22 research outputs found

    Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes

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    The divergence of archaea, bacteria and eukaryotes was a fundamental step in evolution. One marker of this event is a major difference in membrane lipid chemistry between these kingdoms. Whereas the membranes of bacteria and eukaryotes primarily consist of straight fatty acids ester-bonded to glycerol-3-phosphate, archaeal phospholipids consist of isoprenoid chains ether-bonded to glycerol-1-phosphate. Notably, the mechanisms underlying the biosynthesis of these lipids remain elusive. Here, we report the structure of the CDP-archaeol synthase (CarS) of Aeropyrum pernix (ApCarS) in the CTP- and Mg(2+)-bound state at a resolution of 2.4 Å. The enzyme comprises a transmembrane domain with five helices and cytoplasmic loops that together form a large charged cavity providing a binding site for CTP. Identification of the binding location of CTP and Mg(2+) enabled modeling of the specific lipophilic substrate-binding site, which was supported by site-directed mutagenesis, substrate-binding affinity analyses, and enzyme assays. We propose that archaeol binds within two hydrophobic membrane-embedded grooves formed by the flexible transmembrane helix 5 (TM5), together with TM1 and TM4. Collectively, structural comparisons and analyses, combined with functional studies, not only elucidated the mechanism governing the biosynthesis of phospholipids with ether-bonded isoprenoid chains by CTP transferase, but also provided insights into the evolution of this enzyme superfamily from archaea to bacteria and eukaryotes.Cell Research advance online publication 29 September 2017; doi:10.1038/cr.2017.122

    The migration of acetochlor from feed to milk

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    Acetochlor has been widely used globally for its effective weed control, but the dietary intake of associated residues by people has become a major concern nowadays. Milk is regarded as the best solvent to dissolve pesticides due to its fat-rich characteristic. In this study, we aimed to evaluate the transfer of acetochlor from feed to raw milk. Twenty lactating Australian Holstein cows were randomly chosen and divided into 1 control group and 3 treatment groups, feeding acetochlor at the dosages of 0, 0.45, 1.35 and 4.05 g per day during the treatment period. The concentration of acetochlor residues in raw milk was detected by QuEChERS together with a gas chromatography-mass spectrometry (GC-MS) method. The results showed that the highest concentrations of acetochlor residues in raw milk for the three treatment groups had a positive correlation with the dosage levels and the transfer efficiency of the low dose group was only 0.080%, higher than those of the other two groups. Besides, the national estimated daily intake (NEDI) of acetochlor from milk is 1.67 × 10(−5) mg kg(−1), which is 0.08% of the ADI. Overall, we concluded that the risk of acetochlor residues in milk was low, but high-dose acetochlor had a larger impact on milk quality and low-dose acetochlor had potential risks

    Structural and Functional Insights into an Archaeal Lipid Synthase

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    The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation

    Correction:Structural and Functional Insights into an Archaeal Lipid Synthase

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    (Cell Reports 33, 108294-1–9.e1–e4; October 20, 2020) In the originally published version of this article, the supplemental information file containing Figures S1–S7 and Table S1 was inadvertently removed. The complete supplemental information file is now included with the paper online. The production team regrets this error

    Monolithic Fabrication of Metal-Free On-Paper Self-Charging Power Systems

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    Self-charging power systems (SCPSs) are envisioned as promising solutions for emerging electronics to mitigate the increasing global concern about battery waste. However, present SCPSs suffer from large form factors, unscalable fabrication, and material complexity. Herein, a type of highly stable, eco-friendly conductive inks based on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are developed for direct ink writing of multiple components in the SCPSs, including electrodes for miniaturized spacer-free triboelectric nanogenerators (TENGs) and microsupercapacitors (MSCs), and interconnects. The principle of “one ink, multiple functions” enables to almost fully print the entire SCPSs on the same paper substrate in a monolithic manner without post-integration. The monolithic fabrication significantly improves the upscaling capability for manufacturing and reduces the form factor of the entire SCPSs (a small footprint area of ≈2 cm × 3 cm and thickness of ≈1 mm). After pressing/releasing the TENGs for ≈79000 cycles, the 3-cell series-connected MSC array can be charged to 1.6 V while the 6-cell array to 3.0 V. On-paper SCPSs are promising to serve as lightweight, thin, sustainable, and low-cost power supplies.Peer reviewe

    Low-Rank Similarity Metric Learning in High Dimensions

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    Metric learning has become a widespreadly used tool in machine learning. To reduce expensive costs brought in by increasing dimensionality, low-rank metric learning arises as it can be more economical in storage and computation. However, existing low-rank metric learning algorithms usually adopt nonconvex objectives, and are hence sensitive to the choice of a heuristic low-rank basis. In this paper, we propose a novel low-rank metric learning algorithm to yield bilinear similarity functions. This algorithm scales linearly with input dimensionality in both space and time, therefore applicable to high-dimensional data domains. A convex objective free of heuristics is formulated by leveraging trace norm regularization to promote low-rankness. Crucially, we prove that all globally optimal metric solutions must retain a certain low-rank structure, which enables our algorithm to decompose the high-dimensional learning task into two steps: an SVD-based projection and a metric learning problem with reduced dimensionality. The latter step can be tackled efficiently through employing a linearized Alternating Direction Method of Multipliers. The efficacy of the proposed algorithm is demonstrated through experiments performed on four benchmark datasets with tens of thousands of dimensions

    Probe-free label system for rapid detection of Cronobacter genus in powdered infant formula

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    Abstract Cronobacter species previously known as Enterobacter sakazakii poses high risks to neonates and infants. In this work a rapid detection method was developed which combined loop-mediated isothermal amplification with lateral flow assay for detection of Cronobacter species in powdered infant formula. The fast amplification reaction without betaine was established and capable of performing DNA replication within 25 min. Based on the novel probe-free labeling methods, we established a lateral flow assay to capture the specific loop-mediated isothermal amplification amplicons which were labeled with fluorescein isothiocyanate and biotin. And the final detection time of this system was within 40 min. The false positive results of the lateral flow assay induced by primer dimer tagged with fluorescein isothiocyanate and biotin were eliminated by Taq single strand DNA binding protein (4 ng/μL). Simultaneously, the efficiency of the fast loop-mediated isothermal amplification assay was achieved. By injection of Taq SSB into the amplification assay as a replacement for betaine, the novel probe-free method could detect Cronobacter species with high specificity and sensitivity at the detection limit in PIF of 101 cfu/g. Our overall strategy has excellent potential in the rapid diagnosis of Cronobacter species label-free by integrating loop-mediated isothermal amplification and lateral flow assay

    A Novel Fluorescence Aptasensor Based on Magnetic Beads/Gold Nanoparticles/DNA-Stabilized Silver Nanoclusters for Detection of Salmonella Typhimurium

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    Salmonella Typhimurium (S. Typhimurium) is a globally distributed foodborne pathogen, which can lead to outbreaks of foodborne infectious diseases. It is essential to guarantee food safety by timely and correct detection of S. Typhimurium. In this investigation, an original fluorescence aptasensor was constructed to detect S. Typhimurium rapidly and sensitively. Through the coupling of magnetic beads, aptamer, and gold nanoparticles (AuNPs), a fluorescence quenching system with a “sandwich structure” was established. The aptamer acted as a link, and its specific binding to S. Typhimurium could release AuNPs from the system. Meanwhile, fluorescent DNA-stabilized silver nanoclusters (DNA-AgNCs) were synthesized. The fluorescence intensity changes caused by the fluorescence resonance energy transfer between DNA-AgNCs and AuNPs were utilized to detect S. Typhimurium. The purposed aptasensor exhibited high selectivity and sensitivity with a linear response to S. Typhimurium, ranging from 3.7 × 102 to 3.7 × 105 cfu/mL. The limit of detection (LOD) was estimated to be 98 cfu/mL within 2 h 10 min. In addition, this method showed excellent application for detection of S. Typhimurium in artificially contaminated milk, with LOD reaching 3.4 × 102 cfu/mL. Therefore, the developed fluorescence aptasensor has great potential to identify S. Typhimurium in foodstuffs

    Supplemental Material - Using combination of albumin to fibrinogen ratio and prognostic nutritional index model for predicting disease activity in patients with systemic lupus erythematosus

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    Supplemental Material for What Do We Know About people’s Politics? Testing a New Framework for Understanding Different Conceptions of Politics by Hongshuai Zhao, Zikun Huang, Shiqian Wang, Peng Fu, Biqi Fu, Yang Guo, Junming Li, and Qing Luo in Lupus</p
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