15,473 research outputs found
Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)
This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs
A Deterministic Model for One-Dimensional Excluded Flow with Local Interactions
Natural phenomena frequently involve a very large number of interacting
molecules moving in confined regions of space. Cellular transport by motor
proteins is an example of such collective behavior. We derive a deterministic
compartmental model for the unidirectional flow of particles along a
one-dimensional lattice of sites with nearest-neighbor interactions between the
particles. The flow between consecutive sites is governed by a soft simple
exclusion principle and by attracting or repelling forces between neighboring
particles. Using tools from contraction theory, we prove that the model admits
a unique steady-state and that every trajectory converges to this steady-state.
Analysis and simulations of the effect of the attracting and repelling forces
on this steady-state highlight the crucial role that these forces may play in
increasing the steady-state flow, and reveal that this increase stems from the
alleviation of traffic jams along the lattice. Our theoretical analysis
clarifies microscopic aspects of complex multi-particle dynamic processes
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