Biology subjects

MacNeil, M. A.

Publications and source records attributed to MacNeil, M. A..

9 recordsLinked to original sources

bioRxiv2026

Modeling Retinal Ganglion Cell Degeneration from Longitudinal Intraocular Pressure Trajectories

Many experimental studies collect longitudinal physiological measurements while assessing irreversible biological outcomes only at a terminal endpoint, leaving the timing of disease progression unobserved. This disconnect between continuously measured covariates and latent biological events limits quantitative analysis of how physiological stress drives tissue degeneration. We address this problem by formulating retinal ganglion cell (RGC) degeneration in experimental glaucoma as a latent time-to-event process driven by longitudinal intraocular pressure (IOP) exposure. Using monthly IOP measurements and terminal RGC counts from the DBA/2J mouse model of glaucoma, we develop both Cox proportional hazards models and a time-dependent extension based on the Andersen-Gill counting-process formulation, allowing progression risk to depend on both contemporaneous IOP and cumulative pressure burden. We further reconstruct model-implied survival curves from the fitted hazard functions, providing a continuous-time representation of latent disease progression under observed and hypothetical IOP trajectories. Across all disease thresholds and both modeling approaches, cumulative IOP burden above 19 mmHg emerged as the dominant predictor of RGC degeneration, whereas peak and contemporaneous IOP contributed little additional predictive information once sustained exposure was taken into account. HDAP2, a mitochondria-targeted neuroprotective peptide, significantly reduced progression hazard after adjustment for longitudinal IOP exposure, supporting a pressure-independent neuroprotective mechanism. Beyond identifying cumulative pressure exposure as the dominant predictor of neurodegeneration in this experimental model, the proposed framework provides a general strategy for relating longitudinal physiological measurements to latent biological progression. By linking exposure histories to model-implied survival trajectories, it enables trajectory-based risk assessment, prediction under hypothetical IOP trajectories, and quantitative evaluation of therapeutic interventions in experimental systems where biological outcomes are observed only at terminal endpoints.

neuroscience↗

bioRxiv2026

Nutrient content estimation of the world's fishes

Seafood nutrients from global fisheries are of increasing importance for research and policy in food security and nutrition. As the chemical composition of fish is determined by what they eat, their energetic demands, and the environment in which they live, nutrient content reflects aspects of physiology and life history, ecological and environmental traits, as well as evolutionary history. Here we present data from Bayesian model estimates of 12 key nutrients (calcium, iron, phosphorus, magnesium, selenium, zinc, vitamin A, vitamin B9, vitamin B12, vitamin D, omega-3 fatty acids, and protein) in wild fish, using a database of reported nutrient content for freshwater and marine species. We then predict the nutrient content of 5588 fish species with traits available from FishBase. We compare our previous model using traits alone with a new model of both traits and phylogeny, and present the data, code, and predictions for models coded in PyMC. These models and predictions, made freely available through FishBase, can be used to explore the historical, current, and future nutrient content of fisheries catch.

ecology↗

bioRxiv2025

Mitochondrial-Targeted HDAP2 Preserves Retinal Ganglion Cells and Increases Pressure Tolerance in DBA/2J Mice

PurposeRetinal ganglion cell (RGC) loss in glaucoma occurs in a large fraction of patients even after intraocular pressure (IOP) is reduced. Mitochondrial dysfunction is a key mechanism that links elevated IOP to RGC degeneration. We tested whether HDAP2, a novel high-density aromatic peptide that binds cardiolipin to stabilize mitochondrial membranes, can protect RGCs in the DBA/2J mouse model. MethodsDBA/2J mice received HDAP2 (3 mg/kg, intraperitoneally, every other day) starting at 4 months of age for 8 months. IOP was measured each month to track pressure exposure. RGC survival was assessed by counting RBPMS-stained cells in retinal wholemounts and optic nerve axons in semithin toludine blue-stained sections. ResultsHDAP2-treated retinas had [~]49% more RGCs than untreated retinas at similar pressure exposures (p = 0.0063; F(2,59) = 5.524). At mild IOP exposure, HDAP2 preserved 58% more RGCs compared with untreated retinas, and at high IOPs, RGC survival was 180% greater. Kaplan-Meier analysis indicated that HDAP2 increased the threshold for severe RGC loss by 29 mmHg and reduced the chance of developing severe RGC degeneration by a factor of 4.6. Optic nerve axons from treated retinas were also well preserved, with axon morphologies appearing indistinguishable from controls. Axon size distributions did not change significantly among the treatment groups, suggesting that protection by HDAP2 was similar among RGC subtypes. ConclusionsHDAP2 preserved both RGCs and axons in a pressure-dependent manner and increased tolerance to IOP. These results suggest that HDAP2 may complement pressure-lowering therapy, including for normal-tension and treatment-refractory glaucoma.

neuroscience↗

bioRxiv2025

Potential yield and food provisioning gains from rebuilding the worlds coral reef fish stocks

Many coral reefs have fish stocks that are depleted below the level at which sustainable production is maximized. Lower production means that millions of people are losing out on potential food, income and livelihoods. Rebuilding these stocks to maximize sustainable production can contribute towards ending hunger and malnutrition but requires active and effective fisheries management. Yet, for fish stock recovery plans to be implemented, recovery benefits, targets and timeframes need to be quantified. Here, using 1211 individual reef sites and 23 jurisdictions identified globally as being below maximum sustainable production levels, we show that reefs have the potential to increase sustainable yields by nearly 50% if allowed to recover towards their maximum production levels. For individual jurisdictions this recovery represents from 20,000 up to 162 million additional sustainable servings of reef fish per year in comparison to current sustainable production, meeting recommended seafood intake for up to 1. 4 million additional people a year. However, such growth and food provisioning will require fish stocks to double their standing biomass (increase by a median of 32 t/km2). Recovery timeframes range from 6.4 years under the most stringent scenario (a seascape moratorium) to 49.7 years under the maximum harvest scenario that results in recovery. We find that locations with the greatest potential for sustainable gains in yield are among those with the greatest food and micronutrient deficiencies, underscoring both the challenges and opportunities in recovering fish assemblages to achieve their maximum sustainable potential. Significance StatementCoral reef fisheries are a critical food source for people throughout the tropics. However, most reefs around the globe have fish biomass values below those enabling maximal sustainable production, risking food availability, income, and livelihoods. Rebuilding fish assemblages can increase sustainable food supplies, and, if these are well distributed, directly contribute towards enhanced food security. We show that recovering fish stocks on coral reefs can significantly increase the number of sustainable fish servings produced per year and the number of people meeting fish intake recommendations, particularly for countries with high malnutrition. Our study highlights the sustainable food provisioning potential of recovering reef fisheries and quantifies how much recovery would be needed and the time such recovery would take.

ecology↗

bioRxiv2025

Hidden Diversity of Threatened Sharks and Rays in the Global Meat Trade

International wildlife trade is a major source of biodiversity loss, yet many species lie hidden within aggregated data that conceals trade impacts. We overcome this problem for the largest vertebrate wildlife trade globally - shark and ray meat - comprising 438 538 mt yr-1 across more than 150 species, 76% of which are Threatened. Revealed trade contains greater quantities of skates (+10%), hammerheads (+8%), and smoothhounds, dogfishes & tope (+5%), and fewer pelagic sharks (-38%) than previously known. Shorttail yellownose skate, smoothound, silky, mako, and blue sharks are the most underreported meat species, due to aggregated landings from China, Argentina, Japan, and Indonesia, demonstrating international trade in shark and ray meat as a diverse, pervasive, and previously hidden source of fishing mortality for many threatened species.

ecology↗

bioRxiv2025

The nutritional value of invertebrate aquatic foods

Aquatic invertebrates are a diverse, nutrient-dense, and socio-ecologically important food whose contribution to human nutrition is frequently overlooked. We quantify their contribution to global nutrient supplies and estimate the nutrient content of >50,000 macroinvertebrate species. Current aquatic invertebrate production supplies the equivalent annual requirement for >6 billion people in terms of vitamin B12 and selenium; >1 billion people for copper, omega 3 fatty acids, iodine and zinc; and >100 million people for nutrients such as vitamins B2 and B3, iron, manganese, and magnesium. Nutrient composition differs among taxonomic groups, consumption patterns, and environmental and life-history factors. Our study highlights the benefits of integrating aquatic invertebrates into dietary portfolios across global societies, mainstreaming their nutritional importance in development projects, sustainability assessments and food policy.

ecology↗

bioRxiv2023

High density aromatic peptides protect retinal ganglion cells in mouse retina following optic nerve crush injury.

Mitochondrial dysfunction is a critical early driver of retinal ganglion cell (RGC) loss in optic nerve injury. We evaluated whether HDAP2, a mitochondria-targeted aromatic peptide designed to support mitochondrial membrane integrity, could preserve neuronal structure after optic nerve crush (ONC). Systemically administered HDAP2 penetrated the blood-retinal barrier and localized to RGCs and mitochondrial-rich retinal layers. Daily treatment (IP, 3 mg/kg for 14 days) significantly improved RGC survival compared to saline-treated ONC animals. RGC densities increased across central, midperipheral, and peripheral regions, and surviving RGCs exhibited approximately two-fold higher RBPMS expression, suggesting improved cellular health. Transmission electron microscopy revealed that HDAP2 substantially reduced mitochondrial loss within crushed optic nerve axons. Mitochondrial density in HDAP2-treated nerves reached 70% of uninjured levels (0.129 {+/-} 0.029 vs. 0.185 {+/-} 0.017) and was 5.3-fold higher than untreated ONC nerves (0.025 {+/-} 0.012; Kruskal-Wallis p = 0.039; Cohens d = 2.77). Mitochondrial morphology was similar across groups, indicating that HDAP2 prevents mitochondrial loss rather than rescuing damaged organelles. HDAP2-treated nerves also contained a higher density of structurally intact axons, consistent with reduced ultrastructural degeneration following injury. These findings demonstrate that HDAP2 limits mitochondrial loss and attenuates neuronal degeneration after ONC. Together, the results support HDAP2 as a promising therapeutic candidate for protecting CNS projection neurons by maintaining mitochondrial stability after axonal injury.

neuroscience↗

bioRxiv2023

Targeting high-density aromatic peptides to cardiolipin optimizes the mitochondrial membrane potential.

The mitochondrial membrane potential ({Delta}{Psi}m) is created by the accumulation of protons on an outer leaflet of the inner mitochondrial membrane and drives the synthesis of most cellular ATP, which is essential for cellular bioenergetics and survival. The {Delta}{Psi}m also facilitates the electrogenic transport of cations, such as Ca2+, and regulates generation of reactive oxygen species, which serves as a powerful bioenergetic and stress-signaling regulator. Proton trapping on the outer leaflet of the inner mitochondrial membrane of mitochondrial cristae could be controlled by cardiolipin when the local pH is above 8. However, there is presently no technology that effectively targets strong bases to cardiolipin. We have developed a novel, high-density aromatic peptide (HDAP2) to preserve a proton gradient-driven potential in mitochondria by increasing proton trapping on cardiolipin (CL). HDAP2-induced formation of cardiolipin-HDAP2 complexes accumulated positive charges at the head of CL. The HDAP2-CL vesicles could accumulate the mitochondrial transmembrane potential probe, Tetramethylrhodamine (TMRM). This potential could be uncoupled with Carbonyl cyanide m-chlorophenylhydrazone (CCCP) and Dinitrophenol (DNP), indicating that an interaction of HDAP2 with CL could support a proton gradient-driven transmembrane potential. We demonstrated that this novel, water-soluble peptide is cell-permeable, targets mitochondria without causing cell toxicity, and promotes cell survival during serum starvation. Importantly, the HDAP2-cardiolipin complex-mediated optimization of the proton gradient was supported by the ability of HDAP2 to prevent CCCP-mediated mitochondrial depolarization in ARPE-19 cells in a dose-dependent manner. Based on its mechanism of action, HDAP2 could promote cellular homeostasis, which would have broad clinical applicability for the prevention, recovery and reversal of many acute and chronic disease conditions, such as neurodegeneration, ischemia- reperfusion injury, and inflammation.

biochemistry↗

bioRxiv2022

Sustainable reference points for multispecies coral reef fisheries

Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to be data-poor and lack research and monitoring capacity (e.g., long-term fishery data), preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for more than 2000 coral reefs with catch estimates from 99 jurisdictions, we estimate site-specific sustainable reference points for coral reef fisheries and use these to assess the status of coral reef fish stocks. We reveal that more than half of jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, mean fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the worlds coral reef fisheries. TeaserA global assessment of the sustainability of multispecies reef fisheries indicates that more than half of jurisdictions have failed at least one of two key sustainability benchmarks.

ecology↗