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  • Hartmann Patrick posted an update 3 days, 10 hours ago

    The abnormal folding and aggregation of amyloid-β protein (Aβ) is the main reason for the occurrence and development of Alzheimer’s disease (AD). The discovery of novel inhibitors against Aβ aggregation is still the current research focus. Herein, we report the inhibitory effect of ulvan, an acidic polysaccharide from green algae of the genus Ulva, against Aβ fibrillation using thioflavin T (ThT) fluorescence and atomic force microscopy (AFM) assays. It is shown that ulvan effectively inhibits Aβ fibrillogenesis in a concentration-dependent manner and actively inhibits the formation of A11-reactive Aβ oligomers, the most toxic Aβ species. The circular dichroism spectrum reveals that ulvan blocks the conformational transition of Aβ40 from the initial random coil to a β-sheet structure, but it only delays the conformational transition of Aβ42. It is also found that ulvan greatly reduces Aβ-induced cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, ulvan effectively downregulates intracellular reactive oxygen species production and protects PC12 cells from the damage caused by Aβ fibrillation. 3-Methyladenine Moreover, ulvan disaggregates preformed mature fibrils into off-pathway oligomers and greatly decreases their associated cytotoxicity, as revealed using ThT fluorescence, AFM, MTT, and dot-blotting assays. The above results not only fully describe the inhibitory effect of ulvan on Aβ fibrillation and its related cytotoxicity but also provide novel ideas for the development of functional food ingredients from seaweed to treat AD.Accumulation of secondary metabolites in the young shoots of tea plants is developmentally modulated, especially flavonoids. Here, we investigate the developmental regulation mechanism of secondary metabolism in the developing leaves of tea plants using an integrated multiomic approach. For the pair of Leaf2/Bud, the correlation coefficient of the fold change of mRNA and RPFs abundances involved in flavonoid biosynthesis was 0.9359, being higher than that of RPFs and protein (R2 = 0.6941). These correlations were higher than the corresponding correlation coefficients for secondary metabolisms and genome-wide scale. Metabolomic analysis demonstrates that the developmental modulations of the structural genes for flavonoid biosynthesis-related pathways align with the concentration changes of catechin and flavonol glycoside groups. Relatively high translational efficiency (TE > 2) was observed in the four flavonoid structural genes (chalcone isomerase, dihydroflavonol 4-reductase, anthocyanidin synthase, and flavonol synthase). In addition, we originally provided the information on identified small open reading frames (small ORFs) and main ORFs in tea leaves and elaborated that the presence of upstream ORFs may have a repressive effect on the translation of downstream ORFs. Our data suggest that transcriptional regulation coordinates with translational regulation and may contribute to the elevation of translational efficiencies for the structural genes involved in the flavonoid biosynthesis pathways during tea leaf development.A variety of chemicals can be produced in a living host cell via optimized and engineered biosynthetic pathways. Despite the successes, pathway engineering remains demanding because of the lack of specific functions or substrates in the host cell, the cell’s sensitivity in vital physiological processes to the heterologous components, or constrained mass transfer across the membrane. In this study, we show that complex multidomain proteins involved in natural compound biosynthesis can be produced from encoding DNA in vitro in a minimal complex PURE system to directly run multistep reactions. Specifically, we synthesize indigoidine and rhabdopeptides with the in vitro produced multidomain nonribosomal peptide synthetases BpsA and KJ12ABC from the organisms Streptomyces lavendulae and Xenorhabdus KJ12.1, respectively. These in vitro produced proteins are analyzed in yield, post-translational modification and in their ability to synthesize the natural compounds, and compared to recombinantly produced proteins. Our study highlights cell-free PURE system as suitable setting for the characterization of biosynthetic gene clusters that can potentially be harnessed for the rapid engineering of biosynthetic pathways.ATP-binding cassette (ABC) transporters constitute one of the largest protein superfamilies, and they mediate the transport of diverse substrates across the membrane. The molecular mechanism for transducing the energy from ATP binding and hydrolysis into the conformational changes remains elusive. Here, we determined the thermodynamics underlying the ATP-induced global conformational switching for the ABC exporter TmrAB using temperature-resolved pulsed electron-electron double resonance (PELDOR or DEER) spectroscopy. We show that a strong entropy-enthalpy compensation mechanism enables the closure of the nucleotide-binding domains (NBDs) over a wide temperature range. This is mechanically coupled with an outward opening of the transmembrane domains (TMDs) accompanied by an entropy gain. The conserved catalytic glutamate plays a key role in the overall energetics. Our results reveal the thermodynamic basis for the chemomechanical energy coupling in an ABC exporter and present a new strategy to explore the energetics of similar membrane protein complexes.High-throughput computational screening of metal organic frameworks (MOFs) enables the discovery of new promising materials for CO2 capture and H2 purification. The number of synthesized MOFs is increasing very rapidly, and computation-ready, experimental MOF databases are being updated. Screening the most recent MOF database is essential to identify the best performing materials among several thousands. In this work, we performed molecular simulations of the most recent MOF database and described both the adsorbent and membrane-based separation performances of 10 221 MOFs for CO2 capture and H2 purification. The best materials identified for pressure swing adsorption, vacuum swing adsorption, and temperature swing adsorption processes outperformed commercial zeolites and previously studied MOFs in terms of CO2 selectivity and adsorbent performance score. We then discussed the applicability of Ideal Adsorbed Solution Theory (IAST), effects of inaccessible local pores and catenation in the frameworks and the presence of impurities in CO2/H2 mixture on the adsorbent performance metrics of MOFs.

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