0007-0963
    Electronic ISSN: 1365-2133
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 4
    Publication Date: 2011-07-01
    Description: Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 A resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gourdon, Pontus -- Liu, Xiang-Yu -- Skjorringe, Tina -- Morth, J Preben -- Moller, Lisbeth Birk -- Pedersen, Bjorn Panyella -- Nissen, Poul -- England -- Nature. 2011 Jun 29;475(7354):59-64. doi: 10.1038/nature10191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus University, Department of Molecular Biology, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21716286" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Biological Transport ; Calcium ; Cation Transport Proteins/genetics ; Cell Membrane/metabolism ; Copper/*metabolism ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Hepatolenticular Degeneration/genetics ; Humans ; Legionella pneumophila/*chemistry ; Menkes Kinky Hair Syndrome/genetics ; Models, Molecular ; Mutation, Missense/genetics ; Protein Structure, Tertiary ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/chemistry ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-08-10
    Description: As the semiconductor devices of integrated circuits approach the physical limitations of scaling, alternative transistor and memory designs are needed to achieve improvements in speed, density, and power consumption. We report on a transistor that uses an embedded tunneling field-effect transistor for charging and discharging the semi-floating gate. This transistor operates at low voltages (〈/=2.0 volts), with a large threshold voltage window of 3.1 volts, and can achieve ultra-high-speed writing operations (on time scales of ~1 nanosecond). A linear dependence of drain current on light intensity was observed when the transistor was exposed to light, so possible applications include image sensing with high density and performance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Peng-Fei -- Lin, Xi -- Liu, Lei -- Sun, Qing-Qing -- Zhou, Peng -- Liu, Xiao-Yong -- Liu, Wei -- Gong, Yi -- Zhang, David Wei -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):640-3. doi: 10.1126/science.1240961.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai, China. pfw@fudan.edu.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929978" 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
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  • 6
    Publication Date: 2015-01-17
    Description: Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, F H -- Dong, G H -- Zhang, D J -- Liu, X Y -- Jia, X -- An, C B -- Ma, M M -- Xie, Y W -- Barton, L -- Ren, X Y -- Zhao, Z J -- Wu, X H -- Jones, M K -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):248-50. doi: 10.1126/science.1259172. Epub 2014 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Western China's Environmental Systems (Ministry of Education), Lanzhou University, Lanzhou 730000, China. fhchen@lzu.edu.cn ghdong@lzu.edu.cn. ; Key Laboratory of Western China's Environmental Systems (Ministry of Education), Lanzhou University, Lanzhou 730000, China. ; Department of Anthropology, Washington University in St. Louis, St. Louis, MO 63130-48, USA. ; Center for Comparative Archaeology, Department of Anthropology, University of Pittsburgh, Pittsburgh, PA 15260, USA. ; Qinghai Provincial Institute of Cultural Relics and Archaeology, Xining 810007, China. ; Institute of Archaeology, Chinese Academy of Social Sciences, Beijing 100710, China. ; School of Archaeology and Museology, Peking University, Beijing 100871, China. ; McDonald Institute of Archaeological Research, University of Cambridge, Cambridge CB2 3ER, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593179" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization ; Agriculture/*history ; *Altitude ; Archaeology ; Climate ; History, Ancient ; Humans ; Radiometric Dating ; Temperature ; Tibet
    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
    Keywords: EXPRESSION ; TUMORS ; ABERRATIONS ; METHYLATION ; EMBRYONIC STEM-CELLS ; MULTIFORME ; HIGH-GRADE GLIOMAS ; TELOMERES ; INTEGRATED GENOMIC ANALYSIS ; ATRX
    Abstract: Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases(1-4). To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (alpha-thalassaemia/mental retardation syndrome X-linked)(5) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres(6,7), were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis
    Type of Publication: Journal article published
    PubMed ID: 22286061
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  • 8
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 81 (2002), S. 445-447 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Controlled ice nucleation in a microsized water droplet was examined using a microdroplet suspension method. This method allows us to minimize the effect of the container wall and foreign particles. The influence of the water droplet volume on microdrop nucleation is examined quantitatively. It is found that at the microscale, the volume effect exerts a large influence on nucleation kinetics. This technique enabled us to quantify the effect of lysozyme on ice nucleation kinetics. It turns out that lysozyme promotes ice nucleation at relatively high supercoolings by decreasing the interfacial free energy between the nucleating phase and foreign particles. This quantitative measurement of the interfacial effect of additives (impurities) on ice nucleation kinetics will exert a significant impact on the research on the mechanism of antifreeze and nucleation promotion. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 79 (2001), S. 3518-3520 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The fractal structure of nanofiber networks formed in organogels is identified, using an in situ rheological method, together with a coupled supercritical fluid CO2 extraction/scanning electron microscopy technique. The rheological method allows us to have in-line measurements of the fractal growth of the nanofiber networks. In comparison with conventional light scattering techniques, the results obtained from this technique show much less scatter in data. Unlike conventional fractal aggregates, the growth of this type of fractal pattern is governed by a noncrystallographic branching mechanism, which occurs via self-mismatch nucleation and growth. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 76 (2000), S. 67-69 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Electroluminescent (EL) devices using an europium complex Eu(DBM)3 bath as the electron-transport emitting layer were fabricated. The quenching effect of the metal cathode and the unstable nature of the Eu complex under EL operation markedly influence the EL efficiency. By keeping the emitting area far from the metal cathode and partly doping the Eu(DBM)3 bath layer with a hole-transport material, the EL performance was significantly improved. Sharp-band red emissions with turn-on voltage of 3 V, brightness of 820 cd/m2, and external quantum efficiency of 1% were achieved. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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