Biology subjects

Rath, B.

Publications and source records attributed to Rath, B..

5 recordsLinked to original sources

bioRxiv2026

Genome-wide analysis of Heavy metal ATPase (P1B-type ATPase) gene family in Mung bean and their expression analysis under heavy metal (Zn, Cd and Cu) stress

Heavy metal ATPases (HMAs) are important group of transmembrane proteins involved in homeostasis of metal ions in plant systems. In this study, a comprehensive analysis of genome assembly (VC1973A v7.1) resulted in the identification of nine HMA genes (VrHMA) and their corresponding proteins in Mungbean, an agronomically important legume crop known for its nutritional values. VrHMA proteins were also characterized based on their biomolecular features, conserved domains and motifs arrangement, transmembrane helices, pore-line helices, subcellular location and occurrence of signal peptides. Based on sequence homology, nine VrHMAs were clustered into two major substrate-specific groups: VrHMA1, VrHMA5 and VrHMA7 were categorized under the Zn/Co/Cd/Pb ATPase group, whereas the remaining six VrHMAs belong to the Cu/Ag subgroup. Gene structure analysis and promoter scanning revealed the structural divergence and presence of various stress-responsive cis-acting elements, respectively. The expression analysis of VrHMA genes in root and leaf tissues, in response to heavy metal (Zn, Cd and Cu) stress, indicates their role in the uptake, transport and sequestration of metal ions. Interestingly, VrHMA5 showed incremental upregulation in roots in response to all three heavy metal stresses, whereas its expression was only upregulated in the leaf tissues under Zn stress, which indicates its role in vascular transport in V. radiata. In addition, this study provides valuable insights into the functional roles of VrHMA genes and will lay a foundation for future genetic improvement in mung bean aimed at enhanced heavy metal stress tolerance and micronutrient homeostasis.

molecular biology↗

bioRxiv2025

YAP/TEAD4-reagulated placental alkaline phosphatases ALPP and ALPPL2 are immunosuppressive ectonucleotidases modulated by MAPK inhibitors

Placental alkaline phosphatases ALPP and ALPPL2 (ALPP/L2) are promising clinical targets for therapies such as antibody-drug conjugates (ADCs). However, their regulation and biological functions remain unclear. Here, we identify the YAP/TEAD4 signaling axis as the primary regulator of ALPP/L2 expression in tumor cells. Importantly, we demonstrate that inhibitors targeting KRAS, MEK, and ERK upregulate ALPP/L2 expression in vitro and in vivo, thereby enhancing the efficacy of antibody-drug conjugates (ADCs) when used in combination. Moreover, our work reveals a novel immunomodulatory function of ALPP/L2 as cell surface ectonucleotidases that hydrolyze extracellular ATP, ADP, and AMP to adenosine, promoting regulatory T cell infiltration into the tumor microenvironment. Together, these findings reveal a biological function of ALPP/L2 and identify druggable regulators to enhance ALPP/L2-targeted therapies. SIGNIFICANCEThis study uncovers the YAP/TEAD pathway as a positive regulator of the clinically relevant tumor-associated antigens ALPP and ALPPL2. Kras, MEK, or ERK inhibitors enhance ALPP/L2 expression in tumor cells, thereby increasing the efficacy of ALPP/L2-targeted antibody-drug conjugates. These findings offer a promising combination strategy to overcome resistance to ALPP/L2-based therapies caused by low target expression.

cancer biology↗

bioRxiv2023

Spatial Transcriptomic Characterization of Novel Pathologic Niches in IPF

An unmet medical need persists in Idiopathic Pulmonary fibrosis (IPF), for which treatments additional to anti-fibrotic therapy are needed. Single cell RNA sequencing (scRNA-seq) has advanced our understanding of IPF with cell type-specific insights but lacks cellular tissue context. Spatial transcriptomics addresses this by providing spatially resolved gene expression, enabling gene and cell type localization within the tissue environment. We profiled IPF and control patient lung tissue sections using spatial transcriptomics and combined the data with an atlas of integrated IPF scRNA-seq datasets. Through computational analysis, we identified three disease-associated pathologic niches with unique cellular composition / localization and analyzed their cell-cell communication. We identified the Fibrotic niche, comprising Myofibroblasts and Aberrant Basaloid cells, preferentially located around airways and close to the Airway Macrophage niche in the lumen, containing SPP1+ Macrophages. We also identified the Immune niche, distinct foci of lymphoid cells in fibrotic tissue, surrounded by remodeled endothelial vessels. TEASERSpatial transcriptomics localizes genes and cell types in the tissue and identifies pathological cellular niches in IPF and control lungs.

systems biology↗

bioRxiv2019

Senescence-associated metabolomic phenotype in primary and iPSC-derived mesenchymal stromal cells

Long-term culture of primary cells is reflected by functional and secretory changes, which ultimately result in replicative senescence. In contrast, induced pluripotent stem cells (iPSCs) do not reveal any signs of cellular aging while in the pluripotency state, whereas little is known how they senesce upon differentiation. Furthermore, it is largely unclear how the metabolome of cells changes during replicative senescence and if such changes are consistent across different cell types. In this study, we have directly compared culture expansion of primary mesenchymal stromal cells (MSCs) and iPSC-derived MSCs (iMSCs) until they reached growth arrest after a mean of 21 and 17 cumulative population doublings, respectively. Both cell types acquired similar changes in morphology, in vitro differentiation potential, up-regulation of senescence-associated beta-galactosidase, and senescence-associated DNA methylation changes. Furthermore, MSCs and iMSCs revealed overlapping gene expression changes during culture expansion, particularly in functional categories related to metabolic processes. We subsequently compared the metabolome of MSCs and iMSCs at early and senescent passages and observed various significant and overlapping senescence-associated changes in both cell types, including down-regulation of nicotinamide ribonucleotide and up-regulation of orotic acid. Replicative senescence of both cell types was consistently reflected by the metabolic switch from oxidative to glycolytic pathways. Taken together, long-term culture of iPSC-derived MSCs evokes very similar molecular and functional changes as observed in primary MSCs. Replicative senescence is associated with a highly reproducible senescence-associated metabolomics phenotype, which may be used to monitor the state of cellular aging.

cell biology↗

bioRxiv2018

DNA methylation patterns of replicative senescence are strand-specific and reflect changes in chromatin conformation

Culture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These changes might be due to an directly regulated epigenetic process, or to gradual deregulation of the epigenetic state, which is often referred to as "epigenetic drift". We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated in the course of culture expansion of mesenchymal stem cells (MSCs) and other cell types. During reprogramming into induced pluripotent stem cells (iPSCs) particularly the culture-associated hypomethylation is reversed simultaneously with age-associated and pluripotency-associated DNAm changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that upon passaging the DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development and without association to oligoclonal subpolulations of MSCs at later passages. Circularized chromatin conformation capture (4C) revealed reproducible changes in nuclear organization between early and late passages, while there was no preferential interaction with other genomic regions that also harbor culture-associated DNAm changes. Chromatin immunoprecipitation of CTCF did not show significant differences during long-term culture of MSCs, however culture-associated hypermethylation was enriched at CTCF binding sites and hypomethylated CpGs were devoid of CTCF. Taken together, our results indicate that DNAm changes during culture-expansion resembles epigenetic drift, which seems to occur in relation to chromatin conformation.

genomics↗