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  • 1
    Online Resource
    Online Resource
    A tera–electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 380, No. 6652 ( 2023-06-30), p. 1390-1396
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 380, No. 6652 ( 2023-06-30), p. 1390-1396
    Abstract: Observations of the bright gamma-ray burst GRB 221009A at tera–electron volt energies show that it contained a very narrow jet.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.adg9328
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Reduced default mode network functional connectivity in patients with recurrent major depressive disorder
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 18 ( 2019-04-30), p. 9078-9083
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 18 ( 2019-04-30), p. 9078-9083
    Abstract: Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1900390116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 3
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    G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 21 ( 2021-05-25)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 21 ( 2021-05-25)
    Abstract: G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the 〉 1.5 million putative G-4–forming sequences (PQSs), the human genome features 〉 640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS–SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS–SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of 〉 120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, 〉 80% of the G4Vs overlap with transcription factor–binding sites and 〉 14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2013230118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 4
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    Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 8 ( 2021-09-04), p. 2457-2470
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 8 ( 2021-09-04), p. 2457-2470
    Abstract: Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A & gt;G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient’s fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients’ fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab135
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 5
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    Online Resource
    A corticopontine circuit for initiation of urination
    Springer Science and Business Media LLC ; 2018
    In:  Nature Neuroscience Vol. 21, No. 11 ( 2018-11), p. 1541-1550
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 21, No. 11 ( 2018-11), p. 1541-1550
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/s41593-018-0256-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 1494955-6
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  • 6
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    Online Resource
    Tongji University student design competition—Schools
    Acoustical Society of America (ASA) ; 2012
    In:  The Journal of the Acoustical Society of America Vol. 131, No. 4_Supplement ( 2012-04-01), p. 3282-3282
    Details
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 131, No. 4_Supplement ( 2012-04-01), p. 3282-3282
    Abstract: Armstrong (China) Investment Co., Ltd., with support from Tongji University sponsored a school design competition, and this represents the winning student entry. This competition was intended to encourage students to express their knowledge of architectural acoustics and noise control in the design of a school in which acoustical considerations are of significant importance. Design included considerations of 1) the general architectural building design including both shape and location of the building relative to transportation noise sources, and 2) the specific architectural acoustic design of rooms, including noise control both within and between rooms. The design scenario was for a new primary school designed to replace an older school building at a site near Tongji University. The primary school will include grade levels from 1 to 6, with approximately 1000 pupils. This school building will include normal classrooms (number and size based on student population and design standards), cafeteria, auditorium, library, music rooms, gym, dancing room, etc, as are normally found in such a primary school. The school will consist of a single building, which may be a multi-level building.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    URL: Article
    DOI: 10.1121/1.4708273
    RVK:
    EQ 1000
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2012
    detail.hit.zdb_id: 1461063-2
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  • 7
    Online Resource
    Online Resource
    A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 11 ( 2020-03-17), p. 6103-6113
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 11 ( 2020-03-17), p. 6103-6113
    Abstract: Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtype-specific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1912146117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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    SSG: 11
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  • 8
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    Online Resource
    Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 19 ( 2008-05-13), p. 7004-7009
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 19 ( 2008-05-13), p. 7004-7009
    Abstract: MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray ( n = 106), array-based comparative genomic hybridization ( n = 109), cDNA microarray ( n = 76), and tissue array ( n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of ≈15% and at least ≈36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster ( Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0801615105
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
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  • 9
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    Online Resource
    Differential Stimulation of PKC Phosphorylation of Potassium Channels by ZIP1 and ZIP2
    American Association for the Advancement of Science (AAAS) ; 1999
    In:  Science Vol. 285, No. 5433 ( 1999-09-03), p. 1565-1569
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 285, No. 5433 ( 1999-09-03), p. 1565-1569
    Abstract: Targeting of protein modification enzymes is a key biochemical step to achieve specific and effective posttranslational modifications. Two alternatively spliced ZIP1 and ZIP2 proteins are described, which bind to both Kvβ2 subunits of potassium channel and protein kinase C (PKC) ζ, thereby acting as a physical link in the assembly of PKCζ-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kvβ2 by PKCζ. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKCζ. Finally, ZIP1 and ZIP2 coexist in the same cell type and are elevated differentially by neurotrophic factors. These results provide a mechanism for specificity and regulation of PKCζ-targeted phosphorylation.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.285.5433.1565
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 1999
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  • 10
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    An electron transfer path connects subunits of a mycobacterial respiratory supercomplex
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 362, No. 6418 ( 2018-11-30), p. eaat8923-
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6418 ( 2018-11-30), p. eaat8923-
    Abstract: We report a 3.5-angstrom-resolution cryo–electron microscopy structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aat8923
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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