Mohammad Reza Housaindokht

The pathogenic G361A variant of CRAF, associated with increased intrinsic kinase activity in Noonan syndrome (NS), remains poorly understood in terms of its molecular and structural impact on kinase activity. To elucidate the mechanistic implications of the glycine to alanine substitution at residue 361 in CRAF, we employed molecular dynamics simulations. Our findings reveal that this mutation predominantly affects the ATP binding pocket and critical intermolecular interactions within the active cleft that favors the phosphate transfer reaction. Notably, our data highlight significant alterations in key interactions involving Lys470/Asp486 and ATP.Mg²⁺ in CRAF^G361A that are absent in wild‐type CRAF. Additionally, we identified a novel interaction mode between Lys431 and γ‐phosphate in wild‐type CRAF, a residue evolutionarily conserved in CRAFs but not in related kinases such as BRAF, ARAF, and KSR1/2. Furthermore, observed shifts in the αC‐helix and G‐loop relative to the wild‐type correlate with an enlarged ATP‐binding cavity in the mutant, reflecting structural adaptations due to these mutations. Overall, these structural insights underscore the elevated intrinsic kinase activity of the CRAF^G361A variant and provide crucial mechanistic details that could inform the development of specific inhibitors targeting this variant.

Background: Haemagglutinin–neuraminidase (HN) is one of the membrane proteins of Newcastle disease virus (NDV) that plays a significant role during host viral infection. Therefore, antibodies against HN are vital for the host's ability to protect itself against NDV infection due to their critical functions in viral infection. As a result, HN has been a candidate protein in vaccine development against the Newcastle disease virus.Methods: This report used the full‐length sequence of the HN protein of NDV isolated in Iran (VIId subgenotype). We characterize and identify amino acid substitutions in comparison to other more prevalent NDV genotypes, VII subgenotypes and vaccine strains. Furthermore, bioinformatics tools were applied to determine the three‐dimensional structure, molecular dynamics simulation and prediction of B‐cell antigenic epitopes.Results: The results showed that the antigenic regions of our isolate are quite comparable to the other VII subgenotypes of NDV isolated from different geographical places. Moreover, by employing the final 3D structure of our HN protein, the amino acid residues are proposed as a B‐cell epitope by epitope prediction servers, which leads to the introduction of linear and conformational antigenic sites.Conclusions: Immunoinformatic vaccine design principles currently exhibit tremendous potential for developing a new generation of candidate vaccines quickly and economically to eradicate infectious viruses, including the NDV. In order to accomplish this, focus is directed on residues that might be considered antigenic.

A volumetric bar-chart chip (V-chip) is a microfluidic device based on distance-based quantitative measurement that visualizes analyte concentration without the need for apparatus or data processing. This typically utilizes special receptors and catalysis parts that generate oxygen, so ink can be moved inside the channels, and enables instant visual quantitation of the analyte. However, the low stability of some macromolecules, the use of expensive catalysts, and difficulty in controlling the process cause inaccurate readings, and therefore, limit further development and the use of these systems. In this article, we introduced a novel approach that eliminates the use of catalysts in V-chips and provides an efficient and simple path in the design of biosensors. The product of the enzymatic reaction of urease with urea is bicarbonate, which turns into CO₂ gas in an acidic environment. Therefore, the amount of gas produced is proportional to the amount of urea in the sample, and it can be quantitatively measured by visual detection from the amount of ink movement caused by CO₂ gas pressure. This biosensor has a linear response range of 0 to 1000 μg ml⁻¹ and a detection limit of 3.6 μg ml⁻¹ in raw milk. The recovery of urea in raw milk at 100 and 400 μg ml⁻¹ concentrations was 96.5% and 98.9%, respectively. This volumetric chip shows potential for determining urea levels in real samples without requiring additional equipment. The combination of the sensitivity and specificity of enzymatic reactions, inherent gas-generating reactions, and the processability of microchips discussed in this paper can be the basis for the comprehensive development of volumetric chips, which can create a new path for the development of efficient and cheap biosensors.

In this work, the effect of different parameters on catalyst efficiency in the catalytic oxidative desulfurization (ODS) and denitrogenation (ODN) process is studied. A series of samples with different metal compounds, including Ni, Cu, Co, CoNi, CoCu, and CuNi on a reduced graphene oxide (GO) were prepared by an impregnation method. The synthesized samples were carefully characterized by Fourier transform infrared (FTIR), field emission scanning electron microscopy (FESEM), X‐ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET) analysis, and X‐ray powder diffraction (XRD) techniques. The potential of this methodology was illustrated by the oxidation of 84.11% carbazole (CBZ) and 88.36% dibenzothiophene (DBT) in model fuel containing 500 ppmw sulfur and nitrogen. The effect of DBT and CBZ initial concentration and oxidant type on the oxidation process was investigated. The initial concentration of 250 ppmw for DBT and 100 ppmw for CBZ showed more efficiency than other initial concentrations (1,000, 750, 500, 250 ppmw) for DBT and (500, 400, 250, 100 ppmw) for CBZ, and NaClO as an oxidant showed higher performance than H₂O₂, formic acid, and oxygen. The results indicated that the Co‐Cu/rGO catalyst shows higher activity than other prepared catalysts in the oxidation of DBT and CBZ. Moreover, the catalyst could be regenerated three times with no discernible decrease in its catalytic activity. Lastly, the catalytic oxidation of CBZ and DBT was the proposed reaction mechanism.

This study aimed to perform a rational design for molecularly imprinted polymer (MIP) preparation by using pyrrole as the functional monomer for the detection of renal failure biomarkers.