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Paramyxoviruses are negative-polarity RNA viruses of major clinical importance. The dynamic interaction of the RNA-dependent RNA polymerase (RdRP) complex with the encapsidated RNA genome is mechanistically and structurally poorly understood. Having generated recombinant measles (MeV) and canine distemper (CDV) viruses with truncated nucleocapsid (N) protein showing defects in replication kinetics, we have applied a viral evolution approach to the problem. Passaging of recombinants resulted in long-range compensatory mutations that restored RdRP bioactivity in minigenome assays and efficient replication of engineered viruses. Compensatory mutations clustered at an electronically compatible acidic loop in N-core and a basic face of the phosphoprotein X domain (P-XD). Co-affinity precipitations, biolayer interferometry, and molecular docking revealed an electrostatic-driven transiently forming interface between these domains. The compensatory mutations reduced electrostatic compatibility of these microdomains and lowered coprecipitation efficiency, consistent with a molecular checkpoint function that regulates paramyxovirus polymerase mobility through modulation of conformational stability of the P-XD assembly. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)-like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Understanding the conditions for forming new subduction zones at passive continental margins is important for understanding plate tectonics and the Wilson cycle. Previous models of subduction initiation (SI) at passive margins generally ignore effects due to the lateral transition from oceanic to continental lithosphere. Here, we use three-dimensional numerical models to study the possibility of propagating convergent plate margins from preexisting intraoceanic subduction zones along passive margins [subduction propagation (SP)]. Three possible regimes are achieved (i) subducting slab tearing along a STEP fault, (ii) lateral propagation-induced SI at passive margin, and (iii) aborted SI with slab break-off. Passive margin SP requires a significant preexisting lithospheric weakness and a strong slab pull from neighboring subduction zones. The Atlantic passive margin to the north of Lesser Antilles could experience SP if it has a notable lithospheric weakness. In contrast, the Scotia subduction zone in the Southern Atlantic will most likely not propagate laterally. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The layered antiferromagnetic MnBi2Te4 films have been proposed to be an intrinsic quantum anomalous Hall (QAH) insulator with a large gap. It is crucial to open a magnetic gap of surface states. However, recent experiments have observed gapless surface states, indicating the absence of out-of-plane surface magnetism, and thus, the quantized Hall resistance can only be achieved at the magnetic field above 6 T. We propose to induce out-of-plane surface magnetism of MnBi2Te4 films via the magnetic proximity with magnetic insulator CrI3. A strong exchange bias of ∼40 meV originates from the long Cr-eg orbital tails that hybridize strongly with Te p orbitals. By stabilizing surface magnetism, the QAH effect can be realized in the MnBi2Te4/CrI3 heterostructure. Moreover, the high-Chern number QAH state can be achieved by controlling external electric gates. Thus, the MnBi2Te4/CrI3 heterostructure provides a promising platform to realize the electrically tunable zero-field QAH effect. find more Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.