Comparative analysis of essential oil compositions in seven populations of Bakhtiarian savory in natural and field conditions

Bakhtiarian savory (Satureja bachtiarica Bunge) is an endemic herb growing wild in Iran with interesting pharmacological and biological properties. In this research, the variability of essential oil content and phytochemical compositions among seven populations of this species was studied in both natural and field conditions. There was a wide interpopulation variability in phytochemical variation of studied populations under both natural and field conditions, indicating the existence of different chemotypes. Six chemical compositions showed high value in studied plants so that carvacrol and thymol were known as major compounds and confirmed by principal component analysis. Ilam population had the highest thymol in both field (77.10 %) and natural (42.32 %) conditions and was known as a thymol chemotype. Beside, Yazd and Shahrekord populations, respectively, showed the highest carvacrol percentages in both field (84.83 and 63.81 %) and natural (72.50 and 58.05 %) conditions and were known as carvacrol chemotypes. In other populations, carvacrol and thymol were the main components and showed partly equal percentage and these populations were known as carvacrol/thymol chemotypes. According to Pearson correlation analysis, carvacrol was negatively correlated with p-cymene, γ-terpinene and thymol (r = ?0.61, ?0.70 and ?0.98, respectively), indicating very high reverse correlation between carvacrol and thymol. In conclusion, the high value of the essential oil compositions in studied S. bachtiarica populations could provide useful information for conservation and selection of cross parents in breeding programs to develop improved cultivars.     

A Bio-Inspired Approach for the Reduction of Left Ventricular Workload

Previous studies have demonstrated the existence of optimization criteria in the design and development of mammalians cardiovascular systems. Similarities in mammalian arterial wave reflection suggest there are certain design criteria for the optimization of arterial wave dynamics. Inspired by these natural optimization criteria, we investigated the feasibility of optimizing the aortic waves by modifying wave reflection sites. A hydraulic model that has physical and dynamical properties similar to a human aorta and left ventricle was used for a series of in-vitro experiments. The results indicate that placing an artificial reflection site (a ring) at a specific location along the aorta may create a constructive wave dynamic that could reduce LV pulsatile workload. This simple bio-inspired approach may have important implications for the future of treatment strategies for diseased aorta.     

4-(3-Alkyl/benzyl-guanidino)benzenesulfonamides as selective carbonic anhydrase VII inhibitors

The treatment of chronic neuropathic pain remains one of the most challenging of all neurological diseases and very much an art. There exists no consensus for the optimal management of this condition at the moment. Gaining inspiration from recent studies which pointed out the involvement of brain-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform VII in the pathology of various neurodegenerative diseases, which highlighted the relationship between selective inhibition of this isozyme and relieve of neuropathic pain, herein we report the synthesis and CA VII inhibitory activity of novel 4-(3-alkyl/benzyl-guanidino)benzenesulfonamides. Ten benzyl-substituted and five alkyl-substituted 4-guanidinobenzenesulfonamide derivatives were obtained, some of which (7c, 7h, 7m and 7o) exhibited satisfactory selectivity towards CA VII over CA I and II, with K_I-s in the subnanomolar range and good selectivity indexes for inhibiting the target versus the off-target isoforms.     

Risk of coronary artery stenosis in Iranian type 2 diabetics: is there a role for matrix metalloproteinase-3 gene (-1612 5A/6A) polymorphism?

Aim  

To investigate the association of matrix metalloproteinase-3 (MMP-3) polymorphism with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with type 2 diabetes mellitus (T2DM).     

In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane

Charcot‐Marie‐Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes.     

Computationally Design of Inhibitory Peptides Against Wnt Signaling Pathway: In Silico Insight on Complex of DKK1 and LRP6

Wnt signaling pathway plays a major role in the regulation of cell proliferation, migration, tissue homeostasis, tumor progression and cancer. This pathway can be antagonized by different proteins such as DKK proteins, which disrupt the initiatory complex (Frizzled–LRP6 complex). Therefore, interruption of its formation could be a promising strategy for the design of Low-density lipoprotein receptor-Related Protein 6 (LRP6) inhibitors. A computational study was conducted in order to assist in the design of inhibitory peptides against LRP6 as co-receptor of frizzled. Twelve fragments as peptide derivatives of natural ligand of LRP6 receptor (DKK1) were designed using the information from the analysis of the DKK1_C/LRP6 complex, hot spot residues and the secondary structure. These fragments were based on cys2 domain of DKK1. The designed peptides were energy minimized by molecular dynamics simulations in the presence and absence of LRP6 receptor and their binding affinities were investigated via molecular docking using ClusPro, HADDOCK and PRODIGY webservers. Finally, the stability and free energy of binding in peptides were calculated by FoldX software. The results showed that four designed peptides had the highest affinity (the interaction energy: ?10.2867, ?10.1388, ?7.94339 and ?7.57536 kcal/mol) to interact with the receptor which showed the most interacting residues and the lowest free energy of binding. Also, the RMSD, RMSF and RoG of the protein–peptide complex exhibited less structural fluctuations which can be linked to the stability of peptides associated to the receptor. These peptides may be considered as candidates for inhibiting Wnt signaling pathway through LRP6 receptor.     

Deep Subwavelength Confinement of Mid-infrared Plasmon Modes by Coupling Graphene-Coated Nanowire with a Dielectric Substrate

In this paper, we report the realization of highly confined mid-infrared plasmon modes by coupling freestanding graphene-coated nanowire with a dielectric substrate. It is shown that the presence of a nearby dielectric substrate not only breaks the azimuthal symmetry of the plasmon modes but also has a strong impact on the coupling and hybridization of these modes. The degree of interactions with the substrate depends on the permittivity of the substrate, the key structural parameters of the nanowire, the operation frequency and chemical potential of graphene, as well as the gap distance between the nanowire and supporting substrate. It is found that compared to freestanding case, using a high-index substrate and adjusting the gap distance can result in the following benefits: (i) an ultra-small mode area and a long propagation length can be realized simultaneously, (ii) a stronger field enhancement in the low-index gap region and improved figure of merit can be achieved, and (iii) a huge reduction in the crosstalk can be made which is crucial for the realization of high-density integrated nanophotonic devices.     

Population Genetic Structure of Transcaucasian Mole Vole (<Emphasis Type="Italic">Ellobius lutescens</Emphasis>) Along Zagros Mountains,Iran

The Zagros and Alborz mountainous ridges can be regarded as one of the most interesting and known physical barriers responsible for the vicariance event. Based on the probable effect of Zagros Mountains on the rodent population vicariance, a research on Caucasian mole vole phylogeography, population genetic structure and diversity was designed along the mentioned mountainous areas. To this end, a total of 38 tissue samples were collected from the northern parts of the study area to the southern parts. Obtained mitochondrial cytb (1041 bp) sequences were used in this phylogenetic analysis. The phylogenetic analysis was based on the TRN+I evolutionary model and gaining Bayesian phylogenetic tree with maximum verification. By using median joining logic, the relationships between different acquired haplotypes were analyzed. It was shown that the Caucasian mole vole population had been disjointed (based on posterior probability of 1 and 100 bootstraps) along the Zagros mountainous ridges, especially in both geographical extremes located in the northern and southern parts of the mountainous ridges. Meanwhile from the 38 analyzed sequences, 17 haplotypes were obtained, of which 10 haplotypes were unique. The mutational steps between haplotypes were assessed by generating statistical parsimony haplotype networks, which yielded 36 mutational steps between the northern and southern populations. Based on neutrality tests and analyzing their power under sudden population expansions, it was found that this event happened around the northern and southern populations. Genetic distance of two percent between the northern and southern populations indicated the existence of local adaptations by these two groups, which can be regarded as evolutionary units.