• Fuller Mendez posted an update 1 year, 7 months ago

    32%) did not qualitatively pre-test their DCE, and a majority did not report the uncertainty in estimated outcomes (n=18; 64%).

    DCEs in asthma and COPD have focused on treatment benefits and convenience, with less evidence generated on participants’ risk tolerance. Quality criteria and reporting standards are needed to promote study quality and ensure consistency in reporting between studies.

    DCEs in asthma and COPD have focused on treatment benefits and convenience, with less evidence generated on participants’ risk tolerance. SNS-032 Quality criteria and reporting standards are needed to promote study quality and ensure consistency in reporting between studies.Deleterious effects of artificially applied chemicals have highlighted the significance of biocontrol agents as suitable substitute for sustainable agriculture. In present study, three endophytic bacterial strains SV7, SV10 and LV19 showed extensive range of antifungal as well as plant growth promoting activities signifying potential to accomplish the requirement. Phylogenetic analysis revealed 100% similarity of three strains with taxon Firmicute. However, there was division among these isolates on basis of subgroups as SV7 belonged to Exiguobacterium auranticum, SV10 belonged to Paenibacillus sp. and LV19 was best fit in subgroup Priestia koreensis. All strains showed antifungal activity against Fusarium oxysporum on three different media (PDA, NA, LA) with maximum activity (53%) of LV19 strain on NA and least activity (13%) on PDA medium as recorded by zones of inhibition. In growth promotion experiments, combination of LV19 with Fusarium significantly suppressed chances of Fusarium wilt which is commonly caused by Fusarium oxysporum in sunflower plants. Diverse growth parameters (seed germination percentage, lengths and fresh weights of root and shoot) were significantly increased from 34 to 909% over pathogen infected plants only which was further proved by their root colonization analysis. Based on most efficient growth promotion by LV19 strain, expression of five plant defense related genes (SOD, PAL, NPR1, PR5, Chitinase) was evaluated revealing enhanced expression by 1.7-270-folds in consortium of LV19 and Fusarium. Thus, current study provided a scientific justification that bacterial strains in specific LV19 (Priestia koreensis) could be further developed as biocontrol agent with potential of plant growth promotion.Xenorhabdus and Photorhabdus spp. are enteric bacterial symbionts of Steinernema and Heterorhabditis nematodes, respectively. These bacteria produce an extensive set of natural products (NPs) with antibacterial, antifungal, antiprotozoal, insecticidal, or other bioactivities when vectored into insect hemocoel by nematodes. We assessed the in vitro activity of different Xenorhabdus and Photorhabdus cell-free supernatants against important fungal phytopathogens, viz., Cryphonectria parasitica, Fusarium oxysporum, Rhizoctonia solani, and Sclerotinia sclerotiorum and identified the bioactive antifungal compound/s present in the most effective bacterial supernatant using the easyPACId (easy promoter-activated compound identification) approach against chestnut blight C. parasitica. Our data showed that supernatants from Xenorhabdus species were comparatively more effective than extracts from Photorhabdus in suppressing the fungal pathogens; among the bacteria assessed, Xenorhabdus szentirmaii was the most effective species against all tested phytopathogens especially against C. parasitica. Subsequent analysis revealed fabclavines as antifungal bioactive compounds in X. szentirmaii, generated by a polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) hybrid system. Fabclavines are broad-spectrum, heat-stable NPs that have great potential as biological control compounds against fungal plant pathogens. More studies are needed to assess the potential phytotoxicity of these compounds and their effects on non-target organisms before commercialization. KEY POINTS • Chemical fungicides have toxic effects on humans and other non-target organisms. • Alternatives with novel modes of action to supplant current fungicide are needed. • A novel bioactive antifungal compound from Xenorhabdus szentirmaii was identified.6-phosphogluconate dehydrogenase (6PGDH) participates in pentose phosphate pathway of glucose metabolism by catalyzing oxidative decarboxylation of 6-phsophogluconate (6PG) and its absence has been lethal for several eukaryotes. Despite being a validated drug target in many organisms like Plasmodium, the enzyme has not been explored in leishmanial parasites. In the present study, 6PGDH of Leishmania donovani (Ld6PGDH) is cloned and purified followed by its characterization using biochemical and structural approaches. Ld6PGDH lacks the glycine-serine-rich sequence at its C-terminal that is present in other eukaryotes including humans. Leishmanial 6PGDH possesses more affinity for substrate (6PG) and cofactor (NADP) in comparison to that of human. The enzymatic activity is inhibited by gentamicin and cefuroxime through competitive mode with functioning more potently towards leishmanial 6PGDH than its human counterpart. CD analysis has shown higher α-helical content in the secondary structure of Ld6PGDH, while fluorescence studies revealed that tryptophan residues are not completely accessible to solvent environment. The three-dimensional structure was generated through homology modelling and docked with substrate and cofactor. The docking studies demonstrated two separate binding pockets for 6PG and NADP with higher affinity for the cofactor binding, and Asn105 is interacting with substrate as well as the cofactor. Additionally, MD simulation has shown complexes of Ld6PGDH with 6PG and NADP to be more stable than its apo form. Altogether, the present study might provide the foundation to investigate this enzyme as potential target against leishmaniasis. KEY POINTS • Ld6PGDH enzymatic activity is competitively inhibited by gentamicin and cefuroxime. • It displays more helical contents and all structural characteristics of 6PGDH family. • Interaction studies demonstrate higher affinity of cofactor than substrate for Ld6PGDH.

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