Defence Research and Development Establishment

This study presents a proteomic perspective on the long-term persistence and adaptive mechanisms of Yersinia pestis in tap water microcosms at 25°C. Multiple strains representing different biovars were seeded into tap water at high (108 CFU/mL) or low (105 CFU/mL) concentrations. The strains were found to remain viable for 60-120 days. Nano-liquid chromatography coupled with tandem mass spectrometry (nLC-MS/MS) was used to carry out the proteomic profiling of Y. pestis in the tap water microcosms. When compared with pure Y. pestis culture, a substantial number of proteins (~ 72%) continued to express during long term persistence in tap water over time, yet many were found to be differentially expressed. STRING analysis revealed that the differentially expressed proteins included those involved in trans-membrane transport e.g. ABC transporters, sugar and arginine transporters likely supporting nutrient acquisition in nutrient-limited milieu. In addition, proteins related to stress response such as cold-shock proteins (CspA1, CspA2) were also identified, suggesting probable mechanisms for coping with environmental stress. Interestingly, quorum sensing-related regulators, attachment related proteins including Ail & adhesins, and components of the T3SS and T6SS systems were also detected, which may have facilitated the intercellular communication and surface attachment. The infectivity potential was evaluated by mouse challenge assay, and it was found that animals inoculated intraperitoneally with the day 90 sample succumbed to infection. These findings highlight the ability of Y. pestis to persist in tap water while maintaining virulence, underscoring the need for effective decontamination strategies to reduce potential waterborne transmission risks.

Introduction: Botulinum neurotoxins are the most poisonous substances reported and listed in category ‘A’ of biowarfare agents. As serotype identification is a time-consuming process and there is no antidote commercially available, the development of inhibitors against serotypes causing human botulism would be beneficial. In the present study, a ligand-based in silico method was applied to identify the “hits” that could have the potential to act as countermeasures against human-intoxicating BoNTs. Methods: For this purpose, a computational approach using Molegro Virtual Docker and Auto- Dock tools was performed, where around thirty-five derivatives were designed and docked into the catalytic domain of BoNT/A, B, E, and F. The designed compounds were also studied for their ADME properties using an online web tool. Results and Discussion: Analysis of the molecular docking data of the complex by Molegro Virtual Docker revealed a high binding affinity between the target and designed ligands, with the MolDock score between -139.85 and -88.24 kcal/mol, whereas the AutoDock score ranged between -11.65 and -5.30 kcal/mol. Three SMNPIs, A11, A18, and A20, exhibited better binding affinities with the target proteins BoNT/A, /B, E, and /F and could be potential pan-active inhibitors. The ADME/T study showed that the designed ligands were less toxic and possessed drug-resemblance properties by considering the Lipinski, Ghose, Veber, and Egan rules, with a bioavailability score of 0.56. Conclusion: Our study provides insight into ‘hits’, which can lead to further progress in experimental studies and the development of new antidotes for botulism.

The SARS-CoV-2 Omicron (B.1.1.529) variant emerged in early November 2021 and its rapid spread created fear worldwide. This was attributed to its increased infectivity and escaping immune mechanisms. The spike protein of Omicron has more mutations (>30) than any other previous variants and was declared as the variant of concern (VOC) by the WHO. The concern among the scientific community was huge about this variant, and a piece of updated information on circulating viral strains is important in order to better understand the epidemiology, virus pathogenicity, transmission, therapeutic interventions, and vaccine development. A total of 710 samples were processed for sequencing and identification up to a resolution of sub-lineage. The sequence analysis revealed Omicron variant with distribution as follows: B.1.1, B.1.1.529, BA.1, BA.2, BA.2.10, BA.2.10.1, BA.2.23, BA.2.37, BA.2.38, BA.2.43, BA.2.74, BA.2.75, BA.2.76, and BA.4 sub-lineages. There is a shift noted in circulating lineage from BA.1 to BA.2 to BA.4 over a period from January to September 2022. Multiple signature mutations were identified in S protein T376A, D405N, and R408S mutations, which were new and common to all BA.2 variants. Additionally, R346T was seen in emerging BA.2.74 and BA.2.76 variants. The emerging BA.4 retained the common T376A, D405N, and R408S mutations of BA.2 along with a new mutation F486V. The samples sequenced were from different districts of Madhya Pradesh and showed a predominance of BA.2 and its variants circulating in this region. The current study identified circulation of BA.1 and BA.1.1 variants during initial phase. The predominant Delta strain of the second wave has been replaced by the Omicron variant in this region over a period of time. This study successfully deciphers the dynamics of the emergence and replacement of various sub-lineages of SARS-CoV-2 in central India on real real-time basis.

The experiment was carried out from November 2020 to March 2022 at the RVSKVV College of Agriculture's Research Farm, located in Gwalior (M.P.), in the Department of Horticulture. Three replications and a Randomized Block Design were used to set up the experiment. The all soil characteristics analysis both initial and final level after experiment respectively minimum soil pH (7.05, 7.49), EC dsm-1 (0.225, 0.220) and maximum Organic carbon % (2.117, 3.263), Nitrogen Kg ha-1 (177.14,187.29), Phosphorus Kg ha-1 (13.38, 13.58) and Potassium Kg ha-1 (207.88, 229.45) quality parameters were most effectively achieved with treatment T5 RDF 90 % + Vermicompost + (Azotobacter + PSB + KMB) + (Zn + Cu + Fe + Boron). Because sweet orange orchards are located in the Gird Region of Madhya Pradesh, this particular treatment is most suited for use there.

An Organophosphorus Nerve agent, VX [(O-Ethyl S-diisopropylaminomethyl) methylphosphonothiolate] compound interfere with acetylcholine signaling by targeting the AChE enzyme. Studies suggest that in nerve agents poisoning, non-cholinergic effects are also responsible for damages in peripheral tissues including long term damage in brain. Present study reports cholinergic and non-cholinergic effects of VX poisoning and their reversal by combinational therapy using conventional antidotes atropine sulphate and 2-PAM chloride along with N-acetyl cysteine (NAC) as an antioxidant. In present study, it was attempted to prevent the toxic effects of nerve agent poisoning by using combination therapy with NAC so as to prevent both cholinergic and non-cholinergic damages. NAC was chosen as this molecule is available as approved drug for medical conditions including oxidative damage and mucolysis. Results of the study showed that NAC adjuvant treated groups had better recovery not only in cholinesterase level, it maintained intracellular and tissue GSH level, reduced in ROS generation and lipid peroxidation. Cell cycle analysis and histopathological results showed NAC could able to protect the damage. In conclusion it was found that combination therapy of antioxidant; NAC along with standard atropine-oxime treatment is helpful in reducing the cholinergic and oxidative stress mediated toxicity induced by VX.

The experiment was conducted with 22 germplasm and laid out in randomized block design with three replications. The path revealed that days to 50% flowering, days maturity, plant height at harvest, No. of primary branches at harvest, No. of nodes at harvest, root nodules at 60 days, chlorophyll content (SPAD), days to picking 1, days to picking 2, No. of pods per plant, pods length (cm) pod yield (g/plant), shelling (%), pod length (cm), No. of primary branches at 40 days, number of seed, average pod weight (g), No. of seeds per pod had high positive direct effect on pod yield (q/ha) in all the environment under consideration, where as No. of leaves per plant at harvest, dry of 100 seed (g) and shelling (%) showed negative direct effect on pod yield (q/ha) in EI and EII of garden pea genotypes. The contribution of individual traits towards the total divergence was found maximum for pod yield q/ha, No. of leaves at 60 days, days to picking 2, pod length (cm), No. of seeds per pod and dry of 100 seed (g) in E-I and E-II. On the basis of D 2 values, 22 genotypes were grouped into 4 clusters. The cluster III showed maximum intra cluster D 2 value (D 2 = 23.20) followed by cluster I (D 2 = 20.56) and cluster II (D 2 = 19.97), whereas cluster IV showed zero value for intra cluster distance. The highest inter cluster divergence was observed between genotypes of cluster II and IV (70.57), followed by cluster III and cluster IV (57.66), cluster II and cluster III (55.19), cluster I and cluster II (52.44), cluster I and cluster III (36.85). The cluster distance was lowest between clusters I (20.56) and cluster IV (36.56).