Microstructural evolution of the coexistence for spinodal decomposition and ordering in Fe-23Al alloy during aging

The microstructural evolution of the coexistence ofspinodal decomposition and ordering ischaracterized by metallographic microscopy andtransmission electron microscopy in aged Fe-23Al(i.e. Fe-23at%Al) alloy. This paper discusses aphase transition mechanism of the microstructureevolution. The obtained results indicate that the asquenchedFe-23Al alloys with equiaxed grain sizeof about 500μm comprise two kinds of the orderedphase in nano-scale, i.e., B2-FeAl and DO3-Fe 3Alphases. The average size of B2-FeAl orderingphases is about 15nm, while the size of DO3-Fe 3Alordering phases is extreme fine in the as- quenchedFe-23Al alloys. The as-quenched Fe-23Al alloypresents characteristics of the coexistence ofspinodal decomposition and ordering during thesubsequent age ing at 565°C and 520°C. Thedomain size of B2-FeAl ordered phase rapidlyincreases while the one of DO3-Fe 3Al orderedphase slowly develops with the increase in agingtime/with increased ageing time. A conclusion isreached that the coarsening process of both B2-FeAl and DO3-Fe 3Al ordered phase is controlledby the spinodal decomposition mechanism

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear.Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining.Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10μM and 20 μM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining.Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux

Dietary Stress From Plant Secondary Metabolites Contributes to Grasshopper (Oedaleus asiaticus) Migration or Plague by Regulating Insect Insulin-Like Signaling Pathway

Diets essentially affect the ecological distribution of insects, and may contribute to or even accelerate pest plague outbreaks. The grasshopper, Oedaleus asiaticus B-Bienko (OA), is a persistent pest occurring in northern Asian grasslands. Migration and plague of this grasshopper is tightly related to two specific food plants, Stipa krylovii Roshev and Leymus chinensis (Trin.) Tzvel. However, how these diets regulate and contribute to plague is not clearly understood. Ecological studies have shown that L. chinensis is detrimental to OA growth due to the presence of high secondary metabolites, and that S. krylovii is beneficial because of the low levels of secondary metabolites. Moreover, in field habitats consisting mainly of these two grasses, OA density has negative correlation to high secondary metabolites and a positive correlation to nutrition content for high energy demand. These two grasses act as a ‘push-pull,’ thus enabling the grasshopper plague. Molecular analysis showed that gene expression and protein phosphorylation level of the IGF → FOXO cascade in the insulin-like signaling pathway (ILP) of OA negatively correlated to dietary secondary metabolites. High secondary metabolites in L. chinensis down-regulates the ILP pathway that generally is detrimental to insect survival and growth, and benefits insect detoxification with high energy cost. The changed ILP could explain the poor growth of grasshoppers and fewer distributions in the presence of L. chinensis. Plants can substantially affect grasshopper gene expression, protein function, growth, and ecological distribution. Down-regulation of grasshopper ILP due to diet stress caused by high secondary metabolites containing plants, such as L. chinensis, results in poor grasshopper growth and consequently drives grasshopper migration to preferable diet, such as S. krylovii, thus contributing to grasshopper plague outbreaks

Large manipulative experiments revealed variations of insect abundance and trophic levels in response to the cumulative effects of sheep grazing

This study was supported by the National Natural Science Foundation of China, 31672485, the Earmarked Fund for China Agriculture Research System, CARS-34-07, and the Innovation Project of Chinese Academy of Agricultural Sciences.Livestock grazing can affect insects by altering habitat quality; however, the effects of grazing years and intensities on insect abundance and trophic level during manipulative sheep grazing are not well understood. Therefore, we investigated these effects in a large manipulative experiment from 2014 to 2016 in the eastern Eurasian steppe, China. Insect abundance decreased as sheep grazing intensities increased, with a significant cumulative effect occurring during grazing years. The largest families, Acrididae and Cicadellidae, were susceptible to sheep grazing, but Formicidae was tolerant. Trophic primary and secondary consumer insects were negatively impacted by increased grazing intensities, while secondary consumers were limited by the decreased primary consumers. Poor vegetation conditions caused by heavy sheep grazing were detrimental to the existence of Acrididae, Cicadellidae, primary and secondary consumer insects, but were beneficial to Formicidae. This study revealed variations in insect abundance and trophic level in response to continuous sheep grazing in steppe grasslands. Overall, our results indicate that continuous years of heavy- and over- sheep grazing should be eliminated. Moreover, our findings highlight the importance of more flexible sheep grazing management and will be useful for developing guidelines to optimize livestock production while maintaining species diversity and ecosystem health.Publisher PDFPeer reviewe

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Structural basis of Mcm2–7 replicative helicase loading by ORC–Cdc6 and Cdt1

To start DNA replication, the Origin Recognition Complex (ORC) and Cdc6 load a Mcm2-7 double hexamer onto DNA. Without ATP hydrolysis, ORC-Cdc6 recruits one Cdt1-bound Mcm2-7 hexamer, forming an ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) helicase loading intermediate. Here we report a 3.9Å structure of the OCCM on DNA. Flexible Mcm2-7 winged-helix domains (WHD) engage ORC-Cdc6. A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, nearly half of the hexamer. The Cdt1 C-terminal domain extends to the Mcm6 WHD, which binds Orc4 WHD. DNA passes through the ORC-Cdc6 and Mcm2-7 rings. Origin DNA interaction is mediated by an a-helix in Orc4 and positively charged loops in Orc2 and Cdc6. The Mcm2-7 C-tier AAA+ ring is topologically closed by a Mcm5 loop that embraces Mcm2, but the N-tier ring Mcm2-Mcm5 interface remains open. This structure suggests loading mechanics of the first Cdt1-bound Mcm2-7 hexamer by ORC-Cdc6

Optical bulk-boundary dichotomy in a quantum spin Hall insulator

The bulk-boundary correspondence is a key concept in topological quantum materials. For instance, a quantum spin Hall insulator features a bulk insulating gap with gapless helical boundary states protected by the underlying Z2 topology. However, the bulk-boundary dichotomy and distinction are rarely explored in optical experiments, which can provide unique information about topological charge carriers beyond transport and electronic spectroscopy techniques. Here, we utilize mid-infrared absorption micro-spectroscopy and pump-probe micro-spectroscopy to elucidate the bulk-boundary optical responses of Bi4Br4, a recently discovered room-temperature quantum spin Hall insulator. Benefiting from the low energy of infrared photons and the high spatial resolution, we unambiguously resolve a strong absorption from the boundary states while the bulk absorption is suppressed by its insulating gap. Moreover, the boundary absorption exhibits a strong polarization anisotropy, consistent with the one-dimensional nature of the topological boundary states. Our infrared pump-probe microscopy further measures a substantially increased carrier lifetime for the boundary states, which reaches one nanosecond scale. The nanosecond lifetime is about one to two orders longer than that of most topological materials and can be attributed to the linear dispersion nature of the helical boundary states. Our findings demonstrate the optical bulk-boundary dichotomy in a topological material and provide a proof-of-principal methodology for studying topological optoelectronics.Comment: 26 pages, 4 figure

Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

We designed and synthesized synI, which is ~21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems  </p