EVALUATION OF STRESS ALLEVIATING POTENTIAL OF PERGULARIA DAEMIA ON CERTAIN IMMUNOLOGICAL PARAMETERS

Objective: Pergularia daemia [PD] Forsk, commonly called Veliparuthi†in Tamil belongs to the family of Asclepiadaceae. It has been used by villagers as traditional folk medicine for various ailments such as antipyretic, anti-venom, emmenagogue, anti-helminthic, and to treat malarial fever, infantile diarrhea. Scientific reports revealed several pharmacological properties of PD extract. Preliminary in vitro studies on the plant revealed the antioxidant, anti-inflammatory and antimicrobial activities of the plant. So the present study planned to investigate the in vivo stress alleviating the potential of  PD extract on noise stress induced model of wistar albino rats.Methods: Adult Wistar albino rats were exposed to pure tone noise stress for 45 min for one day and the effect of ethanolic PD extract on plasma corticosterone, organ weight body weight ratio of lymphoid organs and adrenal gland,immunological parameters like total leucocyte count, differential leukocyte, neutrophil adherence test and candida phagocytosis was studied.Results: Results revealed that acute stress significantly increased the plasma corticosterone level [p<0.001] and decreased the organ weight body weight ratio of the spleen [p<0.001] and thymus [p<0.01]. It also significantly decreased the total leucocyte count [p<0.001], percentage of neutrophils [p<0.001], eosinophils [p<0.004] and lymphocytes [p<0.001], neutrophil adherence [p<0.001] and enhanced the phagocytic index and avidity index [p<0.001] in acute noise stress exposed groups. Administration of PD extract significantly prevented those acute noise stress-induced changes [p<0.001].Conclusion: We can be  PD extract protected against the noise stress induced changes in albino rats and this stress alleviating and immunomodulatory potential of the plant may be attributed to the phytochemicals and bioactive compounds present in it.Keywords: Stress indices, Immunomodulatory, bioactive compounds, Pergularia daemiaÂ

A novel metaheuristic approach for control of SEPIC converter in a standalone PV system

Fossil fuels are being replaced by renewables. Most of the renewables are intermittent, to have reliable power the renewables have to be conditioned before injecting into the utility grid. The DC-DC converters are perfect power electronic devices for conditioning the renewables. The single ended primary inductor converter (SEPIC) performs the conditioning with a very high voltage transfer gain and minimum ripples. The maximum power extraction from the PV panels is required for providing good quality DC power. Intelligent controllers can make use of optimization techniques. The particle swarm optimization (PSO) technique can optimize the controller to extract the maximum power. The SEPIC converter duty variation is optimized and a comparative analysis with the Buck-Boost converter is done in a MATLAB/Simulink environment. The proposed SEPIC converter system performed well by improving the power tracking by 40% and the system has been analysed in a battery charging environment

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Abstract: Drug-resistant tuberculosis (TB), one of the leading causes of death worldwide, arises mainly from spontaneous mutations in the genome of Mycobacterium tuberculosis. There is an urgent need to understand the mechanisms by which the mutations confer resistance in order to identify new drug targets and to design new drugs. Previous studies have reported numerous mutations that confer resistance to anti-TB drugs, but there has been little systematic analysis to understand their genetic background and the potential impacts on the drug target stability and/or interactions. Here, we report the analysis of whole-genome sequence data for 98 clinical M. tuberculosis isolates from a city in southern India. The collection was screened for phenotypic resistance and sequenced to mine the genetic mutations conferring resistance to isoniazid and rifampicin. The most frequent mutation among isoniazid and rifampicin isolates was S315T in katG and S450L in rpoB respectively. The impacts of mutations on protein stability, protein-protein interactions and protein-ligand interactions were analysed using both statistical and machine-learning approaches. Drug-resistant mutations were predicted not only to target active sites in an orthosteric manner, but also to act through allosteric mechanisms arising from distant sites, sometimes at the protein-protein interface

Whole genome sequencing of bacteriophage NINP13076 isolated against Salmonella enteritidis

Salmonella ranks among the prominent etiological agents responsible for foodborne illnesses on a global scale. Within the scope of this investigation, a bacteriophage capable of eliminating Salmonella enteritidis was isolated using the double-layer agar overlay technique. The phage’s morphological characteristics were elucidated through the application of Transmission Electron Microscopy. The genomic DNA of the phage underwent complete sequencing utilizing the MiSeq platform, with library preparation executed through the NexteraXT library prep kit method accompanied by the NexteraXT index kit. Paired-end sequencing was performed over 2 × 251 cycles read length, employing a Miseq V3 kit within the Illumina MiSeq system. Notably, the phage manifested conspicuous plaques upon S. enteritidis when subjected to the double agar overlay technique. NINP13076 displayed a 22-min latency period with a calculated average burst size of 53 PFU/cell. Phages exhibited resilience to the diverse pH conditions, manifesting no discernible impact on their viability over a storage duration of up to one week. storage at temperatures of 4 ◦C, 26 ◦C, and 37 ◦C demonstrated minimal effects on the phage population, with no statistically significant alterations observed. Genome assembly yielded a draft genome encompassing 161,329 base pairs with a GC content of 44.4 % and achieved coverage at a depth of 104x. Phylogenetic tree analysis unveiled a highly proximate relationship with the Salmonella Phage SSE-121 genome, demonstrating a distance score of 0.1 and signifying its classification as a novel member within the SSE121 virus group

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB

Remodeling of cholinergic input to the hippocampus after noise exposure and tinnitus induction in Guinea pigs

Here, we investigate remodeling of hippocampal cholinergic inputs after noise exposure and determine the relevance of these changes to tinnitus. To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for 2 hr and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gap‐prepulse Inhibition of the acoustic startle (GPIAS) 12 weeks after the first noise exposure, followed by immunohistochemistry. Acoustic Brainstem Response (ABR) thresholds were elevated immediately after noise exposure for all experimental animals but returned to baseline levels several days after noise exposure. ABR wave I amplitude‐intensity functions did not show any changes after 2 or 12 weeks of recovery compared to baseline levels. In animals assessed 2‐weeks following noise‐exposure, hippocampal VAChT puncta density decreased on both sides of the brain by 20–60% in exposed animals. By 12 weeks following the initial noise exposure, changes in VAChT puncta density largely recovered to baseline levels in exposed animals that did not develop tinnitus, but remained diminished in animals that developed tinnitus. These tinnitus‐specific changes were particularly prominent in hippocampal synapse‐rich layers of the dentate gyrus and areas CA3 and CA1, and VAChT density in these regions negatively correlated with tinnitus severity. The robust changes in VAChT labeling in the hippocampus 2 weeks after noise exposure suggest involvement of this circuitry in auditory processing. After chronic tinnitus induction, tinnitus‐specific changes occurred in synapse‐rich layers of the hippocampus, suggesting that synaptic processing in the hippocampus may play an important role in the pathophysiology of tinnitus.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150542/1/hipo23058.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150542/2/hipo23058_am.pd

Phenotypic and genotypic characterization of Mycobacterium tuberculosis pyrazinamide resistance—India, 2018–2020

Pyrazinamide (PZA) is a key first-line antituberculosis drug that plays an important role in eradicating persister Mycobacterium tuberculosis (TB) bacilli and shortening the duration of tuberculosis treatment. However, PZA-resistance is on the rise, particularly among persons with multidrug-resistant (MDR) tuberculosis. This nationwide study was conducted to explore the prevalence of mutations conferring PZA resistance, catalogue mutation diversity, investigate the associations of PZA resistance with specific lineages, examine co-resistance to 13 first- and second-line drugs, and evaluate the diagnostic accuracy of sequencing pncA and panD genes for predicting PZA resistance. Whole genome sequencing was performed on 2,207 M. tuberculosis isolates from 25 States and 4 Union Territories of India. The majority of phenotypically PZA-resistant isolates (77%) harbored 171 distinct mutations in pncA; however, a small number of mutations in panD, rpsA and clpC1 were also observed. A set of novel mutations associated PZA resistance was uncovered, along with an additional 143 PZA resistance-conferring mutations in pncA based on application of WHO-endorsed grading rules. PZA resistance was predominately observed in Lineage 2 and eight lineage-specific resistance markers were identified. Mutations distributed across pncA correlate to 94% of PZA resistance and were the predominant drivers of phenotypic resistance; evidence generated herein substantiates sequencing the entire gene and promoter for comprehensive genotypic-based prediction of PZA resistance. This work provides key insights into the scope of PZA-resistance in India, a high drug-resistant TB burden country, and can support the effectiveness of TB prevention and control efforts