Biology subjects

Wood, J. M.

Publications and source records attributed to Wood, J. M..

14 recordsLinked to original sources

bioRxiv2026

Sex-Dependent Effects of Creatine Hydrochloride on Neuroinflammation, Neuronal Survival, and Inhibitory Synaptic Remodeling Following Traumatic Brain Injury in Mice.

Despite traumatic brain injury (TBI) being a leading cause of death and disability in the United States, there is currently no FDA-approved medication that can prevent, heal, or reverse brain damage caused by TBI. TBI is caused by primary and secondary brain damage resulting in loss of neurons, astrocytic gliosis, and microglial activation which culminate in complex neurological disorders. The goal of the current study was to investigate the neuroprotective potential for Creatine Hydrochloride (C-HCl) supplementation following TBI in wild-type mice. Four C-HCl supplementation paradigms were examined including both 7 day pre-injury and 14-day post-injury treatments consisting of the following: 1) water/water, 2) water/C-HCl (100 mg/kg), 3) C-HCl (100 mg/kg)/C-HCl (100 mg/kg), 4) C-HCl (100 mg/kg)/C-HCl (450 mg/kg). Following controlled cortical impact (CCI) injury at a parietal location, measures of tissue and cellular (neuronal and glial) damage were assessed at 14 days post-injury (dpi). At 14 dpi, there were no significant effects on gross anatomical cavitation, tissue loss, third ventricle expansion, or systemic fluid biomarkers with any treatment group, though female mice exhibited larger baseline lesion boundaries overall compared to male mice. However, microstructural evaluation revealed a profound and sex-dependent effect of C-HCl supplementation in the hippocampus with female mice showing reduced neuroinflammation and male mice displaying reduced neurodegeneration (Fluoro-Jade C staining of neurons) across the CA1 and dentate gyrus (DG) compared to placebo control. Furthermore, mice receiving C-HCl pre-injury followed by high-dose C-HCl post-injury demonstrated distinct remodeling of inhibitory circuits to restore network balance with males significantly modifying presynaptic machinery via vesicular GABA transport (VGAT puncta) in the DG, whereas females reinforced postsynaptic architectural framing through scaffolding elements (gephyrin puncta) in both the CA1 and DG. These results suggest C-HCl supplementation holds promise as a neuroprotective therapeutic strategy for TBI. Crucially, the molecular mechanisms utilized to achieve this brain cell homeostasis are radically distinct between the sexes, females benefit primarily via upstream glial stabilization, while males derive protection via direct downstream neuronal survival. These outcomes highlight a critical requirement for sex-stratified profiling in translational pipelines for neurometabolic interventions for TBI. Ultimately, these data indicate that C-HCl successfully counteracts chronic secondary injury cascades, mitigating neurodegeneration, dampening neuroinflammation, and remodeling inhibitory circuitry to prevent post-traumatic network hyperexcitability.

neuroscience↗

bioRxiv2026

Differential efficiency of sampling devices in the measurement of microbial diversity of Yellowstone National Park hot springs

Metagenomic characterization of low-biomass Yellowstone National Park (YNP) hot spring waters remains challenging because microbial recovery is influenced by filtration methodology, sample preservation, DNA extraction, and sequencing strategy. We characterized thermophilic microbial communities in alkaline YNP hot spring waters (62-90.5{degrees}C) using three high-temperature-compatible filtration systems (Sterivex, Supor, and polycarbonate membranes), automated onsite DNA extraction ({micro}Titan), and shotgun metagenomic sequencing with Illumina short-read and Oxford Nanopore Technologies (ONT) long-read platforms. Across all filtration systems and sequencing workflows, microbial communities were consistently dominated by Bacteria ([~]90% of reads), whereas Archaea represented <10% of recovered sequences. Dominant microbial populations were reproducibly recovered across all approaches; however, recovery of lower-abundance taxa varied among methods. This variability was most evident in polycarbonate-filtered samples, which exhibited greater replicate-to-replicate variation and less consistent detection of microbial species. Thermocrinis ruber and related Aquificae-associated thermophiles dominated the hottest waters (78.5-90.5{degrees}C), whereas warmer effluent-channel waters (63.5-66.5{degrees}C) contained T. ruber together with photosynthetic taxa, including Synechococcus spp. and Candidatus Thermochlorobacter aerophilum. Archaeal communities were primarily represented by Pyrobaculum- and Thermoproteus-related taxa. Non-metric multidimensional scaling analyses indicated that overall community structure was largely unaffected by filtration or sequencing methodology, whereas alpha-diversity metrics showed that filter selection influenced richness and diversity estimates. These findings identify field-deployable workflows for metagenomic characterization of low-biomass thermophilic aquatic systems and demonstrate the importance of integrating filtration and sequencing strategies for studying extremophile microbiomes under remote sampling conditions. IMPORTANCEAccurate characterization of low-biomass geothermal water microbiomes remains challenging because microbial recovery is strongly influenced by sample handling, filtration efficiency, DNA extraction chemistry, and sequencing methodology. This study demonstrated that Yellowstone National Park alkaline hot spring water microbiomes were consistently dominated by Bacteria (>90% of recovered reads), whereas Archaea represented <10% of community abundance across all filtration systems. Although dominant microbial populations were reproducibly recovered, filtration-device selection influenced the recovery of microbial diversity and low-abundance taxa. By integrating field-deployable onsite DNA extraction with ONT shotgun metagenomic sequencing, this work evaluates practical workflows for studying thermophilic planktonic microbial communities under remote field conditions. These findings are relevant, not only to geothermal microbiology, but also to low-biomass environments in medical, pharmaceutical, and aerospace industries, where rapid onsite processing and contamination-aware workflows are essential for preserving authentic microbial signatures in extreme environments.

ecology↗

bioRxiv2026

Perception of effort but not reward sensitivity is impaired in people with Parkinsons disease

Deciding whether and how to act depends on a trade-off between the effort required to execute a given action and the potential reward for completing it. Impairments in this effort-reward trade-off have been proposed to underlie reduced movement vigor, or bradykinesia, in Parkinsons disease (PD). However, several mechanisms could alter the effort-reward trade-off in PD, each with unique implications for understanding and treating bradykinesia. Therefore, we individually examined whether people with PD (both on and off dopamine medication) demonstrated reduced sensitivity to reward value, increased perception of effort, or a biased mapping between effort and reward, compared to age- and sex-matched neurotypical controls. We found that people with PD exhibited increased effort perception and, surprisingly, no reduced sensitivity to reward value or a biased mapping between effort and reward. These findings suggest that effort perception could be an important factor driving bradykinesia in PD.

neuroscience↗

bioRxiv2026

Single-library chromosome-scale diploid assemblies of vole genomes resolve a species-specific duplication implicated in pair bonding

Comparing prairie voles (Microtus ochrogaster), a species that forms lasting pair bonds and exhibits biparental care, with meadow voles (Microtus pennsylvanicus), a non-monogamous species showing maternal care only, provides a framework to examine the genomic basis of behavioral divergence over short evolutionary time. Here, we develop a simplified assembly approach combining PacBio HiFi and CiFi sequencing in a single library and run, producing high-quality contiguous chromosome-scale diploid prairie and meadow vole genomes (2.3 Gbp). Comparative analysis reveals substantial differences, including near-complete Y chromosome divergence and a prairie-vole-specific duplication of Avpr1a, a vasopressin receptor gene implicated in social bonding and autism in humans. These extensive genomic changes suggest rapid chromosome evolution as a driver of the dramatic Microtus radiation, generating [~]60 vole species in >2 million years. This single-library approach facilitates a simplified and more affordable assembly workflow, producing near-complete genomes of diverse species using one sequencing platform.

genomics↗

bioRxiv2025

Forty New Genomes Shed Light on Sexual Reproduction and the Origin of Tetraploidy in Microsporidia

Microsporidia are single-celled, obligately intracellular parasites with growing public health, agricultural, and economic importance. Despite this, Microsporidia remain relatively enigmatic, with many aspects of their biology and evolution unexplored. Key questions include whether Microsporidia undergo sexual reproduction, and the nature of the relationship between tetraploid and diploid lineages. While few high-quality microsporidian genomes currently exist to help answer such questions, large-scale biodiversity genomics initiatives, such as the Darwin Tree of Life project, can generate high-quality genome assemblies for microsporidian parasites when sequencing infected host species. Here, we present 40 new microsporidian genome assemblies from infected arthropod hosts that were sequenced to create reference genomes. Out of the 40, 32 are complete genomes, eight of which are chromosome-level, and eight are partial microsporidian genomes. We characterised 14 of these as polyploid and five as diploid. We found that tetraploid genome haplotypes are consistent with autopolyploidy, in that they coalesce more recently than species, and that they likely recombine. Within some genomes, we found large-scale rearrangements between the homeologous genomes. We also observed a high rate of rearrangement between genomes from different microsporidian groups, and a striking tolerance for segmental duplications. Analysis of chromatin conformation capture (Hi-C) data indicated that tetraploid genomes are likely organised into two diploid compartments, similar to dikaryotic cells in fungi, with evidence of recombination within and between compartments. Together, our results provide evidence for the existence of a sexual cycle in Microsporidia, and suggest a model for the microsporidian lifecycle that mirrors fungal reproduction.

genomics↗

bioRxiv2025

The mouse pangenome reveals the structural complexity of the murine protein coding landscape

We present the first mouse pangenome consisting of 17 high-quality inbred mouse strain genomes with complete annotation. This collection includes 12 widely used classical laboratory strains and 5 wild-derived strains. We have fully resolved previously incomplete genomic regions, including the major histocompatibility complex (MHC), the defensin cluster, T-cell receptor, and Ly49 complexes. Hundreds of non-reference genes identified in previous publications not found in GRCm39, like Defa1, Raet1a, and Klra20 (Ly49T), were localised in the new reference genomes. We conducted the first genome-wide scan of variable number tandem repeats (VNTRs) within the coding regions of mice, identifying over 400 genes with VNTR polymorphisms up to more than 600 repeat copies and repeat units reaching 990 nucleotides. Our strain-specific annotations enhance RNA-Seq analyses, as demonstrated in PWK/PhJ, where we observed a 5.1% improvement in read mapping and expression level differences in 2.1% of coding genes compared to using GRCm39.

genomics↗

bioRxiv2025

ERGA-BGE genome of Cheirolophus tagananensis: an IUCN endangered shrub endemic to the Canary Islands

The reference genome of Cheirolophus tagananensis, locally known as the Cabezon de Taganana, will provide an exceptional opportunity to establish a new framework to develop comparative genomic tools. These tools will help uncover the genetic basis of rapid plant radiations and microevolutionary adaptation processes of insular species on oceanic islands. This genomic resource will also contribute to facilitate the establishment of better informed in situ and ex-situ conservation strategies for this narrow endemic in the face of potential habitat degradation, and support taxonomic studies to better understand genetic diversity at the population, species, and genus levels. A total of 16 contiguous chromosomal pseudomolecules were assembled from the genome sequence. This chromosome-level assembly encompasses 0.62 Gb, composed of 421 contigs and 235 scaffolds, with contig and scaffold N50 values of 4.0 Mb and 36.5 Mb, respectively.

genomics↗

bioRxiv2024

Explicit and implicit locomotor learning in individuals with chronic hemiparetic stroke

Motor learning involves both explicit and implicit processes that are fundamental for acquiring and adapting complex motor skills. However, stroke may damage the neural substrates underlying explicit and/or implicit learning, leading to deficits in overall motor performance. While both learning processes are typically used in concert in daily life and rehabilitation, no gait studies have determined how these processes function together after stroke when tested during a task that elicits dissociable contributions from both. Here, we compared explicit and implicit locomotor learning in individuals with chronic stroke to age- and sex-matched neurologically intact controls. We assessed implicit learning using split-belt adaptation (where two treadmill belts move at different speeds). We assessed explicit learning (i.e., strategy-use) using visual feedback during split-belt walking to help individuals explicitly correct for step length errors created by the split-belts. The removal of visual feedback after the first 40 strides of split-belt walking, combined with task instructions, minimized contributions from explicit learning for the remainder of the task. We utilized a multi-rate state-space model to characterize individual explicit and implicit process contributions to overall behavioral change. The computational and behavioral analyses revealed that, compared to controls, individuals with chronic stroke demonstrated deficits in both explicit and implicit contributions to locomotor learning, a result that runs counter to prior work testing each process individually during gait. Since post-stroke locomotor rehabilitation involves interventions that rely on both explicit and implicit motor learning, future work should determine how locomotor rehabilitation interventions can be structured to optimize overall motor learning. New and noteworthyMotor learning involves both implicit and explicit processes, the underlying neural substrates of which could be damaged by after stroke. While both learning processes are typically used in concert in daily life and rehabilitation, no gait studies have determined how these processes function together after stroke. Using a locomotor task that elicits dissociable contributions from both processes and computational modeling, we found evidence that chronic stroke causes deficits in both explicit and implicit locomotor learning.

neuroscience↗

bioRxiv2023

Reinforcement learning during locomotion

When learning a new motor skill, people often must use trial and error to discover which movement is best. In the reinforcement learning framework, this concept is known as exploration and has been linked to increased movement variability in motor tasks. For locomotor tasks, however, increased variability decreases upright stability. As such, exploration during gait may jeopardize balance and safety, making reinforcement learning less effective. Therefore, we set out to determine if humans could acquire and retain a novel locomotor pattern using reinforcement learning alone. Young healthy male and female participants walked on a treadmill and were provided with binary reward feedback (indicated by a green checkmark on the screen) that was tied to a fixed monetary bonus, to learn a novel stepping pattern. We also recruited a comparison group who walked with the same novel stepping pattern but did so by correcting for target error, induced by providing real time veridical visual feedback of steps and a target. In two experiments, we compared learning, motor variability, and two forms of motor memories between the groups. We found that individuals in the binary reward group did, in fact, acquire the new walking pattern by exploring (increasing motor variability). Additionally, while reinforcement learning did not increase implicit motor memories, it resulted in more accurate explicit motor memories compared to the target error group. Overall, these results demonstrate that humans can acquire new walking patterns with reinforcement learning and retain much of the learning over 24 hours. Significance StatementHumans can learn some novel movements by independently discovering the actions that lead to success. This discovery process, exploration, requires increased motor variability to determine the best movement. However, in bipedal locomotion especially, increasing motor variability decreases stability, heightening the risk of negative outcomes such as a trip, injury, or fall. Despite this stability constraint, the current study shows that individuals do use exploration to find the most rewarding walking patterns. This form of learning led to improved explicit retention but not implicit aftereffects. Thus, the reinforcement learning framework can explain findings across a wide range of motor and cognitive tasks, including locomotion.

neuroscience↗

bioRxiv2023

A reliable and efficient adaptive Bayesian method to assess static lower limb proprioception.

BackgroundLower limb proprioception is critical for maintaining stability during gait and may impact how individuals modify their movements in response to changes in the environment and body state, a process termed "sensorimotor adaptation". However, the connection between lower limb proprioception and sensorimotor adaptation during human gait has not been established. We suspect this gap is due in part to the lack of reliable, efficient methods to assess global lower limb proprioception in an ecologically valid context. New MethodWe assessed static lower limb proprioception using an alternative forced choice task, administered twice to determine test-retest reliability. Participants stood on a dual-belt treadmill which passively moved one limb to stimulus locations selected by a Bayesian adaptive algorithm. At the stimulus locations, participants judged relative foot positions and the algorithm estimated the point of subjective equality (PSE) and the uncertainty of lower limb proprioception. ResultsUsing the Bland-Altman method, combined with Bayesian statistics, we found that both the PSE and uncertainty estimates had good reliability. Comparison with Existing Method(s)Current methods assessing static lower limb proprioception do so within a single joint, in non-weight bearing positions, and rely heavily on memory. One exception assessed static lower limb proprioception in standing but did not measure reliability and contained confounds impacting participants judgments, which we experimentally controlled here. ConclusionsThis efficient and reliable method assessing lower limb proprioception will aid future mechanistic understanding of locomotor adaptation and serve as a useful tool for basic and clinical researchers studying balance and falls.

neuroscience↗

bioRxiv2022

Deletion of proU suppresses proQ phenotypes in Escherichia coli

The ProQ protein interacts as an RNA chaperone with diverse RNA molecules in Escherichia coli. ProQ is implicated in the bacterial osmotic stress response. When the osmotic pressure is high, cells maintain their hydration by accumulating organic solutes denoted osmolytes. Transporters ProP and ProU (which is ProVWX) mediate osmolyte accumulation by Escherichia coli. Mutations at proQ impair ProP activity by reducing ProP levels (the ProQ transport phenotype) but do not impair ProU activity or reduce the level of ProX. The proQ- bacteria are longer than proQ+ bacteria during growth in either low or high salinity medium and they grow slowly at high salinity (the ProQ growth phenotype). In addition, spherical cells with crescent-shaped, nucleic acid-rich foci appear and cells lyse (the ProQ morphological phenotypes). In this work, the proQ transport phenotype was suppressed by deletions of proU, or by an insertion of IS5 in proU, when proP was expressed from the chromosome or from the heterologous, plasmid-based PBAD promoter. A point mutation disrupting the Walker B motif of ProV inactivated ProU but did not suppress the transport phenotype. ProP activities and ProP levels varied in parallel, so proQ and proU act at the same level to regulate ProP expression. Deletion of the proU operon also suppressed the growth and morphological phenotypes. The proU locus may overlap the gene encoding a regulatory sRNA that acts with ProQ, contributing to cellular morphogenesis and osmotic stress tolerance, or the relationship between ProQ and proU may be indirect.

microbiology↗

bioRxiv2022

Machine learning algorithm to characterize antimicrobial resistance associated with the International Space Station surface microbiome

BackgroundAntimicrobial Resistance (AMR) has a detrimental impact on human health on Earth and it is equally concerning in other environments such as space due to microgravity, radiation and confinement, especially for long-distance space travel. The International Space Station (ISS) is ideal for investigating microbial diversity and virulence. The shotgun metagenomics data of the ISS generated during the Microbial Tracking - 1 (MT-1) project and resulting metagenome-assembled genomes (MAGs) across three flights in eight different locations during 12 months were used in this study. The objective of this study was to identify the AMR genes associated with whole genomes of 227 cultivable strains, 21 shotgun metagenome sequences, and 24 MAGs retrieved from the ISS environmental samples that were treated with propidium monoazide (PMA; viable microbes). ResultsWe have analyzed the data using a deep learning model, allowing us to go beyond traditional cut-offs based only on high DNA sequence similarity and extending the catalog of AMR genes. Our results in PMA treated samples revealed AMR dominance in the last flight for Kalamiella piersonii, a bacteria related to urinary tract infection in humans. The analysis of 227 pure strains isolated from the MT-1 project revealed hundreds of antibiotic resistance genes from many isolates, including two top-ranking species that corresponded to strains of Enterobacter bugandensis and Bacillus cereus. Computational predictions were experimentally validated by antibiotic resistance profiles in these two species, showing a high degree of concordance. Specifically, disc assay data confirmed the high resistance of these two pathogens to various beta-lactam antibiotics. ConclusionOverall, our computational predictions and validation analyses demonstrate the advantages of machine learning to uncover concealed AMR determinants in metagenomics datasets, expanding the understanding of the ISS environmental microbiomes and their pathogenic potential in humans.

bioinformatics↗

bioRxiv2021

Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies

Advances in long-read sequencing technologies and genome assembly methods have enabled the recent completion of the first Telomere-to-Telomere (T2T) human genome assembly, which resolves complex segmental duplications and large tandem repeats, including centromeric satellite arrays in a complete hydatidiform mole (CHM13). Though derived from highly accurate sequencing, evaluation revealed that the initial T2T draft assembly had evidence of small errors and structural misassemblies. To correct these errors, we designed a novel repeat-aware polishing strategy that made accurate assembly corrections in large repeats without overcorrection, ultimately fixing 51% of the existing errors and improving the assembly QV to 73.9. By comparing our results to standard automated polishing tools, we outline common polishing errors and offer practical suggestions for genome projects with limited resources. We also show how sequencing biases in both PacBio HiFi and Oxford Nanopore Technologies reads cause signature assembly errors that can be corrected with a diverse panel of sequencing technologies

genomics↗

bioRxiv2020

Ecotype Simulation 2: An improved algorithm for efficiently demarcating microbial species from large sequence datasets

BackgroundMicrobial systematists have used molecular cutoffs to classify the vast diversity present within a natural microbial community without invoking ecological theory. The use of ecological theory is needed to identify whether or not demarcated groups are the ecologically distinct, fundamental units (ecotypes), necessary for understanding the system. Ecotype Simulation, a Monte-Carlo approach to modeling the evolutionary dynamics of a microbial population based on the Stable Ecotype Model of microbial speciation, has proven useful for finding these fundamental units. For instance, predicted ecotypes of Synechococcus forming microbial mats in Yellowstone National Park hot springs, which were previously considered to be a single species based on phenotype, have been shown to be ecologically distinct, with specialization to different temperature and light levels. Unfortunately, development of high-throughput DNA sequencing methods has outpaced the ability of the program to analyze all of the sequence data produced. ResultsWe developed an improved version of the program called Ecotype Simulation 2, which can rapidly analyze alignments of very large sequence datasets. For instance, while the older version takes days to analyze 200 sequences, the new version can analyze 1.92 x 105 sequences in about six hours. The faster simulation identified similar ecotypes as found with the slower version, but from larger amounts of sequence data. ConclusionsBased on ecological theory, Ecotype Simulation 2 provides a much-needed approach that will help guide microbial ecologists and systematists to the natural, fundamental units of bacterial diversity.

bioinformatics↗