We propose a novel approach to generating optical pulling forces on a gold nanowire, which are placed inside or above a hyperbolic metamaterial and subjected to plane wave illumination. Two ...mechanisms are found to induce the optical pulling force, including the concave isofrequency contour of the hyperbolic metamaterial and the excitation of directional surface plasmon polaritons. We systematically study the optical forces under various conditions, including the wavelength, the angle of incidence of light, and the nanowire radius. It is shown that the optical pulling force enabled by hyperbolic metamaterials is broadband and insensitive to the angle of incidence. The mechanisms and results reported here open a new avenue to manipulating nanoscale objects.
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IJS, KILJ, NUK, PNG, UL, UM
Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the ...Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis. We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
P53 pathway inactivation plays an important role in the process of breast cancer tumorigenesis. Post-translational protein modification abnormalities have been confirmed to be an important mechanism ...underlying inactivation of p53. Numerous deubiquitinating enzymes are aberrantly expressed in breast cancer, and a few deubiquitination enzymes can deubiquitinate and stabilize p53. Here, we report that ovarian tumor (OTU) deubiquitinase 3 (OTUD3) is a deubiquitylase of p53 in breast carcinoma (BC).
Correlations between the mRNA expression levels of OTUD3, TP53 and PTEN and the prognosis of BC were assessed with the Kaplan-Meier Plotter tool. OTUD3 protein expression in 80 pairs of specimens in our cohort was examined by immunohistochemistry and western blotting. The relationship among OTUD3, p53, and p21 proteins was analyzed. Half-life analysis and ubiquitylation assay were performed to elucidate the molecular mechanism by which OTUD3 stabilizes p53. The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments. MTS assay for proliferation detection, detection of apoptosis induced by cisplatin and colony formation assay were employed to investigate the functional effects of OTUD3 on breast cancer cells.
OTUD3 downregulation is correlated with a poor prognosis in BC patients. OTUD3 expression is decreased in breast cancer tissues and not associated with the histological grade. OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs. Reduced OTUD3 expression accompanied by decreased p53 abundance is correlated with human breast cancer progression. Ectopic expression of wild-type OTUD3, but not its catalytically inactive mutant, stabilizes and activates p53. Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region. Finally, OTUD3 protects p53 from murine double minute 2 (Mdm2)-mediated ubiquitination and degradation, enabling the deubiquitination of p53 in BC cells.
In summary, we found that OTUD3 may be a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signaling axis may play a critical role in tumor suppression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A FLAG tag consisting of DYKDDDDK is an epitope tag that is frequently and widely used to detect recombinant proteins of interest. In this study, we performed a CRISPR-based genetic screening to ...identify factors involved in the detection of a FLAG-tagged misfolded model protein at the cell surface. In the screening, SLC35B2, which encodes 3'-phosphoadenosine-5'-phosphosulfate transporter 1, was identified as the candidate gene. The detection of FLAG-tagged misfolded proteins at the cell surface was significantly increased in SLC35B2-knockout cells. Furthermore, protein tyrosine sulfation mediated by tyrosyl-protein sulfotransferase 2 (TPST2) suppressed FLAG-tagged protein detection. Localization analysis of the FLAG-tagged misfolded proteins confirmed that defects in tyrosine sulfation are only responsible for enhancing anti-FLAG staining on the plasma membrane but not inducing the localization change of misfolded proteins on the plasma membrane. These results suggest that a FLAG tag on the misfolded protein would be sulfated, causing a reduced detection by the M2 anti-FLAG antibody. Attention should be required when quantifying the FLAG-tagged proteins in the secretory pathway.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to ...be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.
Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.
We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.
Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Liquid-liquid phase separation (LLPS) plays important roles in forming cellular membraneless organelles. However, how host factors regulate LLPS of viral proteins during negative-sense RNA (NSR) ...virus infection is largely unknown. Here, we used
(BYSMV) as a model to demonstrate regulation of host casein kinase 1 (CK1) in phase separation and infection of NSR viruses. We first found that the BYSMV phosphoprotein (P) formed spherical granules with liquid properties and recruited viral nucleotide (N) and polymerase (L) proteins in vivo. Moreover, the P-formed granules were tethered to the ER/actin network for trafficking and fusion. BYSMV P alone formed droplets and incorporated the N protein and the 5' trailer of genomic RNA in vitro. Interestingly, phase separation of BYSMV P was inhibited by host CK1-dependent phosphorylation of an intrinsically disordered P protein region. Genetic assays demonstrated that the unphosphorylated mutant of BYSMV P exhibited condensed phase, which promoted viroplasm formation and virus replication. Whereas, the phosphorylation-mimic mutant existed in diffuse phase state for virus transcription. Collectively, our results demonstrate that host CK1 modulates phase separation of the viral P protein and virus infection.
The geomagnetically induced current (GIC) produced during extreme geomagnetic storms can easily lead to large‐scale blackouts in China due to the increase in the scale of its electric power grid. A ...power grid's resilience is its capability to resist various natural hazards, withstand primary failures, and quickly resume normal operation. To avoid power grid damages, this study developed a resilient power grid, incorporating failure, power flow calculation and recovery models under a uniform induced geoelectric field. We chose a system's performance loss as the resilience evaluation indicator, which intuitively reflected a system's loss under GIC. In addition, the recovery model was optimized using a genetic algorithm, and two resilience improvement measures were proposed. The IEEE‐RTS‐79 system, consisting of 10 generators, 24 buses and 5 transformers, was chosen as an example to verify the feasibility of this study. The results show that the genetic algorithm and optimization measures effectively enhanced the system's resilience indicator and provided a reference for preventing system damages under GIC and quick recovery after possible failures.
Plain Language Summary
Extreme space weather produces large geomagnetic field disturbances; these disturbances propagate down to Earth, inducing secondary geomagnetically induced currents (GICs) in earthed electric power grids. GICs increase transformers' reactive power loss and raise their temperatures; this affects a power system's normal operation, and in extreme cases causes major blackouts. Therefore, it is vital to study power grids' resilience under GIC events. In this study, we calculated the GIC level using a uniform geoelectrical conductivity model. Based on this, we proposed a resilient power grid model consisting of the failure model, power flow calculation model and recovery model, and evaluated optimization strategies. Our results show that the proposed model can improve a power system's recovery performance after possible failure due to GICs and effectively avoid GIC‐related large‐scale blackouts.
Key Points
We proposed a resilience assessment method for transmission systems under extreme space weather
We calculated a resilience indicator and identified multiple effective methods to improve a system’s resilience
We chose the IEEE‐RTS‐79 system as an example to verify the effectiveness of a genetic algorithm and optimization measures
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Forests play a key role in regulating the global carbon cycle, a substantial portion of which is stored in aboveground biomass (AGB). It is well understood that biodiversity can increase the ...biomass through complementarity and mass‐ratio effects, and the contribution of environmental factors and stand structure attributes to AGB was also observed. However, the relative influence of these factors in determining the AGB of Quercus forests remains poorly understood. Using a large dataset retrieved from 523 permanent forest inventory plots across Northeast China, we examined the effects of integrated multiple tree species diversity components (i.e., species richness, functional, and phylogenetic diversity), functional traits composition, environmental factors (climate and soil), stand age, and structure attributes (stand density, tree size diversity) on AGB based on structural equation models. We found that species richness and phylogenetic diversity both were not correlated with AGB. However, functional diversity positively affected AGB via an indirect effect in line with the complementarity effect. Moreover, the community‐weighted mean of specific leaf area and height increased AGB directly and indirectly, respectively; demonstrating the mass‐ratio effect. Furthermore, stand age, density, and tree size diversity were more important modulators of AGB than biodiversity. Our study highlights that biodiversity–AGB interaction is dependent on the regulation of stand structure that can be even more important for maintaining high biomass than biodiversity in temperate Quercus forests.
This study demonstrates that tree species diversity, functional trait composition, stand age, structure (i.e., stand density and tree size diversity), and environmental factors contribute to the geographic variation in aboveground biomass (AGB) of temperate Quercus forests. We concluded that biodiversity–AGB interaction is dependent on the regulation of stand structure that can be even more important for maintaining high biomass than biodiversity in temperate Quercus forests.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Both water-soluble and insoluble components of ambient particulate matter (PM) have been shown to contribute to the oxidative potential (OP) of PM. In this study, we used the dithiothreitol (DTT) ...assay to assess the water-soluble (OPWS−DTT) and total OP (OPtotal−DTT) of ambient fine particles (PM2.5), with water-insoluble OP (OPWI−DTT) determined by difference. Ambient PM2.5 filter samples were collected daily during 2017 in urban Atlanta and were analyzed for OP and major PM components. Results from measurements suggested a measurable contribution of water-insoluble components to OPDTT, which comprised on average 20% of total PM OP. Strong seasonal trends were observed in both volume- and mass-normalized OPtotal−DTT and OPWI−DTT, with higher values in the winter than in the summer, possibly driven by biomass burning emission seasonality. Correlation analysis indicated that all forms of OPDTT measurements were related to organic species and metals. OPtotal−DTT and OPWI−DTT were correlated with brown carbon (BrC) and total metals, especially total crustal elements. A multivariate regression model was developed for OPtotal−DTT based on particle composition data. The model suggested that the variability of OPtotal−DTT was primarily affected by BrC, followed by EC, total Cu and an antagonistic interaction between BrC and total Cu.
•Water-insoluble PM species contributed ~20% of PM2.5 oxidative potential (OP).•Seasonal trends of water-insoluble and total OP were discernible: winter > summer.•Variability in total OP was primarily driven by brown carbon (BrC).•Water-insoluble OP was associated with BrC and total metals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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