Biology subjects

Lucas, K. N.

Publications and source records attributed to Lucas, K. N..

6 recordsLinked to original sources

bioRxiv2026

Cumulative effects of nylon microplastic fibres and warming temperature on the behavior and physiology of marine threespine stickleback (Gasterosteus aculeatus)

Populations are exposed to multiple anthropogenic stressors simultaneously; however, the combined effects are poorly understood. Climate change is starkly impacting marine ecosystems and consequently fishes, with warming temperatures and increases in frequencies and durations of extreme climate events. Concurrently, plastics, such as nylon used in fishing industries, are contaminating marine waters at unprecedented levels, with detrimental effects on fishes. Here we studied the cumulative effects of warming and nylon microplastic fibres on the behavior and physiology of threespine stickleback (Gasterosteus aculeatus) by exposing fish to conditions of 15{degrees}C and 20{degrees}C and nylon concentrations of 0, 1, 10, and 100 mg/g (mg nylon/g food) for 4 weeks. Feeding rates responded complexly to multiple stressors, as increasing concentrations of plastic reduced feeding rates, with warming having an antagonistic effect. Furthermore, we observed "coughing" behaviors in response to ingestion of microfibres and a unique reselection tendency of food items previously selected by conspecifics. Under warming conditions, critical thermal maximum (CTmax) increased; however, exposure to plastics led to reductions in CTmax and thermal safety margins. Given these results, we anticipate reduced acclimation capacities, greater anxiety, and reductions in foraging efficiencies with increasing concentrations of plastic. Cumulatively, these stressors will yield greater energetic trade-offs and decreased accuracy in food selection with stark implications for marine ecosystem dynamics.

ecology↗

bioRxiv2026

Leveraging Homologous Recombination Deficiency via the Repositioned Prodrug CB1954

AO_SCPLOWBSTRACTC_SCPLOWHomologous recombination deficiency (HRD) is an actionable vulnerability found in a substantial fraction of human cancers, yet current HRD-directed therapies are limited by toxicity, incomplete responses, and acquired resistance. Many DNA-damaging agents were developed before DNA repair biomarkers were available, suggesting that abandoned agents may harbor previously unrecognized genotype-selective activity. Here, through a focused screen of DNA-damaging agents in isogenic homologous recombination-proficient and -deficient models, we identify CB1954, a decades-old nitrobenzamide aziridine prodrug, as highly selective for BRCA2-deficient tumor cells. CB1954 forms DNA interstrand crosslinks independent of HR status, but selectively induces DNA-damage signaling, apoptosis, and loss of clonogenic survival in HR-deficient cells. Targeted DDR CRISPR screening and isogenic validation define a distinct repair dependency for the Fanconi anemia and homologous recombination pathways, with limited dependence on mismatch repair or nucleotide excision repair. Genetic and pharmacologic perturbation of NQO2, the bioactivating enzyme for CB1954, reveals a bifurcated mechanism in which NQO2-dependent activation selectively contributes to HRD cytotoxicity, while aziridine-dependent lesions likely account for residual activity in HR-proficient cells. CB1954 exhibits favorable preclinical pharmacokinetic properties and genotype-dependent antitumor activity in BRCA2-deficient xenografts. These findings reposition CB1954 as a historically overlooked HRD-selective agent and demonstrate that biomarker-guided profiling of DNA-damaging agents can uncover new opportunities for precision oncology.

cancer biology↗

bioRxiv2025

Effects of ceratotrichia diameter and packing density on chimaera pectoral fin kinematics

Chimaeras - an ancient group of cartilaginous fishes - swim by flapping their pectoral fins in a distinctive locomotory mode, termed flapping flight, that induces an undulatory wave traveling from the leading edge to the trailing edge of the fin. Recent work on bony fishes has shown that fins with internal structure (fin rays) may behave differently than models made of a single material. Our goal was to understand the potential significance of internal structure for the swimming kinematics of chimaeras. We designed an actuation system based on the kinematic patterns of real chimaeras and examined artificial fins of varying fin ray diameter and packing density to investigate how internal anatomy influences pectoral fin tip amplitude, leading-edge curvature, and the induction of undulatory waves. Both diameter and packing density influenced fin kinematics, but diameter had a much larger effect on fin tip amplitude over the tested ranges. Additionally, established rules for undulatory waves outlined in the flexible foil literature did not hold for our fin models. Our work provides new insights into the anatomical parameters that could influence the evolution of chimaera flapping flight, and pectoral fin locomotion more broadly, and provides direction for possible biomimetic applications.

zoology↗

bioRxiv2025

NAPRT expression and epigenetic regulation in pediatric rhabdomyosarcoma as a potential biomarker for NAMPT inhibition

PurposeNew treatments are needed to improve survival in children with rhabdomyosarcoma (RMS). NAD biosynthesis, regulated by the enzymes NAPRT and NAMPT, represents a metabolic vulnerability due to high NAD turnover in cancers. Although NAMPT inhibitors (NAMPTi) show preclinical promise, clinical translation has been limited by toxicity and the lack of predictive biomarkers. Here, we evaluated NAPRT expression in RMS and its potential as an actionable biomarker to guide NAMPTi therapy. Experimental DesignNAPRT promoter methylation, transcript levels, and protein expression were assessed in RMS cells, PDXs, and primary tumors (n=109) from the Childrens Oncology Group. In vitro sensitivity to NAMPTi was tested in molecularly diverse and isogenic RMS cell lines, examining the role of NAPRT expression in mediating cytotoxicity and the ability of nicotinic acid (NA) to rescue viability. In vivo efficacy was assessed using NAPRT-isogenic orthotopic xenograft models. ResultsNAPRT promoter hypermethylation was found in a subset of RMS models and patient samples. Immunohistochemistry showed loss of NAPRT protein in 30-40% of tumors, defined as <1% tumor cell staining. Methylation modestly correlated with protein expression. NAPRT-silenced cells were highly sensitive to NAMPTi, driven by NAD depletion and not reversible with NA. In vivo, NAMPTi induced significant tumor regression, which was not abrogated with NA administration in NAPRT-silenced models. ConclusionsNAPRT loss occurs in a subset of RMS, offering a potential strategy to expand the therapeutic window of NAMPTi. Further research is needed to understand NAPRT regulation and optimize biomarker assay strategies for use in future clinical trials.

cancer biology↗

bioRxiv2025

Characterizing behavioral and physiological changes in threespine stickleback (Gasterosteus aculeatus) with changing thermal regimes in the Canadian Pacific west coast

Understanding the impacts of sea temperature changes on marine fishes physiology and behavior is critical for marine ecosystem management. Around Vancouver Island, threespine stickleback (Gasterosteus aculeatus) populations thrive in areas that differ by {+/-} 10{degrees}C. To understand the acclimatory potential of stickleback, fish were exposed to cold (10{degrees}C), control (15{degrees}C), or warm (20{degrees}C) water treatments for 4 weeks. Their acclimation response was tested using the novel tank test (NTT), black-white test (BWT), measuring growth, determining critical thermal maxima (CTmax), and measuring heat shock proteins (HSPs). We found that CTmax differed significantly between treatments, however, the increase in acclimation temperature was not proportional to the increase in CTmax. In the BWT, the average number of crosses and duration that fish spent in the white zone was lower in the cold treatment than the control, while these metrics were higher in the warm treatment. A similar trend was observed in the NTT test, with warm treatment having the highest number of crosses and duration in the top third of the tank, and the cold treatment having the lowest. Surprisingly, fish in the cold treatment had a significantly greater change in weight and lowest HSP content than fish kept in the other treatments, which may be associated with energy expenditure and trade-offs for activity. Given these results, greater trade-offs in fish energy usage are anticipated in changing climates due to the acclimation limits of their bodies which would starkly affect ecosystem dynamics. HIGHLIGHTSO_LIClimate change is driving variability in habitats thermal regimes directly impacting the function and performance of animals. C_LIO_LIBehavioral changes (in anxiety or anti-predatory and exploratory behaviors) ensue under changing thermal environments. C_LIO_LIStickleback are reaching the ends of their acclimatory capacity under current peak summer water temperatures. C_LIO_LIConsequences are anticipated with continued warming through trade-offs among energetically expensive processes like behavior, growth, and stress response. C_LI

ecology↗

bioRxiv2020

The fish body functions as an airfoil: surface pressures generate thrust during carangiform locomotion

The anterior body of many fishes is shaped like an airfoil turned on its side. With an oscillating angle to the swimming direction, such an airfoil experiences negative pressure due to both its shape and pitching movements. This negative pressure acts as thrust forces on the anterior body. Here, we apply a high-resolution, pressure-based approach to describe how two fishes, bluegill sunfish (Lepomis macrochirus Rafinesque) and brook trout (Salvelinus fontinalis Mitchill), swimming in the carangiform mode, the most common fish swimming mode, generate thrust on their anterior bodies using leading-edge suction mechanics, much like an airfoil. These mechanics contrast with those previously reported in lampreys - anguilliform swimmers - which produce thrust with negative pressure but do so through undulatory mechanics. The thrust produced on the anterior body of these carangiform swimmers through negative pressure comprises 28% of the total thrust produced over the body and caudal fin, substantially decreasing the net drag on the anterior body. On the posterior region, subtle differences in body shape and kinematics allow trout to produce more thrust than bluegill, suggesting that they may swim more effectively. Despite the large phylogenetic distance between these species, and differences near the tail, the pressure profiles around the anterior body are similar. We suggest that such airfoil-like mechanics are highly efficient, because they require very little movement and therefore relatively little active muscular energy, and may be used by a wide range of fishes since many species have appropriately-shaped bodies. Significance StatementMany fishes have bodies shaped like a low-drag airfoil, with a rounded leading edge and a smoothly tapered trailing region, and move like an airfoil pitching at a small angle. This shape reduces drag but its significance for thrust production by fishes has not been investigated experimentally. By quantifying body surface pressures and forces during swimming, we find that the anterior body shape and movement allows fishes to produce thrust in the same way as an oscillating airfoil. This work helps us to understand how the streamlined body shape of fishes contributes, not only to reducing drag, but also directly to propulsion, and, by quantitatively linking form and function, leads to a more complete understanding fish evolution and ecology.

physiology↗