Biology subjects

Murphy, C. E.

Publications and source records attributed to Murphy, C. E..

6 recordsLinked to original sources

bioRxiv2026

Seasonal differences in predation risk among seagrass epifauna species stabilize community-level predation over time

Predation risk varies through space and time due to changing refuge quality, predator communities, and prey traits. Despite this, ecological research is often focused on measuring average predation risk at the community level. While this can give important information about overall trophic transfer and ecological efficiency, it ignores differences in predation risk among prey species within a community, which may be important determinants of species coexistence and local diversity. We used crustaceans associated with temperate seagrass in Northern California to explore the relationship between seasonal variation in among-species and community-level predation risk for a community of morphologically distinct prey. We measured predation risk of the four most abundant and widespread prey species at six field sites every two to six weeks for one year. At the community level, sites differed significantly in their annual variation in predation risk, and these differences were correlated with the amount of variation in the among-species predation risk. When there was more within-year variation in predation risk among the four prey species, predation risk at the community level was more stable across the year. On the other hand, when each prey species in the community had similar levels of predation risk throughout the year, predation as a community-level process was much more seasonal and variable. Variation in predation risk also changed across a gradient of seagrass cover, a proxy for refuge quality. Sites with greater seagrass cover had less annual variation in community-level predation risk and more variation in predation risk among the four species at any given time point. In contrast, at sites with less eelgrass, all species were consumed at the same rate throughout the year, suggesting previously demonstrated differences in antipredator strategies among species are less relevant in the absence of habitat-forming species. We suggest that larger species-specific differences in predation risk throughout a year result in a more stable level of predation risk for the whole community, and that this may be driven by increased refuge provided by seagrass habitat mediating different prey species relative levels of susceptibility to predation.

ecology↗

bioRxiv2025

Gut microbial interaction networks control autoimmunity to neuroretina

The gut microbiome influences the development of immune-mediated inflammatory diseases, including autoimmune uveitis, a sight-threatening ocular inflammation driven by retina-specific T cells1. Using a model of spontaneous autoimmune uveitis (sEAU) we showed that gut commensals provide immune stimuli that trigger disease2. Here we report that uveitis-promoting microbes are present in human gut flora and that colonization of germ-free (GF) mice with commensals from healthy human donors was sufficient to provoke disease. Severity of sEAU correlated with expansion of Akkermansia and contraction of short-chain fatty acid (SCFA)-producing Firmicutes, followed by decreased SCFA levels and a dominant gut Th1 effector response. Mechanistic gain-of-function experiments, enriching GF sEAU mice with Akkermansia, reproduced these microbiome, metabolite and immune phenotype shifts, and exacerbated disease, suggesting that Akkermansia promotes autoimmunity by outcompeting SCFA-producers and enhancing Th1-type responses. An inverse correlation between Akkermansia (Verrucomicrobia) and Firmicutes was also present in patients with uveitis, multiple sclerosis and Crohns disease. These findings reveal a stereotypic gut microbial interaction network that regulates systemic immune balance, and may represent an ecologically conserved mechanism through which the gut microbiome modulates autoimmune and inflammatory diseases.

immunology↗

bioRxiv2025

A genotoxin associated with colorectal cancer linked to gut dysbiosis in children with cystic fibrosis

Cystic fibrosis (CF) substantially alters the gastrointestinal microbiome from an early age, leading to significant changes in microbial composition and functionality. This study explores the physiological and microbiological factors contributing to dysbiosis in children with cystic fibrosis (cwCF), characterized by an increase in potentially pathogenic Escherichia coli and a decrease in beneficial anaerobes such as Bacteroides. In this study, we employed an in vitro medium representative of the nutritional environment of the CF colon to test the role of factors including mucin, fat, bile, pH, antibiotics and features associated with inflammation (e.g., nitrate, sulfate, formate, reactive oxygen species) on growth of clinical isolates of E. coli and Bacteroides spp. We further examined interactions between these two microbes under CF-like conditions to understand modulators of microbial competition, and identified glycerol, a surrogate of increased fat, as a significant driver of altered microbial competition. Finally, we investigated genetic determinants influencing these microbial interactions, with the focus on glycerol metabolism, by performing a transposon mutagenesis screen in E. coli. Results of this screen pointed to the role of colibactin production in mediating this microbial competition; colibactin is a DNA-damaging genotoxin associated with the increased risk of colorectal cancer (CRC) in CF populations. This work enhances our understanding of mechanisms of microbial competition in the CF gut, while potentially enhancing our understanding of colorectal cancer risk in persons with CF through the identification of early-life microbial biomarkers. Significance StatementThe risk of CRC development in CF populations is significantly increased. This study examines the interplay of altered intestinal physiology in the microbial dysbiosis common in the CF gut, implicating the high fat environment in a competition-mediated depletion of immune-modulating Bacteroides. This work identifies candidate features of the young CF intestine and gut microbiome that may contribute to advanced development of CRC in these populations, informing potential therapeutic approaches.

microbiology↗

bioRxiv2025

Striatal signaling tracks naturalistic short-term fluctuations in hunger-satiety

The neuromodulator dopamine is integral to feeding behavior, believed to modulate food pursuit and satiety. Here, we examine how dopamine signaling in the nucleus accumbens changes during consumption as animals transition from hunger to satiety in naturalistic feeding. Dopamine transiently increases during food approach; however, the magnitude of this approach-related increase diminishes across progressive pellet ingestion, reflecting short-term satiation. These approach-related dopamine transients recover during intermeal intervals. Fasting dissociates the regulation of meal size and frequency, reflecting termination and initiation, respectively, with observable differences in dopamine corresponding to changes in meal size but not frequency. Despite substantially decreasing feeding, pharmacological satiation via a glucagon-like peptide-1 (GLP-1) agonist had no impact on average dopamine transients on food approach but abolished the short-term fluctuations related to on-going eating, suggesting that the GLP-1 agonist disengaged or decoupled dopamine from its modulatory role in meal patterning.

neuroscience↗

bioRxiv2022

Change point estimation by the mouse medial frontal cortex during probabilistic reward learning

There are often sudden changes in the state of environment. For a decision maker, accurate prediction and detection of change points are crucial for optimizing performance. Still unclear, however, is whether rodents are simply reactive to reinforcements, or if they can be proactive to estimate future change points during value-based decision making. In this study, we characterize head-fixed mice performing a two-armed bandit task with probabilistic reward reversals. Choice behavior deviates from classic reinforcement learning, but instead suggests a strategy involving belief updating, consistent with the anticipation of change points to exploit the task structure. Excitotoxic lesion and optogenetic inactivation implicate the anterior cingulate and premotor regions of medial frontal cortex. Specifically, over-estimation of hazard rate arises from imbalance across frontal hemispheres during the time window before the choice is made. Collectively, the results demonstrate that mice can capitalize on their knowledge of task regularities, and this estimation of future changes in the environment may be a main computational function of the rodent dorsal medial frontal cortex.

neuroscience↗

bioRxiv2021

Pupil correlates of decision variables in mice playing a competitive mixed-strategy game

In a competitive game involving an animal and an opponent, the outcome is contingent on the choices of both players. To succeed, the animal must continually adapt to competitive pressure, or else risk being exploited and lose out on rewards. In this study, we demonstrate that head-fixed mice can be trained to play the iterative competitive game matching pennies against a virtual computer opponent. We find that the animals performance is well described by a hybrid computational model that includes Q-learning and choice kernels. Comparing between matching pennies and a non-competitive two-armed bandit task, we show that the tasks encourage animals to operate at different regimes of reinforcement learning. To understand the involvement of neuromodulatory mechanisms, we measure fluctuations in pupil size and use multiple linear regression to relate the trial-by-trial transient pupil responses to decision-related variables. The analysis reveals that pupil responses are modulated by observable variables, including choice and outcome, as well as latent variables for value updating, but not action selection. Collectively, these results establish a paradigm for studying competitive decision-making in head-fixed mice and provide insights into the role of arousal-linked neuromodulation in the decision process.

neuroscience↗