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  • American Association for the Advancement of Science (AAAS)  (6)
  • Natural Sciences  (6)
  • 1
    Online Resource
    Online Resource
    Pan-cancer single-cell landscape of tumor-infiltrating T cells
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 374, No. 6574 ( 2021-12-17)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 374, No. 6574 ( 2021-12-17)
    Abstract: T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics of tumor-infiltrating T cells across cancer types. We built a single-cell RNA-sequencing pan-cancer atlas of T cells for 316 donors across 21 cancer types and revealed distinct T cell composition patterns. We found multiple state-transition paths in the exhaustion of CD8 + T cells and the preference of those paths among different tumor types. Certain T cell populations showed specific correlation with patient properties such as mutation burden, shedding light on the possible determinants of the tumor microenvironment. T cell compositions within tumors alone could classify cancer patients into groups with clinical trait specificity, providing new insights into T cell immunity and precision immunotherapy targeting T cells.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abe6474
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    A Deubiquitinase That Regulates Type I Interferon Production
    American Association for the Advancement of Science (AAAS) ; 2007
    In:  Science Vol. 318, No. 5856 ( 2007-12-07), p. 1628-1632
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 318, No. 5856 ( 2007-12-07), p. 1628-1632
    Abstract: Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA–based screen as a regulator of IFN-I production. Reduction of DUBA augmented the PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect. DUBA bound tumor necrosis factor receptor–associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I response. TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63–linked polyubiquitin chains. DUBA selectively cleaved the lysine-63–linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1145918
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2007
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  • 3
    Online Resource
    Online Resource
    Mapping cell types across human tissues
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Vol. 376, No. 6594 ( 2022-05-13), p. 695-696
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 376, No. 6594 ( 2022-05-13), p. 695-696
    Abstract: Our understanding of how cells form distinct tissues and organs and interact with each other is limited. Recent single-cell RNA sequencing (scRNA-seq) analyses have described the landscapes of individual cell types, along with their abundance and interactions, in homeostasis and diseased conditions ( 1 – 5 ), but these studies are often limited to a single organ. A systematic comparison of cell types across different tissues is needed to understand shared and variable transcriptional features and how these specializations are important for organ function. On pages 711, 712, and 713 of this issue, The Tabula Sapiens Consortium ( 6 ), Eraslan et al. ( 7 ), and Domínguez Conde et al. ( 8 ), respectively, as well as Suo et al. ( 9 ), report pan-tissue single-cell transcriptome atlases covering more than a million cells, including 500 cell types, across more than 30 human tissues from 68 donors. These four studies apply rigorous ontologies to consistently annotate and compare single cells between organs.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abq2116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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    Online Resource
  • 4
    Online Resource
    Online Resource
    Integrative functional genomic analysis of human brain development and neuropsychiatric risks
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 362, No. 6420 ( 2018-12-14)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6420 ( 2018-12-14)
    Abstract: To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type–specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C , SATB2 , SOX5 , TCF4 , and TSHZ3 ) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aat7615
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase
    American Association for the Advancement of Science (AAAS) ; 2004
    In:  Science Vol. 303, No. 5662 ( 2004-02-27), p. 1371-1374
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 303, No. 5662 ( 2004-02-27), p. 1371-1374
    Abstract: Arabidopsis thaliana De-etiolated-1 (AtDET1) is a highly conserved protein, with orthologs in vertebrate and invertebrate organisms. AtDET1 negatively regulates photomorphogenesis, but its biochemical mechanism and function in other species are unknown. We report that human DET1 (hDET1) promotes ubiquitination and degradation of the proto-oncogenic transcription factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1. Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun–activated transcription. These findings characterize a c-Jun ubiquitin ligase and define a specific function for hDET1 in mammalian cells.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1093549
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2004
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    The Genomic Landscapes of Human Breast and Colorectal Cancers
    American Association for the Advancement of Science (AAAS) ; 2007
    In:  Science Vol. 318, No. 5853 ( 2007-11-16), p. 1108-1113
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 318, No. 5853 ( 2007-11-16), p. 1108-1113
    Abstract: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1145720
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2007
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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