MYP2 locus genes: Sequence variations,genetic association studies and haplotypic association in patients with High Myopia

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.     

Photophysical and biological aspects of α, β-unsaturated ketones: Experimental and in silico approach

In this work, four fluorinated α, β-unsaturated ketones named as 3-(3-bromophenyl)−1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)−1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen–Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), ¹H-NMR, ¹³C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1 – 4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds  1 – 4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds.     

Prospects of Inducing Resistance in Fodder Species against Toxic Ions and Metals

ABSTRACT

Experiments were carried out with various salts and their combinations to ascertain the impact of these salts on seedling traits of fodder species and to identify tolerant species. Length-based traits showed a repressed effect, whereas weight-based traits were increased under salt stress. Furthermore, accumulation of Na⁺, Ca²⁺, and Cl^? ions and metals (Cu²⁺, Fe²⁺, and Al³⁺) increased in various organs of seedlings due to various salt treatments. Contrastingly, K⁺, K⁺/Na⁺, and Ca²⁺/Cl^? decreased, showing priority for specific salts. Seedling traits, such as shoot length sensitivity and shoot biomass, provide an effective mean of selection for tolerant or susceptible genotypes. Diverse types of tolerance mechanisms were present in cultivars to detoxify the effect of ions and metals. Cultivars that showed low susceptibility index, high shoot biomass, and high metal concentration were salt includers and could be utilized for bioremediation of the affected areas, whereas tolerant cultivars that showed low susceptibility index, metals concentration, and comparable shoot biomass to that of the control were salt excluders and could be utilized for fodder purposes.     

STUDIES ON AXOPLASMIC TRANSPORT OF INDIVIDUAL PROTEINS: 1–ACETYLCHOLINESTERASE (AChE) IN ACRYLAMIDE NEUROPATHY

Abstract— The axoplasmic transport rate and distribution of acetylcholinesterase (AChe, EC 3.1.1.7) was studied in the sciatic nerves of normal rats and those with a neuropathy due to acrylamide, by measuring the accumulation of the enzyme proximal to single and double ligatures. The single ligature experiments showed that the apparent transport rate of AChE was decreased in acrylamide neuropathy. The double ligature experiments indicated that only 8.1% of AChE was mobile in normal rat sciatic nerve. The mobility of the enzyme in acrylamide-treated rat sciatic nerves was altered to 11.8%. The absolute transport rate of AChE in normal rat sciatic nerve was 567 mm/24 h, and in acrylamide neuropathy it was decreased to 287 mm/24 h.
The amount of AChE activity transported in normal rat sciatic nerve was 2.64 μmol/24 h. The rats with acrylamide neuropathy showed a decrease in the amount of AChE activity moving in the orthograde direction (2.03 μmol/24 h).
The colchicine-binding properties of tubulin protein from sciatic nerves of normal and acrylamide-treated rats were studied. In rats with acrylamide neuropathy, a marked decrease of 75% in tubulin-colchicine binding was observed.     

Mercury Concentrations in Common Tern Sterna hirundo and Slender-billed Gull Larus genei from the Shadegan Marshes of Iran,in North-western Corner of the Persian Gulf

We examined mercury levels in several tissues of Common Terns and Slender-billed Gulls collected from Shadegan Marshes of south-western Iran. In both species, total mercury content was highest in feathers followed by liver, kidney and muscle tissue. We found a significant correlation between mercury concentrations in kidney and breast feather (r?=?0.83, p?<?0.05), breast feather and liver (r?=?0.81, p?<?0.05) as well as liver and kidney (r?=?0.83, p?<?0.05). The contaminant levels in the feathers (11.53 and 15.32 μg/g in breast feather and tail feather, respectively) of Common Terns from Shadegan Marshes are higher than those reported for other tern species from elsewhere in the world, but feather mercury of Slender-billed Gull (6.61 and 5.35 μg/g in breast feather and tail feather, respectively) was similar to those reported for gull species worldwide. Mean values for mercury in the feather of two seabird species were higher than the levels known to cause adverse effects.     

New insights into the structure of PINK1 and the mechanism of ubiquitin phosphorylation

Mutations in PINK1 cause early-onset recessive Parkinson’s disease. This gene encodes a protein kinase implicated in mitochondrial quality control via ubiquitin phosphorylation and activation of the E3 ubiquitin ligase Parkin. Here, we review and analyze functional features emerging from recent crystallographic, nuclear magnetic resonance (NMR) and mass spectrometry studies of PINK1. We compare the apo and ubiquitin-bound PINK1 structures and reveal an allosteric switch, regulated by autophosphorylation, which modulates substrate recognition. We critically assess the conformational changes taking place in ubiquitin and the Parkin ubiquitin-like domain in relation to its binding to PINK1. Finally, we discuss the implications of these biophysical findings in our understanding of the role of PINK1 in mitochondrial function, and analyze the potential for structure-based drug design.     

Cloning, characterization and expression of complete coding sequences of three IgE binding Malassezia furfur allergens, Mal f 7, Mal f 8 and Mal f 9.

Malassezia furfur, formerly known as Pityrosporum orbiculare or P. ovale, is a yeast that colonizes human skin. Normally, this yeast is nonpathogenic but under the influence of predisposing factors it may induce IgE reactivity in patients with atopic dermatitis. Approximately 40-65% of atopic dermatitis patients have IgE antibodies and/or skin reactivity against M. furfur and a higher T-cell response against this yeast is found in atopic dermatitis patients than in healthy individuals. By making a cDNA library displayed on a phage surface, we previously cloned five different IgE-binding proteins, Mal f 5, Mal f 6, MF 7, MF 8 and MF 9, from this yeast. The cDNAs encoding these allergens were sequenced and expressed in Escherichia coli. The sequences of MF 7, MF 8 and MF 9 were not full length (missing their 5'-ends) giving only partial gene products. To obtain complete cDNA sequences, we performed RACE-PCR to amplify the 5'-ends of each cDNA. These PCR products were sequenced and analyzed. The coding sequences of Mal f 7, Mal f 8 and Mal f 9 encode proteins with ORFs of 141 (16.2 kDa), 179 (19.2 kDa) and 126 (14.0 kDa) amino-acid residues, respectively. None of the putative proteins showed significant sequence homology with other known proteins in the searched database. The proteins encoded by the complete cDNA sequences were expressed in E. coli as recombinant proteins. Immunoblotting and radioallergosorbant test data showed that all of the expressed recombinant proteins have the ability to bind serum IgE from atopic dermatitis patients and furthermore, the M. furfur extract could specifically inhibit this IgE binding.     

Antioxidant and Pulmonary Protective Potential of Fraxinus xanthoxyloides Bark Extract against CCl4-Induced Toxicity in Rats

Fraxinus xanthoxyloides is a perennial shrub belonging to family Oleaceae, traditionally used for malaria, jaundice, pneumonia, inflammation, and rheumatism. Our study is aimed to assess the total phenolics (TPC), flavonoids (TFC), terpenoids contents (TTC) and antioxidant profiling of F. xanthoxyloides methanol bark extract (FXBM) and its fractions, hexane, chloroform, ethyl acetate and aqueous, along with high-performance liquid chromatography with diode-array detection (HPLC-DAD). Further, the antioxidant and pulmonary protective potential was explored against carbon tetrachloride (CCl₄)-induced CCl4-induced pulmonary tissue damage in rats. The highest TPC, TFC and TTC were found in FXBM (133.29±4.19 mg/g), ethyl acetate fraction (279.55±10.35 mg/g), and chloroform fraction (0.79±0.06 mg/g), respectively. The most potent antioxidant capacity was depicted by FXBM (29.21±2.40 μg/mg) and ethyl acetate fraction (91.16±5.51 μg/mg). The HPLC-DAD analysis revealed the predominance of gallic, chlorogenic, vanillic and ferulic acid in FXBM. The administration of CCl₄ induced oxidative stress, suppressed antioxidant enzymes′ activities including catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase. Further, it increased thiobarbituric acid reactive substances (TBARS) and H₂O₂ levels, induced DNA injuries and reduced the total protein and glutathione content in lung tissues. The treatment of rats with FXBM restored these biochemical parameters to the normal level. Moreover, the histopathological studies of lung tissues demonstrated that FXBM protected rats′ lung tissues from oxidative damage restoring normal lung functions. Thus, F. xanthoxyloides bark extract is recommended as adjuvant therapy as protective agent for patients with lung disorders.     

Copper: uptake,toxicity and tolerance in plants and management of Cu-contaminated soil

BioMetals - Copper (Cu) is an essential mineral nutrient for the proper growth and development of plants; it is involved in myriad morphological, physiological, and biochemical processes. Copper...