Prospecting endophytic fungal assemblage of Digitalis lanata Ehrh. (foxglove) as a novel source of digoxin: a cardiac glycoside

Endophytes, the chemical synthesizers inside plants, are the microorganisms having mutualistic relationship with the host plant. They can be used by plants for defense in addition to the production of a wide variety of beneficial bioactive secondary metabolites. There are reports that microbial endophytes mimic the bioactive compounds as produced by the plant itself thus making them a promising source of novel compounds. During the present study, endophytes were isolated from the symptomless leaves and stem of the angiosperm, Digitalis lanata (foxglove). Digitalis lanata belongs to the family Plantaginaceae and is an important medicinal plant known for the production of an important glycoside, digoxin having valuable medicinal importance. Glycosides from Digitalis have been reported to be cardiotonic and are widely used in the treatment of various heart conditions namely atrial fibrillation, atrial flutter, heart failure, etc. Endophytic fungi were isolated from Digitalis to screen them for such glycosides as have been found in the plant itself. A total of 35 fungal endophytes were isolated and screened for the production of secondary metabolites. After preliminary analysis by thin layer chromatography for the presence of bioactive compounds, crude extracts of five fungal cultures were selected for HPLC. HPLC chromatograms revealed the production of glycoside digoxin from the five selected endophytic cultures, thus providing a novel, alternative and eco-friendly source for the production of such a pharmaceutically important and valuable drug

A Thiazole Coumarin (TC) turn-on fluorescence probe for AT-base pair detection and multipurpose applications in different biological systems

Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based Thiazole Coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-Activated Cell Sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology

Anti-bacterial activity of neoandrographolide derivatives: In silico interaction with the bacterial target

157-164Natural products and their semi synthesized molecules have been used as efficient antibiotics since a long time. The present global health scenario has raised the demand for novel antimicrobial agents and drug targets that are effective against drug resistant pathogens, emerging infections etc. The current study has promoted the antibacterial activity of the glucoside labdane ‘neoandrographolide’, isolated from the methanolic extract of the medicinal plant Andrographis paniculata. Further modification at its glucoside hydroxyl groups to generate ester and acetonide derivatives was done and the antibacterial potential of these compounds was screened against common bacterial pathogens. Among various derivatives, 4,6-O-(4-methoxybenzylidene) neoandrographolide exhibited promising results. In addition, molecular modeling study of the active compound was also explored to identify its probable binding mode on the bacterial target. The present study reported antibacterial activity of neoandrographolide derivatives for first time and also the bioactive molecule, 4,6-O-(4-methoxybenzylidene) neoandrographolide was examined as a potent antibacterial agent against different strains

Whole exome screening identifies novel and recurrent WISP3 mutations causing progressive pseudorheumatoid dysplasia in Jammu and Kashmir-India

We report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156C > A (NP-003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643+1G > A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families

Нормативно-правові аспекти дослідження витрат торговельних підприємств

У статті досліджено міжнародні та національні нормативно-правові акти, що розкривають суть та методологічні аспекти формування витрат підприємств у бухгалтерському і податковому обліку. (In the article are investigated standard-legal sources that open methodological aspects of formation of costs of the enterprises in the accounting and tax account.