40 results on '"Deng, H."'
Search Results
2. Coherent zero-state and π-state in an exciton-polariton condensate array
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Lai, C. W., Kim, N. Y., Utsunomiya, S., Roumpos, G., Deng, H., Fraser, M. D., Byrnes, T., Recher, P., Kumada, N., Fujisawa, T., and Yamamoto, Y.
- Subjects
Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): C. W. Lai (corresponding author) [1, 2, 3]; N. Y. Kim [1, 2]; S. Utsunomiya [3, 4]; G. Roumpos [1]; H. Deng [1]; M. D. Fraser [1]; T. Byrnes [...]
- Published
- 2007
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3. Chiral kagome superconductivity modulations with residual Fermi arcs.
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Deng H, Qin H, Liu G, Yang T, Fu R, Zhang Z, Wu X, Wang Z, Shi Y, Liu J, Liu H, Yan XY, Song W, Xu X, Zhao Y, Yi M, Xu G, Hohmann H, Holbæk SC, Dürrnagel M, Zhou S, Chang G, Yao Y, Wang Q, Guguchia Z, Neupert T, Thomale R, Fischer MH, and Yin JX
- Abstract
Superconductivity involving finite-momentum pairing
1 can lead to spatial-gap and pair-density modulations, as well as Bogoliubov Fermi states within the superconducting gap. However, the experimental realization of their intertwined relations has been challenging. Here we detect chiral kagome superconductivity modulations with residual Fermi arcs in KV3 Sb5 and CsV3 Sb5 using normal and Josephson scanning tunnelling microscopy down to 30 millikelvin with a resolved electronic energy difference at the microelectronvolt level. We observe a U-shaped superconducting gap with flat residual in-gap states. This gap shows chiral 2a × 2a spatial modulations with magnetic-field-tunable chirality, which align with the chiral 2a × 2a pair-density modulations observed through Josephson tunnelling. These findings demonstrate a chiral pair density wave (PDW) that breaks time-reversal symmetry. Quasiparticle interference imaging of the in-gap zero-energy states reveals segmented arcs, with high-temperature data linking them to parts of the reconstructed vanadium d-orbital states within the charge order. The detected residual Fermi arcs can be explained by the partial suppression of these d-orbital states through an interorbital 2a × 2a PDW and thus serve as candidate Bogoliubov Fermi states. In addition, we differentiate the observed PDW order from impurity-induced gap modulations. Our observations not only uncover a chiral PDW order with orbital selectivity but also show the fundamental space-momentum correspondence inherent in finite-momentum-paired superconductivity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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4. Interchain-expanded extra-large-pore zeolites.
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Gao ZR, Yu H, Chen FJ, Mayoral A, Niu Z, Niu Z, Li X, Deng H, Márquez-Álvarez C, He H, Xu S, Zhou Y, Xu J, Xu H, Fan W, Balestra SRG, Ma C, Hao J, Li J, Wu P, Yu J, and Camblor MA
- Abstract
Stable aluminosilicate zeolites with extra-large pores that are open through rings of more than 12 tetrahedra could be used to process molecules larger than those currently manageable in zeolite materials. However, until very recently
1-3 , they proved elusive. In analogy to the interlayer expansion of layered zeolite precursors4,5 , we report a strategy that yields thermally and hydrothermally stable silicates by expansion of a one-dimensional silicate chain with an intercalated silylating agent that separates and connects the chains. As a result, zeolites with extra-large pores delimited by 20, 16 and 16 Si tetrahedra along the three crystallographic directions are obtained. The as-made interchain-expanded zeolite contains dangling Si-CH3 groups that, by calcination, connect to each other, resulting in a true, fully connected (except possible defects) three-dimensional zeolite framework with a very low density. Additionally, it features triple four-ring units not seen before in any type of zeolite. The silicate expansion-condensation approach we report may be amenable to further extra-large-pore zeolite formation. Ti can be introduced in this zeolite, leading to a catalyst that is active in liquid-phase alkene oxidations involving bulky molecules, which shows promise in the industrially relevant clean production of propylene oxide using cumene hydroperoxide as an oxidant., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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5. Site-specific reactivity of stepped Pt surfaces driven by stress release.
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Liu G, Shih AJ, Deng H, Ojha K, Chen X, Luo M, McCrum IT, Koper MTM, Greeley J, and Zeng Z
- Abstract
Heterogeneous catalysts are widely used to promote chemical reactions. Although it is known that chemical reactions usually happen on catalyst surfaces, only specific surface sites have high catalytic activity. Thus, identifying active sites and maximizing their presence lies at the heart of catalysis research
1-4 , in which the classic model is to categorize active sites in terms of distinct surface motifs, such as terraces and steps1,5-10 . However, such a simple categorization often leads to orders of magnitude errors in catalyst activity predictions and qualitative uncertainties of active sites7,8,11,12 , thus limiting opportunities for catalyst design. Here, using stepped Pt(111) surfaces and the electrochemical oxygen reduction reaction (ORR) as examples, we demonstrate that the root cause of larger errors and uncertainties is a simplified categorization that overlooks atomic site-specific reactivity driven by surface stress release. Specifically, surface stress release at steps introduces inhomogeneous strain fields, with up to 5.5% compression, leading to distinct electronic structures and reactivity for terrace atoms with identical local coordination, and resulting in atomic site-specific enhancement of ORR activity. For the terrace atoms flanking both sides of the step edge, the enhancement is up to 50 times higher than that of the atoms in the middle of the terrace, which permits control of ORR reactivity by either varying terrace widths or controlling external stress. Thus, the discovery of the above synergy provides a new perspective for both fundamental understanding of catalytically active atomic sites and design principles of heterogeneous catalysts., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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6. Moon-forming impactor as a source of Earth's basal mantle anomalies.
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Yuan Q, Li M, Desch SJ, Ko B, Deng H, Garnero EJ, Gabriel TSJ, Kegerreis JA, Miyazaki Y, Eke V, and Asimow PD
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Seismic images of Earth's interior have revealed two continent-sized anomalies with low seismic velocities, known as the large low-velocity provinces (LLVPs), in the lowermost mantle
1 . The LLVPs are often interpreted as intrinsically dense heterogeneities that are compositionally distinct from the surrounding mantle2 . Here we show that LLVPs may represent buried relics of Theia mantle material (TMM) that was preserved in proto-Earth's mantle after the Moon-forming giant impact3 . Our canonical giant-impact simulations show that a fraction of Theia's mantle could have been delivered to proto-Earth's solid lower mantle. We find that TMM is intrinsically 2.0-3.5% denser than proto-Earth's mantle based on models of Theia's mantle and the observed higher FeO content of the Moon. Our mantle convection models show that dense TMM blobs with a size of tens of kilometres after the impact can later sink and accumulate into LLVP-like thermochemical piles atop Earth's core and survive to the present day. The LLVPs may, thus, be a natural consequence of the Moon-forming giant impact. Because giant impacts are common at the end stages of planet accretion, similar mantle heterogeneities caused by impacts may also exist in the interiors of other planetary bodies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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7. Molecular basis of methyl-salicylate-mediated plant airborne defence.
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Gong Q, Wang Y, He L, Huang F, Zhang D, Wang Y, Wei X, Han M, Deng H, Luo L, Cui F, Hong Y, and Liu Y
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- Host Microbial Interactions, Plant Proteins metabolism, Symbiosis, Nicotiana immunology, Nicotiana metabolism, Nicotiana parasitology, Nicotiana virology, Viral Proteins metabolism, Animals, Air, Aphids physiology, Aphids virology, Plant Diseases immunology, Plant Diseases parasitology, Plant Diseases prevention & control, Plant Diseases virology, Plants metabolism, Plants parasitology, Plants virology, Salicylic Acid metabolism, Signal Transduction
- Abstract
Aphids transmit viruses and are destructive crop pests
1 . Plants that have been attacked by aphids release volatile compounds to elicit airborne defence (AD) in neighbouring plants2-5 . However, the mechanism underlying AD is unclear. Here we reveal that methyl-salicylate (MeSA), salicylic acid-binding protein-2 (SABP2), the transcription factor NAC2 and salicylic acid-carboxylmethyltransferase-1 (SAMT1) form a signalling circuit to mediate AD against aphids and viruses. Airborne MeSA is perceived and converted into salicylic acid by SABP2 in neighbouring plants. Salicylic acid then causes a signal transduction cascade to activate the NAC2-SAMT1 module for MeSA biosynthesis to induce plant anti-aphid immunity and reduce virus transmission. To counteract this, some aphid-transmitted viruses encode helicase-containing proteins to suppress AD by interacting with NAC2 to subcellularly relocalize and destabilize NAC2. As a consequence, plants become less repellent to aphids, and more suitable for aphid survival, infestation and viral transmission. Our findings uncover the mechanistic basis of AD and an aphid-virus co-evolutionary mutualism, demonstrating AD as a potential bioinspired strategy to control aphids and viruses., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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8. Generation of genuine entanglement up to 51 superconducting qubits.
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Cao S, Wu B, Chen F, Gong M, Wu Y, Ye Y, Zha C, Qian H, Ying C, Guo S, Zhu Q, Huang HL, Zhao Y, Li S, Wang S, Yu J, Fan D, Wu D, Su H, Deng H, Rong H, Li Y, Zhang K, Chung TH, Liang F, Lin J, Xu Y, Sun L, Guo C, Li N, Huo YH, Peng CZ, Lu CY, Yuan X, Zhu X, and Pan JW
- Abstract
Scalable generation of genuine multipartite entanglement with an increasing number of qubits is important for both fundamental interest and practical use in quantum-information technologies
1,2 . On the one hand, multipartite entanglement shows a strong contradiction between the prediction of quantum mechanics and local realization and can be used for the study of quantum-to-classical transition3,4 . On the other hand, realizing large-scale entanglement is a benchmark for the quality and controllability of the quantum system and is essential for realizing universal quantum computing5-8 . However, scalable generation of genuine multipartite entanglement on a state-of-the-art quantum device can be challenging, requiring accurate quantum gates and efficient verification protocols. Here we show a scalable approach for preparing and verifying intermediate-scale genuine entanglement on a 66-qubit superconducting quantum processor. We used high-fidelity parallel quantum gates and optimized the fidelitites of parallel single- and two-qubit gates to be 99.91% and 99.05%, respectively. With efficient randomized fidelity estimation9 , we realized 51-qubit one-dimensional and 30-qubit two-dimensional cluster states and achieved fidelities of 0.637 ± 0.030 and 0.671 ± 0.006, respectively. On the basis of high-fidelity cluster states, we further show a proof-of-principle realization of measurement-based variational quantum eigensolver10 for perturbed planar codes. Our work provides a feasible approach for preparing and verifying entanglement with a few hundred qubits, enabling medium-scale quantum computing with superconducting quantum systems., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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9. Observation of intrinsic chiral bound states in the continuum.
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Chen Y, Deng H, Sha X, Chen W, Wang R, Chen YH, Wu D, Chu J, Kivshar YS, Xiao S, and Qiu CW
- Abstract
Photons with spin angular momentum possess intrinsic chirality, which underpins many phenomena including nonlinear optics
1 , quantum optics2 , topological photonics3 and chiroptics4 . Intrinsic chirality is weak in natural materials, and recent theoretical proposals5-7 aimed to enlarge circular dichroism by resonant metasurfaces supporting bound states in the continuum that enhance substantially chiral light-matter interactions. Those insightful works resort to three-dimensional sophisticated geometries, which are too challenging to be realized for optical frequencies8 . Therefore, most of the experimental attempts9-11 showing strong circular dichroism rely on false/extrinsic chirality by using either oblique incidence9,10 or structural anisotropy11 . Here we report on the experimental realization of true/intrinsic chiral response with resonant metasurfaces in which the engineered slant geometry breaks both in-plane and out-of-plane symmetries. Our result marks, to our knowledge, the first observation of intrinsic chiral bound states in the continuum with near-unity circular dichroism of 0.93 and a high quality factor exceeding 2,663 for visible frequencies. Our chiral metasurfaces may lead to a plethora of applications in chiral light sources and detectors, chiral sensing, valleytronics and asymmetric photocatalysis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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10. Ferroptosis of tumour neutrophils causes immune suppression in cancer.
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Kim R, Hashimoto A, Markosyan N, Tyurin VA, Tyurina YY, Kar G, Fu S, Sehgal M, Garcia-Gerique L, Kossenkov A, Gebregziabher BA, Tobias JW, Hicks K, Halpin RA, Cvetesic N, Deng H, Donthireddy L, Greenberg A, Nam B, Vonderheide RH, Nefedova Y, Kagan VE, and Gabrilovich DI
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- Humans, Mice, Animals, Tumor Microenvironment, Neoplasms
- Abstract
Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown considerable effectiveness in killing tumour cells in vitro, yet there has been no obvious success in experimental animal models, with the notable exception of immunodeficient mice
1,2 . This suggests that the effect of ferroptosis on immune cells remains poorly understood. Pathologically activated neutrophils (PMNs), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumour immunity3-5 . Here we found that PMN-MDSCs in the tumour microenvironment spontaneously die by ferroptosis. Although decreasing the presence of PMN-MDSCs, ferroptosis induces the release of oxygenated lipids and limits the activity of human and mouse T cells. In immunocompetent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSCs, reduces tumour progression and synergizes with immune checkpoint blockade to suppress the tumour growth. By contrast, induction of ferroptosis in immunocompetent mice promotes tumour growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSCs in the tumour microenvironment that can be pharmacologically modulated to limit tumour progression., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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11. Chemical reprogramming of human somatic cells to pluripotent stem cells.
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Guan J, Wang G, Wang J, Zhang Z, Fu Y, Cheng L, Meng G, Lyu Y, Zhu J, Li Y, Wang Y, Liuyang S, Liu B, Yang Z, He H, Zhong X, Chen Q, Zhang X, Sun S, Lai W, Shi Y, Liu L, Wang L, Li C, Lu S, and Deng H
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- Cell Lineage, Humans, Cell Differentiation, Cellular Reprogramming, Induced Pluripotent Stem Cells cytology
- Abstract
Cellular reprogramming can manipulate the identity of cells to generate the desired cell types
1-3 . The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4-7 . By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8-10 . However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced plasticity13,14 ; it is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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12. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.
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Sun X, Wu B, Chiang HC, Deng H, Zhang X, Xiong W, Liu J, Rozeboom AM, Harris BT, Blommaert E, Gomez A, Garcia RE, Zhou Y, Mitra P, Prevost M, Zhang D, Banik D, Isaacs C, Berry D, Lai C, Chaldekas K, Latham PS, Brantner CA, Popratiloff A, Jin VX, Zhang N, Hu Y, Pujana MA, Curiel TJ, An Z, and Li R
- Subjects
- Animals, Cell Line, Tumor, Discoidin Domain Receptor 1 antagonists & inhibitors, Discoidin Domain Receptor 1 deficiency, Discoidin Domain Receptor 1 genetics, Disease Models, Animal, Extracellular Matrix immunology, Female, Gene Deletion, Gene Knockout Techniques, Humans, Immunocompetence immunology, Immunotherapy, Mice, T-Lymphocytes cytology, T-Lymphocytes immunology, Triple Negative Breast Neoplasms therapy, Collagen metabolism, Discoidin Domain Receptor 1 metabolism, Extracellular Matrix metabolism, Triple Negative Breast Neoplasms immunology, Triple Negative Breast Neoplasms metabolism, Tumor Escape
- Abstract
Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)
1 . The extracellular matrix (ECM) contributes to immune exclusion2 . However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes3,4 . Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity5 , instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellular domain (DDR1-ECD), but not its intracellular kinase domain, is required for immune exclusion. Membrane-untethered DDR1-ECD is sufficient to rescue the growth of Ddr1-knockout tumours in immunocompetent hosts. Mechanistically, the binding of DDR1-ECD to collagen enforces aligned collagen fibres and obstructs immune infiltration. ECD-neutralizing antibodies disrupt collagen fibre alignment, mitigate immune exclusion and inhibit tumour growth in immunocompetent hosts. Together, our findings identify a mechanism for immune exclusion and suggest an immunotherapeutic target for increasing immune accessibility through reconfiguration of the tumour ECM., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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13. Two cGAS-like receptors induce antiviral immunity in Drosophila.
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Holleufer A, Winther KG, Gad HH, Ai X, Chen Y, Li L, Wei Z, Deng H, Liu J, Frederiksen NA, Simonsen B, Andersen LL, Kleigrewe K, Dalskov L, Pichlmair A, Cai H, Imler JL, and Hartmann R
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- Amino Acid Sequence, Animals, Cell Line, Drosophila Proteins metabolism, Drosophila melanogaster metabolism, Drosophila melanogaster virology, Female, Humans, Immunity, Innate genetics, Immunity, Innate immunology, Ligands, Male, Membrane Proteins metabolism, Models, Molecular, NF-kappa B metabolism, Nucleotides, Cyclic metabolism, Nucleotidyltransferases classification, Nucleotidyltransferases deficiency, Nucleotidyltransferases metabolism, RNA, Double-Stranded analysis, RNA, Double-Stranded immunology, RNA, Double-Stranded metabolism, Receptors, Pattern Recognition classification, Receptors, Pattern Recognition deficiency, Receptors, Pattern Recognition immunology, Drosophila melanogaster immunology, Nucleotidyltransferases immunology, Receptors, Pattern Recognition metabolism, Viruses immunology
- Abstract
In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes
1 and eukaryotes2-5 . In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6-8 . Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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14. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants.
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Ku Z, Xie X, Hinton PR, Liu X, Ye X, Muruato AE, Ng DC, Biswas S, Zou J, Liu Y, Pandya D, Menachery VD, Rahman S, Cao YA, Deng H, Xiong W, Carlin KB, Liu J, Su H, Haanes EJ, Keyt BA, Zhang N, Carroll SF, Shi PY, and An Z
- Subjects
- Administration, Intranasal, Angiotensin-Converting Enzyme 2 antagonists & inhibitors, Angiotensin-Converting Enzyme 2 metabolism, Animals, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal genetics, Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacokinetics, Antibodies, Neutralizing administration & dosage, Antibodies, Neutralizing adverse effects, Antibodies, Neutralizing genetics, Antibodies, Neutralizing immunology, Apoptosis Regulatory Proteins chemistry, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins immunology, Apoptosis Regulatory Proteins metabolism, COVID-19 immunology, Dose-Response Relationship, Immunologic, Female, Humans, Immunoglobulin A genetics, Immunoglobulin A immunology, Immunoglobulin G immunology, Immunoglobulin M adverse effects, Immunoglobulin M therapeutic use, Mice, Mice, Inbred BALB C, Protein Engineering, Receptors, Virus antagonists & inhibitors, Receptors, Virus metabolism, SARS-CoV-2 genetics, COVID-19 Drug Treatment, COVID-19 prevention & control, COVID-19 virology, Immunoglobulin M administration & dosage, Immunoglobulin M immunology, SARS-CoV-2 classification, SARS-CoV-2 immunology
- Abstract
Resistance represents a major challenge for antibody-based therapy for COVID-19
1-4 . Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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15. Van der Waals heterostructure polaritons with moiré-induced nonlinearity.
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Zhang L, Wu F, Hou S, Zhang Z, Chou YH, Watanabe K, Taniguchi T, Forrest SR, and Deng H
- Abstract
Controlling matter-light interactions with cavities is of fundamental importance in modern science and technology
1 . This is exemplified in the strong-coupling regime, where matter-light hybrid modes form, with properties that are controllable by optical-wavelength photons2,3 . By contrast, matter excitations on the nanometre scale are harder to access. In two-dimensional van der Waals heterostructures, a tunable moiré lattice potential for electronic excitations may form4 , enabling the generation of correlated electron gases in the lattice potentials5-9 . Excitons confined in moiré lattices have also been reported10,11 , but no cooperative effects have been observed and interactions with light have remained perturbative12-15 . Here, by integrating MoSe2 -WS2 heterobilayers in a microcavity, we establish cooperative coupling between moiré-lattice excitons and microcavity photons up to the temperature of liquid nitrogen, thereby integrating versatile control of both matter and light into one platform. The density dependence of the moiré polaritons reveals strong nonlinearity due to exciton blockade, suppressed exciton energy shift and suppressed excitation-induced dephasing, all of which are consistent with the quantum confined nature of the moiré excitons. Such a moiré polariton system combines strong nonlinearity and microscopic-scale tuning of matter excitations using cavity engineering and long-range light coherence, providing a platform with which to study collective phenomena from tunable arrays of quantum emitters.- Published
- 2021
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16. Publisher Correction: Filling metal-organic framework mesopores with TiO 2 for CO 2 photoreduction.
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Jiang Z, Xu X, Ma Y, Cho HS, Ding D, Wang C, Wu J, Oleynikov P, Jia M, Cheng J, Zhou Y, Terasaki O, Peng T, Zan L, and Deng H
- Published
- 2021
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17. Publisher Correction: A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.
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Yang J, Wang W, Chen Z, Lu S, Yang F, Bi Z, Bao L, Mo F, Li X, Huang Y, Hong W, Yang Y, Zhao Y, Ye F, Lin S, Deng W, Chen H, Lei H, Zhang Z, Luo M, Gao H, Zheng Y, Gong Y, Jiang X, Xu Y, Lv Q, Li D, Wang M, Li F, Wang S, Wang G, Yu P, Qu Y, Yang L, Deng H, Tong A, Li J, Wang Z, Yang J, Shen G, Zhao Z, Li Y, Luo J, Liu H, Yu W, Yang M, Xu J, Wang J, Li H, Wang H, Kuang D, Lin P, Hu Z, Guo W, Cheng W, He Y, Song X, Chen C, Xue Z, Yao S, Chen L, Ma X, Chen S, Gou M, Huang W, Wang Y, Fan C, Tian Z, Shi M, Wang FS, Dai L, Wu M, Li G, Wang G, Peng Y, Qian Z, Huang C, Lau JY, Yang Z, Wei Y, Cen X, Peng X, Qin C, Zhang K, Lu G, and Wei X
- Published
- 2021
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18. Filling metal-organic framework mesopores with TiO 2 for CO 2 photoreduction.
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Jiang Z, Xu X, Ma Y, Cho HS, Ding D, Wang C, Wu J, Oleynikov P, Jia M, Cheng J, Zhou Y, Terasaki O, Peng T, Zan L, and Deng H
- Abstract
Metal-organic frameworks (MOFs)
1-3 are known for their specific interactions with gas molecules4,5 ; this, combined with their rich and ordered porosity, makes them promising candidates for the photocatalytic conversion of gas molecules to useful products6 . However, attempts to use MOFs or MOF-based composites for CO2 photoreduction6-13 usually result in far lower CO2 conversion efficiency than that obtained from state-of-the-art solid-state or molecular catalysts14-18 , even when facilitated by sacrificial reagents. Here we create 'molecular compartments' inside MOF crystals by growing TiO2 inside different pores of a chromium terephthalate-based MOF (MIL-101) and its derivatives. This allows for synergy between the light-absorbing/electron-generating TiO2 units and the catalytic metal clusters in the backbones of MOFs, and therefore facilitates photocatalytic CO2 reduction, concurrent with production of O2 . An apparent quantum efficiency for CO2 photoreduction of 11.3 per cent at a wavelength of 350 nanometres is observed in a composite that consists of 42 per cent TiO2 in a MIL-101 derivative, namely, 42%-TiO2 -in-MIL-101-Cr-NO2 . TiO2 units in one type of compartment in this composite are estimated to be 44 times more active than those in the other type, underlining the role of precise positioning of TiO2 in this system.- Published
- 2020
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19. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.
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Yang J, Wang W, Chen Z, Lu S, Yang F, Bi Z, Bao L, Mo F, Li X, Huang Y, Hong W, Yang Y, Zhao Y, Ye F, Lin S, Deng W, Chen H, Lei H, Zhang Z, Luo M, Gao H, Zheng Y, Gong Y, Jiang X, Xu Y, Lv Q, Li D, Wang M, Li F, Wang S, Wang G, Yu P, Qu Y, Yang L, Deng H, Tong A, Li J, Wang Z, Yang J, Shen G, Zhao Z, Li Y, Luo J, Liu H, Yu W, Yang M, Xu J, Wang J, Li H, Wang H, Kuang D, Lin P, Hu Z, Guo W, Cheng W, He Y, Song X, Chen C, Xue Z, Yao S, Chen L, Ma X, Chen S, Gou M, Huang W, Wang Y, Fan C, Tian Z, Shi M, Wang FS, Dai L, Wu M, Li G, Wang G, Peng Y, Qian Z, Huang C, Lau JY, Yang Z, Wei Y, Cen X, Peng X, Qin C, Zhang K, Lu G, and Wei X
- Subjects
- Animals, Antibodies, Neutralizing immunology, COVID-19, COVID-19 Vaccines, Humans, Macaca mulatta immunology, Macaca mulatta virology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Models, Animal, Models, Molecular, Protein Domains, SARS-CoV-2, Serum immunology, Spleen cytology, Spleen immunology, T-Lymphocytes immunology, Vaccination, Antibodies, Viral immunology, Betacoronavirus immunology, Coronavirus Infections immunology, Coronavirus Infections prevention & control, Pandemics prevention & control, Pneumonia, Viral immunology, Pneumonia, Viral prevention & control, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus immunology, Viral Vaccines immunology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells
1,2 . Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.- Published
- 2020
- Full Text
- View/download PDF
20. Author Correction: H2A.Z facilitates licensing and activation of early replication origins.
- Author
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Long H, Zhang L, Lv M, Wen Z, Zhang W, Chen X, Zhang P, Li T, Chang L, Jin C, Wu G, Wang X, Yang F, Pei J, Chen P, Margueron R, Deng H, Zhu M, and Li G
- Abstract
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
- Full Text
- View/download PDF
21. H2A.Z facilitates licensing and activation of early replication origins.
- Author
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Long H, Zhang L, Lv M, Wen Z, Zhang W, Chen X, Zhang P, Li T, Chang L, Jin C, Wu G, Wang X, Yang F, Pei J, Chen P, Margueron R, Deng H, Zhu M, and Li G
- Subjects
- DNA metabolism, Epigenesis, Genetic, HeLa Cells, Histone-Lysine N-Methyltransferase metabolism, Histones chemistry, Humans, Lysine metabolism, Methylation, Nucleosomes chemistry, Nucleosomes metabolism, Origin Recognition Complex metabolism, DNA Replication genetics, DNA Replication Timing, Histones metabolism, Replication Origin genetics
- Abstract
DNA replication is a tightly regulated process that ensures the precise duplication of the genome during the cell cycle
1 . In eukaryotes, the licensing and activation of replication origins are regulated by both DNA sequence and chromatin features2 . However, the chromatin-based regulatory mechanisms remain largely uncharacterized. Here we show that, in HeLa cells, nucleosomes containing the histone variant H2A.Z are enriched with histone H4 that is dimethylated on its lysine 20 residue (H4K20me2) and with bound origin-recognition complex (ORC). In vitro studies show that H2A.Z-containing nucleosomes bind directly to the histone lysine methyltransferase enzyme SUV420H1, promoting H4K20me2 deposition, which is in turn required for ORC1 binding. Genome-wide studies show that signals from H4K20me2, ORC1 and nascent DNA strands co-localize with H2A.Z, and that depletion of H2A.Z results in decreased H4K20me2, ORC1 and nascent-strand signals throughout the genome. H2A.Z-regulated replication origins have a higher firing efficiency and early replication timing compared with other origins. Our results suggest that the histone variant H2A.Z epigenetically regulates the licensing and activation of early replication origins and maintains replication timing through the SUV420H1-H4K20me2-ORC1 axis.- Published
- 2020
- Full Text
- View/download PDF
22. Interlayer exciton laser of extended spatial coherence in atomically thin heterostructures.
- Author
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Paik EY, Zhang L, Burg GW, Gogna R, Tutuc E, and Deng H
- Abstract
Two-dimensional semiconductors have emerged as a new class of materials for nanophotonics owing to their strong exciton-photon interaction
1,2 and their ability to be engineered and integrated into devices3 . Here we take advantage of these properties to engineer an efficient lasing medium based on direct-bandgap interlayer excitons in rotationally aligned atomically thin heterostructures4 . Lasing is measured from a transition-metal dichalcogenide heterobilayer (WSe2 -MoSe2 ) integrated in a silicon nitride grating resonator. An abrupt increase in the spatial coherence of the emission is observed across the lasing threshold. The work establishes interlayer excitons in two-dimensional heterostructures as a gain medium with spatially coherent lasing emission and potential for heterogeneous integration. With electrically tunable exciton-photon interaction strengths5 and long-range dipolar interactions, these interlayer excitons are promising for application as low-power, ultrafast lasers and modulators and for the study of many-body quantum phenomena6 .- Published
- 2019
- Full Text
- View/download PDF
23. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.
- Author
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Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, Lu Z, Xie J, Churchill H, Xu Y, Zhou Z, Wu G, Yu C, John S, Hirayasu K, Nguyen N, Liu X, Huang F, Li L, Deng H, Tang H, Sadek AH, Zhang L, Huang T, Zou Y, Chen B, Zhu H, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, and Zhang CC
- Subjects
- Animals, Apolipoproteins E metabolism, Arginase metabolism, CD4-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes cytology, Cell Movement, Cell Proliferation, Female, Humans, Immune Tolerance immunology, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute metabolism, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 11 metabolism, Receptors, Cell Surface deficiency, Receptors, Cell Surface genetics, Receptors, Immunologic, Receptors, Urokinase Plasminogen Activator metabolism, Tumor Escape drug effects, Xenograft Model Antitumor Assays, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Receptors, Cell Surface metabolism, Signal Transduction, Tumor Escape immunology
- Abstract
Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia
1 . This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.- Published
- 2018
- Full Text
- View/download PDF
24. Structural basis of ubiquitin modification by the Legionella effector SdeA.
- Author
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Dong Y, Mu Y, Xie Y, Zhang Y, Han Y, Zhou Y, Wang W, Liu Z, Wu M, Wang H, Pan M, Xu N, Xu CQ, Yang M, Fan S, Deng H, Tan T, Liu X, Liu L, Li J, Wang J, Fang X, and Feng Y
- Subjects
- ADP Ribose Transferases chemistry, ADP Ribose Transferases metabolism, Arginine metabolism, Bacterial Proteins, Catalytic Domain, Crystallography, X-Ray, Models, Molecular, Molecular Chaperones metabolism, NAD metabolism, Phosphoric Diester Hydrolases chemistry, Phosphoric Diester Hydrolases metabolism, Protein Processing, Post-Translational, Substrate Specificity, Ubiquitin chemistry, Legionella pneumophila enzymology, Membrane Proteins chemistry, Membrane Proteins metabolism, Ubiquitin metabolism, Ubiquitination
- Abstract
Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl-linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process.
- Published
- 2018
- Full Text
- View/download PDF
25. DWARF14 is a non-canonical hormone receptor for strigolactone.
- Author
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Yao R, Ming Z, Yan L, Li S, Wang F, Ma S, Yu C, Yang M, Chen L, Chen L, Li Y, Yan C, Miao D, Sun Z, Yan J, Sun Y, Wang L, Chu J, Fan S, He W, Deng H, Nan F, Li J, Rao Z, Lou Z, and Xie D
- Subjects
- Allosteric Regulation, Amino Acid Sequence, Carrier Proteins chemistry, Carrier Proteins metabolism, Crystallography, X-Ray, F-Box Proteins chemistry, F-Box Proteins metabolism, Hydrolysis, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Signal Transduction, Arabidopsis chemistry, Arabidopsis Proteins chemistry, Arabidopsis Proteins metabolism, Heterocyclic Compounds, 3-Ring chemistry, Heterocyclic Compounds, 3-Ring metabolism, Lactones chemistry, Lactones metabolism, Plant Growth Regulators chemistry, Plant Growth Regulators metabolism, Receptors, Cell Surface metabolism
- Abstract
Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The α/β hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
- Published
- 2016
- Full Text
- View/download PDF
26. Corrigendum: Failure to replicate the STAP cell phenomenon.
- Author
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De Los Angeles A, Ferrari F, Fujiwara Y, Mathieu R, Lee S, Lee S, Tu HC, Ross S, Chou S, Nguyen M, Wu Z, Theunissen TW, Powell BE, Imsoonthornruksa S, Chen J, Borkent M, Krupalnik V, Lujan E, Wernig M, Hanna JH, Hochedlinger K, Pei D, Jaenisch R, Deng H, Orkin SH, Park PJ, and Daley GQ
- Published
- 2016
- Full Text
- View/download PDF
27. Corrigendum: Hallmarks of pluripotency.
- Author
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De Los Angeles A, Ferrari F, Xi R, Fujiwara Y, Benvenisty N, Deng H, Hochedlinger K, Jaenisch R, Lee S, Leitch HG, Lensch MW, Lujan E, Pei D, Rossant J, Wernig M, Park PJ, and Daley GQ
- Published
- 2016
- Full Text
- View/download PDF
28. Signal integration by Ca(2+) regulates intestinal stem-cell activity.
- Author
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Deng H, Gerencser AA, and Jasper H
- Subjects
- Animals, Cell Proliferation drug effects, Cytosol chemistry, Diet, Drosophila melanogaster drug effects, Drosophila melanogaster metabolism, Glutamic Acid pharmacology, Intestines cytology, Receptors, Metabotropic Glutamate metabolism, Stem Cells metabolism, Calcium metabolism, Drosophila melanogaster cytology, Signal Transduction, Stem Cells cytology
- Abstract
Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify Ca(2+) signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic Ca(2+) oscillations that results in sustained high cytosolic Ca(2+) concentrations. High cytosolic Ca(2+) concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca(2+) oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca(2+) levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue.
- Published
- 2015
- Full Text
- View/download PDF
29. Extra adsorption and adsorbate superlattice formation in metal-organic frameworks.
- Author
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Sung Cho H, Deng H, Miyasaka K, Dong Z, Cho M, Neimark AV, Ku Kang J, Yaghi OM, and Terasaki O
- Abstract
Metal-organic frameworks (MOFs) have a high internal surface area and widely tunable composition, which make them useful for applications involving adsorption, such as hydrogen, methane or carbon dioxide storage. The selectivity and uptake capacity of the adsorption process are determined by interactions involving the adsorbates and their porous host materials. But, although the interactions of adsorbate molecules with the internal MOF surface and also amongst themselves within individual pores have been extensively studied, adsorbate-adsorbate interactions across pore walls have not been explored. Here we show that local strain in the MOF, induced by pore filling, can give rise to collective and long-range adsorbate-adsorbate interactions and the formation of adsorbate superlattices that extend beyond an original MOF unit cell. Specifically, we use in situ small-angle X-ray scattering to track and map the distribution and ordering of adsorbate molecules in five members of the mesoporous MOF-74 series along entire adsorption-desorption isotherms. We find in all cases that the capillary condensation that fills the pores gives rise to the formation of 'extra adsorption domains'-that is, domains spanning several neighbouring pores, which have a higher adsorbate density than non-domain pores. In the case of one MOF, IRMOF-74-V-hex, these domains form a superlattice structure that is difficult to reconcile with the prevailing view of pore-filling as a stochastic process. The visualization of the adsorption process provided by our data, with clear evidence for initial adsorbate aggregation in distinct domains and ordering before an even distribution is finally reached, should help to improve our understanding of this process and may thereby improve our ability to exploit it practically.
- Published
- 2015
- Full Text
- View/download PDF
30. Hallmarks of pluripotency.
- Author
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De Los Angeles A, Ferrari F, Xi R, Fujiwara Y, Benvenisty N, Deng H, Hochedlinger K, Jaenisch R, Lee S, Leitch HG, Lensch MW, Lujan E, Pei D, Rossant J, Wernig M, Park PJ, and Daley GQ
- Subjects
- Animals, Cell Differentiation, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Genomics, Humans, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism
- Abstract
Stem cells self-renew and generate specialized progeny through differentiation, but vary in the range of cells and tissues they generate, a property called developmental potency. Pluripotent stem cells produce all cells of an organism, while multipotent or unipotent stem cells regenerate only specific lineages or tissues. Defining stem-cell potency relies upon functional assays and diagnostic transcriptional, epigenetic and metabolic states. Here we describe functional and molecular hallmarks of pluripotent stem cells, propose a checklist for their evaluation, and illustrate how forensic genomics can validate their provenance.
- Published
- 2015
- Full Text
- View/download PDF
31. Failure to replicate the STAP cell phenomenon.
- Author
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De Los Angeles A, Ferrari F, Fujiwara Y, Mathieu R, Lee S, Lee S, Tu HC, Ross S, Chou S, Nguyen M, Wu Z, Theunissen TW, Powell BE, Imsoonthornruksa S, Chen J, Borkent M, Krupalnik V, Lujan E, Wernig M, Hanna JH, Hochedlinger K, Pei D, Jaenisch R, Deng H, Orkin SH, Park PJ, and Daley GQ
- Subjects
- Animals, Female, Male, Pregnancy, Acids pharmacology, Cell Differentiation, Cellular Reprogramming drug effects, Embryonic Stem Cells cytology, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells drug effects, Placenta cytology, Trophoblasts cytology
- Published
- 2015
- Full Text
- View/download PDF
32. The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1.
- Author
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Han J, Li E, Chen L, Zhang Y, Wei F, Liu J, Deng H, and Wang Y
- Subjects
- Animals, Binding, Competitive, COP-Coated Vesicles chemistry, COP-Coated Vesicles metabolism, Homeostasis, Insulin Resistance, Lipogenesis, Male, Mice, Mice, Obese, Obesity metabolism, Phosphorylation, Protein Processing, Post-Translational, Protein Transport, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Transcription Factors deficiency, Transcription Factors genetics, Vesicular Transport Proteins metabolism, Lipid Metabolism, Liver metabolism, Sterol Regulatory Element Binding Protein 1 metabolism, Transcription Factors metabolism
- Abstract
Abnormal accumulation of triglycerides in the liver, caused in part by increased de novo lipogenesis, results in non-alcoholic fatty liver disease and insulin resistance. Sterol regulatory element-binding protein 1 (SREBP1), an important transcriptional regulator of lipogenesis, is synthesized as an inactive precursor that binds to the endoplasmic reticulum (ER). In response to insulin signalling, SREBP1 is transported from the ER to the Golgi in a COPII-dependent manner, processed by proteases in the Golgi, and then shuttled to the nucleus to induce lipogenic gene expression; however, the mechanisms underlying enhanced SREBP1 activity in insulin-resistant obesity and diabetes remain unclear. Here we show in mice that CREB regulated transcription coactivator 2 (CRTC2) functions as a mediator of mTOR signalling to modulate COPII-dependent SREBP1 processing. CRTC2 competes with Sec23A, a subunit of the COPII complex, to interact with Sec31A, another COPII subunit, thus disrupting SREBP1 transport. During feeding, mTOR phosphorylates CRTC2 and attenuates its inhibitory effect on COPII-dependent SREBP1 maturation. As hepatic overexpression of an mTOR-defective CRTC2 mutant in obese mice improved the lipogenic program and insulin sensitivity, these results demonstrate how the transcriptional coactivator CRTC2 regulates mTOR-mediated lipid homeostasis in the fed state and in obesity.
- Published
- 2015
- Full Text
- View/download PDF
33. Structural basis of ultraviolet-B perception by UVR8.
- Author
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Wu D, Hu Q, Yan Z, Chen W, Yan C, Huang X, Zhang J, Yang P, Deng H, Wang J, Deng X, and Shi Y
- Subjects
- Cations chemistry, Crystallography, X-Ray, Models, Molecular, Protein Conformation radiation effects, Protein Multimerization radiation effects, Tryptophan chemistry, Tryptophan metabolism, Arabidopsis chemistry, Arabidopsis Proteins chemistry, Arabidopsis Proteins radiation effects, Chromosomal Proteins, Non-Histone chemistry, Chromosomal Proteins, Non-Histone radiation effects, Light Signal Transduction radiation effects, Ultraviolet Rays
- Abstract
The Arabidopsis thaliana protein UVR8 is a photoreceptor for ultraviolet-B. Upon ultraviolet-B irradiation, UVR8 undergoes an immediate switch from homodimer to monomer, which triggers a signalling pathway for ultraviolet protection. The mechanism by which UVR8 senses ultraviolet-B remains largely unknown. Here we report the crystal structure of UVR8 at 1.8 Å resolution, revealing a symmetric homodimer of seven-bladed β-propeller that is devoid of any external cofactor as the chromophore. Arginine residues that stabilize the homodimeric interface, principally Arg 286 and Arg 338, make elaborate intramolecular cation-π interactions with surrounding tryptophan amino acids. Two of these tryptophans, Trp 285 and Trp 233, collectively serve as the ultraviolet-B chromophore. Our structural and biochemical analyses identify the molecular mechanism for UVR8-mediated ultraviolet-B perception, in which ultraviolet-B radiation results in destabilization of the intramolecular cation-π interactions, causing disruption of the critical intermolecular hydrogen bonds mediated by Arg 286 and Arg 338 and subsequent dissociation of the UVR8 homodimer.
- Published
- 2012
- Full Text
- View/download PDF
34. Inhibitors selective for mycobacterial versus human proteasomes.
- Author
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Lin G, Li D, de Carvalho LP, Deng H, Tao H, Vogt G, Wu K, Schneider J, Chidawanyika T, Warren JD, Li H, and Nathan C
- Subjects
- Catalytic Domain drug effects, Humans, Hydrogen Bonding, Kinetics, Models, Molecular, Mycobacterium tuberculosis growth & development, Oxazolidinones metabolism, Oxazolidinones pharmacology, Protease Inhibitors chemistry, Proteasome Endopeptidase Complex chemistry, Proteasome Endopeptidase Complex metabolism, Protein Carbonylation drug effects, Protein Conformation drug effects, Protein Subunits, Substrate Specificity, Thiazoles pharmacology, Threonine metabolism, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis enzymology, Protease Inhibitors pharmacology, Proteasome Inhibitors
- Abstract
Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-one compounds kill non-replicating M. tuberculosis and act as selective suicide-substrate inhibitors of the M. tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.
- Published
- 2009
- Full Text
- View/download PDF
35. Ethics: China already has clear stem-cell guidelines.
- Author
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Cheng L, Qiu RZ, Deng H, Zhang YA, Jin Y, and Li L
- Subjects
- China, Federal Government, Humans, Reproductive Techniques, Assisted ethics, Reproductive Techniques, Assisted legislation & jurisprudence, Reproductive Techniques, Assisted standards, Embryo Research ethics, Embryo Research legislation & jurisprudence, Guidelines as Topic, Stem Cells
- Published
- 2006
- Full Text
- View/download PDF
36. Crystal structure and mechanism of a bacterial fluorinating enzyme.
- Author
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Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, and Naismith JH
- Subjects
- Catalysis, Crystallization, Crystallography, X-Ray, Deoxyadenosines chemistry, Deoxyadenosines metabolism, Methionine metabolism, Models, Molecular, Molecular Sequence Data, Pentosyltransferases genetics, Protein Conformation, S-Adenosylmethionine chemistry, S-Adenosylmethionine metabolism, Fluorine metabolism, Pentosyltransferases chemistry, Pentosyltransferases metabolism, Streptomyces enzymology
- Abstract
Fluorine is the thirteenth most abundant element in the earth's crust, but fluoride concentrations in surface water are low and fluorinated metabolites are extremely rare. The fluoride ion is a potent nucleophile in its desolvated state, but is tightly hydrated in water and effectively inert. Low availability and a lack of chemical reactivity have largely excluded fluoride from biochemistry: in particular, fluorine's high redox potential precludes the haloperoxidase-type mechanism used in the metabolic incorporation of chloride and bromide ions. But fluorinated chemicals are growing in industrial importance, with applications in pharmaceuticals, agrochemicals and materials products. Reactive fluorination reagents requiring specialist process technologies are needed in industry and, although biological catalysts for these processes are highly sought after, only one enzyme that can convert fluoride to organic fluorine has been described. Streptomyces cattleya can form carbon-fluorine bonds and must therefore have evolved an enzyme able to overcome the chemical challenges of using aqueous fluoride. Here we report the sequence and three-dimensional structure of the first native fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this organism. Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction.
- Published
- 2004
- Full Text
- View/download PDF
37. Expression cloning of new receptors used by simian and human immunodeficiency viruses.
- Author
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Deng HK, Unutmaz D, KewalRamani VN, and Littman DR
- Subjects
- 3T3 Cells, Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes virology, Cell Line, Chlorocebus aethiops, Cloning, Molecular, Gene Expression, Gene Products, env metabolism, Humans, Macaca, Mice, Molecular Sequence Data, Receptors, CCR5, Receptors, Cytokine genetics, Receptors, Cytokine metabolism, Receptors, HIV genetics, Receptors, Peptide genetics, Sequence Homology, Amino Acid, HIV-1 metabolism, Receptors, G-Protein-Coupled, Receptors, HIV metabolism, Receptors, Peptide metabolism, Simian Immunodeficiency Virus metabolism
- Abstract
Several members of the chemokine-receptor family serve, in conjunction with CD4, as receptors for the entry of human immunodeficiency virus type I (HIV-1) into cells. The principal receptor for entry of macrophage-tropic (M-tropic) HIV-1 strains is CCR5, whereas that for T-cell-line-tropic (T-tropic) strains is CXCR4. Unlike HIV-1, infection with either M-tropic or T-tropic strains of simian immunodeficiency virus (SIV) can be mediated by CCR5, but not CXCR4. SIV strains will also infect CD4+ cells that lack CCR5, which suggests that these strains use as yet unidentified receptors. Here we use an expression-cloning strategy to identify SIV receptors and have isolated genes encoding two members of the seven-transmembrane G-protein-coupled receptor family that are used not only by SIVs, but also by strains of HIV-2 and M-tropic HIV-1. Both receptors are closely related to the chemokine-receptor family and are expressed in lymphoid tissues. One of the receptors is also expressed in colon and may therefore be important in viral transmission. Usage of these new receptors following experimental infection of non-human primates with SIV strains may provide important insight into viral transmission and the mechanisms of SIV- and HIV-induced acquired immune-deficiency syndrome.
- Published
- 1997
- Full Text
- View/download PDF
38. Identification of a major co-receptor for primary isolates of HIV-1.
- Author
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Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, and Landau NR
- Subjects
- 3T3 Cells, Animals, Cell Line, Chemokines metabolism, Chemokines physiology, DNA, Gene Products, env metabolism, HeLa Cells, Humans, Macrophages immunology, Membrane Fusion, Membrane Proteins metabolism, Mice, Molecular Sequence Data, Receptors, CCR5, Receptors, CXCR4, Receptors, Cytokine genetics, Receptors, HIV genetics, Recombinant Proteins metabolism, T-Lymphocytes immunology, T-Lymphocytes virology, Virus Replication, CD4 Antigens metabolism, HIV-1 physiology, Macrophages virology, Receptors, Cytokine metabolism, Receptors, HIV metabolism
- Abstract
Entry of HIV-1 into target cells requires cell-surface CD4 and additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T-cell lines was recently identified and named fusin. However, fusin does not promote entry of macrophage-tropic viruses, which are believed to be the key pathogenic strains in vivo. The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the beta-chemokines RANTES, MIP-1alpha and MIP-1beta.
- Published
- 1996
- Full Text
- View/download PDF
39. Hypothetical SisterKiller.
- Author
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Butcher DL and Deng HW
- Subjects
- Alleles, Models, Genetic, Biological Evolution, Meiosis genetics
- Published
- 1994
- Full Text
- View/download PDF
40. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.
- Author
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Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, and Deng HX
- Subjects
- Amino Acid Sequence, Amyotrophic Lateral Sclerosis enzymology, Animals, Base Sequence, Codon genetics, DNA genetics, Exons, Genome, Human, Humans, Lod Score, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Polymerase Chain Reaction methods, Polymorphism, Genetic, Repetitive Sequences, Nucleic Acid, Sequence Homology, Amino Acid, Amyotrophic Lateral Sclerosis genetics, Isoenzymes genetics, Mutation, Superoxide Dismutase genetics
- Abstract
Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.
- Published
- 1993
- Full Text
- View/download PDF
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