Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes

Background: Trimethylaminuria (TMAU) is a rare genetic disease characterized by the accumulation of trimethylamine (TMA) and its subsequent excretion trough main body fluids, determining the characteristic fish odour in affected patients. We realized an experimental study to investigate the role of several coding variants in the causative gene FMO3, that were only considered as polymorphic or benign, even if the available literature on them did not functionally explain their ineffectiveness on the encoded enzyme. Methods: Mutational analysis of 26 TMAU patients was realized by Sanger sequencing. Detected variants were, subsequently, deeply statistically and in silico characterized to determine their possible effects on the enzyme activity. To achieve this goal, a docking prediction for TMA/FMO3 and an unbinding pathway study were performed. Finally, a TMAO/TMA urine quantification by 1H-NMR spectroscopy was performed to support modelling results. Results: The FMO3 screening of all patients highlighted the presence of 17 variants distributed in 26 different haplotypes. Both non-sense and missense considered variants might impair the enzymatic kinetics of FMO3, probably reducing the interaction time between the protein catalytic site and TMA, or losing the wild-type binding site. Conclusions: Even if further functional assays will confirm our predictive results, considering the possible role of FMO3 variants with still uncertain effects, might be a relevant step towards the detection of novel scenarios in TMAU etiopathogenesis.     

Vlasov equation with non‐homogeneous boundary conditions

We study the one‐dimensional Vlasov equation in a rod with non‐homogeneous dissipative and conservative boundary conditions. The study is carried out by means of the theory of semigroups and affine operators. Existence, uniqueness and positivity of the solution are proved. The explicit form of the solution is derived and an approximating sequence is given. Copyright © 2000 John Wiley & Sons, Ltd.     

Evaluation by Fourier Transform Infrared Spectroscopy of the different crystalline forms in syndiotactic polystyrene samples

Fourier transform infrared (FTIR) spectra of syndiotactic polystyrene (s-PS) semicrystalline samples have been examined by using the spectral subtraction approach. For the crystalline forms including trans-planar chains (trigonal α and orthorhombic β) a number of conformational and structural order effects, not previously described in the literature, have been identified. A method based on the results of the spectral subtraction analysis has been developed for the determination of the crystallinity degree and compared with the standard method based on the wide-angle X-ray diffraction patterns. The spectral subtraction analysis on FTIR spectra allows also an easy evaluation of the amount of α and β crystalline phases (often simultaneously present in melt-crystallized samples) although both contain chains in a same conformation. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35 : 1055–1066, 1997     

Monosaccharide-Directed Selective Internalization of Gold and Silver Nanoparticles in Hepatic Cancer Cells

The therapeutic success of nanomedicines requires nanomaterials to either adhere to the surface or internalize within the cytoplasm. The endocytosis phenomenon is controlled by the nanomaterial's shape, size, composition, charge, and capping molecules. The membrane potential-based non-specific internalization of therapeutic nanomedicines offers limited benefits than receptor-based specific delivery. Glut receptor-based internalization of glucose molecules is a well-known process in cancerous cells, which is one of the most exploited strategies to target cancer cells using nanoparticles. However, the internalization process of other structurally similar monosaccharides (D-Galactose, Mannose, and D-Fructose) conjugated nanoparticles remains to be unexplored. Herein, D-Glucose, D-Galactose, Mannose, and D-Fructose-coated AuNPs and AgNPs have been synthesized and studied the role of Glut receptors in their internalization in liver cancer cells, and compared them with non-cancerous cells. Results revealed that almost all monosaccharide-coated NPs exhibited high uptake in liver cancer cells than non-cancerous cells. Glut-1 receptor is observed to play a key role in the uptake and inhibition of Glut-1 receptors by genistein lead to a significant decrease in nanoparticle uptake. In conclusion, monosaccharide-conjugated nanoparticles can be used to direct the selective internalization of AuNPs and AgNPs in hepatic cancer cells to realize therapeutic and imaging applications.     

Nonstoichiometric interpolyelectrolyte complexes as colloidal dispersions based on NaPAMPS and their interaction with colloidal silica particles

Preparation and characterization of some nonstoichiometric interpolyelectrolyte complexes (NIPECs) as stable colloidal dispersions by the interaction between poly(sodium 2-acrylamido-2-methylpropanesulfonate) (NaPAMPS) and three strong polycations bearing quaternary ammonium salt centres in the backbone, poly(diallyldimethylammonium chloride) (PDADMAC) and two polycations containing N,N-dimethyl-2-hydroxypropyleneammonium chloride units (PCA₅ and PCA₅D₁), have been followed in this study as a function of the polycation structure and polyelectrolyte concentration. Complex characteristics were followed by polyelectrolyte titration, turbidity and quasi-ellastic light scattering. Almost monodisperse NIPECs nanoparticles with a good storage stability were prepared when total concentration of polyelectrolyte was varied in the range 0.85-6.35 mmol/L, at a ratio between charges (n⁻/n⁺) of 0.7. NIPECs as a new kind of flocculants were used to flocculate a stable monodisperse silica suspension. The main advantage of NIPECs as flocculants is the broad flocculation window, which is a very important aspect for industrial applications.