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Self-assembly of the microtubule-associated protein tau into neurotoxic oligomers, fibrils, and paired helical filaments, and cell-to-cell spreading of these pathological tau species are critical processes underlying the pathogenesis of Alzheimer's disease and other tauopathies. Modulating the self-assembly process and inhibiting formation and spreading of such toxic species are promising strategies for therapy development. A challenge in investigating tau self-assembly in vitro is that, unlike most amyloidogenic proteins, tau does not aggregate in the absence of posttranslational modifications (PTM), aggregation inducers, or preformed seeds. The most common induction method is addition of polyanions, such as heparin; yet, this artificial system may not represent adequately tau self-assembly in vivo, which is driven by aberrant phosphorylation and other PTMs, potentially leading to in vitro data that do not reflect the behavior of tau and its interaction with modulators in vivo. To tackle these challenges, methods for in vitro phosphorylation of tau to produce aggregation-competent forms recently have been introduced ( Despres et al. ( 2017 ) Proc. Natl. Acad. Sci. U.S.A. , 114 , 9080 - 9085 ). However, the oligomerization, seeding, and interaction with assembly modulators of the different forms of tau have not been studied to date. To address these knowledge gaps, we compared here side-by-side the self-assembly and seeding activity of heparin-induced tau with two forms of in vitro phosphorylated tau and tested how the molecular tweezer CLR01, a negatively charged compound, affected these processes. Tau was phosphorylated by incubation either with activated extracellular signal-regulated kinase 2 or with a whole rat brain extract. Seeding activity was measured using a fluorescence-resonance energy transfer-based biosensor-cell method. We also used solution-state NMR to investigate the binding sites of CLR01 on tau and how they were impacted by phosphorylation. Our systematic structure-activity relationship study demonstrates that heparin-induced tau behaves differently from in vitro phosphorylated tau. The aggregation rates of the different forms are distinct as is the intracellular localization of the induced aggregates, which resemble brain-derived tau strains suggesting that heparin-induced tau and in vitro phosphorylated tau have different conformations, properties, and activities. CLR01 inhibits aggregation and seeding of both heparin-induced and in vitro phosphorylated tau dose-dependently, although heparin induction interferes with the interaction between CLR01 and tau.

Biomass and its derived carbon materials, due to their glorious application value in the field of microwave absorption, have sparked a new round of research boom. Hereinto, platan seeds-derived carbon-based materials (PSC), offspring from direct carbonization of platan seeds, were ulteriorly processed and subjected to high-temperature carbonization treatment to synthesis PSC/Ni/Co composite with diversified morphology and tunable microwave absorption performance. The effect of nickel and cobalt ion concentrations on the absorption performance of composite materials was investigated in depth. The optimum reflection loss value (RLmin) of PSC/Ni can reach −47.36 dB, while its effective absorption broadband (EAB) is 5.8 GHz, ranging from 12–17.8 GHz, covering almost the whole Ku band. Compared with PSC/Ni composites, PSC/Co fulfils greater advantages in thickness and bandwidth. As for PSC/Ni/Co, the sample exhibits the optimal performance when Ni and Co ions are at equal concentrations, with an RLmin of −48.3 dB and an EAB of 5 GHz (13–18 GHz), which congealed the edges of both. Unequivocally, the morphological polymorphism of carbon-based-derived microwave absorbing materials with platan seeds as the carbon source is crucial to harvset lightweight, efficient and adjustable absorption properties, let alone its relatively simple and feasible preparation method. This may provide a new approach for engineering light-weight, cost effective and eco-friendly absorbing materials. [ABSTRACT FROM AUTHOR]

Flipped blended learning (FBL) has become popular in translator training, requiring teachers to adapt their beliefs and attitudes towards blended learning to design and implement professional training programmes. This study investigates the effects of FBL on competence improvement in translation technology education. Using an action research approach with mixed methods, two iterative cycles of planning, acting, observing and reflecting were conducted. Sixty-six postgraduates participated in the programme, and their academic achievements were quantitatively evaluated through pre- and post-tests for computer-aided translation and revision tasks, practical operation tests and online learning statistics. Qualitative data from Q&A sessions, questionnaires and open-ended interviews revealed the students' perceptions of professional development. The results showed the FBL emphasising interaction with peers, context and content, enhances translators' competence. FBL should not be limited to integrating internet, classroom or laboratory settings alone. Extracurricular learning outside campus can also be integral with the support and guidance of off-campus tutors. [ABSTRACT FROM AUTHOR]