Biology subjects

Anderson, J. J.

Publications and source records attributed to Anderson, J. J..

7 recordsLinked to original sources

bioRxiv2026

Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy

Hippocampal sclerosis is a frequent finding in pediatric epilepsy surgery and has traditionally been regarded as an acquired lesion. It commonly co-occurs with focal cortical dysplasia (FCD IIIa), yet whether hippocampal injury is secondary to seizures or reflects a shared underlying etiology remains unresolved. Here we identified somatic variants activating the RAS-MAPK pathway in 40% of patients with hippocampal sclerosis, but in none with non-sclerotic hippocampus. Gain-of-function variants in PTPN11 were the most common finding, with mutations present in both cortex and hippocampus and enriched in hippocampal neurons, consistent with a shared developmental origin. In mice, Ptpn11D61Y mutants developed profound hippocampal degeneration and gliosis following subthreshold kainic acid exposure, whereas wild-type controls were unaffected. p38-dependent stress pathways were upregulated in patients and mice, suggesting a mechanism through which ERK-p38 crosstalk lowers the threshold for seizure-induced injury. These results provide a genetic explanation for FCD IIIa, elucidate the role of somatic mutations within the RAS-MAPK pathway in driving hippocampal sclerosis, and provide a target for pathway-specific interventions for intractable seizures.

neuroscience↗

bioRxiv2026

Disrupted O-GalNAc glycosylation as a mechanism and biomarker of SLC35A2-associated epilepsy

Rare germline and somatic variants in SLC35A2 cause a spectrum of severe glycosylation disorders that commonly present with epilepsy. SLC35A2 encodes the Golgi transporter for UDP-galactose, but how its deficiency leads to severe neurodevelopmental disorders is unknown. Using a mouse model deficient for Slc35a2 in the forebrain, we identified a specific defect in O-GalNAc glycan synthesis, while other galactose-containing glycoconjugates remained intact. O-GalNAc glycans were absent from their normal location within neuronal tracts of the corpus callosum, and truncated precursors accumulated in the cortex on critical extracellular matrix molecules. Cultured primary neurons lacking Slc35a2 showed impaired development, hyperexcitability, and impaired O-GalNAc glycosylation. Finally, human brain tissue from cases of SLC35A2-associated intractable epilepsy displayed a strong correlation between variant burden and truncated O-GalNAc glycans. These findings provide a mechanistic link between genetic causes of SLC35A2-associated epilepsy and protein O-glycosylation that can be targeted for biomarker and therapeutic development.

neuroscience↗

bioRxiv2020

Process-based model of fish incubation survival for designing reservoir operations: a case study for Sacramento River winter-run Chinook salmon

Allocating reservoir flows to meet societal and ecosystem needs under increasing demands for water and increasing climatic variability presents challenges to resource managers. Often, regulated rivers have been operated to meet flow and temperature compliance points that mimic historical patterns. Because it is difficult to assess if this approach is efficient or equitable, new more process-based approaches to regulation are being advanced. This paper describes such an approach with a model of egg incubation survival of Sacramento River winter-run Chinook salmon (SRWRC, Oncorhynchus tshawytscha). Thermal mortality only occurs in a critical window around egg hatching when the embryo is most sensitive to temperature stress. The duration of the critical window has significant implications for Shasta Reservoir operations that are designed to control temperature during SRWRC incubation. Previous operations sought to maintain a low temperature over the entire incubation period. However, model analysis suggests that targeting cold water directly to the critical egg hatching stage provides higher survival while requiring less cold water resources. The calibrated model is publicly accessible through a web interface connected to real-time river and fish databases and a river temperature forecast model. The system is an example of the next step of river management that integrates databases with hydrological and process-based biological models for real-time analysis and for forecasting effects of river operations on the environment.

ecology↗

bioRxiv2019

Survival of prey growing through gape-limited and apex predators

A mechanistic model based on first principles of growth and predator-prey behavior introduces the effects of a predator size distribution on the survival of rapidly growing prey. The model, fit to Chinook salmon data, can explain the observed increase in ocean survival with smolt ocean entrance length using different predator size-frequency distributions. The model introduces new dimensions to theories on predator-prey interactions and population recruitment and suggests the possibility that fish recruitment control can be highly variable; sometimes dominated by juvenile growth and encounters with gape-limited predators and other times dominated by adult encounters with apex predators. Additionally, a sensitivity analysis suggests that scale and otolith circuli spacing are insensitive indicators of size-selective mortality but the profile of adult survival with juvenile length provides information on the balance of size-dependent and size-independent mortality processes.

ecology↗

bioRxiv2019

Survival of prey growing through gape-limited predators

Juvenile to adult survival of fish is modeled by the rate at which prey progressively escape the size distribution of gape-limited predators through growth. The model characterizes adult survival as a function of the mean and standard deviation of the predator population gape sizes, the ratio of mortality and growth rates and a compensatory growth factor. The model fits the survival of adult returns of Chinook salmon and reveals that a 25% increase in either the initial size at ocean entrance or the growth to mortality rate over the first few months of ocean residence can increase adult survival by a factor of 2 to 3. Additionally, the model proposes a rigorous mechanism through which the size distribution of predators determines the effects of juvenile growth on adult survival. Finally, possible contributions of the model framework to fisheries management and predator-prey theory are noted.

ecology↗

bioRxiv2018

Using river temperature to optimize fish incubation metabolism and survival: a case for mechanistic models

Allocating reservoir flows to societal and ecosystem needs under increasing demands for water and increasing variability in climate presents challenges to resource managers. In the past, managers have operated reservoirs to achieve flow and temperature compliance points based on qualitative predictions of competing needs. Because it is difficult, if not impossible, to assess whether meeting such compliance points is efficient or equitable, new strategies for regulation are being advanced. Critical to these strategies is the need for new models with sufficient biological details to identify the effects of reservoir operations on organism growth and survival in real time. This paper evaluates the adequacy of three models of differing complexity for managing the Sacramento River temperature during the incubation of winter-run Chinook salmon. The models similarly characterize temperature-and density-dependent mortality from egg through fry survival, but use different spatial and temporal resolutions. The models all fit survival data reasonably well, but predict different reservoir operations to protect fish. Importantly, the models with the finer spatial/temporal resolution predict reservoir operations that require less flow and better protect fish when water resources are limited. The paper illustrates that shifting the focus of management from meeting compliance points to meeting the metabolic needs of the organisms yields efficiencies and identifies when water is needed and when it can be saved.

ecology↗

bioRxiv2017

The Relationship Of Survivorship And Body Mass Modeled By Metabolic And Vitality Theories

The relationship between body mass and survivorship is explained by a model that merges metabolic theory relating metabolism to body mass, and vitality theory relating survival to vitality loss and extrinsic mortality. The resulting metabolic-vitality framework hypothesizes mortality results from replicative senescence of the hematopoietic system and predator-prey interactions. Fitting the metabolic-vitality model to body mass and maximum lifespan data of 494 nonvolant mammals yields allometric relationships of body mass to the vitality parameters, from which full survivorship profiles can be predicted from body mass. Comparisons of the mass-derived vitality parameters to those estimated directly from survival data identifies how intrinsic and extrinsic mortality processes of specific populations deviate from the aggregate. Highlighted findings include a mathematical explanation for the shift from Type I to Type II survivorship curves with decreasing body mass, a quantification of the impact of hunting on wild populations and a quantification of the reduce rate of primate aging relative to the aggregate of mammal populations. Finally, the framework allows explorations of the combined effects of animal aging and predation on survival patterns.

ecology↗