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  • 1
    Online Resource
    Online Resource
    “Perfect” designer chromosome V and behavior of a ring derivative
    American Association for the Advancement of Science (AAAS) ; 2017
    In:  Science Vol. 355, No. 6329 ( 2017-03-10)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 355, No. 6329 ( 2017-03-10)
    Abstract: Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024–base pair chromosome synV in the “Build-A-Genome China” course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf4704
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
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  • 2
    Online Resource
    Online Resource
    Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 2 ( 2018-01-09), p. 373-378
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 2 ( 2018-01-09), p. 373-378
    Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1 , TRA-SALL2 , and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates 〉 3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1 , which predicted a poor prognosis in the adult group. Up-regulation of HOXA , MEF2C , and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1717125115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
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  • 3
    Online Resource
    Online Resource
    Extreme mechanical anisotropy in diamond with preferentially oriented nanotwin bundles
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 47 ( 2021-11-23)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 47 ( 2021-11-23)
    Abstract: Mechanical properties of covalent materials can be greatly enhanced with strategy of nanostructuring. For example, the nanotwinned diamond with an isotropic microstructure of interweaved nanotwins and interlocked nanograins shows unprecedented isotropic mechanical properties. How the anisotropic microstructure would impact on the mechanical properties of diamond has not been fully investigated. Here, we report the synthesis of diamond from superaligned multiwalled carbon nanotube films under high pressure and high temperature. Structural characterization reveals preferentially oriented diamond nanotwin bundles with an average twin thickness of ca. 2.9 nm, inherited from the directional nanotubes. This diamond exhibits extreme mechanical anisotropy correlated with its microstructure (e.g., the average Knoop hardness values measured with the major axis of the indenter perpendicular and parallel to nanotwin bundles are 233 ± 8 and 129 ± 9 GPa, respectively). Molecular dynamics simulation reveals that, in the direction perpendicular to the nanotwin bundles, the dense twin boundaries significantly hinder the motion of dislocations under indentation, while such a resistance is much weaker in the direction along the nanotwin bundles. Current work verifies the hardening effect in diamond via nanostructuring. In addition, the mechanical properties can be further tuned (anisotropy) with microstructure design and modification.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2108340118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Structural analysis of human Cdc20 supports multisite degron recognition by APC/C
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 45 ( 2012-11-06), p. 18419-18424
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 45 ( 2012-11-06), p. 18419-18424
    Abstract: The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degrons––the destruction (D) and KEN boxes. APC/C Cdc20 is the target of the spindle checkpoint. Checkpoint inhibition of APC/C Cdc20 requires the binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not understood. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 β propeller with a preformed KEN-box-binding site at its top face. We identify a second conserved surface at the side of the Cdc20 β propeller as a D-box-binding site. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C Cdc20 . Although both motifs contribute to securin ubiquitination by APC/C Cdh1 , securin mutants lacking either motif are efficiently ubiquitinated. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C Cdh1 , suggesting possible competition between the two motifs. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1213438109
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
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  • 5
    Online Resource
    Online Resource
    Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE
    American Association for the Advancement of Science (AAAS) ; 2010
    In:  Science Vol. 330, No. 6012 ( 2010-12-24), p. 1787-1797
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 330, No. 6012 ( 2010-12-24), p. 1787-1797
    Abstract: To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1198374
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
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    SSG: 11
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  • 6
    Online Resource
    Online Resource
    Interannual cycles of Hantaan virus outbreaks at the human–animal interface in Central China are controlled by temperature and rainfall
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 30 ( 2017-07-25), p. 8041-8046
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 30 ( 2017-07-25), p. 8041-8046
    Abstract: Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. In recent decades, repeated outbreaks of hantavirus infections have been reported in Eurasia and America. These outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. Here, we propose a climate–animal–Hantaan virus (HTNV) infection model to address this issue, using a unique dataset spanning a 54-y period (1960–2013). This dataset comes from Central China, a focal point for natural HTNV infection, and includes both field surveillance and an epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven by the confluence of the cyclic dynamics of striped field mouse ( Apodemus agrarius ) populations and climate variability, at both seasonal and interannual cycles. Two climatic variables play key roles in the ecology of the HTNV system: temperature and rainfall. These variables account for the dynamics in the host reservoir system and markedly affect both the rate of transmission and the potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection occur only when climatic conditions are favorable for both rodent population growth and virus transmission. These findings improve our understanding of how climate drives the periodic reemergence of zoonotic disease outbreaks over long timescales.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1701777114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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