RhoA is a small GTPase multifunctional protein that regulates cell proliferation and cytoskeletal reorganization. Regulation of its protein stability plays an important role in its biological ...functions. We have shown that a Skp1-Cul1-F-box (SCF) FBXL19 E3 ubiquitin ligase targets Rac1, a related member of the Rho family for ubiquitination and degradation. Here, SCF(FBXL19) mediates RhoA ubiquitination and proteasomal degradation in lung epithelial cells. Ectopically expressed FBXL19 decreased RhoA wild type, active, and inactive forms. Cellular depletion of FBXL19 increased RhoA protein levels and extended its half-life. FBXL19 bound the small GTPase in the cytoplasm leading to RhoA ubiquitination at Lys(135). A RhoA(K135R) mutant protein was resistant to SCF(FBXL19)-mediated ubiquitination and degradation and exhibited a longer lifespan. Protein kinase Erk2-mediated phosphorylation of RhoA was both sufficient and required for SCF(FBXL19)-mediated RhoA ubiquitination and degradation. Thus, SCF(FBXL19) targets RhoA for its disposal, a process regulated by Erk2. Ectopically expressed FBXL19 reduced phosphorylation of p27 and cell proliferation, a process mediated by RhoA. Further, FBXL19 cellular expression diminished lysophosphatidic acid (LPA)-induced phosphorylation of myosin light chain (MLC) and stress fiber formation. Hence, SCF(FBXL19) functions as a RhoA antagonist during cell proliferation and cytoskeleton rearrangement. These results provide the first evidence of an F-box protein targeting RhoA thereby modulating its cellular lifespan that impacts cell proliferation and cytoskeleton rearrangement.
Deca-brominated diphenyl ether (BDE-209) is shown to be persistent in soil and it's urgent to find an effective method to remove BDE-209 from contaminated soil. In this study, the investigation of ...BDE-209 degradation in three different rice-vegetable rotation soils induced by electron beam (E-beam) irradiation under flooded and non-flooded conditions was conducted. The reductive efficiency of 14C-BDE209 reached the highest level at 50 kGy and the values in flooded soils of rice-eggplant rotation soil (RES), rice-peanut soil (RPS), and rice-chili pepper soil (RCS) were 93.5%, 87.2%, and 73.8%, respectively. The reductive efficiencies in non-flooded soils of RES, RPS, and RCS were 73.4%, 81.0%, and 78%, respectively. The D0.5 values (dose required for reducing 50% BDE-209) of BDE-209 in non-flooded soils were lower than those in flooded soils, suggesting greater degradation efficiency of BDE-209 in non-flooded soils than in flooded soils. The BDE-209 was degraded into higher-brominated PBDEs and lower-brominated PBDEs by E-beam irradiation. The results demonstrate that BDE-209 in the soil can be degraded by E-beam irradiation, non-flooded condition is better than flooded condition for the removal of BDE-209, and the main degradation mechanism of BDE-209 by E-beam irradiation is debromination. This study provides a rapid and effective method for degrading BDE-209 that is persistent in soils, and has important implications for the remediation of soil contaminated by PBDEs in and around E-waste dismantling areas.
Display omitted
•Electron beam irradiation can effectively remove BDE-209 in contaminated soil.•E-beam-radiolytic decomposition rate of BDE-209 increases with radiation dose.•Irradiation cannot promote the mineralization of BDE-209 in contaminated soil.•The remediation method is fast, effective, and environmentally friendly.
Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma ...adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) levels are reduced in humans at high altitude and in mice under hypoxia. eENT1 deletion allows rapid accumulation of plasma adenosine to counteract hypoxic tissue damage in mice. Adenosine signalling via erythrocyte ADORA2B induces PKA phosphorylation, ubiquitination and proteasomal degradation of eENT1. Reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice and accounts for erythrocyte hypoxic memory and faster acclimatization. Our findings suggest that targeting identified purinergic-signalling network would enhance the hypoxia adenosine response to counteract hypoxia-induced maladaptation.
Topological insulator/perovskite manganese oxide composites (Bi2Se3/La0.7Sr0.3MnO3) were prepared using the bonded-exfoliated method and the transport properties were studied. The resistivity of the ...bonded manganese oxide substrate was 6 orders of magnitude larger than that of a Bi2Se3 single crystal, implying that the bonded manganese oxide acted as an insulator substrate. The intrinsic resistance peak of the manganese oxide was present in the temperature-dependent resistivity curve. Metal-insulator transition induced by the magnetic field at a low temperature was observed. The simple parallel model cannot account for the electrical properties, as the conducting manganese oxide grains were bonded by polymeric silicone rubber and resistivity peaks were present only when the thickness of the Bi2Se3 layer was less than 1.043 μm. The spin injection may be present in the composite structure.
Leaf litter decomposability is an important effect trait for ecosystem functioning. However, it is unknown how this effect trait evolved through plant history as a leaf ‘afterlife’ integrator of the ...evolution of multiple underlying traits upon which adaptive selection must have acted. Did decomposability evolve in a Brownian fashion without any constraints? Was evolution rapid at first and then slowed? Or was there an underlying mean‐reverting process that makes the evolution of extreme trait values unlikely? Here, we test the hypothesis that the evolution of decomposability has undergone certain mean‐reverting forces due to strong constraints and trade‐offs in the leaf traits that have afterlife effects on litter quality to decomposers. In order to test this, we examined the leaf litter decomposability and seven key leaf traits of 48 tree species in the temperate area of China and fitted them to three evolutionary models: Brownian motion model (BM), Early burst model (EB), and Ornstein‐Uhlenbeck model (OU). The OU model, which does not allow unlimited trait divergence through time, was the best fit model for leaf litter decomposability and all seven leaf traits. These results support the hypothesis that neither decomposability nor the underlying traits has been able to diverge toward progressively extreme values through evolutionary time. These results have reinforced our understanding of the relationships between leaf litter decomposability and leaf traits in an evolutionary perspective and may be a helpful step toward reconstructing deep‐time carbon cycling based on taxonomic composition with more confidence.
It is unknown how leaf litter decomposability, as an important effect trait, changed through plant history as a leaf ‘afterlife’ integrator of the evolution of multiple underlying traits upon which adaptive selection must have acted. We provided experimental evidence that Ornstein‐Uhlenbeck model best describes the evolution of leaf litter decomposability.
Abstract
We report the discovery of a new unidentified extended
γ
-ray source in the Galactic plane named LHAASO J0341+5258 with a pretrial significance of 8.2 standard deviations above 25 TeV. The ...best-fit position is R.A. = 55.°34 ± 0.°11 and decl. = 52.°97 ± 0.°07. The angular size of LHAASO J0341+5258 is 0.°29 ± 0.°06
stat
± 0.°02
sys
. The flux above 25 TeV is about 20% of the flux of the Crab Nebula. Although a power-law fit of the spectrum from 10 to 200 TeV with the photon index
α
= 2.98 ± 0.19
stat
± 0.02
sys
is not excluded, the LHAASO data together with the flux upper limit at 10 GeV set by the Fermi-LAT observation, indicate a noticeable steepening of an initially hard power-law spectrum with a cutoff at ≈50 TeV. We briefly discuss the origin of ultra-high-energy gamma rays. The lack of an energetic pulsar and a young supernova remnant inside or in the vicinity of LHAASO J0341+5258 challenge, but do not exclude, both the leptonic and hadronic scenarios of gamma-ray production.
Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune ...system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.
Display omitted
•High-throughput study of silver nanocrystals integrates robotic automation with machine learning.•Data-driven modeling illustrates the relationship between optical information and ...morphological characteristics.•Experimental database for multi-parameter controllable synthesis and optical properties contains over 1,200 samples.•Scale-up explorations demonstrate the practical feasibility and scalability of established models.•Colorimetric performance exhibits an ultrabroad linear range and high sensitivity in Hg2+ detection.
Colorimetric determination of trace mercury ions (Hg2+) with high reproducibility and sensitivity is urgently required for water safety and environmental monitoring. Herein, an automated robotic platform is described for high-throughput and controllable synthesis of colloidal silver nanocrystals (Ag NCs) and sensitive/selective colorimetric determination of Hg2+ in aqueous solutions. The predicted models of optical simulation are constructed as data-driven models to evaluate the quality of Ag NCs synthesized by a wet-chemical method. Based on an experimental database derived by optical characterization, the machine-learning (ML) model which covers multiple synthesis parameters is established for uniform synthesis of Ag NCs with controllable sizes matching the classical growth model. Moreover, the database of more than 1,200 valid samples established for the optical properties of Ag NCs is digitized to correlate with their average size. Optimized manual re-synthesis of high-quality Ag NCs demonstrates the practical feasibility and scalability of established models. The prepared Ag NCs can be used directly or modified with polymer ligands for quantitative detection of Hg2+ in the linear range from 0.01 to 200 µM with a detection limit of 3 nM. The strategy provides a scientific and effective way for the high-throughput study of nanoscale optical materials in chemical engineering and environmental monitoring.
Background
The exact animal origin of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains obscure and understanding its host range is vital for preventing interspecies transmission.
...Methods
Herein, we applied single‐cell sequencing to multiple tissues of 20 species (30 data sets) and integrated them with public resources (45 data sets covering 26 species) to expand the virus receptor distribution investigation. While the binding affinity between virus and receptor is essential for viral infectivity, understanding the receptor distribution could predict the permissive organs and tissues when infection occurs.
Results
Based on the transcriptomic data, the expression profiles of receptor or associated entry factors for viruses capable of causing respiratory, blood, and brain diseases were described in detail. Conserved cellular connectomes and regulomes were also identified, revealing fundamental cell‐cell and gene‐gene cross‐talks from reptiles to humans.
Conclusions
Overall, our study provides a resource of the single‐cell atlas of the animal kingdom which could help to identify the potential host range and tissue tropism of viruses and reveal the host‐virus co‐evolution.
Single‐cell atlases of organs and PBMCs in 20 species were constructed. The expression patterns of viral receptors from 24 virus families were characterised in different tissues or PBMC samples to generate a conclusive view on the cellular tropism of viruses. An exploration of cellular communication in brain cells within 11 species was conducted.
PDF
