Photoisomerization as a trigger for Bergman cyclization: synthesis and reactivity of azoenediynes

Cyclic enediynes 1a and 2a containing stable E-azo moiety (azoenediynes) have been synthesized. These compounds upon irradiation with long wavelength UV isomerize to the Z-compounds 1b and 2b, which can be thermally reisomerized to the Z compounds. Reactivity studies toward BC using DSC predictably indicate higher reactivity for the Z-isomers. Our studies may provide a novel way to modulate the reactivity of enediynes under thermal or photochemical conditions.     

Linkage analysis of alcohol dependence using both affected and discordant sib pairs

The basic idea of affected-sib-pair (ASP) linkage analysis is to test whether the inheritance pattern of a marker deviates from Mendelian expectation in a sample of ASPs. The test depends on an assumed Mendelian control distribution of the number of marker alleles shared identical by descent (IBD), i.e., 1/4, 1/2, and 1/4 for 2, 1, and 0 allele(s) IBD, respectively. However, Mendelian transmission may not always hold, for example because of inbreeding or meiotic drive at the marker or a nearby locus. A more robust and valid approach is to incorporate discordant-sib-pairs (DSPs) as controls to avoid possible false-positive results. To be robust to deviation from Mendelian transmission, here we analyzed Collaborative Study on the Genetics of Alcoholism data by modifying the ASP LOD score method to contrast the estimated distribution of the number of allele(s) shared IBD by ASPs with that by DSPs, instead of with the expected distribution under the Mendelian assumption. This strategy assesses the difference in IBD sharing between ASPs and the IBD sharing between DSPs. Further, it works better than the conventional LOD score ASP linkage method in these data in the sense of avoiding false-positive linkage evidence.     

Towards understanding the multifaceted role of SUMOylation in plant growth and development

Post‐translational modifications (PTMs) play a critical role in regulating plant growth and development through the modulation of protein functionality and its interaction with its partners. Analysis of the functional implication of PTMs on plant cellular signalling presents grand challenges in understanding their significance. Proteins decorated or modified with another chemical group or polypeptide play a significant role in regulating physiological processes as compared with non‐decorated or non‐modified proteins. In the past decade, SUMOylation has been emerging as a potent PTM influencing the adaptability of plants to growth, in response to various environmental cues. Deciphering the SUMO‐mediated regulation of plant stress responses and its consequences is required to understand the mechanism underneath. Here, we will discuss the recent advances in the role and significance of SUMOylation in plant growth, development and stress response.     

The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients

Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation‐induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non‐diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho‐mammalian target of rapamycin, p62 and reduced expression of phospho‐AMP‐activated protein kinase and lysosomal membrane‐associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase‐3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.     

Surface-modified sulfur nanoparticles: an effective antifungal agent against Aspergillus niger and Fusarium oxysporum

Surface-modified sulfur nanoparticles (SNPs) of two different sizes were prepared via a modified liquid-phase precipitation method, using sodium polysulfide and ammonium polysulfide as starting material and polyethylene glycol-400 (PEG-400) as the surface stabilizing agent. Surface topology, size distribution, surface modification of SNPs with PEG-400, quantitative analysis for the presence of sulfur in nanoformulations, and thermal stability of SNPs were determined by atomic force microscopy (AFM), dynamic light scattering (DLS) plus high-resolution transmission electron microscopy (HR-TEM), fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray (EDX) spectroscopy, and thermogravimetric analysis (TGA), respectively. A simultaneous study with micron-sized sulfur (S⁰) and SNPs was carried out to evaluate their fungicidal efficacy against Aspergillus niger and Fusarium oxysporum in terms of radial growth, sporulation, ultrastructural modifications, and phospholipid content of the fungal strains using a modified poisoned food technique, spore-germination slide bioassay, environmental scanning electron microscopy (ESEM), and spectrometry. SNPs expressed promising inhibitory effect on fungal growth and sporulation and also significantly reduced phospholipid content.     

Isolation of pure compound R/J/3 from Pluchea indica (L.) Less. and its anti-amoebic activities against Entamoeba histolytica

The plant Pluchea indica is known for its anti-inflammatory, anti-ulcer, anti-pyretic, hypoglycemic, diuretic and anti-microbial activities besides many other pharmacological activities. We have isolated and purified seven compounds from the methanolic root extract of this plant by column chromatography. The compounds were identified by spectroscopic analyses. The anti-amoebic activities of the pure compound R/J/3 was investigated against the HM1 strain of Entamoeba histolytica. The compound, R/J/3 showed the most pronounced anti-proliferative activity at a dose of 50 microg/ml. It also showed a marked activity on cell lysis of trophozoites, 4h after administration. The cell lytic activity was compared with metronidazole (5 microg/ml) as positive control.