Identification of archaeal proteins that affect the exosome function in vitro

Background  

The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors.     

Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults

We hypothesize that the energy strategy of a cell is a key factor for determining how, or if, the immune system interacts with that cell. Cells have a limited number of metabolic states, in part, depending on the type of fuels the cell consumes. Cellular fuels include glucose (carbohydrates), lipids (fats), and proteins. We propose that the cell's ability to switch to, and efficiently use, fat for fuel confers immune privilege. Additionally, because uncoupling proteins are involved in the fat burning process and reportedly in protection from free radicals, we hypothesize that uncoupling proteins play an important role in immune privilege. Thus, changes in metabolism (caused by oxidative stresses, fuel availability, age, hormones, radiation, or drugs) will dictate and initiate changes in immune recognition and in the nature of the immune response. This has profound implications for controlling the symptoms of autoimmune diseases, for preventing graft rejection, and for targeting tumor cells for destruction.     

Clean demarcation of cartilage tissue 23Na by inversion recovery

Monitoring the sodium concentration in vivo using ²³Na MRI can be an important tool for assessing the onset of tissue disorders. Practical clinical ²³Na MRI methods furthermore often do not allow one to use sufficiently small voxel sizes such that only the tissue of interest is seen, but a large signal contamination can arise from sodium in synovial fluid. Here we demonstrate that applying an inversion recovery (IR) technique allows one to distinctly select either the cartilage-bound or the free sodium for visualization in an image. The results are validated both ex vivo and in vivo.     

Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (−10.4 kcal/mol), poncirin had the highest binding energy (−9.4 kcal/mol) with NF-κB and JNK (−9.5 kcal/mol), respectively, and icariin had the highest binding affinity (−9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin’s greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood–brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.     

The effect of data scaling on dual prices and sensitivity analysis in linear programs

In many practical situations scaling the data is necessary to solve linear programs. This note explores the relationships in translating the sensitivity analysis between the original and the scaled problems.     

Selective detection of ordered sodium signals by a jump-and-return pulse sequence

A simple pulse sequence, derived from the shaped pulse optimally exciting the central transition of a spin 3/2, can be used to selectively detect ordered sodium with a given quadrupolar coupling. The pulse sequence consists of two pulses with opposite phases and separated by a delay, called a quadrupolar jump-and-return (QJR) sequence. This QJR sequence is tested with a phantom made of sodium ions in bacteriophage and in aqueous solution and its feasibility for contrast modification based on the quadrupolar coupling is demonstrated.     

Magic sandwich echo relaxation mapping of anisotropic systems

The main objective of this article was (i) to refocus the residual dipolar and quadrupolar interactions in anisotropic tissues employing magic sandwich echo (MSE) imaging and to compare the results with that of conventional spin-echo (SE) imaging, and (ii) to quantify MSE relaxation and dispersion characteristics in bovine Achilles tendon and compare with spin-lattice relaxation time constant in the rotating frame (T(1rho)). Magic sandwich echo weighted images are approximately 75-100% higher in signal-to-noise ratio than the corresponding T(2)-weighted images. Magic sandwich echo relaxation times varied from 13+/-2 to 19+/-3 ms (mean+/-S.D.), depending upon the structural location of tendon. T(2) relaxation times only varied from 4+/-1 to 10+/-3 ms (mean+/-S.D.) on the same corresponding locations. Magic sandwich echo provides approximately 100% enhancement in relaxation times compared to T(2). Preliminary results based on bovine Achilles tendon and cartilage specimens suggest that the MSE technique has potential for refocusing residual dipolar as well as quadrupolar interactions in anisotropic systems and yields higher intensities than conventional SE imaging as well as T(1rho)-encoded imaging, especially at low-burst pulse amplitudes (250 and 500 Hz).     

Compressed sensing sodium MRI of cartilage at 7T: preliminary study

Sodium MRI has been shown to be highly specific for glycosaminoglycan (GAG) content in articular cartilage, the loss of which is an early sign of osteoarthritis (OA). Quantitative sodium MRI techniques are therefore under development in order to detect and assess early biochemical degradation of cartilage, but due to low sodium NMR sensitivity and its low concentration, sodium images need long acquisition times (15-25 min) even at high magnetic fields and are typically of low resolution. In this preliminary study, we show that compressed sensing can be applied to reduce the acquisition time by a factor of 2 at 7 T without losing sodium quantification accuracy. Alternatively, the nonlinear reconstruction technique can be used to denoise fully-sampled images. We expect to even further reduce this acquisition time by using parallel imaging techniques combined with SNR-improved 3D sequences at 3T and 7 T.