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  • 1
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    Deletional tolerance mediated by extrathymic Aire-expressing cells (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-08-09
    Description: The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting naive autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" 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/PMC2532844/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardner, James M -- Devoss, Jason J -- Friedman, Rachel S -- Wong, David J -- Tan, Ying X -- Zhou, Xuyu -- Johannes, Kellsey P -- Su, Maureen A -- Chang, Howard Y -- Krummel, Matthew F -- Anderson, Mark S -- K08 AI076429/AI/NIAID NIH HHS/ -- K08 AI076429-05/AI/NIAID NIH HHS/ -- P01 AI035297/AI/NIAID NIH HHS/ -- P01 AI035297-150009/AI/NIAID NIH HHS/ -- P01 AI035297-159001/AI/NIAID NIH HHS/ -- P01 AI035297-160009/AI/NIAID NIH HHS/ -- P01 AI035297-169001/AI/NIAID NIH HHS/ -- P01 AI035297-170009/AI/NIAID NIH HHS/ -- P01 AI035297-179001/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- P30 DK063720-05/DK/NIDDK NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 8;321(5890):843-7. doi: 10.1126/science.1159407.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18687966" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen Presentation ; Autoantigens/genetics/*immunology ; Autoimmunity ; Cell Proliferation ; Epithelial Cells/immunology ; Gene Expression Regulation ; Glucose-6-Phosphatase/immunology ; Lymph Nodes/cytology/*immunology/metabolism ; Lymphoid Tissue/*cytology/immunology/*metabolism ; Mice ; Mice, Transgenic ; Proteins/immunology ; *Self Tolerance ; Spleen/cytology/immunology/metabolism ; Stromal Cells/immunology/metabolism ; T-Lymphocytes/*immunology ; Thymus Gland/cytology/immunology ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
    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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    Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-16
    Description: Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049919/" 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/PMC3049919/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gupta, Rajnish A -- Shah, Nilay -- Wang, Kevin C -- Kim, Jeewon -- Horlings, Hugo M -- Wong, David J -- Tsai, Miao-Chih -- Hung, Tiffany -- Argani, Pedram -- Rinn, John L -- Wang, Yulei -- Brzoska, Pius -- Kong, Benjamin -- Li, Rui -- West, Robert B -- van de Vijver, Marc J -- Sukumar, Saraswati -- Chang, Howard Y -- R01 CA118750/CA/NCI NIH HHS/ -- R01 CA118750-03/CA/NCI NIH HHS/ -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01 HG004361-03/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 15;464(7291):1071-6. doi: 10.1038/nature08975.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Program in Epithelial Biology, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393566" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chromatin/*genetics ; Chromatin Assembly and Disassembly/*genetics ; Disease Progression ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Homeobox/genetics ; Genome, Human/genetics ; Histones/metabolism ; Humans ; Methylation ; Mice ; Mice, Nude ; Mice, SCID ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis/*genetics ; Neoplasm Transplantation ; Polycomb-Group Proteins ; Prognosis ; RNA Interference ; RNA, Untranslated/biosynthesis/*genetics ; Repressor Proteins/analysis/metabolism ; Survival Rate
    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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  • 3
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    Efficient Generic Construction of CCA-Secure Identity-Based Encryption from Randomness Extraction (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-29
    Description: We propose a generic construction that yields efficient identity-based encryption (IBE) schemes secure against chosen ciphertext attack (CCA) in the standard model. Our construction extends Kiltz et al. 's (Eurocrypt '09) method of constructing CCA-secure public-key encryption schemes via randomness extraction to the identity-based setting. The main idea of our construction is to transform ‘ $\epsilon _1$ -almost $\kappa $ -entropic’ and valid/invalid ciphertext indistinguishable (VI-IND) identity-based hash proof system to the one that satisfies the stronger ‘ $\epsilon _2$ -universal’ and VI-IND property. This transformation is realized by a randomness extractor based on the 4-wise hash function. We demonstrate that our generic construction can produce CCA-secure IBE schemes whose efficiency is comparable with the most efficient but non-generic CCA-secure IBE schemes without random oracles in the literature.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 4
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    Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets [Microbiology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-08-24
    Description: A novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin–neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility.
    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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    Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes (1998)
    Oxford University Press
    Details
    Publication Date: 1998-01-01
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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