An Arabidopsis lipid map reveals differences between tissues and dynamic changes throughout development

Mass spectrometry is the predominant analytical tool used in the field of plant lipidomics. However, there are many challenges associated with the mass spectrometric detection and identification of lipids because of the highly complex nature of plant lipids. Studies into lipid biosynthetic pathways, gene functions in lipid metabolism, lipid changes during plant growth and development, and the holistic examination of the role of plant lipids in environmental stress responses are often hindered. Here, we leveraged a robust pipeline that we previously established to extract and analyze lipid profiles of different tissues and developmental stages from the model plant Arabidopsis thaliana. We analyzed seven tissues at several different developmental stages and identified more than 200 lipids from each tissue analyzed. The data were used to create a web-accessible in silico lipid map that has been integrated into an electronic Fluorescent Pictograph (eFP) browser. This in silico library of Arabidopsis lipids allows the visualization and exploration of the distribution and changes of lipid levels across selected developmental stages. Furthermore, it provides information on the characteristic fragments of lipids and adducts observed in the mass spectrometer and their retention times, which can be used for lipid identification. The Arabidopsis tissue lipid map can be accessed at http://bar.utoronto.ca/efp_arabidopsis_lipid/cgi-bin/efpWeb.cgi .     

A study of the coagulant activity of Indian green pit viper venom

Indian green pit viper venom was studied for its coagulant activity. It was observed that the venom contained a significant amount of coagulant activity, which was similar to thrombin in its action on plasma as well as on fibrinogen. The physicochemical properties studied suggested that the venom coagulant activity lacked both platelet aggregating and factor XIII activating properties. Unlike thrombin, the activity was retained in the presence of heparin and at high temperatures. The activity was inhibited by Diisopropyl fluorophosphate and phenyl methyl sulphonyl fluoride, indicating that it was a serine esterase.     

Competitive interactions between entomopathogenic nematodes and parasitoid venom

Entomopathogenic nematodes and parasitoid larvae of some wasps play important roles in the natural control of the pest insects. However, it has not been excluded that competition between nematodes and wasps may in some cases reduce their efficacy in the pest control. Using caterpillars of Spodoptera littoralis, we examined interactions between the nematode Steinernema carpocapsae and the venom of the parasitoid Habrobracon hebetor. The survival of S. littoralis caterpillars was reduced in a dose-dependent manner when 5 to 500 nematodes or 0.005–0.1 venom units were applied to single caterpillars. High doses of either nematodes or the venom caused death within 1–3 days in all treated hosts. The low doses of nematodes killed caterpillars within a week, in some cases when they attempted to pupate. Caterpillars receiving low venom doses were characterized by extended survival time terminated with death due to starvation. Combined treatment of nematodes and the venom were mutually synergistic and elicited severe lethal effects. The nematodes were fully resistant to the venom and can feed and grow on the symbiotic bacteria in vitro. The venom impairs food processing and causes death of caterpillars due to starvation. Disruption of the hormonal regulation of metamorphosis by ecdysteroids and juvenile hormone could be responsible for defective moults block at different stages of the moulting process, regionally restricted moulting, moults to “intermediates” combining regions of newly secreted larval and pupal cuticles.     

Mn3O4 nanoparticles: Synthesis,characterization and their antimicrobial and anticancer activity against A549 and MCF-7 cell lines

Due to their inexpensive and eco-friendly nature, and existence of manganese in various oxidation states and their natural abundance have attained significant attention for the formation of Mn₃O₄ nanoparticles (Mn₃O₄ NPs). Herein, we report the preparation of Mn₃O₄ nanoparticles using manganese nitrate as a precursor material by utilization of a precipitation technique. The as-prepared Mn₃O₄ nanoparticles (Mn₃O₄ NPs) were characterized by using X-ray powder diffraction (XRD), UV–Visible spectroscopy (UV–Vis), High-Resolution Transmission electron microscopy (HRTEM), Field emission scanning electron microscopy (FESEM), Thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). The antimicrobial properties of the as-synthesized Mn₃O₄ nanoparticles were investigated against numerous bacterial and fungal strains including S. aureus, E. coli, B. subtilis, P. aeruginosa, A. flavus and C. albicans. The Mn₃O₄ NPs inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 40 μg/ml and C. albicans with a MIC of 15 μg/ml. Furthermore, the Mn₃O₄ NPs anti-cancer activity was examined using MTT essay against A549 lung and MCF-7 breast cancer cell lines. The Mn₃O₄ NPs revealed significant activity against the examined cancer cell lines A549 and MCF-7. The IC₅₀ values of Mn₃O₄ NPs with A549 cell line was found at concentration of 98 µg/mL and MCF-7 cell line was found at concentration of 25 µg/mL.     

Modeling and analysis of soybean (Glycine max. L) Cu/Zn,Mn and Fe superoxide dismutases

Superoxide dismutase (SOD, EC 1.15.1.1) is an important metal-containing antioxidant enzyme that provides the first line of defense against toxic superoxide radicals by catalyzing their dismutation to oxygen and hydrogen peroxide. SOD is classified into four metalloprotein isoforms, namely, Cu/Zn SOD, Mn SOD, Ni SOD and Fe SOD. The structural models of soybean SOD isoforms have not yet been solved. In this study, we describe structural models for soybean Cu/Zn SOD, Mn SOD and Fe SOD and provide insights into the molecular function of this metal-binding enzyme in improving tolerance to oxidative stress in plants.     

Comparative modeling of Rab6 proteins: identification of key residues and their interactions with guanine nucleotides

The cytoplasm of a eukaryotic cell consists of a wide variety of membrane bound cell organelles and continuous flow of proteins amongst these organelles is a major challenge and must be stringently maintained in order to continue the correct biochemical functioning inside a cell. The transportation of various proteins amongst these organelles is facilitated by a vast Tubulo-vesicular network mediated by carrier proteins. The Rabs belong to small G proteins super family involved in the regulation and vesicle transport in between the organelles by shuttling between the active GTP and inactive GDP bound states. In this paper we put forth the homology modeling and docking studies of Rab6A proteins (Mus musculus, Gallus gallus and Caenorhabditis elegans) with GTP, GMP-PNP and GDP molecules and a comparative study between these proteins is done to identify key residues out of which serine of the phosphate binding loop (P – loop) and aspartic acid showed prominent interactions with the GTP, GDP and GMP-PNP nucleotides and cogitate that aspartic acid might also help in the stabilization of the switch I region of the Rab proteins besides serine.     

Molecular dynamics and QM/MM-based 3D interaction analyses of cyclin-E inhibitors

Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently undergoing clinical trials, but possibilities remain for the identification and development of novel and improved inhibitors. For example, in silico targeting of ATP-competitive inhibitors of CDKs is of special interest. A series of 3,5-diaminoindazoles was studied using molecular docking and comparative field analyses. We used post-docking short time molecular dynamics (MD) simulation to account for receptor flexibility. The three types of structures, i.e., the highest energy, lowest energy and the structure most resembling the X-ray structure (three complexes) were identified for all ligands. QM/MM energy calculations were performed using a DFT b3lyp/6–31 g* and MM OPLS-2005 force field. Conceptual DFT properties such as the interaction energy of ligand to protein, global hardness (η), HOMO density, electrostatic potential, and electron density were calculated and related to inhibitory activity. CoMFA and CoMSIA were used to account for steric and electrostatic interactions. The results of this study provide insight into the bioactive conformation, interactions involved, and the effect of different drug fragments over different biological activities.     

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India

Background

Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD.

Methods

In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed.

Results

Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p = 0.04), total cholesterol (p = 0.01), ALK (p = 0.04) and gamma-glutamyl transpeptidase (p = 0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1 = 0.1; p = 0.006) and controls (D1 = 0.07; p = 0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p = 0.05)].

Conclusion

Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.