Biology subjects

Ganguly, D.

Publications and source records attributed to Ganguly, D..

12 recordsLinked to original sources

bioRxiv2026

Rationalizing the application of spatial capture-recapture versus space-to-event models for monitoring populations of an endangered social carnivore

Reliable estimates of population size are fundamental to understanding wildlife population status and informing conservation. Obtaining such estimates remains challenging for unmarked species, particularly in tropical countries where logistical and financial constraints limit intensive monitoring. The endangered dhole (Cuon alpinus), a highly social canid without natural markings, is one such species for which robust population estimates remain scarce. We estimated dhole density in the Valparai plateau, a human-dominated agroforest-forest mosaic in India's Western Ghats. We compared Spatially Explicit Capture-Recapture (SECR) models based on individual identification from fecal DNA and Space-to-Event (STE) models based on camera-trap detections. We additionally applied both approaches to individually identifiable leopards (Panthera pardus) to cross-validate STE versus SECR estimates. SECR estimated dhole density at 22 individuals per 100 sq.km, with STE estimates varying substantially depending on how the camera viewshed area was defined. STE estimates based on post hoc viewshed measurements, particularly after reducing the viewshed by 10%, were comparable to SECR estimates. In contrast, STE underestimated leopard density relative to SECR (7 versus 12 per 100 sq.km), although uncertainty intervals overlapped. Ecologically, our results indicate that human-use agroforest mosaics can support dhole densities comparable to, or exceeding, those reported from several Protected Areas, highlighting their potential importance for dhole conservation. More broadly, we argue that STE models may offer a practical and relatively inexpensive approach for baseline monitoring of dholes from camera-trap surveys, but their reliability depends strongly on accurate characterization of the effective viewshed and may vary across species and landscapes.

ecology↗

bioRxiv2026

Leveraging collaborations between researchers, wildlife managers and citizen-volunteers to monitor endangered carnivore populations across space and time

Monitoring populations is fundamental for conserving threatened carnivores, but can be difficult to sustain in the long term across large landscapes. We present a collaborative framework for monitoring dholes (Cuon alpinus) in India's Western Ghats, combining fecal DNA-based individual identification, Spatially Explicit Capture-Recapture (SECR) models, state Forest Department participation, and trained citizen-volunteers. We surveyed across six sites between 2019-2023, encompassing three Protected Areas (Wayanad, Parambikulam, Periyar) and their adjacent Territorial Divisions. Fecal samples were genotyped using a panel of 96 Single Nucleotide Polymorphisms, and detections were analyzed using SECR models to estimate densities. In Wayanad Sanctuary, densities remained stable across 2019, 2022 and 2023, increasing marginally from 15.67 to 19.01 individuals per 100 sq.km. In 2023, densities varied substantially among six sites, from 9.73/100 sq.km in Parambikulam to 29.23 in Nemmara Territorial Division. Field implementation involved an average of 46 Forest Department personnel co-collecting data per site-year. Among former citizen-volunteers who were surveyed for project feedback (N=29), 83% went on to either work or pursue higher education in wildlife-related or -adjacent fields. We demonstrate that molecular individual identification coupled with SECR can provide a practical basis for dhole population assessments while enabling multi-stakeholder participation in field monitoring. Sustained engagement with wildlife managers and locally recruited volunteers can strengthen institutional capacity, facilitate knowledge exchange, and improve continuity of monitoring programs. We argue that integrating molecular ecology with collaborative governance and democratizing field-science offers a scalable pathway for landscape-level monitoring required to guide dhole conservation.

ecology↗

bioRxiv2026

Extracellular DNASE1L3 dysfunction fuels obesity-driven inflammation and metabolic syndrome

Obesity, a global health crisis affecting 16% of the world population, is characterized by chronic inflammation that contributes to health complications such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging evidence suggests that self-DNA released from dying cells aberrantly activates inflammatory responses during obesity. However, the role of extracellular deoxyribonucleases (DNASEs), which at steady state regulate abundance of extracellular self-DNA, remains poorly understood in this context. Here, we show that individuals with obesity exhibit elevated levels of circulating cell-free DNA (cfDNA) with a distinctive end-motif signature, anti-DNASE1L3 autoantibodies and a reduction in circulating DNASE activity. These cfDNA alterations correlate with the severity of obesity and can be corrected by therapeutic intervention such as bariatric surgery. Similarly, mice fed a high-fat diet (HFD) displayed increased cfDNA levels and decreased DNASE activity. Genetic deficiency of the extracellular nuclease DNASE1L3 in mice worsened HFD-induced metabolic complications, including glucose intolerance, insulin resistance, MASLD, and metabolic tissue inflammation. Conversely, targeted supplementation of DNASE1L3 in the liver using adeno-associated viral vectors protected obese mice from developing MASLD and liver inflammation. These findings uncover a novel role of DNASE1L3 in controlling obesity-associated inflammation and its potential therapeutic use for preventing metabolic disease.

pathology↗

bioRxiv2025

Spatio-temporal regulation of ligand trafficking and TLR9 activation involves PIEZO1 mechanosensing in human plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) are specialized innate immune cells which play a pivotal role in antiviral immunity by producing large quantities of type I interferons (IFNs) upon sensing nucleic acids via Toll-like receptor 9 (TLR9). Synthetic oligodeoxynucleotides (ODNs) such as CpGA and CpGB, both containing unmethylated CpG motifs, are commonly used experimental TLR9 agonists. Interestingly, CpGA and CpGB elicit markedly different responses in pDCs - CpGA induces robust IFN- production, whereas CpGB does not. The mechanistic basis underlying this ligand-specific functional divergence has remained unclear. Here, we identify PIEZO1, a mechanosensory ion channel, as a critical determinant of ligand-specific IFN responses in human primary pDCs. We demonstrate that unlike CpGB, CpGA self-associates into larger aggregates that generate membrane tension during cellular uptake, leading to activation of PIEZO1. This activation triggers localized calcium influx and cytoskeletal remodeling, resulting in the formation of local F-actin structures that retain CpGA within early endosomes enabling sustained IRF7 nuclear translocation and robust type I IFN production. Disruption of PIEZO1 or actin polymerization abrogates CpGA-induced IFN production, while pharmacological activation of Piezo1 enhances IFN production in response to CpGB. Thus, these findings uncover a previously unrecognized biophysical checkpoint in nucleic acid sensing, wherein membrane tension is transduced via PIEZO1 into spatially controlled TLR9 signaling. Overall, our study establishes PIEZO1 mechanosensing at the plasma membrane as a key regulatory event in nucleic acid-induced immunity, with different functional outcomes based on the cargo structure, opening potential new avenues for modulating type I IFN responses in infection and autoimmunity.

immunology↗

bioRxiv2024

Three's Company: Anthropogenic factors shape co-occurrence in a meso-carnivore community in a semi-arid shared landscape of western India

O_LIHuman modification of natural landscapes accelerates species extinctions, promotes biological invasions, coerce range shifts, and restructure biotic communities. Mammalian meso-carnivores, considered sentinels of human-use landscapes, may experience increased mortality through road collisions and interactions with free-ranging dogs. Yet they may also benefit through resource subsidisation and decreased competition with larger carnivores. Our understanding of meso-carnivore community structure in modified ecosystems remain severely limited. C_LIO_LIWe examined a meso-carnivore community comprising golden jackal Canis aureus, jungle cat Felis chaus, Indian fox Vulpes bengalensis and desert cat Felis lybica ornata in a semi-arid landscape of Kachchh, western India. First, we mapped their potential habitats and the extent of fragmentation as a measure of vulnerability. We then assessed spatial, temporal and fine-scale spatio-temporal co-occurrence and responses to anthropogenic influences in the meso-carnivore community. We used a combination of camera-trapping and indirect sign surveys within an occupancy modelling framework to generate insights on species space-use and interactions. C_LIO_LIThe most fragmented habitat, open savanna, was positively associated with the occurrence of golden jackal, Indian fox and desert cat. Golden jackal spatially co-occurred with jungle cat and Indian fox with desert cat. Indian fox and desert cat showed spatial avoidance of golden jackal and jungle cat. Meso-carnivores did not show any spatial responses to free-ranging dogs, but showed varied responses to human infrastructure, i.e., settlements, roads and wind turbines, generally co-occurring less with each other in areas with high anthropogenic influence. C_LIO_LISpatially co-occurring meso-carnivores also overlapped substantially in the temporal dimension. Golden jackal and jungle cat showed high temporal overlap with free-ranging dogs, while Indian fox and desert cat appeared to avoid them. Temporally overlapping species generally showed fine-scale spatio-temporal aggregation. C_LIO_LIOur results reveal species-specific responses to anthropogenic factors in the meso-carnivore community, often increasing overlap across space and time in a resource restricted landscape. Future loss of native savanna habitats and an increasing human footprint can elicit competition driven loss of sensitive species leading to homogenisation of the meso-carnivore community. Our findings highlight the importance of considering species-specific responses as well the complex interplay amongst species to conserve multi-carnivore systems across shared, resource-constrained landscapes. C_LI

ecology↗

bioRxiv2022

Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, play a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 play any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension on chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn are crucial for the integrin LFA-1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the outside-in signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.

immunology↗

bioRxiv2022

Pleiotrophin drives a pro-metastatic immune niche within the breast tumor microenvironment

Metastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-kB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment and an immune suppressive microenvironment. Consequently, inhibition of PTN, pharmacologically or genetically, reduces the accumulation of tumor associated neutrophils and reverts local immune suppression resulting in increased T cell activation and attenuated metastasis. Furthermore, inhibition of PTN significantly enhanced the efficacy of immune checkpoint blockade + chemotherapy in reducing metastatic burden in mice. These findings establish PTN as a previously unrecognized driver of a pro-metastatic immune niche and thus represents a promising therapeutic target for the treatment of metastatic breast cancer.

cancer biology↗

bioRxiv2021

Altered DNA methylation in ion transport and immune signalling genes is associated with severity in Pancreatic Ductal Adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the leading cancers worldwide and has a poor survival, with a relative five-year survival rate of only 8.5%. In this study we investigated epigenetic marksassociated with PDAC severity and prognosis, through studying alterations in DNA methylation patterns. MethodsDNA methylome for tumor and adjacent normal tissue samples from PDAC patients (n=7) were generated using Illumina 450K bead chips. Differentially methylated positions (DMPs) were identified with |delta beta| > 0.2 and p-value<0.01 by comparing tumors with the adjacent normal tissues. Validation of differential methylation and associated gene expression at selected genes was carried out in an independent cohort PDAC patient. ResultsWe identified 76 DMPs in PDAC patients that mapped to 43 genes. Among them, 44.7% (n=34) were hypo-methylated and 55.3% (n=42) were hyper-methylated DMPs in cancer samples. The trends of change in methylation at these 76 DMPs from well to moderate were like that from moderate to poorly differentiated cancer samples. The gradual trend in differential methylation was observed both in our cohort and the TCGA-PAAD cohort, suggesting methylation marks can serve as early indicators of disease pathology. Altered promoter methylation, which may affect gene expression, was observed for transcription regulators (BHLHE23, GSC2, FOXE1 and TWIST1), gated ion channels (KCNA6, and CACNB2), tumor suppressors (RASSF1, SPRED2, and NPY) and genes functioning in interferon signalling (SIGIRR, MX2, and OAS2). We also have compared the TCGA-PAAD dataset with normal pancreatic tissue data from GTEx V8 dataset leading to a confluent observation. ConclusionsWe reported the first study on methylome in PDAC tumors from patients in India. We identified altered DNA methylation associated with increasing severity in PDAC among some genes like SIGIRR, MX2 along with other previously reported loci. We also concluded a confluence in our observation when comparing the TCGA-PAAD dataset with GTEx V8 dataset.

cancer biology↗

bioRxiv2021

PRSS2 promotes tumor growth and progression by repressing Tsp-1 in the tumor microenvironment via binding to LRP1

In the earliest stages of tumor development, epithelial tumors (carcinomas) are physically confined to the area of the tissue in which they form. These nascent lesions (carcinomas in situ) are sequestered from the tissue parenchyma by the basement membrane. Within the tissue parenchyma lie a myriad of cell types comprised of fibroblasts, immune and inflammatory cells and endothelial cells. Upon invasion across the basement membrane and into the tissue parenchyma, tumors must manipulate the expression of pro- and anti-tumorigenic proteins such that pro-tumorigenic factors are produced in excess to anti-tumorigenic proteins. One such anti-tumorigenic protein is Thrombospondin-1 (Tsp-1). We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression and in some cases induces tumor regression. Here, we identify a novel tumor-mediated mechanism to repress the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a novel activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1.

cancer biology↗

bioRxiv2020

Spike protein mutational landscape in India: Could Mullers ratchet be a future game-changer for COVID-19?

The dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020, and detected the spike protein variants to emerge from two major ancestors - Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein - host receptor (S-R) complexes for these variants correlated strongly (R2=0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 - June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India. Author summaryEpidemiological features are intricately linked to evolutionary diversity of rapidly evolving pathogens, and SARS-CoV-2 is no exception. Our work suggests the potential of average stability of complexes formed by the circulating spike mutational variants and the human host receptor to track the severity of SARS-CoV-2 infection in a given region. In India, the stability of these complexes for recent variants tend to decrease relative to their ancestral ones, following countrywide declining fatality rate, in contrast to an increasing mutation rate. We hypothesize such a scenario as nascent footprints of Mullers ratchet, proposing large-scale population genomics study for its validation, since this understanding could lead to therapeutic approaches for facilitating mutational meltdown of SARS-CoV-2, as experienced earlier for influenza A virus.

bioinformatics↗

bioRxiv2020

How Fishing Cats Prionailurus viverrinus fish: Describing a felid's strategy to hunt aquatic prey

Hunting strategies are key to carnivore survival (Krebs and Davies 2009;Kamil et al. 2012;Michalko and Pekar 2016). Fishing Cats (Prionailurus viverrinus) persistence in the semi-aquatic niche (Kitchener et al. 2010) despite felids being terrestrial carnivores in general (>95%) (Hunter 2019) suggests the evolution of a successful hunting strategy. Its further suggest selection for hunting in wetlands. What energy conserving strategies did the Fishing Cat borrow from its family and how were these adapted to optimize energy gained from hunting fish, its primary prey? We attempt to answer this by analyzing 197 video footages collected opportunistically from a participatory science initiative conducted over 2.5 years. We found that the felid switches between stationary and active modes of searching for prey depending on the depth of water and the corresponding loss of body heat/energy. For example, diving in deeper waters requires the submergence of the upper portions of the body and loss of more body heat/energy. Our analysis shows that the cat spent much of its time (~52%) sitting and waiting for prey (fish) to come nearer and then took limited attempts to dive into deeper water (2.78%). We suggest that this is a strategy to optimize the net energy gain. In shallow waters where the cat could forage without submerging the upper body it adopted a predominantly active mode of hunting (~96%) to flush out prey. Thus, prominent hunting strategies in the small cat lineage like sit-and-wait and active foraging is adapted to hunt in the water. We recorded a 60% hunting success in deeper waters but did not detect a successful hunt in shallow waters due to the low sample size of data from shallow water hunting. The major caveat in our study is the post-hoc analysis of opportunistically collected data as opposed to data derived from a structured design with predefined objectives. With more sampling from various seasons and landscapes, finer details can be explored which would have conservation implications. For example, we would expect variations in attempts to hunt during cold seasons because heat loss might be less of a challenge in the latter. Quantifying attempts to hunt and successful hunts across seasons could help focus management interventions to minimize negative interactions between fish cultivators and Fishing Cat. The strictly nocturnal activity of fishing cat as demonstrated in our study could be a strategy taken by the cat to avoid humans. Our approach of using participatory-science is relevant for conducting research on mammal behavior in human dominated landscapes.

animal behavior and cognition↗

bioRxiv2018

Proteostasis perturbation destabilizes respiratory complex assembly-intermediates via aggregation of subunits

Proteostasis is maintained by optimum expression, folding, transport, and clearance of proteins. Deregulation of any of these processes triggers widespread protein aggregation and loss of function. Here, we perturbed proteostasis by blocking proteasome-mediated protein degradation and investigated proteome partitioning from soluble to insoluble fraction. Aggregation of Respiratory Chain Complex (RCC) subunits highlights the early destabilization event as revealed by proteome redistribution. Sequence analyses followed by microscopy suggest that low complexity regions at the N-terminus are capable to facilitate aggregation of RCC subunits. As a result, respiratory complex assembly process is impaired due to destabilization of sub-complexes marking the onset of mitochondrial dysfunction and ROS accumulation. Redistribution of Histone proteins and their modifications indicated reprogramming of transcription as adaptive response. Together, we demonstrate susceptibility of RCC subunits to aggregation under multiple proteotoxic stresses providing an explanation for the simultaneous deregulation of proteostasis and bioenergetics in age-related degenerative conditions.

molecular biology↗