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  • 1
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 18 ( 2023-05-02)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 18 ( 2023-05-02)
    Abstract: The anomalous metallic state (AMS) emerging from a quantum superconductor-to-metal transition is a subject of great current interest since this exotic quantum state exhibits unconventional transport properties that challenge the core physics principles of Fermi liquid theory. As the AMS concept is historically derived from disordered two-dimensional (2D) systems, related studies have predominately concentrated on 2D materials. The AMS behaviors in three-dimensional (3D) systems have been rarely reported to date, which raises intriguing questions on the fundamental nature of pertinent physics. Here, we report experimental evidence for a 3D AMS in highly compressed titanium metal that exhibits superconductivity with a critical temperature ( T c ) reaching near-record 25.1 K among elemental superconductors, offering a favorable material template for exploring 3D AMS. At sufficiently strong magnetic fields, unusual transport behaviors set in over a wide pressure range, showcasing AMS hallmarks of a low-temperature saturation resistance below the Drude value and giant positive magnetoresistance. These findings reveal a 3D AMS in simple elemental systems and, more importantly, provide a fresh platform for probing the decades-long enigmatic underlying physics.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 30 ( 2023-07-25)
    Abstract: To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone–receptor pair [R.P. Xiao, Sci STKE 2001 , re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402 , 181–184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390 , 88–91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that G s -biased signaling, but not G i activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-G i , EP4-G s , and EP4-G i in complex with endogenous prostaglandin E 2 (PGE 2 )or two synthetic agonists and comparing with PGE 2 -EP2-G s structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the G s /G i transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE 2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their G s /G i coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for G s /G i coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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    detail.hit.zdb_id: 1461794-8
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    SSG: 12
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  • 3
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Vol. 364, No. 6443 ( 2019-05-31), p. 878-880
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 364, No. 6443 ( 2019-05-31), p. 878-880
    Abstract: Steering the evolution of single spin systems is crucial for quantum computing and quantum sensing. The dynamics of quantum systems has been theoretically investigated with parity-time–symmetric Hamiltonians exhibiting exotic properties. Although parity-time symmetry has been explored in classical systems, its observation in a single quantum system remains elusive. We developed a method to dilate a general parity-time–symmetric Hamiltonian into a Hermitian one. The quantum state evolutions ranging from regions of unbroken to broken P T symmetry have been observed with a single nitrogen-vacancy center in diamond. Owing to the universality of the dilation method, our result provides a route for further exploiting and understanding the exotic properties of parity-time symmetric Hamiltonian in quantum systems.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
    detail.hit.zdb_id: 128410-1
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2017
    In:  Computers in Human Behavior Vol. 72 ( 2017-07), p. 108-114
    In: Computers in Human Behavior, Elsevier BV, Vol. 72 ( 2017-07), p. 108-114
    Type of Medium: Online Resource
    ISSN: 0747-5632
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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    SSG: 7,11
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  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6637 ( 2023-03-17)
    Abstract: Autoimmune diseases such as ankylosing spondylitis (AS) can be caused by emerging neoantigens that break immune tolerance in humans. Posttranslational modifications (PTMs) have been shown to be a critical mechanism that alters protein structure and function to generate neoantigens and induce subsequent autoimmune responses. Previous studies have confirmed that citrulline-modified peptides are a critical source of neoantigens in rheumatoid arthritis. However, the molecular mechanisms underlying neoantigen formation and pathogenic autoreactive responses for AS are largely unknown. There is an urgent need to develop a systematic approach to profiling the possible PTMs in patients with AS and identifying AS-associated PTMs responsible for autoreactive neoantigen production to better understand the etiology of autoimmune diseases. RATIONALE AS has been suggested to be an autoimmune disease because of its clear correlation with certain major histocompatibility complex (MHC) alleles, including HLA-B27. Neoantigens have been hypothesized to induce an aberrant immune response, leading to pathogenic autoreactive T cell responses and autoantibody generation in AS. Here, we developed a systematic open search approach to identify any possible amino acid residues and derivatives in the proteins that are different from the genomic coding sequences. We then applied this information to identify AS-related neoantigens with PTMs within a possible pool of PTM autoantigens and elucidate the pathogenesis of AS. RESULTS An open search approach was applied to identify any possible amino acid derivatives across the proteome of patients with AS. This approach generated a large set of noncoded amino acids representing the mass differences between the coded amino acids and actual residues. Among these, an amino acid derivative with a delta mass of 72.021 showed the greatest increase in patients with AS and resulted from a PTM called cysteine carboxyethylation. In vitro and in vivo experiments demonstrated that carboxyethylation at a cysteine residue of integrin αIIb [ITGA2B (CD41)] was catalyzed by cystathionine beta synthase (CBS) in a process that required 3-hydroxypropionic acid (3-HPA), a metabolite commonly released from gut microbes. Cysteine carboxyethylation induced the lysosomal degradation of ITGA2B and produced neoantigens that triggered MHC-II–dependent CD4 + T cell responses. Fluorescence polarization and enzyme-linked immunosorbent assay (ELISA) demonstrated that the identified carboxyethylated peptide (ITGA2B-ceC96) specifically interacted with HLA-DRA*01/HLA-DRB1*04 and was associated with autoantibody production and T cell responses in HLA-DRB1*04 patients. Additional in vitro assays showed that the neoantigen ITGA2B-ceC96 correlated with 3-HPA levels but was independent of CBS expression. HLA-DRB1 haplotype, the carboxyethylated peptide, specific autoantibodies, and 3-HPA levels in patients with AS all correlated with one another. 3-HPA–treated and ITGA2B-ceC96–immunized HLA-DR4 transgenic mice developed colitis and vertebral bone erosion. Thus, cysteine carboxyethylation induced by the metabolite 3-HPA generates a neoantigen that appears to be critical for autoimmune responses in patients with AS. CONCLUSION Cysteine carboxyethylation is an in vivo protein modification induced by the metabolite 3-HPA, which is commonly released from gut microbes. Carboxyethylated ITGA2B then induces autoantibody production and autoimmune response in AS. Our work provides a systematic workflow to identify differentially modified proteins that are important for neoantigen production in immune disorders. This approach furthers our understanding of AS pathogenesis and may aid in the development of neoantigen-based diagnosis and treatment for AS and other autoimmune diseases. Metabolite-induced cysteine carboxyethylation provokes HLA-restricted autoimmune responses in ankylosing spondylitis. 3-HPA, which is commonly obtained from food and gut microbes, induces carboxyethylation of cysteine residues in integrin αIIb (ITGA2B). Cysteine carboxyethylation requires CBS, and carboxyethylated ITGA2B (ITGA2B-ceC96) peptides are recruited to the HLA-DR4 complex and thereby stimulate CD4 + T cell responses closely related to AS.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 6
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 334, No. 6058 ( 2011-11-18), p. 968-971
    Abstract: The utility of ferroelectric materials stems from the ability to nucleate and move polarized domains using an electric field. To understand the mechanisms of polarization switching, structural characterization at the nanoscale is required. We used aberration-corrected transmission electron microscopy to follow the kinetics and dynamics of ferroelectric switching at millisecond temporal and subangstrom spatial resolution in an epitaxial bilayer of an antiferromagnetic ferroelectric (BiFeO 3 ) on a ferromagnetic electrode (La 0.7 Sr 0.3 MnO 3 ). We observed localized nucleation events at the electrode interface, domain wall pinning on point defects, and the formation of ferroelectric domains localized to the ferroelectric and ferromagnetic interface. These results show how defects and interfaces impede full ferroelectric switching of a thin film.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2011
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    detail.hit.zdb_id: 2066996-3
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    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 7 ( 2005-02-15), p. 2430-2435
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 7 ( 2005-02-15), p. 2430-2435
    Abstract: The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
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    SSG: 11
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