Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg
.
In this study, a novel parameter estimation method for permanent magnet synchronous motor (PMSM) of chaotic particle swarm optimization with dynamic self-optimization (DSCPSO) is proposed, where the ...voltage source inverter (VSI) nonlinearity is estimated simultaneously with the parameters to achieve real-time compensation of VSI nonlinearity. In DSCPSO, the tent chaos theory is introduced into the updating of particle swarm algorithm (PSO) populations, inertia weights and learning factors to enhance its ability to explore potentially better regions. Moreover, a memory tempering annealing (MTA) strategy is employed to guarantee particle pluralistic learning, which combines the superior robustness of the simulated annealing algorithm (SA) while enhancing population diversity. Furthermore, to achieve a reasonable tradeoff between exploration and exploitation, a dynamic lens imaging opposition-based learning (DLIOBL) and domain optimization strategy based on evolutionary information is designed, i.e., DLIOBL in the pre-evolutionary stage guarantees the depth of the exploration learning, while the domain optimization strategy is performed in the post-evolutionary stage accelerates the exploitation operation and avoids the problem of slow convergence in the late stages of PSO. The proposed method is applied to the parameter estimation of PMSM and the experimental results show that, the proposed method can track the VSI nonlinearity and variable parameter better than the conventional method under different working conditions.
Water is essential for the formation of granites, but its origin and role in granite generation (i.e., dehydration vs. water‐fluxed melting) remain uncertain. These issues are addressed by combining ...water abundances and other geochemical indices in zircons from Late Mesozoic granites generated during the destruction of the North China Craton (NCC). The water contents in zircons from the NCC Early Cretaceous granites (763 ppm, median) are much higher than those of the NCC Jurassic granites (424–513 ppm), upper mantle and continental arc magmas (92–477 ppm). More importantly, the higher water contents in the voluminous Early Cretaceous granites also have higher zircon saturation temperatures, εHf(t), and lower δ18O values. These observations suggest a predominantly mantle origin for the water, and water‐fluxed crustal melting, in which larger water ingression produced more voluminous melts. The high‐water flux was likely related to the subduction of the Paleo‐Pacific Plate, which ultimately destabilized the NCC.
Plain Language Summary
The fact that water is essential in generating granites has been known for a long time. However, its detailed role is poorly understood due to heterogeneous source and complex melting reactions involved in the generation of granites. As a fundamental issue of granite genesis, it remains a long‐standing problem to distinguish the two major mechanisms, that is, hydrous‐mineral‐dehydration melting versus external‐water‐added melting. In this study, the water content of zircon combined with other lines of clues of I‐type granites that generated during the destruction of North China Craton (NCC) in Late Mesozoic collectively points to water‐added crustal melting rather than dehydration melting. The isotope composition of zircon suggests a mantle provenance of water. The highest water contents occurred in the Early Cretaceous granites, corresponding to the climax of the NCC destruction. Higher zircon water contents in Early Cretaceous granites indicate higher water‐flux into thelithospheric mantle and overlying crust by the subduction of the paleo‐Pacific plate. Accordingly, water played a significant role in cratonic destruction.
Key Points
Water contents of zircons from North China Craton Jurassic granites are comparable with continental arc magmas
Higher zircon water contents are found in voluminous Early Cretaceous granites generated during the climax of cratonic destruction
Early Cretaceous granites were generated by water‐fluxed crustal melting, the water in which has a predominant mantle origin
Plant invasions driven by global environmental changes (e.g. nutrient enrichment) increasingly threaten natural ecosystems. It is unclear whether reducing nitrogen (N) inputs helps to mitigate plant ...invasions in natural ecosystems.
Using ongoing, landscape‐scale N reductions in the Yangtze River, we combined spatiotemporal surveys before and after reducing N inputs and manipulative experiments to explore how N reductions contributed to native community recovery in estuarine marshes degraded by plant invasions.
We found that native Phragmites australis patches gradually recovered in Spartina alterniflora‐invaded marshes after reducing N inputs. The competitive advantage of S. alterniflora over P. australis decreased with N reduction, shifting the competitive outcomes away from P. australis exclusion to their coexistence.
Synthesis and applications. Our findings reveal that the reversal of nitrogen enrichment may shift ecosystems from being more susceptible to invasion toward successional recovery, offering a promising approach for facilitating native community recovery in the invaded ecosystems. These findings have important implications for restoring invaded ecosystems, especially as global environmental change escalates the extent and impact of invaders by exacerbating current invasions and facilitating new ones.
Our findings reveal that the reversal of nitrogen enrichment may shift ecosystems from being more susceptible to invasion toward successional recovery, offering a promising approach for facilitating native community recovery in the invaded ecosystems. These findings have important implications for restoring invaded ecosystems, especially as global environmental change escalates the extent and impact of invaders by exacerbating current invasions and facilitating new ones.
The CRISPR/dCas9 system is a powerful tool to activate the transcription of target genes in eukaryotic or prokaryotic cells, but lacks assays in complex conditions, such as the biosynthesis of ...secondary metabolites.
In this study, to improve the transcription of the heterologously expressed biosynthetic genes for the production of epothilones, we established the CRISPR/dCas9-mediated activation technique in Myxococcus xanthus and analyzed some key factors involving in the CRISPR/dCas9 activation. We firstly optimized the cas9 codon to fit the M. xanthus cells, mutated the gene to inactivate the nuclease activity, and constructed the dCas9-activator system in an epothilone producer. We compared the improvement efficiency of different sgRNAs on the production of epothilones and the expression of the biosynthetic genes. We also compared the improvement effects of different activator proteins, the ω and α subunits of RNA polymerase, and the sigma factors σ54 and CarQ. By using a copper-inducible promoter, we determined that higher expressions of dCas9-activator improved the activation effects.
Our results showed that the CRISPR/dCas-mediated transcription activation is a simple and broadly applicable technique to improve the transcriptional efficiency for the production of secondary metabolites in microorganisms. This is the first time to construct the CRISPR/dCas9 activation system in myxobacteria and the first time to assay the CRISPR/dCas9 activations for the biosynthesis of microbial secondary metabolites.
Abstract
The Olkhon Terrane is thought to preserve a record of the initial collision of the Siberian Craton with its peripheral orogenic system during the early Paleozoic. However, the related ...tectono‐metamorphic process and its time‐scale remain obscure. To address this issue, new structural observations combined with U‐Pb zircon and monazite and
40
Ar/
39
Ar biotite geochronology were conducted in the migmatitic‐granitic Anga‐Sakhurta Zone of the terrane. An earliest syn‐collisional event associated with the development of a c. 500–480 Ma sub‐horizontal migmatitic fabric is confirmed. This early fabric was affected by later extensional doming in association with emplacement of partial melts (in terms of c. 470–445 Ma granite sills) parallel to the sub‐horizontal mechanical anisotropy. Subsequent upright folding leading to amplification of extensional domal structures and heterogeneous vertical transposition of composite horizontal fabric occurred soon after the doming, as indicated by intrusions of residual melts into the axial planes of the upright folds. The latest episode of deformation was marked by development of greenschist‐facies sinistral shear zones surrounding the Anga‐Sakhurta Zone at c. 420–400 Ma. An updated tectonic model involving (a) Middle–Late Ordovician crustal thinning associated with horizontal crustal flow, (b) Silurian crustal shortening related to northwards movement of Cambrian magmatic arc of the Birkhin Complex to the south, and (c) Early Devonian lateral extrusion and sinistral shearing associated with progression of the Birkhin Complex promontory, is proposed. Results from this study shed lights on the collisional evolution of peri‐Siberian orogenic system during the early stage evolution of the Central Asian Orogenic Belt.
Key Points
The Olkhon Terrane underwent Cambrian–Silurian shortening‐extension cycles and Devonian lateral extrusion and shearing
Cambrian to Devonian tectonic switches in the Olkhon Terrane mark the collisional evolution of peri‐Siberian orogenic system
Geodynamic evolution of the Olkhon Terrane closely matches to that of central segment of the Mongolian Collage
Secondary ion mass spectrometry (SIMS) has a wide range of applications in Earth Science research, thanks to its high precision and sensitivity, and its capacity in direct insitu micromeasurement. ...The technique is operated in ultra‐high vacuum (UHV) conditions, especially for the measurement of volatiles such as hydrogen, or the water content in nominally anhydrous minerals (NAMs). To minimize the water background and obtain accurate and precise water contents in NAMs (eg, olivine) critical parameters such as presputtering time, field aperture (FA), dynamic transfer on/off, and primary beam current intensity were investigated for a CAMECA IMS 1280‐HR system. When the chamber vacuum reaches approximately 2 × 10−9 mbar, we set the DTOS OFF, raster size to 50 μm and primary beam current to 5 nA, and used 2000 μm FA and 170‐second presputtering time. Consequently, an approximately 1.2 ppmw water background and 3.6 ppmw limit of detection (LOD) were yielded, from analyzing the San Carlos olivine. Meanwhile, the water content and homogeneity of a range of olivine minerals were characterized for potential use as reference materials for SIMS water content measurement. Olivine water content calibration curve was also established by comparing the Fourier transform infrared (FTIR) results with the SIMS‐measured 16O1H−/16O− ratios. Accuracy and precision of water content measurement were estimated to be better than approximately 10% in this study.
Background
The aim is to evaluate via meta-analysis bone metabolism and bone mineral density (BMD) in morbidly obese patients before and after bariatric surgery.
Methods
We searched Medline, EMBASE, ...and the Cochrane Library for relevant studies published before January 2014. The following outcomes were evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25-hydroxyvitamin D 25(OH)D, serum or urinary N-telopeptide (NTX), bone-specific alkaline phosphatase (BSAP), and bone mineral density (BMD).
Results
Ten studies, including 344 patients, met our inclusion criteria. Results showed a significant decrease in serum calcium (MD = −0.10, 95 %CI −0.14 to −0.07,
P
< 0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31,
P
< 0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI −1.12 to 3.83,
P
= 0.28) following bariatric surgery. There were significant increases in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66,
P
= 0.02) and BSAP (MD = 7.47, 95 %CI 0.21 to 14.72,
P
= 0.04) but a significant decrease in BMD (MD = −0.08, 95 %CI −0.13 to −0.04,
P
< 0.00001) after bariatric surgery.
Conclusion
BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery. Basal bone metabolism should be evaluated preoperatively. To prevent secondary hyperparathyroidism and bone loss, calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.
Zircon water content is an important physicochemical parameter for many geological processes, yet its measurement by the secondary ion mass spectrometry (SIMS) technique is hampered by the lack of ...suitable reference materials and high water background, especially if large-geometry (LG)-SIMS is used. Here we have described a suite of newly developed reference materials for SIMS zircon water content analysis and a modified micro-analytical technique (using a CAMECA IMS 1280-HR SIMS) that can simultaneously measure the zircon water content and oxygen isotopes. A total of 20 natural zircon grains/sherds were analyzed
via
Fourier transform infrared spectroscopy (FTIR), among which 8 (with good water content result reproducibility) were further analyzed by SIMS. Before the SIMS analysis, FTIR analyzed sample blocks were mounted with a Sn-based alloy to minimize degassing and background water. As in routine SIMS oxygen isotope measurement,
16
O
−
and
18
O
−
were collected using two Faraday cups, and in addition
16
O
1
H
−
was simultaneously measured using an electron multiplier. The measured
16
O
1
H/
6
O ratio was converted into water content, using a calibration line established based on SIMS
16
O
1
H
−
/
16
O
−
ratios
vs.
the FTIR water content. Both the internal and external precisions of corrected δ
18
O are <0.4 permil (2SE or 2SD). The internal precision of
16
O
1
H
−
/
16
O
−
ratios follows a Poisson error theoretical trend and is generally better than 0.3%. The external precision (reproducibility) of
16
O
1
H
−
/
16
O
−
ratios is better than 5% (2SD) for homogenous samples, and uncertainty of the calibrated water content is ∼10%.
Zircon water content is an important physicochemical parameter for many geological processes, yet its measurement by the secondary ion mass spectrometry (SIMS) technique is hampered by the lack of suitable reference materials and high water background, especially if large-geometry (LG)-SIMS is used.
A novel parameter estimation method is proposed for the permanent magnet synchronous generator (PMSG), which is implemented by an enhanced self‐learning particle swarm optimization algorithm with ...Levy flight (SLPSO), and the problem of lower parameter estimation precision of standard PSO is obviated. This method injects currents of different intensities into the d‐axis in a time‐sharing manner to solve the problem of equation under‐ranking, and the mathematical model for full‐rank parameter estimation is developed. The speed term of PSO is simplified to expedite the convergence of PSO, and a strategy with chaotic decline for the inertia weight of PSO is adopted to strengthen its ability to jump out of the local optimum. Moreover, the self‐learning dense fleeing strategy (SLDF) is proposed where particles perform diffusion learning based on population density information and Levy flight, the evolutionary unitary problem and human intervention in the evolutionary process is averted. Furthermore, the memory tempering annealing algorithm (MTA) and greedy algorithm (GA) is integrated into the algorithm, MTA can facilitate the exploration of potentially better regions, and GA for local optimization enhances the convergence speed and accuracy in late stage of the algorithm. Comparing the proposed method with several existing PSO algorithms through simulation and experiments, the experimental data show that the proposed method can effectively track variable parameters under different working conditions and has better robustness.
A novel parameter estimation method is proposed for the permanent magnet synchronous generator (PMSG), which is implemented by an enhanced self‐learning particle swarm optimization algorithm with Levy flight (SLPSO), and the problem of lower parameter estimation precision of standard PSO is obviated. This method injects currents of different intensities into the d‐axis in a time‐sharing manner to solve the problem of equation under‐ranking, and the mathematical model for full‐rank parameter estimation is developed. The speed term of PSO is simplified to expedite the convergence of PSO, and a strategy with Chaotic decline for the inertia weight of PSO is adopted to strengthen its ability to jump out of the local optimum.
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