Comparative metagenomic analysis of rice soil samples revealed the diverse microbial population and biocontrol organisms against plant pathogenic fungus Magnaporthe oryzae.

Intensive cropping degrades soil quality and disrupts the soil microbiome. To understand the effect of rice monocropping on soil-microbiome, we used a comparative 16S rRNA metagenome sequencing method to analyze the diversity of soil microflora at the genomic level. Soil samples were obtained from five locations viz., Chamarajnagara, Davangere, Gangavathi, Mandya, and Hassan of Karnataka, India. Chemical analysis of soil samples from these locations revealed significant variations in pH (6.00-8.38), electrical conductivity (0.17-0.69 dS m-1), organic carbon (0.51-1.29%), available nitrogen (279-551 kg ha-1), phosphorous (57-715 kg ha-1) and available potassium (121-564 kg ha-1). The 16S metagenome analysis revealed that the microbial diversity in Gangavathi soil samples was lower than in other locations. The soil sample of Gangavathi showed a higher abundance of Proteobacteria (85.78%) than Mandya (27.18%). The Firmicutes were more abundant in Chamarajnagar samples (36.01%). Furthermore, the KEGG pathway study revealed enriched nitrogen, phosphorus, and potassium metabolism pathways in all soil samples. In terms of the distribution of beneficial microflora, the decomposers were more predominant than the nutrient recyclers such as nitrogen fixers, phosphorous mineralizers, and nitrifiers. Furthermore, we isolated culturable soil microbes and tested their antagonistic activity in vitro against a fungal pathogen of rice, Magnaporthe oryzae strain MG01. Six Bacillus sp. and two strains of Trichoderma harzianum showed higher antagonistic activity against MG01. Our findings indicate that metagenome sequencing can be used to investigate the diversity, distribution, and abundance of soil microflora in rice-growing areas. The knowledge gathered can be used to develop strategies for maintaining soil quality and crop conservation to increase crop productivity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02783-y.

Molecular computations of preferential interactions of proline, arginine.HCl, and NaCl with IgG1 antibodies and their impact on aggregation and viscosity.

Preferential interactions of excipients with the antibody surface govern their effect on the stability of antibodies in solution. We probed the preferential interactions of proline, arginine.HCl (Arg.HCl), and NaCl with three therapeutically relevant IgG1 antibodies via experiment and simulation. With simulations, we examined how excipients interacted with different types of surface patches in the variable region (Fv). For example, proline interacted most strongly with aromatic surfaces, Arg.HCl was included near negative residues, and NaCl was excluded from negative residues and certain hydrophobic regions. The differences in interaction of different excipients with the same surface patch on an antibody may be responsible for variations in the antibody's aggregation, viscosity, and self-association behaviors in each excipient. Proline reduced self-association for all three antibodies and reduced aggregation for the antibody with an association-limited aggregation mechanism. The effects of Arg.HCl and NaCl on aggregation and viscosity were highly dependent on the surface charge distribution and the extent of exclusion from highly hydrophobic patches. At pH 5.5, both tended to increase the aggregation of an antibody with a strongly positive charge on the Fv, while only NaCl reduced the aggregation of the antibody with a large negative charge patch on the Fv. Arg.HCl reduced the viscosities of antibodies with either a hydrophobicity-driven mechanism or a charge-driven mechanism. Analysis of this data presents a framework for understanding how amino acid and ionic excipients interact with different protein surfaces, and how these interactions translate to the observed stability behavior.

Multiple infestations of gastrointestinal parasites - Probable cause for high mortality of Spot-billed Pelican (Pelecanus philippensis) at Kokrebellur Community Reserve, India.

We witnessed mortalities of Spot-billed Pelicans Pelecanus philippensis between December 2017 and May 2018 in Mandya and Mysuru districts of Karnataka, especially at Kokrebellur Community Reserve in Mandya district. The region has experienced severe drought in recent years with negligible water in all the water tanks. A total of 67 Spot-billed Pelicans died in five locations, of which 55 adult birds died at Kokrebellur. We collected four dead pelicans along with 97 fecal samples of live birds at Kokrebellur, water samples from nine water tanks around Kokrebellur, and six fish samples. We isolated the endoparasite eggs by following sedimentation and flotation technique, and counted the eggs from the water and fecal samples, and identified at the genus level using light microscope. We approximately counted the endoparasites by dissecting the fish and conducting a necropsy on dead pelicans. Endoparasite eggs were detected in seven of the nine water tanks. Each fish sample had at least 50-100 L3 stage worms of Contracaecum sp., and 880.0 ±â€¯459.3SD of Contracaecum sp., worms in the digestive tracts and 60.0 ±â€¯36.5SD worms of Echinostoma sp. in the intestine of the four dead pelicans. The endoparasite prevalence was 84.5% (N = 83) with a mean abundance of 368.2 ±â€¯561.5SD eggs/g in the fecal samples of live pelicans. Contracaecum sp., Echinostoma sp. and Opisthorchis viverrini were recorded in 51, 67 and nine fecal samples respectively. The high load of endoparasite eggs in the water tanks, an infestation of Contracaecum sp. in fishes and a heavy load of fully-grown worms of Contracaecum sp. and Echinostoma sp. in the adult pelicans are indicative of their high mortality in Kokrebellur Community Reserve. The coordinated program was initiated with the support of all stakeholders to control the endoparasites in water, fish, and pelicans.

Zinc is the molecular "switch" that controls the catalytic cycle of bacterial leucyl-tRNA synthetase.

The Escherichia coli (E. coli) leucyl-tRNA synthetase (LeuRS) enzyme is part of the aminoacyl-tRNA synthetase (aaRS) family. LeuRS is an essential enzyme that relies on specialized domains to facilitate the aminoacylation reaction. Herein, we have biochemically characterized a specialized zinc-binding domain 1 (ZN-1). We demonstrate that the ZN-1 domain plays a central role in the catalytic cycle of E. coli LeuRS. The ZN-1 domain, when associated with Zn(2+), assumes a rigid architecture that is stabilized by thiol groups from the residues C159, C176 and C179. When LeuRS is in the aminoacylation complex, these cysteine residues form an equilateral planar triangular configuration with Zn(2+), but when LeuRS transitions to the editing conformation, this geometric configuration breaks down. By generating a homology model of LeuRS while in the editing conformation, we conclude that structural changes within the ZN-1 domain play a central role in LeuRS's catalytic cycle. Additionally, we have biochemically shown that C159, C176 and C179 coordinate Zn(2+) and that this interaction is essential for leucylation to occur, but is not essential for deacylation. Furthermore, calculated Kd values indicate that the wild-type enzyme binds Zn(2+) to a greater extent than any of the mutant LeuRSs. Lastly, we have shown through secondary structural analysis of our LeuRS enzymes that Zn(2+) is an architectural cornerstone of the ZN-1 domain and that without its geometric coordination the domain collapses. We believe that future research on the ZN-1 domain may reveal a possible Zn(2+) dependent translocation mechanism for charged tRNA(Leu).

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.

Out-patients Prescriptions are Safe from Drug Interactions or Not: A Pilot Study Report.

The objective of the research work was to analysis the out patients drug interactions and alerts the healthcare professionals to prevent the future complications. The study was done in three pharmacies within a 200 meters distance of each other. The doctors involved were made aware of the study but data were collected without their knowledge. All prescriptions presented to the three pharmacies were analyzed during the five-month study period. A total of 500 prescriptions were analyzed and 64 drug-drug interactions were detected giving a drug-drug interaction rate of 12.8 percent but 436 (87.2%) prescriptions are free from drug interactions. Moderate drug interactions were found in 10.2%, Severe were 2.6% and contraindicated were 0% and also disease wise drug interaction analysis were carried out during the study results, more number of drug interactions reported in central nerves system followed by diabetes mellitus. Outpatient visits resulted in minimal numbers of clinically important drug-drug interactions, these interactions can have significant implications due to medication-related morbidity and mortality. Pharmacists can play a critical role in managing the medication therapy of patients at risk for clinically important drug-drug interactions.

Synthesis and evaluation of tricyclic dipyrido diazepinone derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity.

A series of tricyclic dipyrido diazepinone derivatives 6(a-f) bearing different substituents at the tenth position of diazepinone ring were designed and are characterized by 1H NMR, FTIR and X-Ray crystallography studies. The synthesised derivatives are tested in-vitro phospholipase A2 (PLA2) enzyme inhibitory activity and in-vivo anti-inflammatory activity against purified group I and group II PLA2 enzymes from the snake venom and human pleural fluid. Compounds bearing aromatic ring with different substituents at different positions shown varied specificity. The 6f derivative with strong electron withdrawing nitro (-NO2) and trifluoromethyl (-CF3) groups at ortho and para positions respectively shown greater inhibitory activity. Inhibitory effect of the compound appeared to be direct interaction with active site and likely competes with substrates as supported by substrate dependent and calcium independent assays. The IC50 value of potent PLA2 inhibitor 6f was 22.1 microM and showed similar potency in the neutralization of in vivo PLA2 induced mouse paw edema and hemolytic activity.