Biology subjects

Dash, P.

Publications and source records attributed to Dash, P..

8 recordsLinked to original sources

bioRxiv2026

Biogeography and cryptic diversity of the ancient centipede genus Digitipes (Scolopendromorpha) in South and Southeast Asia

Understanding the relative roles of vicariance and dispersal in shaping diversity and distribution patterns is central to historical biogeography. In this study, we investigate the historical biogeography of the ancient centipede genus Digitipes Attems, 1930 from South and Southeast Asia. First, we determined the phylogenetic position of the genus Digitipes within the Order Scolopendromorpha (n=414) by assembling primary and published sequences (n=30) for two mtDNA markers (COI, 16S) and one nuclear marker (28S) using Maximum Likelihood and Bayesian inference. We further used single-locus and multi-locus coalescent-based species delimitation methods to identify putative species within the genus Digitipes. We then used three fossil calibrations to estimate divergence times in a Bayesian framework, and used the resulting time-calibrated phylogeny for biogeographic analysis in a likelihood framework (BioGeoBEARS). The genus Digitipes was monophyletic with strong support, with SEA lineages nested within the Indian clade and sister to the D. barnabasi species complex from the Western Ghats. D. pruthii, the Eastern Ghats species, was nested with the Western Ghats species clade. A single-locus mPTP-based species-delimitation method suggested the presence of 24 putative species, far exceeding the number of morphologically described species, indicating an underestimation of species diversity. Divergence time estimates suggest that Digitipes began diversifying around 126 mya (100-159 mya), affirming its Gondwanan origin. Time-stratified ancestral area reconstruction suggested that early vicariance, followed by jump dispersal and range expansion, shaped the distribution of the genus Digitipes in South and Southeast Asia. There was one dispersal event from India to Southeast Asia, following a transient land connection between them, around 50 mya, supporting the Out-of-India hypothesis. Additionally, three jump dispersal events and five range expansions explained diversification within peninsular India. Particularly, D. pruthii originated from a jump dispersal event from the Central Western Ghats to the Eastern Ghats around 37 mya. Our results highlight the importance of an integrative taxonomic framework to delineate hidden diversity and to obtain robust species hypotheses for testing biogeographic hypotheses.

evolutionary biology↗

bioRxiv2025

AKNA drives neural stem cell fate transition through differential localization and coordinating the modulation of chromatin from H3K27me3 to H3K27ac

Neuronal stem cells (NSCs) play pivotal role in adult neurogenesis, however, detail mechanisms of obtaining pluripotency or undergoing differentiation remain unknown. Herein, how AT-hook protein AKNA regulates pluripotency and stemness in neuroblastoma cells is demonstrated by gene knockdown, immunofluorescence, chromatin immunoprecipitation (ChIP), localization of AKNA, signaling interactions and transcriptional activity. AKNA was abundant and mostly nuclear during induction of pluripotency and its knockdown reduced stemness, even in presence of other pluripotency factors, including OCT4 and SOX2. During the course of induction of differentiation, AKNA remain localized in the cytosol, essential for regulated differentiation. Cytosolic retention of AKNA is possibly driven by FAK signaling. In the nucleus, AKNA promotes KDM6B demethylase for H3K27me3 demethylation to H3K27, and subsequently promotes CBP/p300 to acetylate H3K27 to H3K27ac deposition on promoter region of respective genes to trigger their transcription. Data obtained from knockdown and overexpression of AKNA and KDM6B further reinforce its importance that, they physically interact to drive pluripotency and stemness. These findings establish AKNA as a critical regulator for NSCs fate determination in association with epigenetic modifiers and signaling pathway, offering potential targets for neuroblastoma therapies and regenerative medicines for neurodegenerative diseases.

molecular biology↗

bioRxiv2023

Massively parallel characterization of transcriptional regulatory elements in three diverse human cell types

The human genome contains millions of candidate cis-regulatory elements (CREs) with cell-type-specific activities that shape both health and myriad disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these CREs. Here, we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of over 680,000 sequences, representing a nearly comprehensive set of all annotated CREs among three cell types (HepG2, K562, and WTC11), finding 41.7% to be functional. By testing sequences in both orientations, we find promoters to have significant strand orientation effects. We also observe that their 200 nucleotide cores function as non-cell-type-specific on switches providing similar expression levels to their associated gene. In contrast, enhancers have weaker orientation effects, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, we develop sequence-based models to predict CRE function with high accuracy and delineate regulatory motifs. Testing an additional lentiMPRA library encompassing 60,000 CREs in all three cell types, we further identified factors that determine cell-type specificity. Collectively, our work provides an exhaustive catalog of functional CREs in three widely used cell lines, and showcases how large-scale functional measurements can be used to dissect regulatory grammar.

genomics↗

bioRxiv2021

A Co-abundant Gene Analysis for Identification of Gut Microbial Strains Associated with Immune Responses to Oral Cholera Vaccine

The degree of protection conferred after receiving an oral cholera vaccine (OCV) varies based on age, prior exposure to Vibrio cholerae, and unknown factors. Recent evidence suggests that the microbiota may mediate some of the unexplained differences in oral vaccine responses. We used metagenomic sequencing of the microbiota at the time of vaccination, and then related microbial features to immune responses after OCV using a reference-independent gene-level analysis. We found that the presence of sphingolipid-producing bacteria was associated with the development of protective immune responses after OCV. We experimentally tested these results by stimulating human macrophages with Bacteroides xylanisolvens metabolites and found that sphingolipid-containing extracts increased innate immune responses to OCV antigens. Our findings demonstrate a new analytic method for translating metagenomic sequencing data into strain-specific results associated with a biological outcome, and in validating this tool, we identified that microbe-derived sphingolipids impact in vitro immune responses to OCV antigens.

microbiology↗

bioRxiv2020

Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutated receptor binding domain with ACE2 receptor

SARS-CoV-2 is a RNA Coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). It has affected the whole world including Odisha, a state in eastern India. Many people migrated in the state from different countries as well as states during this SARS-CoV-2 pandemic. As per the protocol laid by ICMR and Health & Family welfare of India, all the suspected cases were tested for SARS-CoV-2 infection. The aim of this study was to analyze the RNA binding domain (RBD) sequence of spike protein from the isolates collected from the throat swab samples of COVID-19 positive cases and further to assess the RBD affinity with ACE2 of different species including human. Whole genome sequencing for 35 clinical SARS-CoV-2 isolates from COVID-19 positive patients was performed using ARTIC amplicon based sequencing. Sequence analysis and phylogenetic analysis was carried out for the Spike and RBD region of all isolates. The interaction between the RBD and ACE2 receptor of five different species was also analysed. Except three isolates, spike region of 32 isolates showed one/multiple alterations in nucleotide bases in comparison to the Wuhan reference strain. One of the identified mutation at 1204 (Ref A, RMRC 22 C) in the RBD of spike protein was identified which depicted a stronger binding affinity with human ACE2 receptor compared to the wild type RBD. Furthermore, RBDs of all the Indian isolates are capable of binding to ACE2 of human, bat, hamster and pangolin. As mutated RBD showed stronger interaction with human ACE2, it could potentially result in higher infectivity. The study shows that RBDs of all the studied isolates have binding affinity for all the five species, which suggests that the virus can infect a wide variety of animals which could also act as natural reservoir for SARS-CoV-2.

microbiology↗

bioRxiv2018

Macrophage migration inhibitory factor (MIF) of Syrian golden hamster (Mesocricetus auratus) has similar structure and function as human MIF and promotes pancreatic tumor growth in vivo

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize structure and function of hamster MIF, and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant hamster MIF (rha-MIF) was cloned, expressed and purified in bacterial expression system. The rha-MIF primary sequence, biochemical properties and crystal structure analysis showed a greater similarity with human MIF. The crystal structure of hamster MIF illustrates that it forms a homotrimer as known in human and mouse. However, hamster MIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that rha-MIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of rha-MIF into HapT1 pancreatic tumor bearing hamsters significantly enhanced the tumor growth and tumor associated angiogenesis. Together, the current study shows a structural and functional similarity between hamster and human MIF. Moreover, it has demonstrated that a high-level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.

biochemistry↗

bioRxiv2018

A strain of an emerging Indian pathotype of Xanthomonas oryzae pv. oryzae defeats the rice bacterial blight resistance gene xa13 without inducing a clade III SWEET gene and is nearly identical to a recent Thai isolate

The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae (Xoo) injects transcription activator-like effectors (TALEs) that bind and activate host susceptibility (S) genes important for disease. Clade III SWEET genes are major S genes for bacterial blight. The resistance genes xa5, which reduces TALE activity generally, and xa13, a SWEET11 allele not recognized by the cognate TALE, have been effectively deployed. However, strains that defeat both resistance genes individually were recently reported in India and Thailand. To gain insight into the mechanism(s), we completely sequenced the genome of one such strain from each country and examined the encoded TALEs. Strikingly, the two strains are clones, sharing nearly identical TALE repertoires, including a TALE known to activate SWEET11 strongly enough to be effective even when diminished by xa5. We next investigated SWEET gene induction by the Indian strain. The Indian strain induced no clade III SWEET in plants harbouring xa13, indicating a pathogen adaptation that relieves dependence on these genes for susceptibility. The findings open a door to mechanistic understanding of the role SWEET genes play in susceptibility and illustrate the importance of complete genome sequence-based monitoring of Xoo populations in developing varieties with effective disease resistance.

pathology↗

bioRxiv2018

Cell type-dependent effects of ellagic acid on cellular metabolism

Ellagic acid is a botanical polyphenol which has been shown to have numerous effects on cellular function. Ellagic acid can induce apoptosis and inhibit the proliferation of various cancer cell types in vitro and in vivo. As such, ellagic acid has attracted significant interest as a potential chemotherapeutic compound. One mechanism by which ellagic acid has been proposed to affect cellular physiology is by regulating metabolic pathways. Here we show the dose-dependent effects of ellagic acid on cellular energy production and downstream induction of the apoptotic program in HEK293, HeLa, MCF7, and HepG2 cells. At physiologically relevant doses, eallgic acid has pleiotropic and cell-type specific effects on mitochondrial function. At high doses ellagic acid can also influence glycolytic pathways and induce cell death. Our results demonstrate that ellagic acid can influence mitochondrial function at therapeutically relevant concentrations. The observed effects of ellagic acid on cellular respiration are complex and cell type-specific, which may limit the chemotherapeutic utility of this compound.

cell biology↗