Biology subjects

Potdar, S.

Publications and source records attributed to Potdar, S..

16 recordsLinked to original sources

bioRxiv2026

No detectable effect of P2 neurons on female post-mating changes in sleep and feeding in Drosophila melanogaster

In many insects, females exhibit behavioral changes after mating. This plasticity can be mediated by interactions between male-derived seminal fluid proteins (SFPs) and the female nervous system. The Drosophila melanogaster seminal fluid protein Sex Peptide (SP) causes mated females to sleep less during the day and consume more food than unmated females, among other behavioral changes. Although the SP-sensing neural circuits that convey information to the females brain are known, the downstream neurons that affect post-mating behaviors remain unknown. P2 neurons in the flys central brain are good candidates for regulating post-mating changes in sleep and food consumption, as they express feeding- and sleep-responsive neuropeptide F (NPF), directly innervate the flys sleep center (the dorsal fan-shaped body, dFB), and are responsible for social-isolation-induced changes in sleep and food consumption. Using the GAL4/UAS system, we activated or silenced P2 neurons in mated and unmated females. We measured sleep duration using Drosophila Activity Monitors (DAM) and food consumption using Capillary Feeder (CAFE) and blue-dye assays. We found that P2-neurons are not responsible for post-mating changes in sleep and food consumption: mated females slept less during the day and ate more compared to unmated females irrespective of P2 neuron perturbation. Together, these results indicate that P2 neurons are unlikely to be primary downstream neurons through which male-transferred SP regulates post-mating sleep and food consumption. Future studies could determine whether P2 neurons regulate other post-mating behaviors or modulate sleep and feeding behaviors in a context-dependent manner.

genetics↗

bioRxiv2026

Proteomic consequences of male mate preference learning and female phenotype in the butterfly Bicyclus anynana

Mate preference learning, where individuals use past social experience to choose mates, is prevalent in many species. Yet its consequences on reproductive investment, and whether individuals differentially invest in reproduction based on their learned perception of the mates phenotype, are unknown. We addressed these questions using the butterfly Bicyclus anynana, where males acquire individual preferences for artificially painted 0-UV dorsal hindwing spotted (DHSN) females, who then lay more eggs. We measured the spermatophore proteins transferred by naive and experienced males to females manipulated to have preferred (0-DHSN) and unpreferred (2-DHSN) wing patterns. Using data independent acquisition (DIA), we identified 2144 proteins in the B. anynana spermatophore transferred to the female during mating. Experienced males that mated with preferred and unpreferred females had more differentially abundant (DA) proteins in their spermatophores that have functions in circadian rhythms, oogenesis, and neural signalling than naive males. Proteins associated with oogenesis were DA in spermatophores transferred to preferred females, which may contribute to why preferred females lay more eggs. Overall, our study provides evidence for the role of experience-induced behavioural plasticity in tailoring male ejaculates in butterflies and identifies proteins that influence female physiology and behaviours which directly affect the pairs overall reproductive fitness.

animal behavior and cognition↗

bioRxiv2026

Site-Dependent Decoupling of Drug-Biomarker Associations in Clear Cell Renal Cell Carcinoma Revealed by Functional Profiling of Patient-Derived Cell Models

Clear cell renal cell carcinoma (ccRCC) frequently exhibits primary and acquired resistance to standard-of-care therapies, underscoring the need for improved strategies to predict therapeutic response and prioritize patient-specific treatments. Although recent multi-omic and single-cell studies have provided insight into the molecular landscape of ccRCC, molecular alterations alone incompletely predict drug sensitivity. We prospectively profiled tumors from 28 patients with localized and metastatic ccRCC by integrating molecular characterization, functional drug sensitivity and resistance testing in patient-derived cell models, and longitudinal clinical data. Although genomic biomarkers suggested potentially actionable therapies in 27/28 patients, functional testing revealed discordance between genomic actionability and ex vivo drug sensitivity, whereas linear mixed-effects modelling uncovered 16 novel copy-number-based features associated with sensitivity to 11 drugs. Genotype-drug response associations were largely preserved between primary tumors and vena cava thrombi but frequently disrupted in distant metastases. Integrating functional drug testing with multi-omic profiling reveals vulnerabilities not apparent from genomic data alone, refines therapeutic actionability, captures interpatient and intersite heterogeneity in ccRCC, and provides a scalable framework for individualized treatment prioritization.

cancer biology↗

bioRxiv2026

Neurotranscriptomic signatures of natural variation in mate preference learning in two subspecies of Heliconius melpomene butterflies

Many animals change their behavior in response to social experiences by learning. Although social learning is adaptive, not all individuals learn. In Heliconius melpomene, H. m. malleti males respond to 2-day prior failed copulation experience by decreasing courtship, whereas H. m. rosina males do not. Here, we explore the transcriptomic differences in both the neural (brain) and sensory (eyes, antennae) tissues underlying this natural diversity in male aversive mate-preference learning. While the transcriptomic profiles of the two subspecies are inherently different across all three tissues, we found the greatest difference between the good (H. m. malleti), and bad (H. m. rosina) mate-preference learners in the brain, followed by the sensory tissues. Known learning genes and Gene Ontology terms were associated with differences in mate-preference learning, suggesting conserved learning pathways across animals. Genes within putative magic loci associated with colors, odors, and locomotion, were also differentially expressed between H. m. malleti and H. m. rosina, suggesting multimodal sensory processing may drive behavioral variance in these two subspecies. Overall, our study identifies genetic underpinnings for differences in preference learning, both in neural processing and sensory tissues. Selection on these genes/networks could result in preference learning-induced reinforcement, leading to reproductive isolation and speciation.

evolutionary biology↗

bioRxiv2026

Altered immune and treatment response gene expression signatures among poverty-exposed children with B-ALL

Children diagnosed with cancer typically receive standardized treatment regimens. Despite highly protocolized care, children living in poverty experience a greater risk of cancer relapse and higher mortality compared to their more affluent peers.1,2 Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, and children with ALL exposed to poverty are more likely to experience early relapse.3 Using single-cell RNA sequencing to analyze leukemic blasts and their microenvironment at diagnosis we found that poverty-exposed patients with standard-risk B-ALL exhibit transcriptional signatures of steroid resistance at time of diagnosis. Additionally, we observe increased expression of inflammatory signatures in myeloid cells and reduced effector signatures in CD8+ T-cells in children with B-ALL living in poverty. Further investigation of the mechanisms underlying these associations may identify opportunities for risk-adapted therapeutic strategies to improve disease outcomes in pediatric ALL.

cancer biology↗

bioRxiv2025

A STAT5B-driven mouse model of hepatosplenic γδ T-cell lymphoma reveals therapeutic efficacy of JAK inhibition

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive neoplasm associated with poor responses to standard chemotherapy regimens and low survival rates. No targeted therapies are available for HSTCL, and preclinical models to test new treatment options have not been established. The JAK-STAT signaling cascade is a key dysregulated pathway in HSTCL, and STAT5BN642His the most frequent somatic mutation in the disease. Here, we report on newly established clonal, murine {gamma}{delta} T-cell lymphoma cell lines initiated and driven by oncogenic STAT5BN642H, which recapitulate key immunophenotypic features, gene expression profiles and typically low cytolytic activity of patient-derived human HSTCL cells. CRISPR-Cas9 mediated knockout demonstrated growth dependence on STAT5BN642H. Murine C15 cells were allo-engrafted intravenously into both immunodeficient and immunocompetent mice to model an aggressive HSTCL-like disease at high penetrance, with recipient mice displaying hepatosplenomegaly and destructive {gamma}{delta} T cell organ infiltration, including bone marrow and blood involvement. We identified the potential of JAK inhibition as a targeted treatment strategy for HSTCL, and found the clinically approved JAK inhibitor upadacitinib to display selective anti-tumor efficacy against STAT5B-mutated HSTCL cell lines in vitro, in vivo, and in primary HSTCL patient samples. Overall, we describe the first robust STAT5B-driven preclinical model resembling features of HSTCL in an immune competent setting. This tool is expected to accelerate the study of HSTCL disease mechanisms and the testing of novel therapies. Our data further present the JAK inhibitor upadacitinib as a promising targeted treatment option for STAT5B-mutated HSTCL.

cancer biology↗

bioRxiv2025

Morphological cell profiling for drug repurposing against SARS-CoV-2 infection

Antiviral drug discovery has traditionally focused on targeting viral proteins, while host-directed strategies remain largely underexplored. Here, present a systematic drug repurposing strategy leveraging morphological profiling to identify host-targeting antivirals. Our image-based approach combines viral protein immunostaining with high-content Cell Painting analysis to simultaneously assess viral replication and provide in-depth analysis of host cell responses. By screening 5,275 repurposable drugs against SARS-CoV-2 infected cells, we identified compounds that reversed the infected cell phenotype, including ones not detected by conventional cytopathicity and antibody-based assays. A counter-screen excluded compounds whose antiviral activity was likely driven by drug-induced phospholipidosis (DIPL). Pathway enrichment analysis of compounds validated by both Cell Painting dose-response and DIPL assays, revealed host processes frequently hijacked by viruses, including innate immune responses and kinases. Among the top hits, both novel candidates, such as serdemetan, and previously reported broad-spectrum antivirals, such as sunitinib, were identified. Our approach constitutes an adaptable and scalable platform suited for diverse viral pathogens and cell systems. We provide a resource of open access screening data, images, and automated analysis pipelines to advance both antiviral discovery and pandemic preparedness.

microbiology↗

bioRxiv2025

Spatial artefact detection improves reproducibility of drug screening experiments

Reliable and reproducible drug screening experiments are essential for drug discovery and personalized medicine. Here, we demonstrate how systematic experimental errors negatively impact reproducibility, and that conventional quality control (QC) methods based on plate controls fail to detect these errors. To address this limitation, we developed a control-independent QC approach using normalized residual fit error (NRFE) to identify systematic errors in drug screening experiments. Comprehensive analysis of >100,000 duplicate measurements from the PRISM pharmacogenomic study revealed that the NRFE-flagged experiments show three-fold lower reproducibility between technical replicates. By integrating NRFE with existing QC methods to analyze 41,762 matched drug-cell line pairs between two datasets from the Genomics of Drug Sensitivity in Cancer project, we improved the cross-dataset correlation from 0.66 to 0.76. Available as an R package at https://github.com/IanevskiAleksandr/plateQC, plateQC provides a robust toolset for enhancing drug screening data reliability and consistency for basic research and translational applications.

bioinformatics↗

bioRxiv2025

Consistency in floral volatiles impacts plant-pollinator interactions in the face of environmental change in the Eastern Himalayas

Floral scents are an important mediator of many plant-pollinator interactions. However, environmental and ecological change could affect the synthesis and emission of volatile chemicals that constitute floral scents, potentially influencing pollinator perception of scents. We investigated the effects of elevation and warming on the floral scents of multiple co-occurring alpine meadow plant species along an elevational gradient in the Eastern Himalayas (3000 - 4000 masl). We also investigated pollinator responses in the same locations using 3-D printed floral models that replicated the differing volatile constituents. Finally, we assessed how pollinator preferences changed with variations in elevation, flowering season and location. We found that elevation and in-situ warming using Open Top Chambers (OTC) led to significant intraspecific variation in the composition of floral scents, both in terms of quality and quantity of volatiles released. Nevertheless, conspecific floral scents across elevations were more similar to each other than to other species. Cafeteria assays using artificial floral models revealed that pollinator preferences were driven by a small number of volatiles (p-cymene, 2-pentylfuran and -pinene), but these preferences were abolished in a novel plant-pollinator community where the same floral volatiles were not detected. Our results suggest that the local odourscape established by the floral community present plays a key role in plant-pollinator interactions. This emphasizes the need to incorporate ecological impacts such as changes in community into climate change analyses to understand the long-term impacts of human activity on co-evolutionary relationships like pollination. Significance StatementFloral scents are important for most plant-pollinator interactions, and can be affected by environmental factors like elevation and temperature. Our study shows that elevation and simulated in situ warming change the composition of floral scents, yet scents from the same species were more similar to each other across elevations and temperatures than to other species. Further, pollinator preferences to these scents replicated in artificial models persisted in spite of variation in temperature and elevation, but not in a novel plant-pollinator community containing floral species not releasing those volatiles. This emphasizes the need to incorporate factors such as floral community composition into our understanding of the long-term impacts of climate change and human activity on co-evolutionary relationships like pollination.

ecology↗

bioRxiv2023

Behavioural changes in aposematic Heliconius melpomene butterflies in response to their predatory bird calls

Prey-predator interactions have resulted in the evolution of many anti-predatory traits. One of them is the ability for prey to listen to predators and avoid them. Although prey anti-predatory behavioural responses to predator auditory cues are well described in a wide range of taxa, studies on whether butterflies change their behaviours in response to their predatory calls are lacking. Heliconius butterflies are unpalatable and form Mullerian mimicry rings as morphological defence strategies against their bird predators. Like many other butterflies in the Nymphalidae family, Heliconius butterflies possess auditory organs, which are hypothesized to have evolved to assist with predator detection. Here we test whether Heliconius melpomene change their behaviour in response to their predatory bird calls by observing the behaviour of male and female H. m. plessini exposed to calls of Heliconius avian predators: rufous-tailed jacamar, migratory Eastern kingbird, and resident tropical kingbird. We also exposed them to the calls of the toco toucan, a frugivorous bird as a control bird call, and an amplified greenhouse background noise as a noise control. We found that individuals changed their behaviour in response to jacamar calls only. Males increased their walking and fluttering behaviour, while females did not change their behaviour during the playback of the jacamar call. Intersexual behaviours like courtship, copulation, and abdomen lifting did not change in response to bird calls. Our findings suggest that despite having primary predatory defences like toxicity and being in a mimicry ring, H. m. plessini butterflies changed their behaviour in response to predator calls. Furthermore, this response was predator specific, as H. m. plesseni did not respond to either the Eastern kingbird or the tropic kingbird calls. This suggests that Heliconius butterflies may be able to differentiate predatory calls, and potentially the birds associated with those calls. HighlightsO_LIMany prey animals change their behaviour in response to their predators calls. C_LIO_LIWhether butterflies alter behaviour in response to bird predator calls is unknown. C_LIO_LIWe show that Heliconius melpomene change behaviour in response to jacamar calls. C_LIO_LIMales increased walking and fluttering, but did not alter courting behaviour. C_LIO_LIH. melpomene did not respond to predatory Eastern kingbird or tropical kingbird calls. C_LI

animal behavior and cognition↗

bioRxiv2021

Effects of food availability cycles on phase and period of activity/rest rhythm in Drosophila melanogaster

Foraging and feeding are indispensable for survival and their timing depends not only on the metabolic state of the animal but also on the availability of food resources in their environment. Since both these aspects are subject to change over time, these behaviours exhibit rhythmicity in occurrence. As the locomotor activity of an organism is related to its disposition to acquire food, and peak feeding in fruit flies has been shown to occur at a particular time of the day, we asked if cyclic food availability can entrain their rhythmic activity. By subjecting flies to cyclic food availability i.e., feeding/starvation (FS) cycles, we provided food cues contrasting to the preferred activity times and observed if this imposed cycling in food availability could entrain the activity/rest rhythm. We found that phase control, which is a property integral to entrainment, was not achieved despite increasing starvation duration of FS cycles (FS12:12, FS10:14 and FS8:16). We also found that flies subjected to T21 and T26 FS cycles were unable to match period of the activity rhythm to short or long T-cycles. Taken together these results show that external food availability cycles do not entrain the activity/rest rhythm of fruit flies. However, we find that starvation induced hyperactivity causes masking which results in phase changes. Additionally, T-cycle experiments resulted in minor period changes during FS treatment. These findings highlight that food cyclicity by itself may not be a potent zeitgeber but may act in unison with other abiotic factors like light and temperature to help flies time their activity appropriately.

animal behavior and cognition↗

bioRxiv2020

PRAK-03202: A triple antigen VLP vaccine candidate against SARS CoV-2

The rapid development of safe and effective vaccines against SARS CoV-2 is the need of the hour for the coronavirus outbreak. Here, we have developed PRAK-03202, the worlds first triple antigen VLP vaccine candidate in a highly characterized S. cerevisiae-based D-CryptTM platform, which induced SARS CoV-2 specific neutralizing antibodies in BALB/c mice. Immunizations using three different doses of PRAK-03202 induces antigen specific (Spike, envelope and membrane proteins) humoral response and neutralizing potential. PBMCs from convalescent patients, when exposed to PRAK-03202, showed lymphocyte proliferation and elevated IFN-{gamma} levels suggestive of conservation of epitopes and induction of T helper 1 (Th1)-biased cellular immune responses. These data support the clinical development and testing of PRAK-03202 for use in humans.

immunology↗

bioRxiv2020

Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments

Functional profiling of a cancer patients tumor cells holds potential to tailor personalized cancer treatment. Here we report the utility of Fresh Uncultured Tumor-derived EpCAM+ epithelial Cells (FUTC) for ex vivo drug response interrogation. Analysis of murine Kras mutant FUTCs demonstrated pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. Applying FUTC profiling on non-small cell lung cancer patient samples, we generated robust drug response data in 18 of 19 cases, where the cells exhibited targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling was used to guide compassionate treatment. FUTC profiling identified selective sensitivity to disulfiram and the combination of carboplatin plus etoposide and the patient received substantial clinical benefit from the treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.

cancer biology↗

bioRxiv2020

Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate

Spike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a "Corona" like morphology, and uniform size distribution.

biochemistry↗

bioRxiv2019

Mechanosensory stimulation via Nanchung expressing neurons can induce daytime sleep in Drosophila

The neurogenetic bases of sleep, a phenomenon considered crucial for well-being of organisms has recently been under investigation using the model organism Drosophila melanogaster. Although sleep is a state where sensory threshold for arousal is enhanced, it is known that certain kinds of repetitive sensory stimuli such as rocking, can in fact promote sleep in humans. Here we report that orbital motion aided mechanosensory stimulation promotes sleep in Drosophila, independent of the circadian clock, but controlled by the homeostatic system. Mechanosensory receptor nanchung (Nan) expressing neurons in the chordotonal organs mediate this sleep induction - flies where these neurons are either silenced or ablated display significantly reduced sleep induction upon mechanosensory stimulation. Transient activation of the Nan-expressing neurons also enhances sleep levels confirming the role of these neurons in sleep induction. Thus, we show for the first time that mechanosensory stimulation promotes sleep even in flies D. melanogaster and that it is mediated by proprioceptors.

neuroscience↗

bioRxiv2017

Sleep deprivation negatively impacts reproductive output in Drosophila melanogaster

Most animals sleep or exhibit a sleep-like state, yet the adaptive significance of this phenomenon remains unclear. Although reproductive deficits are associated with lifestyle induced sleep deficiencies, how sleep loss affects reproductive physiology is poorly understood, even in model organisms. We aimed to bridge this mechanistic gap by impairing sleep in female fruit flies and testing its effect on egg output. We find that sleep deprivation by feeding caffeine or by mechanical perturbation results in decreased egg output. Transient activation of wake-promoting dopaminergic neurons decreases egg output in addition to sleep levels, thus demonstrating a direct negative impact of sleep deficit on reproductive output. Similarly, loss-of-function mutation in dopamine transporter fumin (fmn)leads to both significant sleep loss and lowered fecundity. This demonstration of a direct relationship between sleep and reproductive fitness indicates a strong driving force for the evolution of sleep.

neuroscience↗