Biology subjects

Srivastava, P. K.

Publications and source records attributed to Srivastava, P. K..

6 recordsLinked to original sources

bioRxiv2026

Evidence of residual Brugia malayi infection in TAS-III cleared areas of coastal Odisha: Findings from Molecular Xenomonitoring

BackgroundLymphatic filariasis (LF), caused by Wuchereria (W) bancrofti, Brugia malayi and Brugia (B) timori, remains a major public health problem known for its disfiguring and debilitating effects despite notable progress under the Global Program to Eliminate Lymphatic Filariasis (GPELF). Following recent national directives (2024) restructuring implementation units (IUs) to the block level, all TAS-cleared blocks now require re-evaluation using night blood surveys (NBS) or filarial test strip (FTS) kits. Molecular Xenomonitoring (MX) is recommended as a post-validation surveillance method for detecting active LF transmission in vectors. Therefore, an exploratory study was conducted in two coastal districts of Odisha, namely Jagatsinghpur and Puri, which cleared TAS-III, to investigate the presence of B. malayi and W. bancrofti infections in filaria-transmitting vectors. Methodology/Principal FindingsAdult female mosquitoes were collected from three villages across Jagatsinghpur and Puri districts during March-April 2025. Species were identified morphologically, segregated and pooled. The pooled samples were screened for the presence of filarial DNA using species-specific PCR assays. Of 1,518 collected adult female mosquitoes, 22.6% were Culex quinquefasciatus, 18.3% were Mansonia (Mn) annulifera, and 4.3% were Mansonia uniformis. Among 33 pools screened, six pools were positive for B. malayi DNA (18.18% pool positivity; infection rate 2.88%, 95% CI: 1.23-5.74), in Mn. annulifera, whereas W. bancrofti was not detected. Conclusions/SignificanceThe study provides the first molecular confirmation of B. malayi infection in Mn. annulifera, indicating a persistent Brugian transmission in Odisha even after the implementation of mass drug administration. The Study highlights MX as a sensitive, non-invasive surveillance tool for detecting residual infection in post-MDA and post-TAS settings. The study underscores the need for a standardized MX protocol and integration with entomological monitoring to sustain national LF elimination targets by 2027. Author SummaryLymphatic filariasis is a mosquito-borne disease that can cause severe, disfiguring swelling of the limbs and other lasting disabilities, and it remains a serious public health problem in India. National programmes in India are actively working to eliminate it by giving preventive medicines to communities, conducting surveys to confirm that transmission has ceased, and once an area passes, this treatment is withdrawn. However, it is not always clear whether the parasite has truly disappeared or is still lingering at very low levels. In this study, we searched for the parasite directly inside mosquitoes, an approach that does not require collecting blood from people. We sampled mosquitoes from two coastal districts of Odisha, India, that had already passed the required surveys and stopped treatment. We found the parasite Brugia malayi in Mansonia mosquitoes, the first time this has been shown using this molecular method in the region, although the more common filarial parasite was not detected. Our findings show that transmission can smoulder on even after an area is judged free of disease. Because India has no available rapid field test for this particular parasite, we argue that examining mosquitoes should become a routine safeguard for the countrys elimination effort.

zoology↗

bioRxiv2024

circRNA-miRNA-mRNA networks reveal a proangiogenic action of circNPHP1 in human ischemic heart disease

BackgroundIschemic heart disease (IHD) is characterized by insufficient myocardial blood flow in the left ventricle and aggravated by diabetes mellitus. Endothelial resilience and reparative angiogenesis are tightly controlled processes. Gene expression is regulated by multimodal interactions between RNA species. Circular RNAs (circRNAs) can sponge microRNAs (miRNAs) to reduce the repressive effects of miRNAs on its messenger RNA (mRNAs) targets. MethodsLeft ventricle whole RNA-sequencing (circRNAs, mRNAs) and small RNA- sequencing (miRNAs) datasets were obtained from 3 patient groups: IHD with/out T2DM and controls (N=11 to 12/group) as part of a prospective observational cardiac surgery study. The interactions between differentially expressed (DE) circRNAs, miRNA and mRNAs were identified with a customized bioinformatics pipeline. The emerging networks were screened using endothelial-specific RNA-sequencing datasets from GEO resulting in EC-rich networks. CircRNAs from these networks were subsequently screened (RT-PCR) in endothelial cells (ECs) exposed to disease-mimicking conditions vs control. Afterwards, circRNA pulldown allowed to interrogate the circRNA-miRNAs interactome in ECs. EC biology assays using loss-of-function and gain-of-function approaches corroborated the study. ResultsWe identified novel circRNA-miRNA-mRNA interactions in the human diseased heart. CircNPHP1, which is upregulated in IHD with/out Type-2 diabetes mellitus (T2DM), sponges miR-221-3p to de-repress VEGF-A and BCL2, increasing the angiogenic capacity of ECs under disease and disease-mimicking conditions. ConclusionsThe interactions between individual members of different RNA species are affected by IHD. The therapeutic value of circNPHP1/miR-221-3p axis could be further investigated. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/597402v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@18a3b0forg.highwire.dtl.DTLVardef@2b5dc1org.highwire.dtl.DTLVardef@11848c3org.highwire.dtl.DTLVardef@1511c9e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe found a novel circRNA-miRNA-mRNA network in IHD and Type 2 diabetes. C_LIO_LICircNPHP1 regulates angiogenesis and proliferation in the cardiac ECs exposed to conditions mimicking IHD and Type 2 diabetes. C_LIO_LIWe elucidated a novel pro-angiogenic subnetwork commanded by circNPHP1/miR-221-3p/BCL2/VEGFA. C_LIO_LIWe identified circNPHP1 as a potential new target for therapeutic angiogenesis. C_LI

cell biology↗

bioRxiv2024

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Liver hepatocellular carcinoma (LIHC) is one of the most frequent types of malignant cancer in the globe. The identification of new biomarkers for the LIHC is critical. We used TCGA-LIHC gene expression datasets for this study. Several feature selection methods were used to find the top gene signatures that distinguish LIHC cancer from normal samples. Eleven machine learning algorithms were used on these selected characteristics, and model performance evaluation revealed that Naive Bayes Classifiers (AUC = 0.965) performs the best for a selection of 55 protein coding genes. Among 55 protein coding genes we found B4GALNT1 (Beta-1,4-N-acetyl-galactosaminyltransferase 1) which is differentially regulated in LIHC. With several evidence B4GALNT1 plays crucial role in tumorigenesis in many cancers, therefore we conducted systematic bioinformatics approach with mutational and structural analysis of B4GALNT1 in LIHC. Moreover, survival analysis, immune cell infiltration, most significant associated methylated CpG probe and access the accuracy of B4GALNT1 conducted to find the potential role of B4GALNT1. The results suggested that B4GALNT1 was significantly expressed in most cancers including LIHC. Finally, 16 missense mutations identified through cBioportal, Cosmic Database, and Human Variant Database, among which 6 mutations (P64Q, S131F, A311S, R340Q, D478H, and P507Q) found to be deleterious when analysed by in-silico prediction algorithms such as SIFT, PolyPhen2, I Mutent2 and CADD in LIHC. Molecular Dynamics simulation analysis was performed to understand the atomic details of the structure and functional changes. Results from this study suggest the impact of these missense variants on the structure of the B4GALNT1 protein and its pathogenic relevance. Our study demonstrated that B4GALNT1 may be evaluated as a novel target for liver cancer therapy because it has been found to be overexpressed in Liver and correlates with a poor prognosis.

bioinformatics↗

bioRxiv2023

Interleukin 11-induced microRNAs as functional mediators and circulating biomarkers of cardiac fibrosis

BackgroundCardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis (AS). Cardiac fibrosis is brought about by uncontrolled extracellular matrix (ECM) deposition by myofibroblasts. Interleukin-11 (IL-11) has been firmly demonstrated to be a major trigger of multi-organ fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis requires further characterisation. Recent studies indicate that microRNA (miRNA) dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. In this study, we explored the hypothesis that miRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated miRNAs as circulating biomarkers of cardiac fibrosis in AS patients. Methods and ResultsUsing computational approaches, we identified miRNA-497-5p and miRNA-27b-5p as potential new downstream profibrotic effectors of IL-11 in fibroblasts. We next confirmed that both miRNAs increased in healthy rat CF stimulated with IL-11 and in CF derived from post-infarction failing hearts. At the functional level, miRNA-497-5p and miRNA-27b-5p inhibition indirectly reduced the mRNA expression of collagen 1 (Col1a1). Conversely, transfection of CFs with mimics for each of the two miRNAs promoted fibroblast-to-myofibroblast transition and increased Col1a1 levels. We provided evidences that miRNA-27b-5p and miRNA-497-5p converge to promote hypoxia-inducible factor 1 signalling, by targeting its regulator EGLN (PHD) family members. The clinical relevance of our findings was confirmed using left ventricle (LV) specimens obtained from surgical patients with AS. The miRNA-27b-5p and miRNA-497-5p measured in the LV, peripheral plasma and plasma extracellular vesicles correlated with the severity of LV fibrosis, indicating these miRNAs potential as new circulating biomarkers of cardiac fibrosis. ConclusionsIn this study, we have newly identified the potential value of miRNA-27b-5p and miRNA-497-5p as actionable biomarkers of the profibrotic response to IL-11 in the heart. Future studies should validate the translational potential of the miRNAs as new clinical biomarkers and therapeutic targets.

molecular biology↗

bioRxiv2022

Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour

Translating genome-wide association loci to therapies requires knowledge of the causal genes, their directionality of effect and the cell-types in which they act. To infer these relationships in the human brain, we implemented Mendelian randomisation using single cell-type expression quantitative trait loci (eQTLs) as genetic anchors. Expression QTLs were mapped across 8 major cell-types in brain tissue exclusively ascertained from donors with no history of brain disease. We report evidence for a causal association between the change in expression of 118 genes and one or more of 16 brain phenotypes, revealing candidate targets for risk mitigation and opportunities for shared preventative therapeutic strategies. We highlight key causal genes for neurodegenerative and neuropsychiatric disease and for each, we report its cellular context and the therapeutic directionality required for risk mitigation. Our use of control samples establishes a new resource for the causal interpretation of GWAS risk alleles for human brain phenotypes.

neuroscience↗

bioRxiv2017

A Systems-Level Framework For Drug Discovery Identifies Csf1R As A Novel Anti-Epileptic Drug Target

The identification of mechanistically novel drug targets is highly challenging, particularly for diseases of the central nervous system. To address this problem we developed and experimentally validated a new computational approach to drug target identification that combines gene-regulatory information with a causal reasoning framework (\"causal reasoning analytical framework for target discovery\" - CRAFT). Starting from gene expression data, CRAFT provides a predictive functional genomics framework for identifying membrane receptors with a direction-specified influence over network expression. As proof-of-concept we applied CRAFT to epilepsy, and predicted the tyrosine kinase receptor Csf1R as a novel therapeutic target for epilepsy. The predicted therapeutic effect of Csf1R blockade was validated in two pre-clinical models of epilepsy using a small molecule inhibitor of Csf1R. These results suggest Csf1R blockade as a novel therapeutic strategy in epilepsy, and highlight CRAFT as a systems-level framework for predicting mechanistically new drugs and targets. CRAFT is applicable to disease settings other than epilepsy.

systems biology↗