Biology subjects

Wolfe, T.

Publications and source records attributed to Wolfe, T..

7 recordsLinked to original sources

bioRxiv2026

Patterns of subcortical tissue iron levels across the lifespan measured with functional MRI

Iron is essential for neurophysiological health. Prior work has shown that subcortical tissue iron levels are the highest among all brain regions but also change over the lifespan. Recent functional MRI (fMRI) studies have provided evidence that an fMRI-derived iron-sensitive signal may index relative iron concentration in subcortical regions. In this context, we aimed to characterize the lifespan trajectory of this fMRI-derived iron-sensitive signal (relative iron quantification) in 10 subcortical regions and 14 thalamic nuclei from 881 healthy participants aged 12 to 88 years, using resting-state fMRI. Regressions were run with age as a predictor, separately for males (N = 429) and females (N = 452). The main results show non-linear effects of age, with an overall increase in iron levels across most subcortical regions within each sex. Six of the 14 thalamic nuclei in male participants had similar slopes of their lifespan iron levels, showing some homogeneity. The thalamic nuclei of female participants showed less agreement in slopes. This study provides new insight into the typical trajectory of iron levels across all major subcortical regions throughout the lifespan.

neuroscience↗

bioRxiv2026

Investigating cognitive enrichment for dairy calves through behavioral measures of participation and engagement: a pilot study

Introducing cognitive enrichment from an early age has the potential to enhance an animals capacity to learn both simple and complex tasks, promote neural plasticity, and support cognitive development. This is applicable for young cattle who are at a critical stage in their development and could benefit from the influence cognitive enrichment has on their behavioral expression. This study aims to explore the effects cognitive enrichment has on weaned dairy calves through analyzing behavioral measures of voluntary participation and short-term behavioral reactions to enrichment exposure. Our study involved a total of five pairs of weaned calves (n=8 treatment; n=2 control). The treatment groups were presented with three variations of a puzzle box, each equipped with unique challenges that offer different solutions (push, slide, pull). These boxes were provided to the calves twice daily over the span of nine days in an isolated corridor located behind their pen. We hypothesized that motivated calves would consistently engage with cognitive enrichment voluntarily over time and express directed natural behaviors, reflecting sustained participation across repeated trials. Results demonstrated that calves consistently visited the cognitive enrichment area across trials, with an average latency of 75.7 {+/-} 47.0s from the pen to the enrichment. Secondly, the calves spent a significant proportion of trial time within the enrichment area at 65% (870.1 {+/-} 21s). Lastly, all calves expressed a broad range of behaviors in line with their natural exploration within the enrichment area, while the puzzle box treatment groups expressed higher durations of behavioral expressions when compared to the control (F=11.7, p<0.0001). Combined, these results indicate the calves motivations to voluntarily participate in a cognitive challenge. While these are promising findings for cognitive enrichment and its applicability to dairy calves, further work is needed to understand broader parameters. Specifically, how can social dynamics influence enrichment interaction in groups, how can this type of enrichment be implemented on farms, and what are the long-term effects to providing cognitive enrichment in the early stages of development.

zoology↗

bioRxiv2026

Interkingdom glycine conjugates of indole-3-carboxylates are Ah receptor ligands

Substituted indoles are conserved metabolites across all kingdoms of life and may function as a mediators of inter- and intra-species communication. Indole-3-carboxylates (indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA)) represent abundant tryptophan-derived AHR agonists in human serum, potentially influencing AHR-dependent physiology. LC-MS analysis of mouse serum, urine and cecal/fecal contents reveals that both IAA and IPA undergo host and microbial mediated glycine conjugation to facilitate urinary elimination. Notably, at physiologically detectable human serum concentrations (M), IAA-Glycine retains human AHR activation potential. Comparative in silico docking simulations corroborate IAA-Glycine as a direct ligand for the human AHR. Data suggest, in contrast to xenobiotic ligands, AHR activation by endogenous tryptophan metabolites is greater in humans than in mice. These results underscore the role of microbial and host-derived amino acid conjugation in generating bioactive metabolites. Thus, positioning interkingdom auxin chemistry within human physiology and revealing an unexpected link between plants, microbes, and humans.

biochemistry↗

bioRxiv2026

Responses of dairy cows following a change in housing system and social group: a living lab experiment

To investigate how the disturbances associated with a relocation to a bedded-pack barn, such as a housing system change, a milking system change and a social regrouping, impacts the behavior of lactating dairy cows, 38 cows from a total of 9 tie-stall or free-stall commercial farms were moved to a newly built bedded-pack barn on an enrollment basis, with a social regrouping occurring after 2 weeks. Scan sampling of video data was done to assess behavior expression in the pen, and live data was collected to assess milking reactivity and animal handling procedures. Results indicate that the cows adapted quickly to the relocation to the new housing system as there were no changes in the locations in the pen, the body positions or the behaviors of cows in time between arrival and regrouping. The social regrouping had a bigger impact with a decrease in 16% of the observed time spent lying and an increase of 9.7% of the observed time spent feeding. Cows also adapted quickly to the milking procedures with a rapid decrease in the occurrence of negative social interactions between cows at the parlor, and in needing less human-animal manipulations and less time to be brought to the parlor. The housing system of origin had a slight effect on behaviors with cows from tie-stalls spending 1.7 times more of the observed time lying than free-stall cows, and free-stall cows spending 1.6 times more of the observed time feeding than tie-stall cows. This study provides a better understanding of how dairy cows respond to disturbances and is encouraging for producers that need to make changes to their current housing system as cows were shown to be quickly adaptable to the challenges presented to them. SummaryDairy cows from cubicle systems were shown to adapt quickly after a relocation to a bedded pack barn, the first use of a milking parlor, and a social regrouping. This was supported by limited changes observed in their behaviors after the disturbances, and observed deviations were temporary and short-lived. Animal handling procedures also observed a quick improvement in time with the trips to the milking parlor needing 2x less time and 3.5x fewer physical contacts from handlers after 5 days. These results are encouraging to producers needing to make changes to their barns.

zoology↗

bioRxiv2024

Population-level age effects on the white matter structure subserving cognitive flexibility in the human brain

Cognitive flexibility, a mental process crucial for adaptive behavior, involves multi-scale functioning across several neuronal organization levels. While the neural underpinnings of flexibility have been studied for decades, limited knowledge exists about the structure and age-related differentiation of the white matter subserving brain regions implicated in cognitive flexibility. This study investigated the population-level relationship between cognitive flexibility and properties of white matter across two periods of adulthood, aiming to discern how these associations vary over different life stages and brain tracts. We propose a novel framework to study age effects in brain structure-function associations. First, a meta-analysis was conducted to identify neural regions associated with cognitive flexibility. Next, the white matter projections of these neural regions were traced through the Human Connectome Project tractography template to identify the white matter structure associated with cognitive flexibility. Then, a cohort analysis was performed to characterize myelin-related macromolecular features using a subset of the UK Biobank magnetic resonance imaging (MRI) data, which has a companion functional/behavioral dataset. We found that (1) the wiring of cognitive flexibility is defined by a subset of brain tracts, which present undifferentiated features early in adulthood and significantly differentiated types in later life. (2) These MRI-derived properties are correlated with individual subprocesses of cognition, which are closely related to cognitive flexibility function. (3) In late life, myelin-related homogeneity of specific white matter tracts implicated in cognitive flexibility declines with age, a phenomenon not observed in early life. Our findings support the age-related differentiation of white matter tracts implicated in cognitive flexibility as a natural substrate of adaptive cognitive function. Significance StatementCognitive flexibility function facilitates adaptation to environmental demands. Brain changes affecting structural organization during the lifespan are theorized to impact cognitive flexibility. This study characterizes how the brains connectivity is correlated with cognitive flexibility function throughout adulthood. By analyzing myelin-related properties of white matter, this study found that certain parts of the brains wiring related to cognitive flexibility become more differentiated with advanced age. These age-related features appear as a natural characteristic of the human brain that may impact specific aspects of adaptive thinking, like shifting between tasks or updating information.

neuroscience↗

bioRxiv2023

Contribution of circulating host and microbial tryptophan metabolites towards Ah receptor activation

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that plays an integral role in homeostatic maintenance by regulating cellular functions such as cellular differentiation, metabolism, barrier function, and immune response. An important but poorly understood class of AHR activators are compounds derived from host and bacterial metabolism of tryptophan. The commensal bacteria of the gut microbiome are major producers of tryptophan metabolites known to activate the AHR, while the host also produces AHR activators through tryptophan metabolism. We used targeted mass spectrometry-based metabolite profiling to determine the presence and metabolic source of these metabolites in the sera of conventional mice, germ-free mice, and humans. Surprisingly, sera concentrations of many tryptophan metabolites are comparable between germ-free and conventional mice. Therefore, many major AHR-activating tryptophan metabolites in mouse sera are produced by the host, despite their presence in feces and mouse cecal contents. AHR activation is rarely studied in the context of a mixture at relevant concentrations, as we present here. The AHR activation potentials of individual and pooled metabolites were explored using cell-based assays, while ligand binding competition assays and ligand docking simulations were used to assess the detected metabolites as AHR agonists. The physiological and biomedical relevance of the identified metabolites was investigated in the context of cell-based models for cancer and rheumatoid arthritis. We present data here that reframe AHR biology to include the presence of ubiquitous tryptophan metabolites, improving our understanding of homeostatic AHR activity and models of AHR-linked diseases.

biochemistry↗

bioRxiv2020

Neuromesodermal Progenitors Advance Network Formation of Spinal Neurons and Support Cells in Neural Ribbons In Vitro and Unprotected Survival in a Rat Subacute Contusion Model

Improved human stem cell interventions to treat CNS trauma requires continued expansion of in vitro models and delivery platforms to fill gaps in analysis and treatment. Transplanted neural stem cells (NSCs) face unique, multi-faceted challenges beyond survival that include differentiation, maturation, and integration into a complex cytokine-releasing microenvironment that impinges on a multipotent cell type. Alternate strategies to transplant neurons and neuronal networks deserve reevaluation, particularly since novel differentiation protocols mimicking region-specific developmental and positional cues have recently emerged. To investigate transplantation of neurons and their early networks, we generate in vitro neural ribbons containing spinal neurons and support cells anatomically matched for cervical spinal cord injury (SCI). These glutamate-responsive, electrically-active neural ribbons apply a new hiPSC differentiation strategy transiting through neuromesodermal progenitors (NMps) to derive developmentally relevant spinal motor neurons (SMNs), interneurons (INs), and oligodendrocyte progenitor cells (OPCs). Bioinformatic profiling validates region-specific identities. Neurons and neuronal networks are functionally evaluated for action potential firing, calcium signaling, population activity, and synaptogenesis. NMp-derived neurons survive in vivo within the subacute phase hemi-contusion injury cavity when delivered either as free suspension or as encapsulated networks of pre-formed CNS cytoarchitectures. Delivery as encapsulated networks further supports survival of lower cell numbers and rapid graft penetration into host tissue. Neural network ribbons therefore provide a novel intermediary approach between cell suspensions and complex organoids for investigating network formation and early transplantation events with hiPSC-derived neurons, providing flexibility to rapidly tune cell type(s), cell ratios, and traceable biomarkers. Significance StatementIn the two decades since human stem cell technologies have emerged, the challenge has remained to improve the developmentally relevant derivation of therapeutic cells. The ability to now generate anatomically matched neurons for SCI necessitates a re-evaluation of these cells and their networks in vitro and in vivo. In this study, we apply developmental cues via neuromesodermal progenitors to generate spinal neurons from hiPSCs. Genetic and functional evaluation of these cells as in vitro neuronal networks, due to their capacity to survive and graft effectively within the rat subacute contusion cavity, offer novel approaches for customizing SCI transplantation. This work demonstrates a strategy to develop transplantable, chemically-responsive networks linking in vitro models with injury customization towards improved in vivo outcomes.

neuroscience↗