Biology subjects

Biswas, N.

Publications and source records attributed to Biswas, N..

14 recordsLinked to original sources

bioRxiv2026

Understanding the role of IQ motif-containing GTPase-activating protein 1 as a potential disruptor of the essential adhesion module at cell-cell junctions

A key mechanism of stabilization of Cadherin-based cell-cell adhesions is through a mechanically modulated interaction to cortical actin filaments. This interaction is facilitated by a cytoplasmic adhesion module comprising of a complex of {beta}-catenin/-catenin. Recent evidence shows that under specific conditions the {beta}-catenin/-catenin complex gets disrupted because of mechanical disregulation of the junction maintenance machinery. The IQ motif-containing GTPase-activating protein 1 (IQGAP1) plays apparently a vital role as an internal regulator of the adhesion module, which competes for binding on {beta}-catenin with -catenin and is able to dissociate the latter from the adhesion complex. The underlying molecular mechanism is poorly understood with no clear evidence on what types of interactions are critical for a potential disruption. In this work, we combine steered-molecular-dynamics simulations and a multi-step protein-protein docking framework to dissect how mechanical detachment of -catenin from the adhesion complex modulates the interactions between IQGAP1 and {beta}-catenin. Our simulations show that as -catenin detaches from {beta}-catenin, IQGAP1 docks with progressively favorable scores. Interfacial analysis and subsequent mutagenesis studies, allow us to predict a molecular mechanism for an IQGAP1-driven disruption of the junctional adhesion module that centers on early onset of key favorable electrostatic interactions.

biophysics↗

bioRxiv2026

The LIF-LIFR Axis Promotes Liver Regeneration via Modulation of Angiogenesis and HGF Release from LSECs

Liver sinusoidal endothelial cells (LSECs) play essential roles in liver regeneration after injury, but the underlying mechanisms remain incompletely defined. Here we report that leukemia inhibitory factor (LIF), which is rapidly induced after liver injury, acts as a key regulator of LSECs-driven liver regeneration through interaction with LSECs-enriched LIF receptor (LIFR). LIF directly stimulates LSECs proliferation and induces hepatocyte growth factor (HGF) release in a dose-dependent manner via LIFR signaling in LSECs, thereby indirectly promoting hepatocyte proliferation. Systemic LIF neutralization or endothelial cells (ECs)-specific Lifr loss impairs liver regeneration, whereas low-titer AAV-mediated LIF expression increases vascular density, elevates circulating HGF, and improves early liver recovery after partial hepatectomy (PHx) in mice. Together, these findings establish LIF-LIFR as a previously unrecognized endothelial axis to promote hepatocyte proliferation and suggest potential therapeutic strategies to enhance liver repair in patients. HighlightsO_LILIF is upregulated after liver injury and LIF neutralization impairs liver recovery. C_LIO_LILIFR displays the highest expression in ECs; endothelial-specific Lifr deletion delays liver regeneration after injury. C_LIO_LILIF mediates a positive feedback loop including LSECs proliferation as well as HGF release via LIFR pathway. C_LIO_LILIF overexpression increases liver-to-body weight ratio in a dose-dependent manner and accelerates liver regeneration at early stage. C_LI Abstract Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/707802v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@13b42feorg.highwire.dtl.DTLVardef@1ab6390org.highwire.dtl.DTLVardef@115c157org.highwire.dtl.DTLVardef@1486993_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Catestatin improves heart metabolic flexibility by promoting mitochondrial structure and function

Hypertension, a major cause of cardiomyopathy, is one of the most critical risk factors for heart failure and mortality worldwide. Loss of metabolic flexibility of cardiomyocytes is one of the major causes of heart failure. Although Catestatin (CST) treatment is known to be both hypotensive and cardioprotective, its effect on cardiac metabolism is unknown. In this study, we undertook a transcriptomic approach to identify differentially expressed genes that were filtered using Boolean implication relationships to develop a model of gene regulation in saline or CST-supplemented CST knockout (CST-KO) mice. The analysis revealed a set of gene signatures (fibroblast, cardiomyocyte, and macrophage) rescued after CST supplemented CST-KO mice compared to wild-type. Furthermore, we independently validated these gene signature models using publicly available patient datasets. Since the gene signature includes genes related to glucose, fatty acid metabolism, and mitochondrial function, we assessed the glucose and fatty acid uptake after CST treatment. We found that CST treatment can restore the cardiac metabolic inflexibility in CST-KO heart due to the metabolic shift of glucose utilization to fatty acid as energy source. Binding studies after immunoprecipitation and mass spectrometry revealed CST binding with ATP synthase, supported by molecular simulation and computational modeling that predicted CST binding to /{beta} subunit of ATP synthase. Colocalization of CST with mitochondria and increased mitochondrial membrane potential and ATP production upon CST treatment in neonatal cardiomyocytes further exhibit CST as a key regulator of cardiac metabolism and mitochondrial function.

physiology↗

bioRxiv2024

Native trees within plantations and surrounding forest cover are essential for bird conservation in cashew-dominated landscapes within a biodiversity hotspot

O_LIAnnually, agriculture is responsible for about 60% of tropical forest loss globally. C_LIO_LIstrategies in agricultural landscapes range from enhancing farm-level habitat diversity to retaining forest cover within landscapes. A critical question is determining the relative influence of native trees within farms and forest cover around them on avian diversity, trait responses and species persistence in tree-based systems in landscapes where protected areas are often absent, often the case in lowland tropical forest ecosystems. C_LIO_LIBy sampling birds across gradients of cashew plantation intensification and varying levels of surrounding cashew and forest cover, we examined the relative influence of site- and landscape-level factors on species composition, taxonomic, functional, and phylogenetic diversity, as well as species- and trait-specific responses, and whether phylogenetic relationships among bird species influenced these responses. C_LIO_LIAt the community level, forests, cashew agroforests, and cashew monocultures hosted compositionally different bird communities. Site-level variables, specifically the proportion of native trees, influenced taxonomic and phylogenetic diversity, while landscape-level variables had no effect. None of the predictor variables accounted for the variation in functional diversity. C_LIO_LIAt the species level, site-level variables, specifically the proportion of native trees, and landscape-level variables, particularly cashew cover around plantations, had positive and negative impacts on species responses, respectively. At the trait level, evergreen forest specialists were associated positively with the proportion of native trees and negatively associated with cashew cover. Resident species had a positive association with forest cover. We found a phylogenetic signal in species responses to predictor variables, indicating that closely-related species responded similarly to predictor variables. C_LIO_LISynthesis and applications: To retain taxonomic and phylogenetic diversity and ensure persistence of evergreen forest specialists, it is essential to retain native trees within cashew plantations and maintain surrounding forest cover. Future policies should incentivise the retention and restoration of forest patches and restrict the felling of native trees within cashew plantations. C_LI

ecology↗

bioRxiv2024

H2O2 mediated MAPK-mTOR crosstalk determines the XIAP and FLIP degradation pathways and development of resistance to Imatinib

Abnormal or aggregated proteins degradation is very crucial to protect the cell against proteotoxic stress. Cellular proteins are usually degraded in a ubiquitin-dependent manner by proteasomes and macro-autophagy/autophagy. Both processes use ubiquitin, binding of which target them to proteasomes via ubiquitin-like domains or to phagophores (the precursors to autophagosomes) via Atg8/LC3 binding motifs. Since both pathways use ubiquitin, the question that arises is how degradative pathway choice is achieved. Here in this paper, we have shown that mTOR pathway acts as major player in deciding which degradation pathway to choose. Here, we used Imatinib resistant (K562R) and Imatinib-sensitive (K562S) K562 cell as our previous study showed that Ubiquitin-proteasome pathway is selected for degradation of two proteins XIAP and FLIP in Imatinib-resistant K562 cells. H2O2 treatment in K562R cells degrades XIAP and FLIP via proteasomal pathway whereas H2O2 degrades them via lysosomal pathway in K562S cells. We found H2O2 mediated mTOR activation suppressed autophagy pathway in K562R cells and protein takes proteasomal degradation rout. However, proteins get degraded via autophagy when mTOR remains suppressed in K562S cells. We also found that H2O2-mediated activation of activation of ERK in turn activated mTOR in K562R cells because ROS inhibited ERK phosphorylation and thus mTOR remained inhibited in K562S cells. Moreover, we found that endogenous H2O2 levels are way higher in K562R cells than in K562S cells. Finally, and most interestingly, our data clearly suggested that activation of mTOR is responsible for developing resistance to Imatinib in K562R cells. Thus, this paper delineates a very crucial role of H2O2 and mTOR in both the selection of protein degradation pathway and development of drug resistant.

cancer biology↗

bioRxiv2024

Chronic disturbance of moist tropical forests favours deciduous over evergreen tree communities across a climate gradient in the Western Ghats

It is well established that climatic factors such as water stress and chronic anthropogenic disturbances such as biomass extraction influence tropical forest tree community structure, richness and composition. However, while the standalone effects of these two drivers on plant communities are well-studied, their interactive effects are not. Moist tropical forests in Indias Western Ghats face a dual threat from increasingly erratic precipitation (and consequent water stress), and an intensifying anthropogenic footprint. Here, we sampled 120 tree plots (0.05 ha each) across forests with varying histories of biomass extraction and a gradient in climate water deficit (CWD, a proxy for water stress) within a 15,000 km2 landscape in the northern Western Ghats and examined whether and how disturbance history modulates relationships of tree community structure and composition with climate. As expected, tree species richness increased with decreasing water stress in less- and historically-disturbed forests but remained low in repeatedly-disturbed forests. The increase in evergreen species richness with decreasing water stress was far slower in repeatedly-disturbed forests than other categories, and the relative abundance of evergreens in the repeatedly-disturbed forests (25%) was half that in less-disturbed forests (50%) of comparable water stress in the driest parts. Overall, we show that disturbance can amplify threats from climate change to wet forest-associated evergreen tree species, many of which are threatened, while benefiting more widely distributed dry forest-associated deciduous species. In the northern Western Ghats, where much of the remaining forest cover is disturbed and dominated by deciduous tree species, the persistence of evergreen tree flora hinges on protecting existing evergreen forest patches from future disturbances and restoring locally appropriate evergreen species in secondary forests.

ecology↗

bioRxiv2024

IL6 mediated cFLIP downregulation increases the migratory and invasive potential of triple negative breast cancer cell line

c-FLIP (cellular FLICE-Like Inhibitor of Apoptotic protein) which belongs to the negative regulators of the death receptor pathway, control apoptosis in a number of cancers. literatures suggest that its overexpression facilitate cancer progression and also helps in the drug resistance. However, there is a very few data available to show how it control metastasis. Moreover, how cFLIP is regulated during the progression of cancer into advanced stage and its mechanism of action on tumor cell migration and invasion is yet to be known. Our TCGA data analysis has shown that cFLIP is downregulated in many cancers, including breast cancer, especially at the later stages. when, we analysed and compared early-stage breast carcinoma cell line MCF7 (luminal) and advanced stage triple negative cell line MDAMB-231, which is highly metastatic, we found a negative correlation between cFLIP expression and metastasis. Our results indicated that Il6, one of the most prominent cytokines inside tumor microenvironment, activated p38 and the later helped in cFLIP downregulation in MDA-MB-231 cell line. Moreover, we have found that cFLIP negatively regulated autophagy and this autophagy downregulation resulted in decrease in metastasis. Thus, we have shown, for the first time, a complete interconnecting pathway in which IL6 mediated p38 activation directly influences metastasis by regulating autophagy via cFLIP downregulation.

cancer biology↗

bioRxiv2023

Reciprocal inflammatory signals establish profibrotic cross-feeding metabolism

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung remodeling and collagen deposition that leads to respiratory failure. Myeloid cells are abundant in IPF lung and in murine lung fibrosis, but their functional effects are incompletely understood. Using mouse and human lung models, we show that ornithine produced by myeloid cells expressing Arg1 serves as a substrate for proline and collagen synthesis by lung fibroblasts. The predominant Arg1-expressing myeloid cells in mouse lung were macrophages, but in IPF lung, high-dimensional imaging revealed ARG1 to be expressed mainly in neutrophils. Arg1 inhibition suppressed both ornithine levels and collagen expression in cultured, precision-cut IPF lung slices and in murine lung fibrosis. These results were confirmed in macrophage-specific Arg1 KO mice. Furthermore, we find that this pathway is regulated by cell-to-cell crosstalk, starting with purinergic signaling: Fibroblast eATP receptor P2rx4 was necessary for fibroblast IL-6 expression, which in turn was necessary for Arg1 expression by myeloid cells. Taken together, our findings define an immune-mesenchymal circuit that governs profibrotic metabolism in lung fibrosis.

immunology↗

bioRxiv2023

Conservation value of low-elevation forests for birds in agroforestry-dominated landscapes in a biodiversity hotspot

O_LIProtected areas (PAs) and multi-use landscapes beyond PAs play important and complementary roles in conserving global biodiversity. Across the tropical forest biome, remnant forests and agroforestry plantations in mixed-use landscapes often have high taxonomic diversity, but their ability to sustain functionally and phylogenetically diverse assemblages and retain conservation-priority species is unclear. Additionally, our understanding of impacts of land-use change across species, function and communities is poor. C_LIO_LIIn Indias Western Ghats (WG) biodiversity hotspot, like in many other tropical regions, PAs cover just 12% of the land and are concentrated in higher elevations. Here, in an approximately 15,000 km2 landscape in the northern WG, we compared bird communities across six land-use categories: state-owned high-elevation PAs and low-elevation Reserved Forests beyond PAs, and privately-owned periodically clear-felled low-elevation forests and three types of low-elevation agroforestry plantations (cashew, mango, and rubber). C_LIO_LIWe sampled 184 line transects totalling 137.5 km across habitats, compared taxonomic, functional, and phylogenetic diversity metrics and used joint species distribution models to test for species-trait-habitat associations. C_LIO_LIForests in general and lowland forests in particular had higher taxonomic, functional and phylogenetic diversity, and higher occurrence probabilities of evergreen forest-affiliated, conservation-priority, and frugivores than agroforestry plantations. The ranking of land-use types varied across indicators, with rubber ranking higher than cashew and mango for functional and phylogenetic diversity but lower in species occurrence probabilities. C_LIO_LISynthesis and Applications: Our findings underscore the irreplaceability of less-disturbed forests for birds in mixed-use landscapes, especially when considering multiple dimensions of biodiversity, habitat specialists, and conservation-priority species. We advocate the simultaneous examination at multiple levels (community, species and traits) to determine the impacts of land-use change as divergent information of conservation importance is gleaned from each level. Reserved and private forests of low elevations of the Northern Western Ghats are critical for avian conservation, given that they harbour significant diversity, and the absence of representative PAs in the region. Given the vulnerability of these low-elevation forests to conversion for non-forestry activities and overexploitation for fuelwood, there is a need to develop viable models of partnership with landowners in these multi-use landscapes for ecological restoration of degraded forests. C_LI

ecology↗

bioRxiv2023

The Resolvin D2-GPR18 Axis Enhances Bone Marrow Function and Limits Hepatic Fibrosis in Aging

Aging is associated with non-resolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a pro-resolving ligand that acts through the G-protein coupled receptor (GPCR) called GRP18. Using an unbiased screen, we report increased Gpr18 expression in macrophages from old mice and in livers from elderly humans that is associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lack GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, monocyte-derived macrophages and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly upon the bone marrow to increase monocyte-macrophage progenitors. Using a transplantation assay we further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice, and transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, our study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

physiology↗

bioRxiv2021

Genomic surveillance and phylodynamic analyses reveal emergence of novel mutation and co-mutation patterns within SARS-CoV2 variants prevalent in India

Emergence of distinct viral clades has been observed in SARS-CoV2 variants across the world and India. Identification of the genomic diversity and the phylodynamic profiles of the prevalent strains of the country are critical to understand the evolution and spread of the variants. We performed whole-genome sequencing of 54 SARS-CoV2 strains collected from COVID-19 patients in Kolkata, West Bengal during August to October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad available in GISAID database. Spatio-temporal evolutionary dynamics of the pathogen across various regions and states of India over three different time periods in the year 2020 were analyzed. We estimated the clade dynamics of the Indian strains and compared the clade specific mutations and the co-mutation patterns across states and union territories of India over the time course. We observed that GR, GH and G (GISAID) or 20B and 20A (Nextstrain) clades were the prevalent clades in India during middle and later half of the year 2020. However, frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating emergence of newer mutations in the viral population prevailing in the country. Further, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested within the Indian patients.

genomics↗

bioRxiv2020

Leish-ExP: a database of exclusive proteins from Leishmania parasite

Leishmaniasis is a complex disease caused by different species of genus Leishmania, which affects millions of people spanning over 88 countries causing extensive mortality and morbidity. Leishmaniasis exists in three clinical forms; cutaneous, mucocutaneous and visceral. Anti-leishmanial therapy is one of the challenging fields due to the presence of wide range of Leishmania species and host response against the pathogenic infection. Clinical survey reveals toxicity of drugs and trial compounds causing death among patients and predominant resistance to different class of antimonials among the leishmaniasis patient. Identification of appropriate target protein is a primary and important phase of drug development and Leishmania is a suitable system for targeted drug development as it branched out quite early from the higher eukaryotes like human. With the advancement of genomic era and availability of whole genome sequences of Leishmania species, relevant information on their respective genes and proteins are now easily extracted. Hence, in the current study, to aid the targeted drug therapy, an exhaustive whole genome scale comparative sequence analysis was performed to identify genes/proteins exclusive to Leishmania. Subsequently, further filtration was employed to identify the individual Leishmania species specific gene/proteins. Among such proteins, a considerable number was found to have no recognizable structure and functions. Hence, efforts were taken to characterize these Leishmania exclusive gene/proteins via providing additional sequence, structure, localization and functional information. All the information about each of these Leishmania exclusive gene/proteins from five different Leishmania species has been systemically categorized and represented in the form a user-friendly database called Leish-ExP, which is freely available at http://www.hpppi.iicb.res.in/Leish-ex.

bioinformatics↗

bioRxiv2020

Analysis of Pan-Omics Data in Human Interactome Network (APODHIN)

Analysis of Pan-Omics Data in Human Interactome Network (APODHIN) is a platform for integrative analysis of transcriptomics, proteomics, genomics, and metabolomics data for identification of key molecular players and their interconnections exemplified in cancer scenario. APODHIN works on a meta-interactome networks consisting of human protein-protein interactions, miRNA-target gene regulatory interactions, and transcription factor-target gene regulatory relationships, respectively. In its first module, APODHIN maps proteins/genes/miRNAs from different omics data in its meta-interactome network and extracts the network of biomolecules that are differentially altered in the given scenario. Using this context specific, filtered interaction network, APODHIN identifies topologically important nodes (TINs) implementing graph theory based network topology analysis and further justifies their role via pathway and disease marker mapping. These TINs could be used as prospective diagnostic and/or prognostic biomarkers and/or potential therapeutic targets. In its second module, APODHIN attempts to identify cross pathway regulatory and protein-protein interaction (PPI) links connecting signaling proteins, transcription factors, and miRNAs to metabolic enzymes via utilization of single-omics and/or pan-omics data and implementation of mathematical modeling. Interconnections between regulatory components such as signaling proteins/TFs/miRNAs and metabolic pathways need to be elucidated more elaborately in order to understand the role of oncogene and tumor suppressors in regulation of metabolic reprogramming during cancer. APODHIN platform contains a web server component where users can upload single/multi omics data to identify TINs and cross-pathway links. Tabular, graphical and 3D network representations of the identified TINs and cross-pathway links are provided for better appreciation. Additionally, this platform also provides a database part where cancer specific, single and/or multi omics dataset centric meta-interactome networks, TINs, and cross-pathway links are provided for cervical, ovarian, and breast cancers, respectively. APODHIN platform is freely available at http://www.hpppi.iicb.res.in/APODHIN/home.html.

bioinformatics↗

bioRxiv2019

Novel sampling strategies and a coarse-grained score function for docking homomers, flexible heteromers, and oligosaccharides using Rosetta in CAPRI Rounds 37-45

CAPRI Rounds 37 through 45 introduced larger complexes, new macromolecules, and multi-stage assemblies. For these rounds, we used and expanded docking methods in Rosetta to model 23 target complexes. We successfully predicted 14 target complexes and recognized and refined near-native models generated by other groups for two further targets. Notably, for targets T110 and T136, we achieved the closest prediction of any CAPRI participant. We created several innovative approaches during these rounds. Since Round 39 (target 122), we have used the new RosettaDock 4.0, which has a revamped coarse-grained energy function and the ability to perform conformer selection during docking with hundreds of pre-generated protein backbones. Ten of the complexes had some degree of symmetry in their interactions, so we tested Rosetta SymDock, realized its shortcomings, and developed the next-generation symmetric docking protocol, SymDock2, which includes docking of multiple backbones and induced-fit refinement. Since the last CAPRI assessment, we also developed methods for modeling and designing carbohydrates in Rosetta, and we used them to successfully model oligosaccharide-protein complexes in Round 41. While the results were broadly encouraging, they also highlighted the pressing need to invest in (1) flexible docking algorithms with the ability to model loop and linker motions and in (2) new sampling and scoring methods for oligosaccharide-protein interactions.

biophysics↗