The toxic natural product tutin causes epileptic seizures in mice by activating calcineurin.

Tutin, an established toxic natural product that causes epilepsy in rodents, is often used as a tool to develop animal model of acute epileptic seizures. However, the molecular target and toxic mechanism of tutin were unclear. In this study, for the first time, we conducted experiments to clarify the targets in tutin-induced epilepsy using thermal proteome profiling. Our studies showed that calcineurin (CN) was a target of tutin, and that tutin activated CN, leading to seizures. Binding site studies further established that tutin bound within the active site of CN catalytic subunit. CN inhibitor and calcineurin A (CNA) knockdown experiments in vivo proved that tutin induced epilepsy by activating CN, and produced obvious nerve damage. Together, these findings revealed that tutin caused epileptic seizures by activating CN. Moreover, further mechanism studies found that N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors and voltage- and Ca2+- activated K+ (BK) channels might be involved in related signaling pathways. Our study fully explains the convulsive mechanism of tutin, which provides new ideas for epilepsy treatment and drug development.

Correction to: 'The effect of alkali-soluble lignin on purified core cellulase and hemicellulase activities during hydrolysis of extractive ammonia-pretreated lignocellulosic biomass'.

[This corrects the article DOI: 10.1098/rsos.171529.].

The effect of alkali-soluble lignin on purified core cellulase and hemicellulase activities during hydrolysis of extractive ammonia-pretreated lignocellulosic biomass.

Removing alkali-soluble lignin using extractive ammonia (EA) pretreatment of corn stover (CS) is known to improve biomass conversion efficiency during enzymatic hydrolysis. In this study, we investigated the effect of alkali-soluble lignin on six purified core glycosyl hydrolases and their enzyme synergies, adopting 31 enzyme combinations derived by a five-component simplex centroid model, during EA-CS hydrolysis. Hydrolysis experiment was carried out using EA-CS(-) (approx. 40% lignin removed during EA pretreatment) and EA-CS(+) (where no lignin was extracted). Enzymatic hydrolysis experiments were done at three different enzyme mass loadings (7.5, 15 and 30 mg protein g-1 glucan), using a previously developed high-throughput microplate-based protocol, and the sugar yields of glucose and xylose were detected. The optimal enzyme combinations (based on % protein mass loading) of six core glycosyl hydrolases for EA-CS(-) and EA-CS(+) were determined that gave high sugar conversion. The inhibition of lignin on optimal enzyme ratios was studied, by adding fixed amount of alkali-soluble lignin fractions to EA-CS(-), and pure Avicel, beechwood xylan and evaluating their sugar conversion. The optimal enzyme ratios that gave higher sugar conversion for EA-CS(-) were CBH I: 27.2-28.2%, CBH II: 18.2-22.2%, EG I: 29.2-34.3%, EX: 9.0-14.1%, ßX: 7.2-10.2%, ßG: 1.0-5.0% (at 7.5-30 mg g-1 protein mass loading). Endoglucanase was inhibited to a greater extent than other core cellulases and xylanases by lignin during enzyme hydrolysis. We also found that alkali-soluble lignin inhibits cellulase more strongly than hemicellulase during the course of enzyme hydrolysis.

Influence of Carbon Nanotube Coatings on Carbon Fiber by Ultrasonically Assisted Electrophoretic Deposition on Its Composite Interfacial Property.

Carbon nanotube (CNT) coatings were utilized to enhance the interfacial properties of carbon fiber (CF)/epoxy(EP) composites by ultrasonically assisted electrophoretic deposition (EPD). A characterization of the CF surface properties was done before and after coating (surface chemistry, surface morphologies, and surface energy). The result shows that oxygenated groups concentrations of the CF surfaces experienced significant increases from 12.11% to 24.78%. Moreover, the uniform and homogeneous CNT films were tightly attached on the surface of CF, and the surface wettability of CF is significant improved by enhanced surface free energy when introduced ultrasonic during the EPD process. In addition, the interlaminar shear strength (ILSS) and water absorption of CF/EP composite were measured. Scanning electron microscopy (SEM) revealed that the fracture mechanisms of the new interface layer formed by depositing CNTs on the CF surface contributed to the enhancement of the mechanical performance of the epoxy. This means that the efficient method to improve interfacial performance of composites has shown great commercial application potential.