Biology subjects

Bonanno, J.

Publications and source records attributed to Bonanno, J..

4 recordsLinked to original sources

bioRxiv2026

The GNMT N-terminus Couples Folate Feedback to Methyl-donor Homeostasis

Maintenance of S-adenosylmethionine (SAM) homeostasis is essential for methylation of biomolecules, nucleotide and polyamine synthesis, and redox homeostasis. While all methyltransferases consume SAM, only a subset of highly tissue specific methyltransferases regulates SAM homeostasis. Among them, glycine N-methyltransferase (GNMT) is enriched in the liver and its dysregulated activity has been linked to compromised liver function. GNMT is inhibited by the methyl carrier 5-methyltetrahydrofolate (5mTHF), suggesting a negative-feedback mechanism regulating its activity. Here, we identify the GNMT N-terminal tail, and specifically phosphorylation at serine 9 (S9ph), as a regulatory modification linking folate-dependent feedback inhibition to SAM homeostasis. Structural and biochemical analyses and molecular dynamics simulations revealed that the N-terminal tail is required for catalytic turnover of SAM and for 5mTHF binding. Phosphoproteomic analysis showed that GNMT S9ph is abundant in mouse liver and further enriched in aged mice. Consistent with loss of folate-dependent negative feedback, both distal N-terminal truncation (residues 1-8) and a phosphomimetic substitution abolished 5mTHF binding while maintaining catalytic activity. In hepatocyte cell lines lacking endogenous GNMT, lentiviral overexpression of constitutively active GNMT mutants depleted SAM, increased SAH, disrupted protein methylation, impaired growth, and induced transcriptional responses consistent with methyl-donor stress. Together, these findings identify the GNMT N-terminus as a tunable phosphoregulatory domain that dynamically regulates GNMT activity and cellular methylation potential.

biochemistry↗

bioRxiv2025

REVS: A New Open-Source Platform for High-Resolution Analysis of Rodent Wheel Running Behavior

BackgroundRodent wheel running is widely used in neuroscience and preclinical research to assess locomotor function, recovery post-trauma or disease, circadian rhythms, and exercise physiology. However, most existing wheel-running systems offer limited metrics, lack flexibility in hardware, or require costly proprietary software, reducing their usefulness for detailed behavioral phenotyping--especially in models of injury or rehabilitation. New methodWe developed REVS (Revolution Evaluation and Visualization Software), a low-cost, open-source hardware and software platform for analyzing and visualizing rodent wheel running behavior. REVS captures wheel revolutions using Hall effect sensors and computes 13 day-level behavioral metrics along with detailed bout-level data. Users can interactively explore high-resolution temporal features and export data in Open Data Commons (ODC)-compatible formats. REVS supports customizable wheel types, facilitating use in animals with motor and/or sensory impairments. ResultsWe validated REVS using a mouse model of partial spinal cord injury, where fine motor control is compromised. REVS detected impairments in 10 of 13 behavioral metrics post-injury, with varied recovery trajectories across measures. Principal component analysis revealed that recovery was closely linked to bout quality and intensity, rather than timing. Comparison with existing methodsUnlike commercial and open-source systems, REVS offers more detailed metrics, customizable wheel compatibility, seamless blending with common vivarium hardware, integrated data visualizations, and ODC-compatible data export. It also supports flexible analysis across individuals and groups. ConclusionsREVS provides a powerful, scalable tool for granular behavioral phenotyping in rodent studies, enhancing reproducibility and revealing insights into subtle locomotor changes associated with injury, recovery, and intervention. HighlightsO_LIREVS enables detailed analysis of voluntary wheel running in rodents C_LIO_LIThe platform combines low-cost hardware with open-source analysis software C_LIO_LIREVS computes 13 behavioral metrics across daily and bout-level timescales C_LIO_LIWe identified a unique lesion and recovery profile after partial spinal cord injury C_LIO_LIREVS supports ODC-compatible data export for transparency and reuse C_LI

neuroscience↗

bioRxiv2024

Population estimates of shorebirds on the Atlantic Coast of southern South America generated from large-scale, simultaneous, volunteer-led surveys

Population abundance and trend estimates are crucial to science, management, and conservation. Shorebirds, which are abundant in many coastal habitats and play important roles in coastal ecosystems, are facing some of the most dramatic population declines of any group of birds globally. However, accurate and up-to-date population estimates are lacking for most shorebird species. We thus conducted comprehensive, simultaneous, and community scientist-led surveys of the entire Atlantic Coast of southern South America -- stretching from central Brazil to Tierra del Fuego -- to gather counts of shorebirds that we combined with remote sensing analyses and two-step hurdle models that accounted for presence and abundance. Our objectives were to estimate shorebird densities by habitat, identify high-concentration areas, understand the environmental factors affecting their distributions, and provide population estimates for both Nearctic and Neotropical species. We counted a total of 37,207 shorebirds of 17 species and, from those counts, estimated that nearly 1.1 million shorebirds use the regions coastline. We also found that shorebirds occurred in the highest densities in shallow water wetland habitats and that fewer shorebirds occupied areas that were further away from estuaries. Although not directly comparable, our results suggest the population sizes of the Nearctic species whose nonbreeding ranges are predominantly in southern South America may have declined substantially since previous estimates. At the same time, our study represents the first empirically derived population estimates for Neotropical breeding shorebird species and indicates that they are far more abundant than previously thought. Taken together, our results highlight the power of community scientists to carry out structured protocols at continental scales and generate critical data for a group of at-risk species.

ecology↗

bioRxiv2022

Flexible perceptual encoding by discrete gamma events

Spatiotemporal patterns of activity in the neocortex are linked to cognitive processes underlying behavior. However, identifying discrete underlying events within highly dynamic cortical network fluctuations remains a critical challenge. Here, we demonstrate a novel analytical method to track network events underlying state-dependent {beta}- (15-30Hz) and {gamma}- (30-80Hz) range activity in mouse primary visual cortex (V1). We find that {gamma} events are selectively associated with enhanced visual encoding by V1 neurons and {gamma} event rate increases prior to visually-cued behavior, accurately predicting single trial visual detection. This relationship between {gamma} events and behavior is sensory modality-specific and rapidly modulated by changes in task objectives. These findings illuminate a distinct role for transient patterns of cortical activity, indicating that {gamma} supports flexible encoding according to behavioral context.

neuroscience↗