Biology subjects

Panwar, A.

Publications and source records attributed to Panwar, A..

8 recordsLinked to original sources

bioRxiv2025

Decoding Rice Seed Storage Proteins: From Gene Identification to Structural Prediction

Rice seed storage proteins (SSPs) serve as the primary source of dietary protein, energy, and nutrition; however, our understanding of these proteins remains limited, hindering efforts aimed at enhancing grain nutritional quality. To address this, we conducted a comprehensive genome-wide analysis of rice SSPs, encompassing phylogenetic relationships, domain and motif characterization, promoter cis-element mapping, expression profiling, and 3D structural modeling. Through homology- and domain-based searches, we identified 65 SSP-encoding genes, including 19 previously uncharacterized members. Phylogenetic analysis and domain comparisons revealed evolutionary proximity between albumins and prolamins; and between globulins and glutelins. Albumins, glutelins and prolamins clustered tandemly implying that duplication has driven SSP expansion. Transcriptomic evidence indicated that albumins, globulins, and glutelins were transcriptionally active from S2 seed development stage, whereas prolamins initiated expression from S3 stage. Promoter analysis revealed several seed-specific cis-regulatory elements, with CAATBOX1, EBOXBNNAPA, and DOFCOREZM being the most prevalent. Structural modeling showed that albumins and prolamins predominantly adopted -helical conformations, whereas globulins and glutelins were enriched in {beta}-strands and coils. This integrated analysis offers valuable insights into the classification, evolution, regulation, and structure of rice SSPs, providing a foundational resource for advancing grain nutritional improvement strategies.

plant biology↗

bioRxiv2025

Brain Stroke Prediction: A PSO Optimized Stacked Ensemble Machine Learning Approach with SMOTEEN Data Balancing

Prediction of stroke is a critical challenge in healthcare, where early intervention can significantly reduce risks and improve patient outcomes. Traditional methods often struggle with imbalanced datasets and low prediction accuracy. This paper proposes a novel approach to address these issues by combining PSO-optimized Stacked Ensemble ML Classifiers with SMOTEEN data balancing to predict strokes effectively. The technique optimizes 3 Baseline ML Classifiers(RF, SVM, XGB) using Particle Swarm Optimization (PSO) and Stacked Ensemble approach is applied that significantly improving prediction performance. The proposed methodology achieved an impressive 95.57% accuracy, outperforming conventional models such as SVM, LR, RF, KNN, XGB. Overall, the PSO-optimized stacked ensemble approach outperforms traditional machine learning techniques in stroke prediction, providing a more accurate and robust model for early detection and intervention.

bioengineering↗

bioRxiv2024

A novel repressor-activator-competitor module comprising C2H2 zinc finger and NAC transcription factors regulates rice grain development

Grain size and quality are crucial agronomic traits. We have characterized a seed-preferential C2H2 zinc finger transcriptional repressor, ZOS1-15. Its overexpression, knock-down and knock-out plants indicated a negative control over grain size due to altered cell expansion. ZOS1-15 homodimerized and directly interacted with co-repressor TOPLESS and histone deacetylases to form a repression complex. ZOS1-15 also interacted with Mediator subunit MED14_1 and a seed-preferential transcriptional activator, ONAC024, with three alternatively spliced isoforms. The ectopic expression of ONAC024 negatively affected plant growth and development. Seed-preferential overexpression and knock-down plants showed ONAC024 as a positive regulator of grain length due to increased cell proliferation and expansion. CRES-T generated transgenic rice plants indicated a functional divergence amongst ONAC024 isoforms. Tandem interactions were observed between ONAC024-ONAC023-ONAC026-ONAC020. ZOS1-15 and ONAC024 functioned antagonistically to regulate grain amylose and SSP accumulation while ONAC023 affected only amylose. ZOS1-15 and ONAC024 directly regulated the expression of two SSP encoding genes. Binding of ONAC024 was competed by ONAC025-MADS29 complex. The seed-preferential overexpression of SS1/ ONAC025 resulted in decreased grain size and amylose content, but higher yield. This study proposes a repressor-activator-competitor module, wherein ZOS1-15, ONAC024, ONAC023, ONAC025 along with their interactors synergistically and antagonistically regulate multiple aspects of rice grain development.

plant biology↗

bioRxiv2024

Screening of glucose binding proteins for the development of biosensors

Selecting suitable glucose-binding proteins (GBPs) is vital for biosensor development for medical diagnostics and quality control in the food industry. Biosensors offer advantages such as high specificity, selectivity, fast response time, continuous measurement, and cost-effectiveness. The current work utilized a combination of molecular docking, molecular dynamics (MD) simulations, and free energy calculations to develop a high-throughput bioinformatics pipeline to select GBP candidates from an extensive protein database (37,325 proteins). Using molecular docking, GBPs with good binding affinity to glucose (1,447 candidates) were virtually screened from the Protein Data Bank. MD simulations ascertained the binding dynamics of a few selected candidates. Further, steered MD (Brownian dynamics fluctuation-dissipation-theorem) was used to estimate binding free energies of the ligand-protein complex. Correlations between ligand-binding parameters obtained from longer MD simulations and binding parameters interpreted from significantly faster docking simulations were investigated. The correlation plots suggested that a combination of threshold values of the following three docking parameters: docking binding energy, binding cavity depth, and the number of hydrogen bonds between the ligand and binding site residues can be used to predict candidate GBPs reliably. Thus, a high-throughput and accurate protein selection process based on relatively faster docking simulations was proposed to screen GBPs for glucose biosensing.

bioinformatics↗

bioRxiv2024

Age-related memory CD8 T cells induce and track Alzheimers-like neurodegeneration

Cerebral (A{beta}) plaque and (pTau) tangle deposition are hallmarks of Alzheimers disease (AD), yet are insufficient to confer complete AD-like neurodegeneration experimentally. Factors acting upstream of A{beta}/pTau in AD remain unknown, but their identification could enable earlier diagnosis and more effective treatments. T cell abnormalities are emerging AD hallmarks, and CD8 T cells were recently found to mediate neurodegeneration downstream of tangle deposition in hereditary neurodegeneration models. The precise impact of T cells downstream of A{beta}/fibrillar pTau, however, appears to vary depending on the animal model used. Our prior work suggested that antigen-specific memory CD8 T ("hiT") cells act upstream of A{beta}/pTau after brain injury. Here we examine whether hiT cells influence sporadic AD-like pathophysiology upstream of A{beta}/pTau. Examining neuropathology, gene expression, and behavior in our hiT mouse model we show that CD8 T cells induce plaque and tangle-like deposition, modulate AD-related genes, and ultimately result in progressive neurodegeneration with both gross and fine features of sporadic human AD. T cells required Perforin to initiate this pathophysiology, and IFN{gamma} for most gene expression changes and progression to more widespread neurodegenerative disease. Analogous antigen-specific memory CD8 T cells were significantly elevated in the brains of human AD patients, and their loss from blood corresponded to sporadic AD and related cognitive decline better than plasma pTau-217, a promising AD biomarker candidate. Our work is the first to identify an age-related factor acting upstream of A{beta}/pTau to initiate AD-like pathophysiology, the mechanisms promoting its pathogenicity, and its relevance to human sporadic AD. Significance StatementThis study changes our view of Alzheimers Disease (AD) initiation and progression. Mutations promoting cerebral beta-amyloid (A{beta}) deposition guarantee rare genetic forms of AD. Thus, the prevailing hypothesis has been that A{beta} is central to initiation and progression of all AD, despite contrary animal and patient evidence. We show that age-related T cells generate neurodegeneration with compelling features of AD in mice, with distinct T cell functions required for pathological initiation and neurodegenerative progression. Knowledge from these mice was applied to successfully predict previously unknown features of human AD and generate novel tools for its clinical management.

neuroscience↗

bioRxiv2022

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of autism associated gene Zmynd11 prior to onset of motor symptoms

Mutations in TDP-43 are known to cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). TDP-43 binds to and regulates splicing of several RNA including Zmynd11. Zmynd11 is a transcriptional repressor and a potential E3 ubiquitin ligase family member, known for its role in neuron and muscle differentiation. Mutations in Zmynd11 have been associated with autism with significant developmental motor delays, intellectual disability, and ataxia. Here, we show that Zmynd11 is aberrantly spliced in the brain and spinal cord of transgenic mice overexpressing a mutant human TDP-43 (A315T), and that these changes occur before the onset of motor symptoms.

neuroscience↗

bioRxiv2021

Traditional use of Cissampelos pareira L. for hormone disorder and fever provides molecular links of ESR1 modulation to viral inhibition

Bioactive fractions or compounds obtained from medicinal plants have been used for the treatment of multiple diseases. This effect could be due to common pathways underlying these conditions that are targeted by such medicines. In this study, we explored the molecular basis of action of one such herbal formulation Cissampelos pareira, used for the treatment of female hormone disorders and fever. Genome-wide expression studies on MCF7 cell lines treated with Cipa extract were carried out using Affymetrix arrays. Transcriptome analysis revealed a downregulation of signatures of estrogen response governed by estrogen receptor (ER). Molecular docking analysis identified 38 constituent molecules in Cipa that potentially bind ({Delta}G< -7.5) with ER at the same site as estrogen. Cipa transcriptome signatures show high positive connectivity (https://clue.io/) scores with protein translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is also an ER coactivator. Cipa exhibits antiviral activity in dengue infected MCF7 cells that is decreased upon ESR1 (estrogen receptor 1) gene knockdown. This approach reveals a novel pathway involving ESR1-RPL7 axis that could be a potential target in dengue viral infection.

genomics↗

bioRxiv2020

Genome-wide comparisons and extrapolations of AU-rich elements in Plants with Homo sapiens

The Adenylate-Uridylate Rich elements (AREs) are adenine and uracil abundant sequences, established in ephemeral mRNAs, principally present in the 3 untranslated region (3 UTR). AREs are widely accepted as a cause of high turnover of the mRNAs containing them (Bakheet, 2001; Barreau, 2005; Shaw and Kamen, 1986). The mammalian ARE-mRNAs primarily translate into nuclear transcription factors, oncoproteins, cytokines, and G-protein-coupled receptors which indicates their indispensable role in the regulation of gene transcription during cell growth and differentiation, and the immune response (Chen and Shyu, 1995; Wilson et al., 1999). The present study is an attempt to comprehensively analyze the eloquent presence of AU rich elements in genome, transcriptome and 3UTR of three important plant species (Arabidopsis thaliana, Oryza sativa and Zea mays) and compare the statistics of putative ARE motifs in plants with H.sapiens. Statistical analysis of genome-wide putative AU-rich elements revealed the explicit presence of ARE motifs in plants. This is the first study that analyses the presence of Adenylate-Uridylate Rich elements (AREs) in three different plants which can be further validated through experiments.

bioinformatics↗