77 research outputs found

    The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity

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    Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity

    Influence of the Vertex Region on Spin Dynamics in Artificial Kagome Spin Ice

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    We present experimental and theoretical studies of spin-wave mode dynamics in artificial kagome spin ice vertices made of three identical 15-nm thick elongated Ni80Fe20 nanoislands (macrospins). We consider several possible configurations, from completely disjointed macrospins (full dipolar interelement interactions) to fully jointed macrospins (full dipolar-exchange interactions). Using angular-resolved magnetic field dependent broadband ferromagnetic resonance (FMR), we demonstrate the occurrence of a mode localized in the vertex region as indicated by the distinct behavior of the FMR spectra at different angles and configurations. Theoretical calculations using micromagnetic simulations support the existence, origin, and behavior of this mode by interpreting it as a localized, quasi-uniform Kittel mode. Our findings pave the way for designing the most appropriate network consisting of ferromagnetic nanomagnets for specific application purposes in magnonics

    Mutual Influence Between Macrospin Reversal Order and Spin-Wave Dynamics in Isolated Artificial Spin-Ice Vertices

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    We theoretically and experimentally investigate magnetization reversal and associated spin-wave dynamics of isolated threefold vertices that constitute a Kagome lattice. The three permalloy macrospins making up the vertex have an elliptical cross section and a uniform thickness. We study the dc magnetization curve and the frequency versus field curves (dispersions) of those spin-wave modes that produce the largest response. We also investigate each macrospin reversal from a dynamic perspective, by performing micromagnetic simulations of the reversal processes, and revealing their relationships to the soft-mode profile calculated at the equilibrium state immediately before reversal. The theoretical results are compared with the measured magnetization curves and ferromagnetic resonance spectra. The agreement achieved suggests that a much deeper understanding of magnetization reversal and accompanying hysteresis can be achieved by combining theoretical calculations with static and dynamic magnetization experiments

    Electrically controlled long-distance spin transport through an antiferromagnetic insulator

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    Spintronics uses spins, the intrinsic angular momentum of electrons, as an alternative for the electron charge. Its long-term goal is in the development of beyond-Moore low dissipation technology devices. Recent progress demonstrated the long-distance transport of spin signals across ferromagnetic insulators. Antiferromagnetically ordered materials are however the most common class of magnetic materials with several crucial advantages over ferromagnetic systems. In contrast to the latter, antiferromagnets exhibit no net magnetic moment, which renders them stable and impervious to external fields. In addition, they can be operated at THz frequencies. While fundamentally their properties bode well for spin transport, previous indirect observations indicate that spin transmission through antiferromagnets is limited to short distances of a few nanometers. Here we demonstrate the long-distance, over tens of micrometers, propagation of spin currents through hematite (\alpha-Fe2O3), the most common antiferromagnetic iron oxide, exploiting the spin Hall effect for spin injection. We control the spin current flow by the interfacial spin-bias and by tuning the antiferromagnetic resonance frequency with an external magnetic field. This simple antiferromagnetic insulator is shown to convey spin information parallel to the compensated moment (N\'eel order) over distances exceeding tens of micrometers. This newly-discovered mechanism transports spin as efficiently as the net magnetic moments in the best-suited complex ferromagnets. Our results pave the way to ultra-fast, low-power antiferromagnet-insulator-based spin-logic devices that operate at room temperature and in the absence of magnetic fields

    The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins

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    The highly conserved 5'-3' exonuclease Xrn1 regulates gene expression in eukaryotes by coupling nuclear DNA transcription to cytosolic mRNA decay. By integrating transcriptome-wide analyses of translation with biochemical and functional studies, we demonstrate an unanticipated regulatory role of Xrn1 in protein synthesis. Xrn1 promotes translation of a specific group of transcripts encoding membrane proteins. Xrnl-dependence for translation is linked to poor structural RNA contexts for translation initiation, is mediated by interactions with components of the translation initiation machinery and correlates with an Xrnl-dependence for mRNA localization at the endoplasmic reticulum, the translation compartment of membrane proteins. Importantly, for this group of mRNAs, Xrn1 stimulates transcription, mRNA translation and decay. Our results uncover a crosstalk between the three major stages of gene expression coordinated by Xrn1 to maintain appropriate levels of membrane proteins

    Emergent dynamic chirality in a thermally driven artificial spin ratchet

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    Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells

    Long distance transport of magnon spin information in a magnetic insulator at room temperature

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    The transport of spin information has been studied in various materials, such as metals, semiconductors and graphene. In these materials, spin is transported by diffusion of conduction electrons. Here we study the diffusion and relaxation of spin in a magnetic insulator, where the large bandgap prohibits the motion of electrons. Spin can still be transported, however, through the diffusion of non-equilibrium magnons, the quanta of spin wave excitations in magnetically ordered materials. Here we show experimentally that these magnons can be excited and detected fully electrically in linear response, and can transport spin angular momentum through the magnetic insulator yttrium iron garnet (YIG) over distances as large as 40 micrometer. We identify two transport regimes: the diffusion limited regime for distances shorter than the magnon relaxation length, and the relaxation limited regime for larger distances. With a model similar to the diffusion-relaxation model for electron spin transport in (semi)conducting materials, we extract the magnon relaxation length lambda = 9.4 micrometer in a 200 nm thin YIG film at room temperature

    Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

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    Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.We thank Drs Yingying Li, Feng Gao and Beatrice H. Hahn for providing codon-optimized HIV-1 Gag expression vector, Drs James Hoxie and Susan Zolla-Pazner for supplying anti-Nef and -p24 antibodies, respectively through the NIH AIDS reagent program. We also thank Dr Song Gao for providing SLFN13-tRNA structure information, and Dr Maria-Eugenia Gas Lopez and Dr Ester Gea-Mallorquí for advise. This work was supported by following grants: M.K.I., JSPS Oversea Research Fellowship and Takeda Science Foundation; A.E.C., PT17/0009/0019 (ISCIII/MINECO and FEDER); M.J.B., RTI2018-101082-B-I00 and PID2021-123321OB-I00 [MINECO/FEDER]), and the Miguel Servet program by ISCIII (CP17/00179 and CPII22/00005); C.B., M.R.R., C.D.C., European Union’s Horizon 2020 research and innovation program under grant agreement 681137-EAVI2020 and NIH grant P01-AI131568; J.D., the Spanish Ministry of Science and Innovation (PID2019106959RB-I00/AEI/10.13039/501100011033); A.M., the Spanish Ministry of Science and Innovation (PID2019-106323RB-I00 AEI//10.13039/501100011033) and the institutional “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M).info:eu-repo/semantics/publishedVersio
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