The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists ...of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR
)
stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser
504
and Ser
506
. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.
Ag nanoparticles were
in-situ
grown on the surface of MXene nanosheets to prepare thermally conductive hetero-structured MXene@Ag fillers. With polyvinyl alcohol (PVA) as the polymer matrix, ...thermally conductive MXene@Ag/PVA composite films were fabricated by the processes of solution blending, pouring, and evaporative self-assembly. With the same mass fraction, MXene@Ag-III (MXene/Ag, 2:1, w/w) presents more significant improvement in thermal conductivity coefficient (λ) than MXene@Ag, single MXene, Ag, and simply blending MXene/Ag. MXene@Ag-III/PVA composite films show dual functions of excellent thermal conductivity and electromagnetic interference (EMI) shielding. When the mass fraction of MXene@Ag-III is 60 wt.%, the in-plane λ (λ
∥
), through-plane λ (λ
⊥
), and EMI shielding effectiveness (EMI SE) are 3.72 and 0.41 W/(m·K), and 32 dB, which are increased by 3.1, 1.3, and 105.7 times than those of pure PVA film (0.91 and 0.18 W/(m·K), and 0.3 dB), respectively. The 60 wt.% MXene@Ag-III/PVA composite film also has satisfying mechanical and thermal properties, with Young’s modulus, glass transition temperature, and heat resistance index of 3.8 GPa, 58.5 and 175.3 °C, respectively.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•“Line-Plane”-like hetero-structured thermally conductive GO@MWCNTs fillers are prepared by electrostatic self-assembly.•The λ of GO@MWCNTs/PDMS composites contain 20 wt% of GO@MWCNTs ...reaches 2.10 W/(m·K).•Thermally conductive GO@MWCNTs/PDMS composites present good thermal conduction stability.
Graphite oxide (GO) and cetyltrimethylammonium bromide (CTAB) modified multi-walled carbon nanotubes (m-MWCNTs) are utilized to fabricate “Line-Plane”-like hetero-structured thermally conductive GO@MWCNTs fillers by electrostatic self-assembly, which are then introduced into polydimethylsiloxane (PDMS) to fabricate thermally conductive GO@MWCNTs/PDMS composites. When the mass ratio of GO to m-MWCNTs is 2:1, GO@MWCNTs fillers have optimal morphologies and thermal conductivity contribution. When the mass fraction of GO@MWCNTs is 20 wt%, the thermal conductivity coefficient (λ) of GO@MWCNTs/PDMS composites reaches 2.10 W/(m·K), 950% higher than that of pure PDMS (0.20 W/(m·K)), which is also superior to the λ of MWCNTs/PDMS (0.68 W/(m·K)), GO/PDMS (1.59 W/(m·K)) and (GO/MWCNTs)/PDMS (1.28 W/(m·K)) composites with the same amount of single or hybrid thermally conductive fillers. Meantime, the GO@MWCNTs/PDMS composites also present good thermal conduction stability (average λ after 15 heating-cooling cycles in the temperature of 21 to 100°C is 2.14 W/(m·K)) and thermal stability (heat resistance index is 249.3°C).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic ...genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists ...of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-theta (PKC-theta) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-theta to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser.sup.504 and Ser.sup.506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-theta as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.
The objective of this study is to establish an ankylosing spondylitis (AS) thoracolumbar fracture finite element (FE) model and provide a proper posterior fixation choice from the biomechanical ...perspective. The ankylosing spondylitis T9-L5 FE model was built and the range of motion (ROM) was compared to previous studies. The L1 transverse fracture was simulated and was separately fixed by five different patterns. The pull force and yielding force of the screws, the von Mises stress of the internal fixation, and the displacement of fracture site were analyzed to evaluate the proper fixation pattern for thoracolumbar fracture of AS. ROM of AS model was obviously restricted comparing to the normal vertebral experimental data. All the fixation patterns can stabilize the fracture. At least four levels of fixation can reduce the von Mises stress of the internal fixation. Four levels fixation has a higher pull force than the six levels fixation. Skipped level fixation did not reduce the stress, pull force and yielding force. The kyphosis correction did not change the biomechanical load. At least 4 levels fixation was needed for AS thoracolumbar fracture. The cemented screws should be chosen in 4 levels fixation to increase the holding of the screws. The skipped fixation has no advantage. The kyphosis correction can be chosen after weighing the pros and cons.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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