31,297 research outputs found
Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.
HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein
Gene length as a regulator for ribosome recruitment and protein synthesis : theoretical insights
The authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the São Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-délégation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.Peer reviewedPublisher PDFPublisher PD
Bi-Lipschitz geometry of weighted homogeneous surface singularities
We show that a weighted homogeneous complex surface singularity is metrically
conical (i.e., bi-Lipschitz equivalent to a metric cone) only if its two lowest
weights are equal. We also give an example of a pair of weighted homogeneous
complex surface singularities that are topologically equivalent but not
bi-Lipschitz equivalent.Comment: 5 pages. Added result that nonhomogeneous cyclic quotients are not
conica
Bifurcations in the wake of a thick circular disk
Using DNS, we investigate the dynamics in the wake of a circular disk of aspect ratio χ = d/w = 3(where d is the diameter and w the thickness) embedded in a uniform flow of magnitude U0 perpendicular to its symmetry axis. As the Reynolds number Re = U0d/ν is increased, the flow is shown to experience an original series of bifurcations leading to chaos. The range Re ∈ [150, 218] is analysed in detail. In this range, five different non-axisymmetric regimes are successively encountered, including states similar to those previously identified in the flow past a sphere or an infinitely thin disk, as well as a new regime characterised by the presence of two distinct frequencies. A theoretical model based on the theory of mode interaction with symmetries, previously introduced to explain the bifurcations in the flow past a sphere or an infinitely thin disk (Fabre et al. in Phys Fluids 20:051702, 2008), is shown to explain correctly all these results. Higher values of the Reynolds number, up to 270, are also considered. Results indicate that the flow encounters at least four additional bifurcations before reaching a chaotic state
Büchwald-Hartwig reaction applied to synthesis of new luminescent liquid crystal triarylamines derived from isoxazoles
© 2015 Taylor & Francis Group, LLC. The present work describes the synthesis and characterization of novel series of triarylamines isoxazoles (TAA) addressed to the organic photovoltaic materials. Diarylisoxazoles were synthesized by sequential [3+2] 1,3-dipolar cycloaddition reaction between arylnitrile oxides and selected arylalkenes followed by MnO2-oxidation. Isoxazoles were coupled to diarylamines by Büchwald-Hartwig reaction to afford desired compounds 6a-k. Some TAA display liquid-crystalline behaviour and UV-Vis absorption and fluorescence emission were analysed for all samples of TAA 6a-k
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