An agent-based model for mRNA export through the nuclear pore complex

mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport dynamics, is not known. It is also unclear whether the rate-limiting step for transport occurs at the nuclear basket, in the central channel, or on the cytoplasmic face of the nuclear pore complex. Using previously published biophysical and biochemical parameters of mRNA export, we implemented a three-dimensional, coarse-grained, agent-based model of mRNA export in the nanosecond regime to gain insight into these issues. On running the model, we observed that mRNA export is sensitive to the number and distribution of transport receptors coating the mRNA and that there is a rate-limiting step in the nuclear basket that is potentially associated with the mRNA reconfiguring itself to thread into the central channel. Of note, our results also suggest that using a single location-monitoring mRNA label may be insufficient to correctly capture the time regime of mRNA threading through the pore and subsequent transport. This has implications for future experimental design to study mRNA transport dynamics.     

Grading cartilage damage with diffuse reflectance spectroscopy: Optical markers and mechanical properties

Osteoarthritis (OA) is one of the most common joint diseases worldwide. Unfortunately, clinical methods lack the ability to detect OA in the early stages. Timely detection of the knee joint degradation at the level of tissue changes can prevent its progressive damage. Here, diffuse reflectance spectroscopy (DRS) in the NIR range was used to obtain optical markers of the cartilage damage grades and to assess its mechanical properties. It was observed that the water content obtained by DRS strongly correlates with the cartilage thickness (R = .82) and viscoelastic relaxation time (R = .7). Moreover, the spectral parameters, including water content (OH-band), protein content (CH-band), and scattering parameters allowed for discrimination between the cartilage damage grades (10⁻⁴ < P ≤ 10⁻³). The developed approach may become a valuable addition to arthroscopy, helping to identify lesions at the microscopic level in the early stages of OA and complement the surgical analysis.     

General mean‐field theory for mechanical hysteresis of network‐like macromolecules

In the framework of the mean‐field theory for the order parameter, which characterizes the degree of deviating the structure of a network‐like macromolecule from its natural state under the action of the external force, its mechanical hysteresis is considered. Elastic hysterical properties of a macromolecule are studied as a function of the applied force, temperature and some other parameters controlling the viscous‐elastic behavior of network‐like macromolecules. Proteins 2014; 82:3188–3193. © 2014 Wiley Periodicals, Inc.     

Repeated sequences with unusual properties from the divergent region of Crithidia oncopelti maxicircle kinetoplast DNA

Summary The occurrence of bacterial promoter-like sequences was shown in the divergent region ofCrithidia oncopelti maxicircular kinetoplast DNA. A promoter-cloning vector based on the neomycin phosphotransferase II (NPT II) gene was used to localize promoters in three homologous blocks of repeated sequences. The elements found displayed greater promoter strength inEscherichia coli than the normal promoter of the NPT II gene. Sequences of three promoter-containing inserts from different blocks were determined and typical prokaryotic promoter sequences were localized.     

Synthesis of N-substituted morpholine nucleoside derivatives

Abstract

Herein, we report the synthesis of substituted morpholino nucleoside derivatives starting from ribonucleosides. The present protocol shows high functional group tolerance, uses mild reaction conditions, and gives moderate to good yields. This transformation is based on two sequential pathways: (i) the oxidation of the ribonucleosides to the corresponding dialdehyde using sodium periodate and (ii) the reductive amination of the in situ generated dialdehydes with the hydrochloride salts of various the alkylamines.