Biology subjects

Bhaskar, S.

Publications and source records attributed to Bhaskar, S..

7 recordsLinked to original sources

bioRxiv2026

Human landscape modification shapes foraging preferences and sucrose responsiveness of honey bees in Asia

Landscape composition is central in shaping how pollinators utilise floral resources, yet its influence on foraging behaviour of co-occurring Asian honey bees remains underexplored. Resolving this gap is crucial to understand how closely-related, native and introduced species maintain foraging efficiency in rapidly changing environments. We investigated nectar preferences, sucrose responsiveness, and foraging task partitioning in three co-occurring honey bee species in India: Apis florea (native open-nesting), Apis cerana (native cavity-nesting), and Apis mellifera (introduced cavity-nesting), across forest, agricultural, and urban landscapes. Landscape type strongly influenced crop sugar concentrations of honey bees. While all species collected high-concentration nectar in forests, A. mellifera and A. cerana collected lower concentrations than A. florea in urban habitats. A. florea showed consistent preference for high-concentration nectar across landscapes. Complementing this, sucrose responsiveness assays revealed a lower responsiveness of A. florea compared to cavity-nesting species. Foraging task partitioning differed among species, but interestingly, also among landscapes. While A. cerana predominantly collected nectar, A. mellifera foraged equally for pollen, nectar and water, and A. florea shifted task allocation across landscapes. In conclusion, we provide the first comparative evidence that landscape composition and species characteristics jointly shape foraging preferences and organisation of foraging labour in Asian honey bees.

ecology↗

bioRxiv2026

Colour preference and constancy in the giant Asian honey bee Apis dorsata

Tropical pollinators forage in environments where floral resources vary in space and time, requiring flexible strategies to optimise foraging efficiency. One such strategy, floral constancy - the temporary restriction to a single flower type - strongly influences foraging success and plant-pollinator interactions. We aimed to: (1) quantify spontaneous colour preferences and constancy in the Asian giant honeybee Apis dorsata, (2) test whether reward concentration modulates these preferences, (3) evaluate how quickly learned associations override spontaneous biases, (4) determine whether bees can use multiple colour associations simultaneously, and (5) assess whether local floral spectral patterns correlate with bee preferences. Bees trained to a neutral UV-grey stimulus showed a strong spontaneous preference and high constancy to blue, revealing a robust short-wavelength bias. Crucially, the strength of this spontaneous bias depended on reward concentration; Low-reward conditions elicited strong blue constancy, whereas high-reward conditions weakened it, demonstrating that reward expectation shapes spontaneous colour choices. This bias was flexible. When bees learned that yellow was rewarding they switched their preferences. Bees sequentially trained to both colours visited blue and yellow, showing no overall bias, or effect of the last-trained colour, indicating that recent experiences disrupt colour-specific constancy and generate largely random foraging choices. Bees were capable of learning and retaining two colours simultaneously, effectively suppressing the influence of spontaneous preferences. Finally, analysis of the communitys floral spectral distribution revealed a strong dominance of short-wavelength flowers, suggesting that long-term selection by the local floral environment may underlie the spontaneous blue preference observed in A. dorsata.

animal behavior and cognition↗

bioRxiv2025

SARC028 samples reveal an interplay between TGF-beta, interferon signaling and low HLA class I expression as contributors to Ewing sarcoma checkpoint blockade resistance

PurposeEwing sarcoma, in contrast to some adult sarcoma subtypes, generally does not respond to single agent immunotherapy targeting PD1. The features of Ewing sarcoma that preclude the effectiveness of immunotherapy remain largely unknown. To address this question, we utilized biopsies from patients with Ewing sarcoma obtained pre- and post-pembrolizumab (anti-PD1) therapy from the phase 2 clinical trial SARC028 to interrogate the Ewing tumor microenvironment and features associated with resistance to checkpoint inhibition. Experimental DesignWe utilize multiplexed immunofluorescence, spatial proteomics and spatial transcriptomics to analyze paired pre- and 8 weeks post-treatment biopsy specimens from patients with Ewing sarcoma enrolled on SARC028. ResultsPembrolizumab therapy did not alter the quantity of immune cell infiltration in Ewing tumor biopsies. Analysis of tumor-associated protein markers revealed increased immunoregulatory markers after pembrolizumab. Spatial transcriptomics identified ten cellular neighborhoods (CN) across patients consisting of specific cell subsets. CN10 was consistently observed across patients with poor response. This cellular neighborhood was enriched for a tumor subpopulation with high TGF-{beta} response, low interferon (IFN) response, and low HLA class I expression. IFN response, HLA class I expression, and overall immune infiltration were correlated. ConclusionsAnalyses of the tumor microenvironment from Ewing sarcoma biopsies reveals an immunosuppressive triad, the disruption of which should be pursued to improve antitumor immunity. This work highlights the unique insight that can be gained from the analysis of paired patient Ewing sarcoma tumor biopsy samples from clinical trials. Statement of translational relevanceSingle agent checkpoint inhibitors have demonstrated limited clinical benefit in bone sarcomas, including Ewing sarcoma (EwS). While in vitro and limited patient tumor analyses have suggested mechanisms of immunotherapy resistance in EwS, tumor biopsies following checkpoint inhibitor administration have not been examined. SARC028 was a phase II study investigating blockade of programmed cell death-1 (PD-1) in patients with relapsed/refractory sarcomas, including EwS. Tumor biopsies were collected prior to and 8 weeks after anti-PD1 therapy. Here, we leverage a unique opportunity to understand EwS immunotherapy resistance through analysis of paired tumor samples from SARC028. Using a multi-omics approach, we identify features of EwS that contribute to primary resistance to anti-PD1 including TGF-{beta}, reduced interferon signaling and low HLA class I expression. This study provides an improved understanding of tumor characteristics driving poor response to immunotherapy in relapsed EwS and will guide the development of future trials to modulate this immunosuppressive axis.

cancer biology↗

bioRxiv2024

Immunocompetent murine model of Ewing sarcoma reveals role for TGFβ inhibition to enhance immune infiltrates in Ewing tumors during radiation

Ewing sarcoma (ES) is an aggressive cancer diagnosed in adolescents and young adults. The fusion oncoprotein (EWSR1::FLI1) that drives Ewing sarcoma is known to downregulate TGFBR2 expression (part of the TGF{beta} receptor). Because TGFBR2 is downregulated, it was thought that TGF{beta} likely plays an inconsequential role in Ewing biology. However, the expression of TGF{beta} in the Ewing tumor immune microenvironment (TIME) and functional impact of TGF{beta} in the TIME remains largely unknown given the historical lack of immunocompetent preclinical models. Here, we use single-cell RNAseq analysis of human Ewing tumors to show that immune cells, such as NK cells, are the largest source of TGF{beta} production in human Ewing tumors. We develop a humanized (immunocompetent) mouse model of ES and demonstrate distinct TME signatures and metastatic potential in these models as compared to tumors developed in immunodeficient mice. Using this humanized model, we study the effect of TGF{beta} inhibition on the Ewing TME during radiation therapy, a treatment that both enhances TGF{beta} activation and is used to treat aggressive ES. Utilizing a trivalent ligand TGF{beta} TRAP to inhibit TGF{beta}, we demonstrate that in combination with radiation, TGF{beta} inhibition both increases ES immune cell infiltration and decreases lung metastatic burden in vivo. The culmination of these data demonstrates the value of humanized models to address immunobiologic preclinical questions in Ewing sarcoma and suggests TGF{beta} inhibition as a promising intervention during radiation therapy to promote metastatic tumor control.

cancer biology↗

bioRxiv2024

Inhibition of Proteasome Activity Facilitates Definitive Endodermal Specification of pluripotent Stem Cells by influencing YAP signaling

Understanding the molecular players that control the specification of definitive endoderm is imperative to obtain the homogenous population of pancreatic {beta}-cells from stem cells. Though the Ubiquitin proteasome system (UPS) has been envisaged as a crucial intracellular protein degradation system, its role in germ layer specification remains elusive. In this study, using a mouse embryonic stem cells model system (mESCs) we observed decreased proteasomal activity specifically during endoderm, but not in meso- or ecto-derm differentiation. Extraneous inhibition of proteasomal activity during differentiation enhanced the expression of endodermal genes specifically. Enhancing proteasomal activity by including the activator IU1 in the induction culture, inhibited definitive endodermal differentiation. Further, inhibiting proteasomal activity at the definitive endodermal stage resulted in enhanced generation of insulin-positive cells. A similar increase in endodermal gene expression by inhibiting proteasomal activity was observed in miPSC and hiPSC differentiated towards endodermal lineage. Mechanistic insight showed no contribution of endoplasmic reticulum unfolded protein response but revealed the involvement of the YAP signaling pathway in proteasome-inhibited enhanced endodermal differentiation. Unravelling the specific involvement of UPS in endodermal cell fate specification in pluripotent stem cells paves the way for obtaining better qualitative and quantitative definitive endodermal cells for plausible cellular therapy in the future.

cell biology↗

bioRxiv2022

Zic3 enables bimodal regulation of tyrosine hydroxylase expression in dopaminergic neurons of olfactory bulb and midbrain

Dopaminergic (DA) neurons in the Olfactory bulb (OB) are involved in odor detection and discrimination. Transcription factor (TF) regulatory network responsible for their fate specification remains poorly understood and the spatial regulation of DA neurons remains elusive. In this study, mice exposed to odor stimulant exhibited specific upregulation of Zinc finger transcription factor of Cerebellum (ZIC) 3 along with Tyrosine Hydroxylase (TH). Stringent co-expression analysis showed ZIC3 and TH dual positive neurons in OB. Genetic manipulation showed ZIC3 to be both essential and sufficient to drive TH expression and essential for odor perception. ZIC3 interacts with ER81 and binds to region encompassing ER81 binding site in DA neurons and is indispensable for TH expression. In midbrain (MB), in the absence of ER81, ZIC3 switches its molecular partner and binds to Pitx3 promoter-a DA fate determinant. Under ectopic expression of ER81 in MB DA neurons, propensity of ZIC3 binding to Pitx3 promoter is compromised and its occupancy on Th promoter encompassing ER81 binding site is established, finally culminating in desired TH expression. Together, these findings reveal a unique ZIC3 mediated bimodal regulation of TH in OB and MB to ultimately facilitate DAergic fate.

neuroscience↗

bioRxiv2022

Monoallelically-expressed Noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression

Out of the several hundred copies of rRNA genes that are arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, [~]50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to differential expression of rRNAs. However, the mechanism(s), controlling the dosage of active versus inactive rRNA genes in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influences rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosome. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs that by forming constrained nucleolar territories on individual NORs contribute to rRNA expression.

cell biology↗