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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 48 ( 2021-11-30)
    Abstract: Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis.
    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: 2021
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 52 ( 2009-12-29), p. 22187-22192
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 52 ( 2009-12-29), p. 22187-22192
    Abstract: DNA methylation and histone modification are two major epigenetic pathways that interplay to regulate transcriptional activity and other genome functions. Dnmt3L is a regulatory factor for the de novo DNA methyltransferases Dnmt3a and Dnmt3b. Although recent biochemical studies have revealed that Dnmt3L binds to the tail of histone H3 with unmethylated lysine 4 in vitro, the requirement of chromatin components for DNA methylation has not been examined, and functional evidence for the connection of histone tails to DNA methylation is still lacking. Here, we used the budding yeast Saccharomyces cerevisiae as a model system to investigate the chromatin determinants of DNA methylation through ectopic expression of murine Dnmt3a and Dnmt3L. We found that the N terminus of histone H3 tail is required for de novo methylation, while the central part encompassing lysines 9 and 27, as well as the H4 tail are dispensable. DNA methylation occurs predominantly in heterochromatin regions lacking H3K4 methylation. In mutant strains depleted of H3K4 methylation, the DNA methylation level increased 5-fold. The methylation activity of Dnmt3a largely depends on the Dnmt3L's PHD domain recognizing the histone H3 tail with unmethylated lysine 4. Functional analysis of Dnmt3L in mouse ES cells confirmed that the chromatin-recognition ability of Dnmt3L's PHD domain is indeed required for efficient methylation at the promoter of the endogenous Dnmt3L gene. These findings establish the N terminus of histone H3 tail with an unmethylated lysine 4 as a chromatin determinant for DNA methylation.
    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: 2009
    detail.hit.zdb_id: 209104-5
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  • 3
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Vol. 366, No. 6462 ( 2019-10-11), p. 216-221
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 366, No. 6462 ( 2019-10-11), p. 216-221
    Abstract: Higher-efficiency, lower-cost refrigeration is needed for both large- and small-scale cooling. Refrigerators using entropy changes during cycles of stretching or hydrostatic compression of a solid are possible alternatives to the vapor-compression fridges found in homes. We show that high cooling results from twist changes for twisted, coiled, or supercoiled fibers, including those of natural rubber, nickel titanium, and polyethylene fishing line. Using opposite chiralities of twist and coiling produces supercoiled natural rubber fibers and coiled fishing line fibers that cool when stretched. A demonstrated twist-based device for cooling flowing water provides high cooling energy and device efficiency. Mechanical calculations describe the axial and spring-index dependencies of twist-enhanced cooling and its origin in a phase transformation for polyethylene fibers.
    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
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    detail.hit.zdb_id: 2066996-3
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 15 ( 2023-04-11)
    Abstract: Composite-polymer-electrolytes (CPEs) embedded with advanced filler materials offer great promise for fast and preferential Li + conduction. The filler surface chemistry determines the interaction with electrolyte molecules and thus critically regulates the Li + behaviors at the interfaces. Herein, we probe into the role of electrolyte/filler interfaces (EFI) in CPEs and promote Li + conduction by introducing an unsaturated coordination Prussian blue analog (UCPBA) filler. Combining scanning transmission X-ray microscope stack imaging studies and first-principle calculations, fast Li + conduction is revealed only achievable at a chemically stable EFI, which can be established by the unsaturated Co–O coordination in UCPBA to circumvent the side reactions. Moreover, the as-exposed Lewis-acid metal centers in UCPBA efficiently attract the Lewis-base anions of Li salts, which facilitates the Li + disassociation and enhances its transference number (t Li + ). Attributed to these superiorities, the obtained CPEs realize high room-temperature ionic conductivity up to 0.36 mS cm −1 and t Li + of 0.6, enabling an excellent cyclability of lithium metal electrodes over 4,000 h as well as remarkable capacity retention of 97.6% over 180 cycles at 0.5 C for solid-state lithium–sulfur batteries. This work highlights the crucial role of EFI chemistry in developing highly conductive CPEs and high-performance solid-state batteries.
    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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    detail.hit.zdb_id: 1461794-8
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  • 5
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 4 ( 2006-01-24), p. 1030-1035
    Abstract: Identification of the specific cytogenetic abnormality is one of the critical steps for classification of acute myeloblastic leukemia (AML) which influences the selection of appropriate therapy and provides information about disease prognosis. However at present, the genetic complexity of AML is only partially understood. To obtain a comprehensive, unbiased, quantitative measure, we performed serial analysis of gene expression (SAGE) on CD15 + myeloid progenitor cells from 22 AML patients who had four of the most common translocations, namely t(8;21), t(15;17), t(9;11), and inv(16). The quantitative data provide clear evidence that the major change in all these translocation-carrying leukemias is a decrease in expression of the majority of transcripts compared with normal CD15 + cells. From a total of 1,247,535 SAGE tags, we identified 2,604 transcripts whose expression was significantly altered in these leukemias compared with normal myeloid progenitor cells. The gene ontology of the 1,110 transcripts that matched known genes revealed that each translocation had a uniquely altered profile in various functional categories including regulation of transcription, cell cycle, protein synthesis, and apoptosis. Our global analysis of gene expression of common translocations in AML can focus attention on the function of the genes with altered expression for future biological studies as well as highlight genes/pathways for more specifically targeted therapy.
    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: 2006
    detail.hit.zdb_id: 209104-5
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  • 6
    Online Resource
    Online Resource
    Institute of Electrical and Electronics Engineers (IEEE) ; 2021
    In:  IEEE/ACM Transactions on Audio, Speech, and Language Processing Vol. 29 ( 2021), p. 1503-1513
    In: IEEE/ACM Transactions on Audio, Speech, and Language Processing, Institute of Electrical and Electronics Engineers (IEEE), Vol. 29 ( 2021), p. 1503-1513
    Type of Medium: Online Resource
    ISSN: 2329-9290 , 2329-9304
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2021
    detail.hit.zdb_id: 2751224-1
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  • 7
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 50 ( 2018-12-11)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 50 ( 2018-12-11)
    Abstract: Phytochrome A (phyA) is the only plant photoreceptor that perceives far-red light and then mediates various responses to this signal. Phosphorylation and dephosphorylation of oat phyA have been extensively studied, and it was shown that phosphorylation of a serine residue in the hinge region of oat phyA could regulate the interaction of phyA with its signal transducers. However, little is known about the role of the hinge region of Arabidopsis phyA. Here, we report that three sites in the hinge region of Arabidopsis phyA (i.e., S590, T593, and S602) are essential in regulating phyA function. Mutating all three of these sites to either alanines or aspartic acids impaired phyA function, changed the interactions of mutant phyA with FHY1 and FHL, and delayed the degradation of mutant phyA upon light exposure. Moreover, the in vivo formation of a phosphorylated phyA form was greatly affected by these mutations, while our data indicated that the abundance of this phosphorylated phyA form correlated well with the extent of phyA function, thus suggesting a pivotal role of the phosphorylated phyA in inducing the far-red light response. Taking these data together, our study reveals the important role of the hinge region of Arabidopsis phyA in regulating phyA phosphorylation and function, thus linking specific residues in the hinge region to the regulatory mechanisms of phyA phosphorylation.
    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: 2018
    detail.hit.zdb_id: 209104-5
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    SSG: 11
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  • 8
    Online Resource
    Online Resource
    Wiley ; 1989
    In:  International Journal of Psychology Vol. 24, No. 1-5 ( 1989-01), p. 639-641
    In: International Journal of Psychology, Wiley, Vol. 24, No. 1-5 ( 1989-01), p. 639-641
    Type of Medium: Online Resource
    ISSN: 0020-7594 , 1464-066X
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    Language: English
    Publisher: Wiley
    Publication Date: 1989
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    SSG: 5,2
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 34 ( 2023-08-22)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 34 ( 2023-08-22)
    Abstract: Abscisic acid (ABA), a classical plant hormone, plays an essential role in plant adaptation to environmental stresses. The ABA signaling mechanisms have been extensively investigated, and it was shown that the PYR1 (PYRABACTIN RESISTANCE1)/PYL (PYR1-LIKE)/RCAR (REGULATORY COMPONENT OF ABA RECEPTOR) ABA receptors, the PP2C coreceptors, and the SnRK2 protein kinases constitute the core ABA signaling module responsible for ABA perception and initiation of downstream responses. We recently showed that ABA signaling is modulated by light signals, but the underlying molecular mechanisms remain largely obscure. In this study, we established a system in yeast cells that was not only successful in reconstituting a complete ABA signaling pathway, from hormone perception to ABA-responsive gene expression, but also suitable for functionally characterizing the regulatory roles of additional factors of ABA signaling. Using this system, we analyzed the roles of several light signaling components, including the red and far-red light photoreceptors phytochrome A (phyA) and phyB, and the photomorphogenic central repressor COP1, in the regulation of ABA signaling. Our results showed that both phyA and phyB negatively regulated ABA signaling, whereas COP1 positively regulated ABA signaling in yeast cells. Further analyses showed that photoactivated phyA interacted with the ABA coreceptors ABI1 and ABI2 to decrease their interactions with the ABA receptor PYR1. Together, data from our reconstituted yeast ABA signaling system provide evidence that photoactivated photoreceptors attenuate ABA signaling by directly interacting with the key components of the core ABA signaling module, thus conferring enhanced ABA tolerance to light-grown plants.
    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
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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