Biology subjects

Ratliff, J.

Publications and source records attributed to Ratliff, J..

4 recordsLinked to original sources

bioRxiv2025

Characterizing neuronal population geometry with AI equation discovery

The activity of visual cortical neurons forms a population code representing image stimuli. There is, however, a discrepancy between our understanding of this code at the single-cell and population levels: direct measurements indicate the population code is high-dimensional, but established models of single-cell tuning give rise to low-dimensional codes. We reconciled this discrepancy by developing an AI science system to find a new parsimonious, interpretable equation for visual cortical orientation tuning. Candidate equations were expressed as short computer programs and evolved by Large Language Models (LLMs) using graphical diagnostics. The resulting equation not only improved single-cell fits, but also accurately modelled the population codes high-dimensional geometry. A novel parameter of the AI-discovered equation, which controls single-cell tuning smoothness, gives rise to high-dimensional population codes. The same parameter drives high-dimensional coding in head-direction cells, suggesting a common coding strategy across brain regions. We used this equation to hypothesize a circuit mechanism generating high-dimensional population codes, and to demonstrate the advantages of these codes in a simulated hyperacuity task. These results show that tuning smoothness has a key role in controlling population code geometry, and demonstrate how AI equation discovery can deliver interpretable models accelerating scientific understanding in neuroscience and beyond.

neuroscience↗

bioRxiv2025

Community and functional stability in a working bioreactor degrading 1,4-dioxane at the Lowry Landfill Superfund Site

1,4-dioxane (dioxane) is an emerging contaminant that poses risks to human and environmental health. Bacterial dioxane degradation is increasingly being studied as a method to remove dioxane from contaminated water. However, there is a lack of studies on microbial community structures and functions within efficient, large scale, biodegradation-based remediation technologies. The Lowry Landfill Superfund Site (Colorado, USA) uses an on-site, pump-and-treat facility to remove dioxane from contaminated groundwater by biodegradation. Here, 16S rRNA and shotgun metagenomic sequencing were used to describe microbial community composition, soluble di-iron monooxygenase (SDIMO) alpha hydroxylases, and potential for dioxane degradation and horizontal gene transfer in bioreactor support media from the facility. Support media showed diverse microbial communities dominated by Nitrospiraceae, Nitrososphaeraceae, and Nitrosomonadaceae. Pseudonocardia were also detected, suggesting a potential presence of known dioxane-degraders. Candidate SDIMOs belonged mostly to Group V, followed by Groups IV, II, and I (based on read depth). The most abundant Group V clade contained 38 proteins that were phylogenetically related to DxmA-like proteins, including that of Pseudonocardia dioxanivorans CB1190 (a known dioxane degrader). Seventeen Lowry contigs containing DxmA-like proteins contained protein-coding genes potentially involved in chemical degradation, transcriptional regulation, and chemical transport. Interestingly, these contigs also contained evidence of potential horizontal gene transfer, including toxin-antitoxin proteins, phage integrase proteins, putative transposases, and putative miniature inverted-repeat transposable elements. These findings improve our understanding of potential dioxane biodegradation mechanisms in a functioning remediation system. Further studies are needed to definitively confirm microbial activity and enzymatic activity towards dioxane removal in this site. IMPORTANCEAs an environmental contaminant, 1,4-dioxane poses risks for water quality and human health. Used as a solvent and chemical stabilizer in a variety of manufacturing and industrial applications, microbiological methods of detoxification and mitigation are of interest. The degradation of 1,4-dioxane by the bacterium Pseudonocardia spp. is the best understood example; however, these studies are largely based on single isolate, bench-scale, or in silico experiments. Consequently, a knowledge gap exists on bacterial degradation of 1,4-dioxane at environmentally relevant concentrations using functioning remediation technologies at scale. This study addresses this gap directly by describing microbial taxa, enzymes, and potential horizontal gene transfer mechanisms associated with an active treatment plant located on a 1,4-dioxane-impacted U.S. Environmental Protection Agency (EPA) superfund site. As 1,4-dioxane contamination gains more attention, these findings may prove useful for future facilities aiming to promote and optimize removal by biodegradation.

microbiology↗

bioRxiv2025

Mapping Hand Function with Simultaneous Brain-Spinal Cord Functional MRI

INTRODUCTIONHand motor control depends on intricate brain-spinal cord interactions that regulate muscle activity. Hand function can be disrupted by injury to the brain, spinal cord, and peripheral nerves leading to weakness and impaired coordination. Functional MRI (fMRI) can map motor-related neural activity and potentially characterize the mechanisms underlying hand weakness and diminished coordination. Although brain motor control has been extensively studied, spinal cord mechanisms remain less explored. Here we use simultaneous brain-spinal cord fMRI to map neural activity related to hand strength and dexterity across the central nervous system using force matching and finger tapping tasks. This study pioneers the use of simultaneous brain-spinal cord fMRI to comprehensively map hand function, offering novel insights into coordinated motor processing across the central nervous system. METHODSWe performed simultaneous brain-spinal cord fMRI in 28 right-handed healthy volunteers (age: 40.0 {+/-} 13.8 years, 14 females, 14 males) using a 3T GE SIGNA Premier scanner equipped with a 21-channel head-neck coil. Participants performed a force-matching task at 10%, 20%, and 30% of maximum voluntary contraction using a hand dynamometer. For the finger tapping task, participants completed button-presses at 1 Hz with a 5-button response pad for three task levels: single-digit response with the second digit only (low), single-digit response with all digits in a sequential order (medium), single-digit response with all digits in a random order (high). Visual cues and feedback were provided during the tasks. Brain and spinal cord images were processed separately using FSL and the Spinal Cord Toolbox, with motion correction, physiological noise filtering, and spatial normalization to standard templates. Subject level activity maps were generated and entered into group level analyses to explore both activations and deactivations. For the brain, we used a mixed effect design with a voxelwise threshold of Z score > 3.10 and cluster threshold of p < 0.05. For the spinal cord, we used a fixed effect design with a voxelwise threshold of Z score > 1.64 and cluster threshold of p < 0.05. Region of interest (ROI) analyses were conducted to examine localized changes in activation across task levels RESULTSBoth tasks elicited activation in motor and sensory regions of the brain and spinal cord, with graded responses in the left primary motor (M1), left primary sensory (S1) cortex, and right spinal cord gray matter across task levels. Deactivation of the right M1 and S1 was also present for both tasks. Deactivation of the left spinal cord gray matter was present in the high task level of the force matching task. The ROI analysis findings complemented the group level activity maps. DISCUSSIONOur study provides a detailed map of brain-spinal cord interactions in hand function, revealing graded neural activation and inhibition patterns across motor and sensory regions. Interhemispheric inhibition, reflected in right M1 deactivation, likely restricts extraneous motor output during unilateral tasks. For force matching, the deactivation of the left ventral and dorsal horns of the spinal cord, provides the first evidence that the inhibition of motor areas during a unilateral motor task extends to the spinal cord. Whether this inhibition results from direct descending modulation from the brain or interneuronal inhibition in the cord remains to be interrogated. These findings expand our understanding of central motor control mechanisms and could inform rehabilitation strategies for individuals with motor impairments. CONCLUSIONSOur simultaneous brain-spinal cord fMRI approach provides novel insights into the neural coordination of hand function, enhancing our understanding of motor control and its modulation. This approach may offer a foundation for studying motor dysfunction in conditions such as stroke, spinal cord injury, and neurodegenerative diseases.

neuroscience↗

bioRxiv2018

Neural circuit robustness to acute, global physiological perturbations

Neural function depends on underlying physiological processes that are highly sensitive to physical variables such as temperature. However, some robustness to perturbations in these variables manifests at the circuit level, suggesting that circuit properties are organized to tolerate consistent changes in underlying parameters. We show that a crustacean pacemaker circuit is robust to two global perturbations - temperature and pH - that differentially alter circuit properties. Consistent with high variability in underlying circuit parameters, we find that the critical temperatures and pH values where circuit activity breaks down vary widely across animals. Despite variability in critical points the network state transitions at these critical points are consistent, implying that qualitative circuit dynamics are preserved across animals, in spite of high quantitative parameter variability. Surprisingly, robustness perturbations in pH only moderately affect temperature robustness. Thus, robustness to a global perturbation does not necessarily imply sensitivity to other global perturbations.

bioinformatics↗