Biology subjects

Pandey, J.

Publications and source records attributed to Pandey, J..

9 recordsLinked to original sources

bioRxiv2026

Variation in infant subcortical brain development from 6 to 12 months in Down syndrome

IntroductionDown syndrome (DS), arising from Trisomy 21, is the most common genetic condition associated with intellectual disability. While smaller total brain volumes have been consistently observed in DS, no longitudinal neuroimaging studies have examined volumetric brain development in DS during infancy, a period of rapid neural growth when interventions may have the greatest impact. MethodHigh-resolution T1- and T2-weighted images were acquired during natural sleep in a multisite longitudinal cohort of 44 infants with DS and 39 control infants without DS at ages 6 and 12 months. Neuroimaging data were harmonized to reduce batch effects, and a novel deep-learning, repeated-measures segmentation approach was applied to optimize neuroanatomical segmentations. Total intracranial volume (ICV) and bilateral absolute subcortical volumes (amygdala, caudate, hippocampus, pallidum, putamen, thalamus) were first directly compared in infants with and without DS at 6 and 12 months. Hierarchical linear modeling (HLM) evaluated longitudinal group differences for each structure, accounting for sex, gestational age, and laterality. Subcortical group differences estimated by HLM were also compared to group differences in total ICV. ResultsICV in infants with DS was lower than controls at 6 months (12.6%; p<.001) and 12 months (16.3%; p<.001). Subcortical structures displayed a range of lower volumes (6.9%-13.1%; ps[≤].003) in infants with DS, although the caudate and putamen were exceptions. Caudate volumes were on average lower in DS but not significantly different from controls, while putamen volumes were on average higher in DS but not significantly different from controls, except for the right putamen, which was significantly larger (5.3%; p=.018) at 6 months. In HLM, ICV and all subcortical structures showed slower growth in DS from 6 to 12 months, except for the amygdala and putamen, which displayed similar growth rates to controls. DS-associated reductions in subcortical volumes were similar in magnitude to ICV, although 12-month caudate and 6- and 12-month putamen volumes were enlarged relative to ICV. ConclusionInfants with DS exhibited substantially reduced ICV and widespread reductions in subcortical volumes and growth from 6-12 months. Across a range of volumetric differences, findings were most distinct in the basal ganglia, for which volume reductions were attenuated in the caudate, while the putamen was uniquely enlarged with comparable growth to controls. These observations support early regional specificity in the neural impact of Trisomy 21 and underscore the utility of infant neuroimaging to inform biologically based interventions and clinical trial readiness in DS.

neuroscience↗

bioRxiv2025

Early cell cycle genes in cortical organoid progenitors predict interindividual variability in infant brain growth trajectories

Human induced pluripotent stem cell (iPSC) derived cortical organoids (hCOs) model neurogenesis on an individuals genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from which they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who have undergone longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of cortical hem cells were associated with in vivo cortical growth rates. Cell cycle associated genes expression in early progenitors at the crux of fate decision trajectories were correlated with cortical growth rate from 6-12 months of age, and were enriched in microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types influencing infant cortical surface area expansion.

neuroscience↗

bioRxiv2024

A first-in-Plasmodium study on tRNA intron splicing endonuclease PfTSEN1 and its substrate expression in clinical stage malaria

Mature tRNAs play critical role in several cellular processes including protein translation, post-translational-modifications and programmed-cell-death. Maturation of pre-tRNAs require removal of 5-leaders, 3-trailers, splicing of introns and addition of conserved 3-terminal CCA sequence. The tRNA splicing mechanism, an essential step in tRNA maturation govern by a tRNA splicing endonuclease. While the existence of functional tRNA splicing endonuclease(s) in Plasmodium falciparum has not been identified, its significance in other eukaryotes suggests a potential role in tRNA splicing event. Our study identified total tRNAs in Plasmodium and characterize a PftRNA splicing endonuclease (annotated as PfTSEN1) recognised recently as a component of ribonucleoprotein (RNP) complex, and synthesized a naphthoquinone derivative as a novel anti-malarial compound ( TSENi) targeting the functional activity of this protein. Enzyme activity assays elucidated that PfTSEN1 catalyses splicing of in vitro transcribed pre-tRNAleu, the expression of which was confirmed during the clinical stages of malaria parasite by RT-PCR. Interestingly, TSENi binds to and inhibits enzymatic activity of PfTSEN1, and showed potent anti-malarial activity against chloroquine-sensitive 3D7 and resistant strains Dd2 of P. falciparum. Overall, our study deliver key knowledge towards the functional role of PftRNA splicing endonuclease, and its inhibitor TSENi as potent anti-malarial.

molecular biology↗

bioRxiv2024

Clonal spheroids capture functional and genetic heterogeneity of head and neck cancer

Head and neck cancer squamous cell carcinoma (HNSCC) cells exhibit both structural and functional diversity, making them valuable models for understanding tumor heterogeneity at clinical levels. In this study, we generated single-cell-derived spheroids (SCDS) from HNSCC cell lines and patient tumor cells using scaffold- and non-scaffold-based methods to assess this variability. A distinct structural variability among these SCDS, categorized as hypo- and hyperproliferative spheroids based on size, was observed. Hyperproliferative spheroids demonstrated heightened proliferative and tumorigenic potential and increased sensitivity to cisplatin and radiation, while hypoproliferative spheroids exhibited enhanced migratory capabilities. Single-cell RNA sequencing (scRNA-seq) of hypo- and hyperproliferative spheroids provided insights into the transcriptional landscape of HNSCC cells, validating the observed structural and functional heterogeneities within primary tumors. These functionally and genetically characterized spheroids offer valuable tools for the development of next-generation therapeutics. Statement of SignificanceEstablishment and characterization of single-cell-derived spheroids from head and neck cancer cells, employing scaffold and non-scaffold materials, demonstrate functional and genetic heterogeneity. Single-cell analysis reveals correlations between genetic diversity and spheroid functionality. These characterized spheroids offer potential for advancing therapeutics development.

cancer biology↗

bioRxiv2022

Examining Anxiety and Risk-taking in Healthy Male and Female Wistar Rats using Spatial and Temporal Analysis of Elevated Plus Maze

The Elevated Plus Maze (EPM) offers a standard set up for understanding anxiety, unconditioned risk-avoidance in rodents. The animal shows a preference for enclosed safe arms and avoids risky, open arms that evoke anxiety due to elevated platform (unconditioned response to elevation). A few rodent studies aiming to understand sex-skewed representation in anxiety disorders use the maze and report that more females compared to males show high levels of anxiety and risk-avoidance on an elevated platform. Ethograms derived from examining animal behaviour in the EPM provide precise measures of behaviour of interest, enabling objective assessment of anxiety and risk behaviour. We report two new parameters that might be critical for quantitative analysis of EPM task as a measure of anxiety with reference to sex-differences in risk-taking: (a) spatial preference for arms (open & closed) (b) temporal shift in arm preference in task trials. We first report results from the conventionally derived measures confirming that males spent more time in the open arms indicating low anxiety and higher risk-taking. Preferences for the two open and two closed arms were non-uniform for males and females; male showed stronger preference for one of the two risky open arms, and females showed a stronger preference for one of the two safe closed arms. Temporal analyses indicated that males spent more time in open arms in 3 out of 6 time bins (time blocks), and females spent more time in the closed arms in 5 out of 6 time bins (time blocks), however, counter-intuitively, females showed larger increase in time spent in open arms in the last phase potentially indicating greater regulation of anxiety and increased risk-taking. Inclusion of spatial and temporal parameters in EPM studies might improve our understanding of cognitive and biological sex-differences pertaining to anxiety, and risky behaviour.

animal behavior and cognition↗

bioRxiv2020

Plant Prionome maps reveal specific roles of prion-like proteins in stress and memory

Prions can be considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been demonstrated to be present in plants, but their role in plant stress and memory remains largely unexplored. In this work, we report the widespread presence of PrLPs in plants through a comprehensive analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with plant prionomes. Investigation of the rice transcriptome further delineated the role of PrLPs in stress and developmental responses, leading us to explore whether and to what extent PrLPs may build stress memory. The rice prionome is significantly enriched for Transposons/Retrotransposons (Ts/RTRs), and we derived transcriptional regulatory inferences from diurnal gene expression revealing a complex regulatory network between PrLPs, transcription factors and genes known to be involved in stress priming, as well as transient and trans-generational plant memory. Overall, our data suggest that plant memory mechanisms may rely upon protein-based signals embedded in PrLPs, in addition to chromatin-based epigenetic signals and provides important insights into the anticipated role of prions in stress and memory.

plant biology↗

bioRxiv2020

Computational investigation for modelling the protein-protein interaction of TasA(28-261)with TapA(33-253); a decisive process in biofilm formation by Bacillus subtilis

Biofilms have significant role in microbial persistence, antibiotic resistance and chronic infections; consequently, there is a pressing need for development of novel "anti-biofilm strategies". One of the fundamental mechanisms involved in biofilm formation is protein-protein interactions of amyloid like proteins (ALPs) in extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of biomolecular interaction with conventional structure biology tools including X-Ray diffraction and Nuclear Magnetic Resonance is technically challenging, expensive and time-consuming. In contrast, modelling such interactions is time-efficient, economical and might provide deeper understanding of structural basis of interactions. Therefore, during the present study, protein-protein interaction of TasA(28-261)-TapA(33-253) (which is a decisive process for biofilm formation by Bacillus subtilis) was modeled using in silico approaches viz., molecular modelling, protein-protein docking and molecular dynamics simulations. Results identified amino-acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with PCA and FEL analyses. Results presented here represent novel finding and we hypothesize that aa identified during the present study could be targeted for inhibition of biofilm formation by B. subtilis.

bioinformatics↗

bioRxiv2020

Multi-epitope based peptide vaccine design against SARS-CoV-2 using its spike protein

SARS-CoV-2 has been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia, and economic recession, the virus has brought together countries to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities concerning the design of vaccines are being worked upon. We attempted a structure-based approach utilizing a combination of epitope prediction servers and Molecular dynamic (MD) simulations to develop a multi-epitope-based subunit vaccine that involves the two subunits of the spike glycoprotein of SARS-CoV-2 (S1 and S2) coupled with a substantially effective chimeric adjuvant to create stable vaccine constructs. The designed constructs were evaluated based on their docking with Toll-Like Receptor (TLR) 4. Our findings provide an epitope-based peptide fragment that can be a potential candidate for the development of a vaccine against SARS-CoV-2. Recent experimental studies based on determining immunodominant regions across the spike glycoprotein of SARS-CoV-2 indicate the presence of the predicted epitopes included in this study.

bioinformatics↗

bioRxiv2017

Evolution and Engineering of Allosteric Regulation in Protein Kinases

Allosteric regulation - the control of protein function by sites far from the active site - is a common feature of proteins that enables dynamic cellular responses. Reversible modifications such as phosphorylation are well suited to mediate such regulatory dynamics, yet the evolution of new allosteric regulation demands explanation. To understand this, we mutationally scanned the surface of a prototypical kinase to identify readily evolvable phosphorylation sites. The data reveal a set of spatially distributed \"hotspots\" that coevolve with the active site and preferentially modulate kinase activity. By engineering simple consensus phosphorylation sites at these hotspots we successfully rewired in vivo cell signaling. Beyond synthetic biology, the hotspots are frequently used by the diversity of natural allosteric regulatory mechanisms in the kinase family and exploited in human disease.\n\nONE SENTENCE SUMMARYCell signaling is easily rewired by introducing new phosphoregulation at latent allosteric surface sites.

systems biology↗