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1.
J Cell Biol ; 223(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38526325

RESUMO

N6, 2'-O-dimethyladenosine (m6Am) is a widespread RNA modification catalyzed by the methyltransferase PCIF1 (phosphorylated CTD interacting factor 1). Despite its prevalence, the biological functions of m6Am in RNA remain largely elusive. Here, we report a critical role of PCIF1-dependent m6Am RNA modification in ciliogenesis in RPE-1 cells. Our findings demonstrate that PCIF1 acts as a negative regulator of ciliation through its m6Am methyltransferase activity. A quantitative proteomic analysis identifies BICD2 as a downstream target of PCIF1, with PCIF1 depletion resulting in a significant increase in BICD2 levels. BICD2 depletion leads to a significant reduction in ciliation. Crucially, the ciliary phenotype in PCIF1-depleted cells is reversed upon BICD2 knockdown. Further investigations reveal that PCIF1 regulates BICD2 protein levels through its m6Am catalytic activity, which reduces the stability and translation efficiency of BICD2 mRNA. Single-base resolution LC-MS analysis identifies the m6Am site on BICD2 mRNA modified by PCIF1. These findings establish the essential involvement of PCIF1-dependent m6Am modification in ciliogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , 60705 , Proteínas Associadas aos Microtúbulos , Proteínas Nucleares , Proteômica , Metiltransferases/genética , RNA , RNA Mensageiro/genética , Humanos , Linhagem Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo
2.
Cell Discov ; 8(1): 25, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277482

RESUMO

Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m1A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m1A modification remains largely unknown. Here we find that the m1A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m1A sites on mRNA of Aurora A, a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3, but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m1A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.

3.
Materials (Basel) ; 15(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35207885

RESUMO

The supercritical carbon dioxide Brayton cycle is a promising power conversion option for green energies, such as solar power and nuclear reactors. The material challenge is a tremendous obstacle for the reliable operation of such a cycle system. A large body of research indicates that high-temperature corrosion of heat-resisting alloys by CO2 results in severe oxidation and, in many cases, concurrent internal carburization. This paper mainly reviews the oxidation behavior, carburization behavior and stress corrosion behavior of heat-resisting alloys in high temperature CO2. Specifically, the main factors affecting the oxidation behavior of heat-resistant alloys, such as environmental parameters, surface condition and gaseous impurity, are discussed. Then, carburization is explored, especially the driving force of carburization and the consequences of carburization. Subsequently, the effects of the environmental parameters, alloy type and different oxide layers on the carburizing behavior are comprehensively reviewed. Finally, the effects of corrosion on the mechanical behavior and stress corrosion cracking behavior of heat-resisting alloys are also summarized. The corrosion performances of heat-resisting alloys in high temperature CO2 are systematically analyzed, and new scopes are proposed for future material research. The information provided in this work is valuable for the development of structural material for the supercritical carbon dioxide Brayton cycle.

4.
Cell Res ; 31(11): 1199-1211, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34480124

RESUMO

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.


Assuntos
Centríolos , Peixe-Zebra , Animais , Autofagia , Cílios , Feminino , Humanos , Proteínas Associadas aos Microtúbulos/genética , Mães
5.
Adv Mater ; 33(39): e2103257, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365697

RESUMO

Superconductors with nontrivial band structure topology represent a class of materials with unconventional and potentially useful properties. Recent years have seen much success in creating artificial hybrid structures exhibiting the main characteristics of 2D topological superconductors. Yet, bulk materials known to combine inherent superconductivity with nontrivial topology remain scarce, largely because distinguishing their central characteristic-the topological surface states-has proved challenging due to a dominant contribution from the superconducting bulk. In this work, a highly anomalous behavior of surface superconductivity in topologically nontrivial 3D superconductor In2 Bi, where the surface states result from its nontrivial band structure, itself a consequence of the non-symmorphic crystal symmetry and strong spin-orbit coupling, is reported. In contrast to smoothly decreasing diamagnetic susceptibility above the bulk critical field, Hc2 , as seen in conventional superconductors, a near-perfect, Meissner-like screening of low-frequency magnetic fields well above Hc2 is observed. The enhanced diamagnetism disappears at a new phase transition close to the critical field of surface superconductivity, Hc3 . Using theoretical modeling, the anomalous screening is shown to be consistent with modification of surface superconductivity by the topological surface states. The possibility of detecting signatures of the surface states using macroscopic magnetization provides a new tool for the discovery and identification of topological superconductors.

6.
FEBS Lett ; 595(10): 1462-1472, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33686659

RESUMO

Centrosomal protein FOR20 has been reported to be crucial for essential cellular processes, including ciliogenesis, cell migration, and cell cycle in vertebrates. However, the function of FOR20 during mammalian embryonic development remains unknown. To investigate the in vivo function of the For20 gene in mammals, we generated For20 homozygous knockout mice by gene targeting. Our data reveal that homozygous knockout of For20 results in significant embryonic growth arrest and lethality during gestation, while the heterozygotes show no obvious defects. The absence of For20 leads to impaired left-right patterning of embryos and reduced cilia in the embryonic node. Deletion of For20 also disrupts angiogenesis in yolk sacs and embryos. These results highlight a critical role of For20 in early mammalian embryogenesis.


Assuntos
Padronização Corporal/genética , Perda do Embrião/genética , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/patologia , Deleção de Genes , Animais , Cílios/patologia , Embrião de Mamíferos/irrigação sanguínea , Desenvolvimento Embrionário , Feminino , Heterozigoto , Homozigoto , Masculino , Camundongos , Camundongos Knockout , Neovascularização Patológica , RNA Mensageiro/genética
7.
Adv Mater ; 33(5): e2004138, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33346397

RESUMO

Higher-order exchange interactions and quantum effects are widely known to play an important role in describing the properties of low-dimensional magnetic compounds. Here, the recently discovered 2D van der Waals (vdW) CrI3 is identified as a quantum non-Heisenberg material with properties far beyond an Ising magnet as initially assumed. It is found that biquadratic exchange interactions are essential to quantitatively describe the magnetism of CrI3 but quantum rescaling corrections are required to reproduce its thermal properties. The quantum nature of the heat bath represented by discrete electron-spin and phonon-spin scattering processes induces the formation of spin fluctuations in the low-temperature regime. These fluctuations induce the formation of metastable magnetic domains evolving into a single macroscopic magnetization or even a monodomain over surface areas of a few micrometers. Such domains display hybrid characteristics of Néel and Bloch types with a narrow domain wall width in the range of 3-5 nm. Similar behavior is expected for the majority of 2D vdW magnets where higher-order exchange interactions are appreciable.

8.
Nat Commun ; 11(1): 3725, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709947

RESUMO

One of the long-sought-after goals in light manipulation is tuning of transmitted interference colours. Previous approaches toward this goal include material chirality, strain and electric-field controls. Alternatively, colour control by magnetic field offers contactless, non-invasive and energy-free advantages but has remained elusive due to feeble magneto-birefringence in conventional transparent media. Here we demonstrate an anomalously large magneto-birefringence effect in transparent suspensions of magnetic two-dimensional crystals, which arises from a combination of a large Cotton-Mouton coefficient and relatively high magnetic saturation birefringence. The effect is orders of magnitude stronger than those previously demonstrated for transparent materials. The transmitted colours of the suspension can be continuously tuned over two-wavelength cycles by moderate magnetic fields below 0.8 T. The work opens a new avenue to tune transmitted colours, and can be further extended to other systems with artificially engineered magnetic birefringence.

9.
Nat Commun ; 9(1): 4058, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30283060

RESUMO

Despite their energy-efficient merits as promising light-weight structural materials, magnesium (Mg) based alloys suffer from inadequate corrosion resistance. One primary reason is that the native surface film on Mg formed in air mainly consists of Mg(OH)2 and MgO, which is porous and unprotective, especially in humid environments. Here, we demonstrate an environmentally benign method to grow a protective film on the surface of Mg/Mg alloy samples at room temperature, via a direct reaction of already-existing surface film with excited CO2. Moreover, for samples that have been corroded obviously on surface, the corrosion products can be converted directly to create a new protective surface. Mechanical tests show that compared with untreated samples, the protective layer can elevate the yield stress, suppress plastic instability and prolong compressive strains without peeling off from the metal surface. This environmentally friendly surface treatment method is promising to protect Mg alloys, including those already-corroded on the surface.

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