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Different tauopathies are characterized by specific amyloid filament folds that are conserved between patients. Disease-specific tau filament folds probably reflect the specific pathological contexts leading to their formation including isoforms or post-translational modifications. Little is known, however, as to whether and how intrinsic conformational tendencies of the tau sequence itself contribute to its polymorphism. Using cryo-EM structure determination we find that a short amyloidogenic C-terminal peptide consisting of residues 350-362 of the tau repeat domain adopts the same polymorphic conformations in isolation as it does in the context of major disease-associated protofilament folds. Biophysical characterisation and molecular modelling show that the amyloid conformations adopted by this peptide constitute core structural motifs stabilizing distinct disease-associated tau filament folds. In accordance this segment also contributes to the efficient propagation of human AD tau seeds in tau reporter cells while it is irrelevant to heparin-induced recombinant seeds. Our findings suggest that tau 350-362 is key to the propagation of disease-associated tau polymorphs and that the conformational preferences of this segment predispose to the topological diversity observed in tau filament folds.

The rapid appearance of herbicide-resistant weeds combined with a lack of novel herbicides being brought to market reduces crop production, thereby threatening food security worldwide. Here, we report on the use of the previously identified cellulose biosynthesis-inhibiting chemical compound C17 as a potential herbicide. Toxicity tests showed that C17 efficiently inhibits the growth of various weeds and widely cultivated dicotyledonous crops, whereas only slight or no growth inhibition was observed for monocotyledonous crops. Surprisingly, when exposed to a mixture of C17 and one of two well-known cellulose biosynthesis inhibitors (CBIs), isoxaben and indaziflam, an additive growth inhibition was observed, demonstrating that C17 has a different mode of action that can be used to sensitize plants toward known CBIs. Moreover, we demonstrate that a C17-resistant CESA3 allele can be used as a positive transformation selection marker and that C17 resistance can be obtained through genome engineering of the wild-type CESA3 allele using clustered regularly interspaced short palindromic repeats-mediated base editing. This editing system allowed us to engineer C17 tolerance in an isoxaben-resistant line, resulting in double herbicide-resistant plants.

Several applications such as liquid?liquid extraction in micro-fluidic devices are concerned with the flow of two immiscible liquid phases. Two characteristic flow regimes are observed in these systems: the stratified flow and the slug flow. In this work, two phase (liquid?liquid) stratified flows in a rectangular geometry are first analyzed. The influence of physical properties, in particular the viscosity of the two liquids, on the velocity profiles is determined analytically. The flow profiles are classified in the parameter space of physical properties (viscosity ratio) and operating conditions (flow-rate ratio). Viscosity affects the shapes of the velocity profile and the dispersion of a solute in each phase. The question addressed is: can the viscosity of a fluid be exploited to improve extraction efficiency? This would then give us an extra degree of freedom to control and improve extraction efficiency when there can be more than one possible candidate for extractant. The mass transfer behavior in the liquid?liquid system is numerically simulated using both a finite-difference and a finite-volume method. This helps understanding of the role of various operating conditions as pressure drop, flow rate, etc on the behavior of the system. Our analysis can be used to establish guidelines for carrying out experiments. It is found that the effect of the difference in the shape of the flow profiles on mass transfer is not very significant for some modes of operation. The predictions of our model are compared with experimental results from the literature.