D224V and S128Y mutation in FSHRED influence thumb movement differentially: An intricate insight gained by short-term molecular dynamics simulation

Follicle-stimulating hormone-follicle-stimulating hormone receptor (FSH-FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH-FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis, respectively. Using short-term molecular dynamics simulations, the atomic scale investigations reveal that the binding pattern of sTYS with FSH and movement of the thumb region of FSHR show distinct contrasting patterns in the two mutants, which supposedly could be a critical factor for differential FSHR behavior in activating and inactivating mutations.     

Studies on the interaction between nanodiamond and human hemoglobin by surface tension measurement and spectroscopy methods

In this study, a novel method to probe molecular interactions and binding of human hemoglobin (Hb) with nanodiamond (ND) was introduced based on the surface tension measurement. This method complements conventional techniques, which are basically done by zeta potential and dynamic light scattering (DLS) measurements, near and far circular dichroism (CD) spectroscopy, intrinsic and extrinsic fluorescence spectroscopy. Addition of ND to Hb solution increased the surface tension value of Hb–ND complex relative to those of Hb and ND molecules. The zeta potential values reveled that Hb and ND provide identical charge distribution at pH 7.5. DLS measurements demonstrated that Hb, ND, and ND–Hb complex have hydrodynamic radiuses of 98.37 ± 4.57, 122.07 ± 7.88 nm and 62.27 ± 3.70 at pH of 7.5 respectively. Far and near UV-CD results indicated the loss of α-helix structure and conformational changes of Hb, respectively. Intrinsic fluorescence data demonstrated that the fluorescence quenching of Hb by ND was the result of the static quenching. The hydrophobic interaction plays a pivotal role in the interaction of ND with Hb. Fluorescence intensity changes over time revealed conformational change of Hb continues after the mixing of the components (Hb–ND) till 15 min, which is indicative of the denaturation of the Hb relative to the protein control. Extrinsic fluorescence data showed a considerable enhancement of the ANS fluorescence intensity of Hb–ND system relative to the Hb till 60 nM of ND, likely persuaded by greater exposure of nonpolar residues of Hb hydrophobic pocket. The remarkable decrease in T_m value of Hb in Hb–ND complex exhibits interaction of Hb with ND conducts to conformational changes of Hb. This study offers consequential discrimination into the interaction of ND with proteins, which may be of significance for further appeal of these nanoparticles in biotechnology prosecution.     

New potentials for 3-hydroxy-3-methyl-glutaryl-coenzymeA reductase inhibitors: Possible applications in retarding diabetic complications

The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid-lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid-lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti-inflammatory, and antiproliferative properties beyond their lipid-lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications.     

Synthesis, characterization, and crystal structures of hydrotris(2-mercapto-1-imidazolyl)borate-based zinc(II) and copper(I) complexes

The reaction of the tripod ligand hydrotris(2-mercapto-1-imidazolyl)borate Tm^xylyl with zinc(II) perchlorate in methanol afforded the mononuclear complex of the type [Tm^xylyl-Zn(mim^xylyl)]ClO₄ (1). Whereas under the same conditions, the reaction with copper(II) perchlorate gives rise to the simultaneous formation of the dinuclear copper(I) complex [Tm^xylylCu]₂ (2). The chemical formulae of the complexes have been characterized by elemental chemical analysis, IR-NMR spectroscopies, and single crystal X-ray methods. In complex 1, the zinc(II) atom displays a distorted tetrahedral environment. While in complex 2, the Tm^xylyl ligand bridges the two copper(I) atoms in an asymmetric manner with trigonal geometry. The inverted conformation of the ligand Tm^xylyl at the boron center, allows the B-H units to be directed towards the copper centers. The greater reactivity of the borohydride groups towards metal centers enhances the reduction of Cu(II) to Cu(I). The obtained kinetic results for the methylation reactions of 1 and 2 indicate that these bound thione complexes are less suitable to electrophilic attack than the thiolate ligand.     

A case of amniotic membrane transplantation in non-healing Nocardia asteroides keratitis

A patient with severe non-healing microscopically proven Nocardia keratitis was treated with maximal topical amikacin followed by amniotic membrane transplantation (AMT) 2 months later (single-layer epithelial side-down). Epithelial healing was achieved, but neovascularization continued. This case report indicates that AMT combined with topical antibiotic provides pain relief and allows epithelial healing in severe Nocardia keratitis.     

Quantifying the effects of root reinforcement of Persian Ironwood (Parrotia persica) on slope stability; a case study: Hillslope of Hyrcanian forests,northern Iran

Forest vegetation is known to enhance the stability of slopes by reinforcing soil and increasing its shear resistance through root system. The effects of root reinforcement depend on the morphological characteristics of the root system, the tensile strength of single roots, and the spatial distribution of the roots in soil. In the present study the results of research carried out in order to evaluate the biotechnical characteristics of the root system of Persian Ironwood (Parrotia persica), in northern Iran are presented. Profile trenching method was used to obtain root area ratio (RAR) values for uphill and downhill sides of the individual trees. For each species, single root specimens were sampled and tested for their tensile strength. It was found that root density generally decreases with depth according to an exponential law. Maximum RAR values were located within the first 0.1 m, with maximum rooting depth at about 0.65 m. RAR values ranged from 0.001% at lower depths to 1.39% near the surface, at upper 0.1 m depth. Significant differences of RAR values, rooting depth and root cohesion between uphill and downhill were observed, however, the differences were not significant for number of roots (ANCOVA). Downhill profiles had higher RAR values, rooting depth and root cohesion. In general, root tensile strength tends to decrease with diameter according to a power law, as observed by other researchers. Downhill roots were significantly stronger in tensile strength than uphill ones. Inter-species variation of tensile strength in downhill roots was also observed. The resulting data were used to evaluate the reinforcing effects in terms of increased shear strength of the soil, using Wu/Waldron Model. The root reinforcement provided by Persian Ironwood is about 46.0 kPa in the upper layers and 0.3 kPa in the deeper horizons. The results of Spearman test revealed a significant correlation between RAR and c_r and that best followed by a power law. The results presented in this paper contribute to expanding the knowledge on biotechnical characteristics of Persian Ironwood on slope reinforcement.