Biology subjects

Meyer, A. C.

Publications and source records attributed to Meyer, A. C..

4 recordsLinked to original sources

bioRxiv2025

Dense Longitudinal Precision Neuroimaging of Recovery from Traumatic Brain Injury

Traumatic brain injury (TBI) disrupts white matter tracts essential for cognition and emotion. Diffusion tensor imaging (DTI) can noninvasively measure white matter integrity. However, DTI has been inconsistent in predicting patient recovery from TBI, possibly due to the complex, dynamic, and individual-specific process of post-TBI white matter remodeling. Here, we employed dense longitudinal neuroimaging to track white matter recovery weekly over six months after a TBI within a single patient and a control in a similar age group (21 vs. 24 y.o.). In the patient, but not in the control, DTI metrics precisely tracked parabolic trajectories across time, with early structural alterations continuing for more than 15 weeks before reversing direction. The extent of alteration in each tract was correlated with the time until reversal. These continuous DTI changes also mediated recovery of cognitive and emotional function, suggesting they are not passive markers of damage but dynamic processes underlying functional improvement. Complementary diffusion basis spectrum imaging (DBSI) revealed an initial phase of cellular loss followed by inflammatory remodeling, vascular adaptations, and persistent metabolic activity. Our findings indicate that recovery does not follow predefined phases but rather individualized transition points, which could define optimal windows for rehabilitation. Identifying these inflection points may enable personalized interventions aligned with biologically relevant structural shifts, rather than broad recovery periods.

neuroscience↗

bioRxiv2025

Proteomic profiling of zinc homeostasis mechanisms in Pseudomonas aeruginosa through data-dependent and data-independent acquisition mass spectrometry

Zinc is central to the function of many proteins, yet the mechanisms of zinc homeostasis and their interplay with other cellular systems remain underexplored. In this study, we employ data-dependent acquisition (DDA) and data-independent acquisition (DIA) mass spectrometry to investigate proteome changes in Pseudomonas aeruginosa under conditions of different zinc availability. Using these methods, we detected 2143 unique proteins, 1578 of which were identified by both DDA and DIA. We demonstrated that most of the previously described Zn homeostasis systems exhibit proteomic responses that follow similar trends to those seen in transcriptomics studies. However, some proteins that are considered instrumental in Zn homeostasis, notably those in Zn transporter ZnuABC, were not detected by our methods, although other proteins of other uptake systems were abundant. Furthermore, changes in abundance of multiple Zn-metalloproteins and Zn-independent homologs were clearly observable, with respective increases and decreases when Zn was provided, though the magnitude of these changes varied. Most of the Zn-metalloproteins observed were located in one of two Zur-regulated operons between PA5534 and PA5541. This study provides a view of Zn homeostasis mechanisms that is complementary to existing transcriptomics investigations: as gene transcripts are not strictly proportional to the actual distribution of proteins within a cell, analysis of the proteome offers another way to assess the relative use and importance of similar or ostensibly redundant systems in different conditions and can highlight shifts in metal prioritization between metalloproteins.

microbiology↗

bioRxiv2021

Activation of Adipocyte mTORC1 Increases Milk Lipids in a Mouse Model of Lactation

Human milk is the recommended nutrient source for newborns. The mammary gland comprises multiple cell types including epithelial cells and adipocytes. The contributions of mammary adipocytes to breast milk composition and the intersections between mammary nutrient sensing and milk lipids are not fully understood. A major nutrient sensor in most tissues is the mechanistic target of rapamycin 1 (mTORC1). To assess the role of excess nutrient sensing on mammary gland structure, function, milk composition, and offspring weights, we used an Adiponectin-Cre driven Tsc1 knockout model of adipocyte mTORC1 hyperactivation. Our results show that the knockout dams have higher milk fat contributing to higher milk caloric density and heavier offspring weight during lactation. Additionally, milk of knockout dams displayed a lower percentage of saturated fatty acids, higher percentage of monounsaturated fatty acids, and a lower milk {omega}6: {omega}3 ratio driven by increases in docosahexaenoic acid (DHA). Mammary gland gene expression analyses identified changes in eicosanoid metabolism, adaptive immune function, and contractile gene expression. Together, these results suggest a novel role of adipocyte mTORC1 in mammary gland function and morphology, milk composition, and offspring growth.

physiology↗

bioRxiv2021

A murine model of the human CREBRFR457Q obesity-risk variant does not influence energy or glucose homeostasis in response to nutritional stress

Obesity and diabetes have strong heritable components, yet the genetic contributions to these diseases remain largely unexplained. In humans, a missense variant in Creb3 regulatory factor (CREBRF) [rs373863828 (p.Arg457Gln); CREBRFR457Q] is strongly associated with increased odds of obesity but decreased odds of diabetes. Although virtually nothing is known about CREBRFs mechanism of action, emerging evidence implicates it in the adaptive transcriptional response to nutritional stress downstream of TORC1. The objectives of this study were to generate a murine model with knockin of the orthologous variant in mice (CREBRFR458Q) and to test the hypothesis that this CREBRF variant promotes obesity and protects against diabetes by regulating energy and glucose homeostasis downstream of TORC1. To test this hypothesis, we performed extensive phenotypic analysis of CREBRFR458Q knockin mice at baseline and in response to acute (fasting/refeeding), chronic (low- and high-fat diet feeding), and extreme (prolonged fasting) nutritional stress as well as with pharmacological TORC1 inhibition. The results demonstrate that the murine CREBRFR458Q model of the human CREBRFR457Q variant does not influence energy/glucose homeostasis in response to these interventions. Alternative preclinical models and/or studies in humans will be required to decipher the mechanisms linking this variant to human health and disease.

genetics↗