Biology subjects

Dey, P.

Publications and source records attributed to Dey, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Dynamic microtubules drive yolk-cytoplasm segregation in the syncytial Drosophila embryo

Yolk-cytoplasm segregation is among the earliest spatial organization events in the developing embryo of many oviparous animals. The segregation process is intimately linked to early embryonic cleavage and pattern formation, and exhibits a wide range of spatial and temporal diversity. However, the underlying cytoskeletal mechanism remains largely unknown, except for a small number of species. Using quantitative live imaging, we investigated yolk segregation in the Drosophila embryo during the syncytial nuclear cycles 11-14. We find that the yolk vesicles move progressively inward in spatial and temporal coordination with the inward expanding microtubule networks that are nucleated from centrosomes positioned at the cortex, whereas cortical actin meshwork remains spatially restricted. Using the gnu RNAi embryo to decouple nuclear migration and division from cytoskeletal dynamics, we establish causality with targeted pharmacological disruption and find that microtubule dynamics is required for yolk segregation, while depolymerization of actin has no discernible effect. In support of a mechanism of growth-propelled passive displacement, microtubule plus end comets come in apparent contact with yolk vesicles, and injected, inert microbeads are displaced towards the embryo center presumably by the same pushing force. These findings identify microtubule polymerization as a predominant driver of yolk-cytoplasm segregation in Drosophila and suggest that diverse cytoskeletal mechanisms evolved to accomplish this crucial reorganization process

developmental biology↗

bioRxiv2026

Spatial immune ecosystems govern therapeutic response in HER2-low breast cancer

HER2 low breast cancer represents a clinically important but biologically heterogeneous disease state, and the spatial immune programs underlying therapeutic response remain poorly understood. Here, we used single-cell spatial transcriptomics to characterize HER2 low and HER2 high breast tumors and define microenvironmental features associated with treatment sensitivity and resistance. We identified diverse malignant, stromal, and immune compartments, with dendritic cells emerging as a highly remodeled population in HER2 low tumors. Focused analysis resolved distinct dendritic cell states, including homeostatic cDC2, IFN activated mature cDC, classical functional cDC2, plasmacytoid DC, and ITGAX positive monocyte derived DC populations. Spatial proximity analysis further revealed that resistant HER2 low tumors exhibited increased segregation of tumor epithelial cells from effector immune populations and enrichment of myeloid-rich immune niches, consistent with an immune-restricted spatial architecture. Independent TCGA BRCA validation confirmed the clinical relevance of these dendritic-cell states, with elevated homeostatic cDC2 signatures predicting poor survival, whereas inflammatory dendritic cell signatures were associated with favorable outcomes. Resistant HER2 low tumors were characterized by enrichment of homeostatic and classical cDCs, depletion of IFN-activated cDCs and pDCs, altered tumor myeloid T cell communication, and expansion of spatially organized resistant niches, whereas sensitive tumors retained immune-intermixed niches enriched for antigen presentation and effector immune interactions. Together, these findings demonstrate that therapeutic resistance in HER2 low breast cancer is driven by coordinated spatial remodeling of dendritic-cell states and immune architecture, identifying dendritic cell myeloid niche organization as a potential biomarker and therapeutic vulnerability.

cancer biology↗

bioRxiv2026

PS FAD mutants and γ-secretase inhibition accumulate VEGFR2-derived peptide VCTF1 suppressing brain VEGFR2 dimerization, angiogenesis and neuroprotection.

Efficient cerebrovasculature is vital to neuronal health and cognition and evidence shows that most dementia patients have cerebrovascular abnormalities. Brain vasculature is regulated by Vascular Endothelial Growth Factors (VEGFs) binding VEGF receptor2 (VEGFR2) and stimulating angiogenesis and neuroprotection. Here we show that an ADAM17 cleavage of extracellular VEGFR2 produces the membrane-bound {gamma}-secretase substrate VEGFR2/CTF1 (called VCTF1), comprising the transmembrane and intracellular domains of VEGFR2. VCTF1 binds full-length VEGFR2 monomers suppressing its dimerization a function that is required for VEGFR2 activation and downstream angiogenesis and neuroprotection. Presenilin1 (PS1) Familial Alzheimers disease (FAD) mutants exert dominant negative effects on the {gamma}-secretase processing of VCTF1 increasing its concentration and abolishing VEGF-A-induced VEGFR2 dimerization/activation and downstream VEGFR2 signaling, endothelial cell functions and angiogenesis. {gamma}-Secretase inhibitors or PS1 reduction have similar effects on VCTF1 accumulation and VEGFR2 dimerization/activation and downstream signaling and functions as PS1 FAD mutants. Moreover, PS1 FAD mutants increase vulnerability of brain neurons to ischemic stress and abolish VEGF-A-induced neuroprotection and cognition. Together, these data show that VCTF1 suppresses VEGFR2 dimerization and downstream signaling and functions of the brains VEGF-A-/VEGFR2 angiogenic and neuroprotection systems. Importantly, we detected molecular markers of decreased VEGFR2 dimerization and angiogenic dysfunction in human brain tissue from PS1 FAD mutant genotypes. Our data reveal a pathway through which FAD mutants may promote dementia by increasing accumulation of VCTF1 and decreasing angiogenesis, neuroprotection, and cognition, suggesting that PS1 FAD patients may benefit from therapeutic methods that decrease brain VCTF1.

neuroscience↗

bioRxiv2026

Imbalance of Ciliary Programs Drives Fibroblast Differentiation and Fibrotic Signaling in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic fibrotic disease characterized by accumulation of activated profibrotic myofibroblasts in multiple organs. The mechanisms triggering pathogenic fibroblast to myofibroblast reprogramming in SSc, and maintaining the activated myofibroblast state, are not well known. Recent studies show that primary cilia (PC), solitary sensory organelles that integrate diverse chemical and mechanical signaling pathways, may regulate fibroblast fates. Here, using an orthogonal multimodal strategy spanning human cohorts, single-cell trajectories, and targeted perturbation models, we identify a fundamental imbalance in cilia-program dynamics as a unifying driver of fibrotic activation in SSc. Meta-analysis of skin biopsies integrating eight microarray datasets and two independent scRNA-seq cohorts, revealed a conserved 15-gene cilia signature that is altered in SSc. Single-cell trajectory mapping resolved a principal progenitor[->] secretory-like [->] myofibroblast differentiation axis, where SSc fibroblasts displayed spatially dysregulated ciliary programs that established a prolonged, disassembly-dominant "cilia-off" state. Notably, this ciliary imbalance appeared to emerge before the transition to fibrotic gene programs, positioning cilia disruption as an initiating, not secondary, event in fibroblast programming. Consistent with these transcriptomic findings, PC length was significantly reduced in SSc skin and cultured fibroblasts. Mechanistically, genetic and pharmacological perturbation studies demonstrated that cilia disruption is sufficient to drive fibrotic programs. These data establish a reciprocal regulatory framework in which shortened cilia promote sustained activation of TGF-{beta}-Hippo feed-forward signaling, driving fibroblast-to-myofibroblast transition and amplifying fibrotic responses. Together, these findings position the imbalance between ciliary assembly and disassembly as a central determinant of fibrotic fibroblast fate in SSc. Moreover, they indicate that therapeutically stabilizing primary cilia, "ciliotherapy", can reset pathological fibroblast trajectories and represents a promising antifibrotic strategy for SSc and other fibrotic conditions. TeaserDisrupted Primary Cilia Drives Pathophysiology of Systemic Sclerosis.

cell biology↗

bioRxiv2025

FTO promotes skeletal muscle differentiation and regeneration by regulating m6A-modified c-Myc

Recent studies have revealed the crucial role of m6A RNA methylation in various myogenic processes. However, the specific function and underlying molecular mechanisms of this modification in vivo during skeletal muscle differentiation and regeneration remain unclear. In this study, we examine the role and mechanism of the m6A RNA demethylase fat mass and obesity-associated protein (FTO) in skeletal muscle differentiation and regeneration in mice. Our findings demonstrate that FTO is upregulated during both skeletal muscle differentiation and regeneration and is essential for these key myogenic processes. We show that exogenous FTO expression in primary myoblasts enhances differentiation, whereas FTO knockdown inhibits it. Additionally, FTO knockout in mouse muscle stem cells impairs muscle regeneration. FTO promotes skeletal muscle differentiation and regeneration by directly targeting and regulating m6A-modified c-Myc, a well-known repressor of myogenesis. The IGF2BP2 reader protein recognizes m6A-modified c-Myc in undifferentiated myoblasts and stabilizes it. As FTO levels increase during myoblast differentiation, m6A levels on c-Myc decrease. This reduction prevents IGF2BP2 from binding to c-Myc, thereby destabilizing c-Myc levels and promoting differentiation. Overall, our findings underscore the significance of the novel FTO/c-Myc/IGF2BP2 axis in skeletal muscle differentiation and regeneration.

developmental biology↗

bioRxiv2025

Targeting a novel chloroquine derivative to lysosomes induces massive and irreversible damage to lysosomes and suppresses autophagosomes and lysosomes assembly in cancer

Pancreatic ductal adenocarcinoma (PDAC) exhibits profound therapy resistance driven by lysosome dependent nutrient recycling, metabolic adaptation, and stress tolerance. Current lysosome-targeting agents such as chloroquine (CQ) and hydroxychloroquine (HCQ) show limited efficacy due to transient activity and dose-limiting toxicities. To overcome these limitations, we developed Lysostilbenes, a new class of hybrid small molecules combining the CQ pharmacophore with lysosome-disrupting trans-4,4'-dihydroxystilbene. Lysostilbene-4 emerged as the lead candidate, demonstrating [~]30-40-fold greater cytotoxicity against PDAC cells than parental compounds, while sparing non-malignant cells. At nanomolar concentrations, Lysostilbene-4 induced rapid, irreversible lysosomal membrane permeabilization (LMP), initiating a lysosome mitochondria apoptotic cascade via cathepsin-B release, BID cleavage, BAX activation, and caspase-mediated apoptosis. In parallel, it abrogated lysosomal recovery by impairing repair, lysophagy, autophagosome maturation, and uncoupling TFEB-driven transcriptional programs from effective lysosome biogenesis. TFEB knockout further sensitized PDAC cells, underscoring TFEB as a key determinant of lysosomal resilience and a potential predictive biomarker. Importantly, Lysostilbene-4 was well tolerated in preclinical mouse models at supra-therapeutic doses without systemic toxicity. These findings position Lysostilbene-4 as a first-in-class lysosome-targeting therapeutic that enforces sustained lysosomal collapse while disabling adaptive recovery mechanisms, providing a mechanistically precise and safe strategy against PDAC.

cancer biology↗

bioRxiv2025

TWEAK Signaling Drives the Transition from Psoriasis to Atopic Dermatitis-like Inflammation in Paradoxical Skin Reactions

Targeted biologics have significantly advanced the treatment of inflammatory skin diseases such as psoriasis; however, some patients paradoxically develop eczematous skin reactions during or after anti-TNF, IL-17, or IL-23 therapy. Although these paradoxical reactions resemble atopic dermatitis clinically and histologically, the molecular mechanisms that drive their development are not fully understood. Here, we generated high-resolution cellular and spatial maps of healthy skin, psoriasis, atopic dermatitis, and paradoxical reactions using single-cell RNA sequencing, spatial transcriptomics, immunohistochemistry, and in vitro assays. In paradoxical reactions, we identified a distinct transcriptional landscape characterized by myeloid and T-cell expansion and an altered keratinocyte phenotype shaped by TWEAK signaling. Mechanistically, we showed that TWEAK synergizes with IL-13 to drive the Th2/type I interferon-polarized epithelial program. Notably, anti-TNF therapy induced TWEAK gene expression in myeloid cells, suggesting a compensatory inflammatory circuit. Together, these findings identify the TWEAK-IL-13 axis as a central driver of paradoxical skin reactions and provide a mechanistic framework for how cytokine blockade may rewire cutaneous immune responses. One Sentence Summary The TWEAK-IL-13 signaling axis is a key driver of immune reprogramming underlying paradoxical skin reactions.

immunology↗

bioRxiv2025

VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia

Preeclampsia affects approximately 1 in 10 pregnancies, leading to severe complications and long-term health risks for both mother and offspring. While the etiology remains unclear, preeclampsia has been linked to both autoimmunity and the timing of menarche. Through human single-cell and spatial analyses, coupled with in vitro, in vivo, and ex vivo models, we demonstrate that VGLL3, a transcription co-regulator in the Hippo pathway, is upregulated in preeclamptic placentas. VGLL3 promotes immune activation, impairs trophoblast differentiation, and induces endothelial dysfunction, all of which contribute to pregnancy-related hypertension, fetal growth restriction, and offspring mortality. Our data reveal that VGLL3 acts upstream of preeclampsia-associated processes, including the production of sFLT1, a key biomarker of the disease. Notably, targeting VGLL3--either by genetic deletion in mouse placentas or through therapeutic inhibition in human placentas--protects against preeclampsia and alleviates disease pathology. These findings position VGLL3 as a promising novel therapeutic target for preeclampsia.

immunology↗

bioRxiv2025

Cumulative pregnancy and postnatal environmental exposures impact social behaviour in male mice associated with epigenetic, ribosomal, and immune dysregulation

Environmental exposures across critical developmental windows can significantly influence brain development and contribute to the pathogenesis of neurodevelopmental disorders (NDDs). Emerging clinical evidence suggests that cumulative environmental factors during early development result in more pronounced disease phenotypes in offspring. Here, we developed a triple-hit model using C57Bl/6JAusb mice to examine the cumulative effects of antenatal social stress, antenatal chronic high-fat diet consumption, and postnatal poly(I:C) exposure on neurodevelopmental outcomes in offspring. Male triple-hit offspring displayed autism-like social deficits and an overall increased susceptibility to neurodevelopmental behavioural alterations in adulthood compared to male non-stressed controls. Conversely, these behavioural changes were not observed amongst female triple-hit offspring. Single-cell RNA (scRNA) transcriptomic and bulk proteomic sequencing were performed in male triple-hit offspring across peripheral blood immune cells and brain tissue. scRNA sequencing in microglia, astrocytes, and oligodendrocytes revealed dysregulation in critical glial cell processes, ribosomal functions, and chromatin remodelling. Similar functional themes were observed across peripheral blood macrophages, neutrophils, and naive B cells - displaying immune and ribosomal dysregulation at the transcriptional level. Proteomics pathway enrichment analyses revealed significantly reduced protein abundance in ribosomal biogenesis, translation, and chromatin remodelling functions in both peripheral blood immune cells and brain tissue. We also observed synaptic dysfunction in the blood and brain proteome. Overall, using our unique triple-hit model, we demonstrate that multiple early life environmental exposures drive NDD-associated behaviours in a sex-specific manner; and is associated with overlapping central and peripheral molecular mechanisms that have clinical relevance to NDD pathogenesis.

developmental biology↗

bioRxiv2025

DANCE: An open-source analysis pipeline and low-cost hardware to quantify aggression and courtship in Drosophila

Quantifying animal behavior is pivotal for identifying the underlying neuronal and genetic mechanisms involved. Computational approaches have enabled automated analysis of complex behaviors such as aggression and courtship in Drosophila. However, existing approaches rely on rigid, rule-based algorithms and expensive hardware, limiting sensitivity to behavioral variations and accessibility. Here, we describe the Drosophila Aggression and Courtship Evaluator (DANCE), a low-cost, open-source platform that combines machine learning-based classifiers and inexpensive hardware to quantify aggression and courtship. DANCE consists of six novel behavioral classifiers trained using a supervised machine learning algorithm. DANCE classifiers address key limitations of rule-based algorithms, capturing dynamic behavioral variations more effectively. DANCE hardware is constructed using repurposed medicine blister packs and acrylic sheets, with recordings performed using smartphones, making it affordable and accessible. Benchmarking demonstrated that DANCE hardware performs comparably to sophisticated, high-cost setups. We validated DANCE in diverse contexts, including social isolation versus enrichment, which modulates aggression and courtship; RNAi-mediated downregulation of the neuropeptide Dsk; and optogenetic silencing of dopaminergic neurons, which promotes aggression. DANCE provides a cost-effective and portable solution for studying Drosophila behaviors in resource-limited settings or near natural habitats. Its accessibility and robust performance democratize behavioral neuroscience, enabling rapid screening of genes and neuronal circuits underlying complex social behaviors.

neuroscience↗

bioRxiv2024

Trophic transfer and bioaccumulation of nanoplastics in Coryphaena hippurus (Mahi-mahi) and effect of depuration

Ocean plastic pollution is a global concern, exacerbated by the distinctive physiochemical characteristics of nanoplastics (NPs), making it crucial to study the impacts on marine animals. While most studies focus on the impacts of waterborne NP exposure, trophic transfer is another key transport mechanism that may also provide insight into the potential transfer of NPs to humans through the food chain. This study investigates polystyrene NP transfer to Coryphaena hippurus (mahi-mahi) larvae, a widely consumed fish and significant marine predator, during the early life stage. Using a two-step food chain, Brachionus plicatilis (rotifers) were exposed to NPs, and subsequently fed to C. hippurus larvae, with exposure durations ranging from 24 to 96 h. Significant NP transfer was observed via the food chain, varying with exposure duration. A depuration study over 72 h, simulating environmental intermittent NP exposure, revealed substantial NP excretion but also notable retention in the larvae. Biodistribution analysis indicated that most NPs accumulated in the gut, with a significant portion remaining post-depuration and some translocating to other body parts. Despite no significant effects on body length and eye diameter during this short study period, histopathological analysis revealed intestinal tissue damage in the larvae. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/606698v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@828cfcorg.highwire.dtl.DTLVardef@f6092borg.highwire.dtl.DTLVardef@d3efc6org.highwire.dtl.DTLVardef@22dcb2_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2024

Trait distribution in Geometrid moth assemblages does not vary along a western Himalayan elevational gradient

Elevation gradients pose challenges for flying insects due to temperature and air density shifts, impacting their thermoregulation, flight abilities and subsequently species distribution patterns. Geometrid moths are a model group for studying these traits among insects. This study examines how trait-patterns and niche differentiation of Geometrid moth assemblages change with elevation. Investigating 697 specimens of 120 Geometrid moth species, I assessed species diversity, turnover, and various traits related to body size and flight capabilities along a 1500m elevation span in the western Himalayas. Results indicate a decline in species diversity along the elevational gradients, accompanied by consistent turnover from lower to higher elevations. Despite this pattern, elevation did not significantly influence morphological traits related to thermal sensitivity (body size) and flight capability (wing loading and manoeuvrability) at the assemblage level in Geometrid moths. Furthermore, there was no significant niche differentiation among species across elevations. This supports the argument that species with similar ecological roles persist through turnover, maintaining consistency in trait values across assemblages. These findings from the paleotropics align with patterns observed in Geometrid moths across neotropical and temperate regions, highlighting the importance of trait-based approaches in understanding species responses to environmental changes. Summary StatementThis study examines how Geometrid moth assemblages in the western Himalayas respond to elevational gradients, revealing consistent turnover, stable traits, and no significant niche differentiation, emphasizing trait-based species adaptation

ecology↗

bioRxiv2023

Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway

Colon cancer is among the most lethal and prevalent malignant tumours in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit Schisandra chinensis, has been reported for its anti-cancer properties. However, no studies to date have been done to characterise the exact molecular mechanisms regarding the anti-tumorigenic effect of Sch B in colon cancer. A comprehensive analysis of the molecular mechanism for the anti-tumorigenic effect of Sch B on human colon cancer cells was performed using combination of Raman spectroscopy, RNA-seq, computational docking and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumour growth in vivo. Our findings provide essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

pharmacology and toxicology↗

bioRxiv2023

Real-time assessment of the impacts of polystyrene and silver nanoparticles on hatching process and early-stage development of Artemia using a microfluidic platform

The development of real-time in-situ monitoring techniques is key to advancing a mechanistic understanding of the impacts of marine pollution, which is challenging to acquire through traditional end-point toxicity testing. We investigated the impacts of different nanopollutants on the hatching process and early-stage development of marine organisms, a vulnerable life stage, by observing oxygen consumption in real-time and morphological changes at regular intervals using a microfluidic platform. Here, two common and distinct nanoparticle (NP) types - polystyrene (PS) nanoplastic and silver (Ag) nanometal, were examined to assess and compare impacts on the hatching process and nauplius stage (first larval stage) of Artemia, a widely used zooplankton model in ecotoxicological studies. The study was conducted over a wide range of doses that are relevant to different environmental conditions, ranging from 0-1 mg/L, over a period of 24 hours. The hatching process of Artemia is comprised of four distinct stages which can be differentiated by metabolism and morphology: hydration, differentiation, emergence, and hatching. During hatching, NP exposure altered the time needed for the resumption of dormant Artemia cysts (hydration duration) at the lowest dose, dramatically prolonged the differentiation stage, and slowed embryo emergence from the cysts. The remaining time for the hatching stage during the experimental timeframe was also shortened. Overall, the presence of NPs led to increased oxygen consumption in multiple stages of the hatching process. Hatchability increased significantly with NP concentration although mortality showed an inverse pattern. This may be attributed to the increased aggregation of NPs in saltwater with increasing concentration which limits bioavailability during hatching but may be more readily consumed post-hatch. Ag NPs had a greater effect on hatching and mortality in comparison to PS NPs. A significant impact of NPs on swimming speed was observed, with a decrease observed in the presence of PS NPs and an increase observed in the presence of Ag NPs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/553636v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@3224e3org.highwire.dtl.DTLVardef@13d81corg.highwire.dtl.DTLVardef@d14163org.highwire.dtl.DTLVardef@1bfd44_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIUtilization of oxygen sensor integrated microfluidic chip and microscopy for ecotoxicological study. C_LIO_LIBioaccumulation of NPs affected hatching stages and respiration leading to inhibition of hatchability, with greater toxicity of silver NPs. C_LIO_LINPs caused significant mortality and alteration in swimming performance. C_LI

ecology↗

bioRxiv2023

A trait-based understanding of the vulnerability of a paleotropical moth community to predation by a sympatric bat with flexible foraging strategies

O_LIPrey profitability for a predator hunting diverse prey varies with species and seasons. Whereas prey selection by aerial-hawking or gleaning bats is well established, this is challenging to establish in species that adopt both these strategies flexibly. Measurable prey traits coupled with availability in the foraging grounds help characterize the vulnerability of prey species to predation. C_LIO_LIIn the Western Ghats of India, a global biodiversity hotspot, we studied an anthropogenic landscape, where insectivorous bats are abundant and diverse, but their impact on moth communities is little understood. We investigated the morphological traits of a sympatric moth community that make them more vulnerable to predation by Megaderma spasma, a bat with flexible foraging strategies. We also established the seasonal composition of moth prey in the diet of the bat. C_LIO_LIWe analyzed the discarded prey remains from several roosts, collected over three years, for seasonal patterns in the diet and selective hunting. Through light-trapping, we collected moth specimens in different seasons to assess the morphological traits of the moth community available in the foraging area of the bat. C_LIO_LIThe traits likely to affect the profitability of prey moths were measured: forewing length, hindwing length, wingspan, and body length (a proxy for body size); forewing area, hindwing area, maneuverability, and wing loading (as a proxy for evasive flight capability), and forewing aspect ratio (as a proxy for wing shape). C_LIO_LIOur results showed that consumed moth prey diversity varies seasonally, with moths belonging to the Hepialidae family being preferred in the wet season. Moths belonging to the Sphingidae family were the most abundant in the diet, followed by Erebidae and Hepialidae. Sphingid moths have the lowest maneuverability, and highest forewing aspect ratio; the Hepialidae moths have the maximum body size followed by Sphingids thus confirming our hypothesis that larger moths with low evasive capabilities are more vulnerable to predation. C_LIO_LIAssessing vulnerability at the prey community level, we establish a framework for future research on moth-bat interactions from the diverse and less-explored paleotropical communities. Additionally, the study reiterates the usefulness of trait-based approaches to understanding prey-predator dynamics. C_LI

ecology↗

bioRxiv2023

PROTEOMICS OF HYPOTHERMIC ADAPTATION REVEALS THAT RBM3 ENHANCES MITOCHONDRIAL METABOLISM AND MUSCLE STEM-CELL DIFFERENTIATION

Adaptation to hypothermic stress is important for skeletal muscle cells, but a comprehensive knowledge of molecular mediators is lacking. We show that adaptation to mild hypothermia (320C) improves the ability of skeletal muscle myoblasts to differentiate into myotubes in vitro. We performed proteomic analysis of mouse myoblasts exposed to mild hypothermia for various time points and identified dynamic changes in mitochondrial metabolism and proteostasis. This revealed that RBM3, an RNA-binding protein, increases progressively with acute and chronic exposure to hypothermic stress, and is necessary for the enhanced differentiation upon hypothermic adaptation. We also demonstrate that overexpression of RBM3 at physiological temperatures is sufficient to (i) enhance mitochondrial metabolism as judged by a decrease in the AMPK energy-sensing pathway, (ii) increase levels of proteins associated with translation and increase levels of 4E-BP1 phosphorylation, (iii) increase stem cell markers (MyoD1, PAX7), and improve differentiation of myoblasts from both young and aged mice.

biochemistry↗

bioRxiv2023

Pharmacologically targeting KRASG12D in PDAC models:tumor cell intrinsic and extrinsic impact

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which new therapeutic interventions are needed. Here we assessed the cellular response to pharmacological KRAS inhibition, which target the central oncogenic factor in PDAC. In a panel of PDAC cell lines, pharmaceutical inhibition of KRASG12D allele, with MRTX1133 yields variable efficacy in the suppression of cell growth and downstream gene expression programs in 2D culture. CRISPR screens identify new drivers for enhanced therapeutic response that regulate focal adhesion and signaling cascades, which were confirmed by gene specific knockdowns and combinatorial drug synergy. Interestingly, MRTX1133 is considerably more efficacious in the context of 3D cell cultures and in vivo PDAC patient-derived xenografts. In syngeneic models, KRASG12D inhibition elicits potent tumor regression that did not occur in immune-deficient hosts. Digital spatial profiling on tumor tissues indicates that MRTX1133 activates interferon-{gamma} signaling and induces antigen presentation that modulate the tumor microenvironment. Further investigation on the immunological response using single cell sequencing and multispectral imaging reveals that tumor regression is associated with suppression of neutrophils and influx of effector CD8+ T-cells. Thus, both tumor cell intrinsic and extrinsic events contribute to response and credential KRASG12D inhibition as promising strategy for a large percentage of PDAC tumors.

cancer biology↗

bioRxiv2023

The impact of selected abiotic factors on zooplankton hatching process through real-time, in-situ observation

Current studies on abiotic impacts on marine microorganisms often focus on endpoint analysis (e.g., hatching rates, survival). Here, we demonstrate that a mechanistic understanding can be obtained through real-time measurement of respiration and morphology in controlled microenvironments over extended time periods. As a demonstration, temperature and salinity are chosen to represent critical abiotic parameters that are also threatened by climate change and a target species of Artemia, a prominent zooplankton whose reproduction can affect the marine food pyramid. Different temperatures (20, 35, and 30{o}C) and salinities (0, 25, 50, and 75 ppt) are shown to significantly alter the duration of hatching stages, metabolic rates, and hatchability. Higher temperatures and moderate salinity boosted metabolic reactivation of latent cysts, while higher temperatures alone sped up the process. Hatchability is inversely related to the duration of the differentiation stage of hatching, which persisted longer at lower temperatures and salinities. Initial oxygen availability affects respiration but not hatchability owing to temperature and salinity interactions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/524934v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1d796aborg.highwire.dtl.DTLVardef@e4cc10org.highwire.dtl.DTLVardef@111415corg.highwire.dtl.DTLVardef@1da1414_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗