The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal struct...

Applying the method from recently developed fluctuation theorems to the stochastic dynamics of single macromolecules in ambient fluid at constant temperature, we establish two Jarzynski-type equalities: (1) between the log-mean-exponential (LME) of the irreversible heat dissiption of a driven molecule in nonequilibrium steady-state (NESS) and ln P(ness)(x) and (2) between the LME of the work do...

We compiled >200 nuclear export signal (NES)-containing CRM1 cargoes in a database named NESdb. We analyzed the sequences and three-dimensional structures of natural, experimentally identified NESs and of false-positive NESs that were generated from the database in order to identify properties that might distinguish the two groups of sequences. Analyses of amino acid frequencies, sequence logos...

The human norepinephrine transporter (NET) is implicated in many neurological disorders and is a target of tricyclic antidepressants and nisoxetine (NX). We used molecular docking simulations to guide the identification of residues likely to affect substrate transport and ligand interactions at NET. Mutations to alanine identified a hydrophobic pocket in the extracellular cavity of NET, compris...

In the theory of algebraic group actions on affine varieties, the concept of a Kempf– Ness set is used to replace the categorical quotient by the quotient with respect to a maximal compact subgroup. Using recent achievements of “toric topology,” we show that an appropriate notion of a Kempf–Ness set exists for a class of algebraic torus actions on quasiaffine varieties (coordinate subspace arra...

ammalian sex-determining factors with homology to DNA binding proteins are required for splicing, according to a study by Paolo SassoneCorsi and coworkers at the Université Louis Pasteur (Strasbourg, France). Examination of high mobility group (HMG) domain containing SRY and Sox proteins demonstrated a surprising but clear association with splicing complexes. SRY, the testis-determining factor ...

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of t...

The theory of multiresolution decomposition and wavelets is used to study the e ective properties of a thin elastic plate with surface mass density or sti ness heterogeneity, subjected to time-harmonic forcing. The heterogeneity possesses microand macro-scale variations, and has a macroscale outer dimension. It is shown that the microscale mass variation has practically no e ect on the macrosca...

Current methods for measuring sti!ness during human arm movements are either limited to one-joint motions, or lead to systematic errors. The technique presented here enables a simple, accurate and unbiased measurement of endpoint sti!ness during multi-joint movements. Using a computer-controlled mechanical interface, the hand is displaced relative to a prediction of the undisturbed trajectory. ...

We investigate kinetic models of a system in contact with several spatially homogeneous thermal reservoirs at different temperatures. We explicitly find all spatially homogeneous non-equilibrium stationary states (NESS). We then consider the question of whether there are also non spatially uniform NESS. This remains partly open in general, except for a class of models to which we can apply prob...