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Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr. Jan 2026

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …


Current And Emerging Therapeutic Strategies For The Treatment Of Duchenne Muscular Dystrophy, Miguel A. Lopez Perez, Noah L. Weisleder Jan 2026

Current And Emerging Therapeutic Strategies For The Treatment Of Duchenne Muscular Dystrophy, Miguel A. Lopez Perez, Noah L. Weisleder

Molecular and Cellular Biochemistry Faculty Publications

Background/Objectives: Duchenne muscular dystrophy (DMD) is a fatal, progressive neuromuscular disorder caused by mutations in the dystrophin gene, leading to the absence of functional dystrophin protein. As the largest gene in the human genome, the DMD locus is highly susceptible to mutations, contributing to a prevalence of approximately 1 in 3800–6300 live male births worldwide. This review aims to provide a comprehensive and critical synthesis of current and emerging therapeutic strategies for DMD.

Methods: We conducted a narrative review of the literature, integrating findings from clinical trials, regulatory approvals, and preclinical studies. We categorized therapeutic approaches into mutation-agnostic and mutation-specific …


Adipose Tissue-Derived Small Extracellular Vesicles In Plasma Reveal Molecular Circuitries Underlying Glucose Intolerance, Shalini Mishra, Yixin Su, Ashish Kumar, Sangeeta Singh, Brian S. Finlin, Fang-Chi Hsu, Jingyun Lee, Cristina M. Furdui, Philip A. Kern, Swapan K. Das, Gagan Deep Jan 2026

Adipose Tissue-Derived Small Extracellular Vesicles In Plasma Reveal Molecular Circuitries Underlying Glucose Intolerance, Shalini Mishra, Yixin Su, Ashish Kumar, Sangeeta Singh, Brian S. Finlin, Fang-Chi Hsu, Jingyun Lee, Cristina M. Furdui, Philip A. Kern, Swapan K. Das, Gagan Deep

Internal Medicine Faculty Publications

Objective: Glucose tolerance (GT) is a major effector for adipose tissue (AT) remodeling in obesity, yet its molecular mechanisms remain incompletely defined. We hypothesized that the biophysical and molecular profiles of AT-derived small extracellular vesicles (sEVAT) change in response to glucose availability and differ by GT status.

Methods: sEVAT were isolated from plasma of individuals with normal GT (NGT) and impaired GT (IGT) (n = 5/group) at fasting (0 h) and 1 h post glucose challenge during oral glucose tolerance test (OGTT). sEVAT were characterized for size, concentration, surface expression of insulin receptor-α (INSRα), proteome, …


Cultus: Eco-Phenomenology In The Work Of John Steinbeck, Robinson Jeffers, And Jack London, Carter D. Johnson Jan 2026

Cultus: Eco-Phenomenology In The Work Of John Steinbeck, Robinson Jeffers, And Jack London, Carter D. Johnson

Theses and Dissertations--English

In the face of increasingly dire environmental crises, proposed solutions have gravitated toward imperatives for faster, cleaner, and more efficient technologies and resources. While practical solutions are necessary, they are entirely insufficient to deal with an underlying issue driving environmental degradation: unbridled instrumental reason. In this dissertation, I suggest a theoretical posture, cultus, which attempts to balance the necessity of instrumental action with the guiding counterweight of receptivity. Furthermore, I argue that such personal receptivity is uniquely fostered in aesthetic experiences, attuning the individual to the non-identical and renewing a relationship of care.

I examine the life and work of …


A Collection Of Mussels: Ancestors, More-Than-Human Relations, And The Transformation Of Shell-Bearing Places In The Green River Valley, Kentucky, Karen A. Stevens Jan 2026

A Collection Of Mussels: Ancestors, More-Than-Human Relations, And The Transformation Of Shell-Bearing Places In The Green River Valley, Kentucky, Karen A. Stevens

Theses and Dissertations--Anthropology

For over a century, archaeological investigations in the Lower Ohio River Valley have provided extensive evidence of Indigenous Ancestors’ lifeways and practices. However, interpretations of shell-bearing sites have largely been shaped by Eurocentric and Western perspectives, often framing Indigenous actions as responses to environmental shifts rather than as expressions of dynamic social, spiritual, and ecological relationships. Within this historical context, explanations for the relatively abrupt decline of freshwater mollusk collection at the end of the Archaic Period (ca. 3000 cal yr BP) have primarily emphasized environmental change, particularly fluctuations in riverine conditions and resource availability. Yet, these explanations often overlook …


A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay Jan 2026

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …


Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart Jan 2026

Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone …


Promptable Segmentation For Adaptive And Data-Efficient Medical Image Analysis, Tyler Ward Jan 2026

Promptable Segmentation For Adaptive And Data-Efficient Medical Image Analysis, Tyler Ward

University of Kentucky Doctoral Dissertations

Image segmentation is a fundamental task in computer vision. While segmentation models have traditionally been trained in a fully-supervised manner, recent approaches have leveraged large-scale pre-training and prompting mechanisms to great effect. However, the performance of such approaches often degrades when applied to domain-specific tasks like medical image analysis. A major reason for this lies is that these models are trained on large, labeled datasets of natural images, which have drastically different characteristics compared to medical images, limiting the generalizability of the methods when applied to medical data. This dissertation presents several data-efficient, adaptive, and promptable medical image segmentation models. …


Association Of Serotonin And Ergot Alkaloids On Tissue Partitioning And Contractile Response Of Bovine Blood Vessels, Eriton E. L. Valente, David L. Harmon, John May, Huihua Ji, Ronald J. Trotta, James L. Klotz Jan 2026

Association Of Serotonin And Ergot Alkaloids On Tissue Partitioning And Contractile Response Of Bovine Blood Vessels, Eriton E. L. Valente, David L. Harmon, John May, Huihua Ji, Ronald J. Trotta, James L. Klotz

Animal and Food Sciences Faculty Publications

Ergot alkaloids can bind serotonin (5-HT) receptors interfering with many physiological functions. However, the mechanism has not been completely established. The objective was to evaluate whether the association of 5-HT and the ergot alkaloid, ergovaline, in a 24-h pre-incubation can affect vascular tissue partitioning and contractile responses. Cross-sections of saphenous veins from five steers were used. In the tissue partitioning experiment, the treatments were the combination of three levels of ergovaline (2.01 × 10−8 M, 2.01 × 10−7 M and 2.01 × 10−6 M) with three levels of 5-HT and a control (5 × 10−8 M, …


Abca12 Frameshift Deletion In Domestic Cats With Ichthyosis Fetalis, Jeanna M. Blake, Melissa P. Swan, Kari J. Ekenstedt Jan 2026

Abca12 Frameshift Deletion In Domestic Cats With Ichthyosis Fetalis, Jeanna M. Blake, Melissa P. Swan, Kari J. Ekenstedt

Veterinary Science Faculty Publications

Background: Ichthyosis fetalis (IF), also known as harlequin ichthyosis, is a rare and often fatal autosomal recessive congenital skin disorder. It is characterized by thickened, hard skin plaques and deep skin fissures that limit mobility and cause malformations of the eyes, lips and ears. Affected individuals are highly susceptible to life-threatening infections due to the disruption of the skin's protective barrier. To date, IF and its genetic basis have not been described in domestic cats.

Objectives: To characterize the gross clinical, histopathological and genetic features of IF in two stray, random-bred domestic short-hair (DSH) littermates.

Animals: Two deceased female neonatal …


Elevated Temperatures Disrupt Wolbachia-Induced Feminisation And Reshape Microbial Community Dynamics Across Generations In A Spider Host, Virginija Mackevicius-Dubickaja, Jennifer A. White, Ellen E. Williams, Eyal Klement, Yuval Gottlieb, Matthew R. Doremus Jan 2026

Elevated Temperatures Disrupt Wolbachia-Induced Feminisation And Reshape Microbial Community Dynamics Across Generations In A Spider Host, Virginija Mackevicius-Dubickaja, Jennifer A. White, Ellen E. Williams, Eyal Klement, Yuval Gottlieb, Matthew R. Doremus

Entomology Faculty Publications

Longitudinal microbial interactions within a host are challenging to study, leading to a focus on constructed microbial communities in vitro settings. Here, we take advantage of a naturally defined microbial community within a spider host to study how elevated temperatures influence microbial dynamics and phenotypes across host generations. The spider Mermessus fradeorum hosts up to five endosymbionts, including a Wolbachia strain, W1, which induces feminisation, causing genetic males to develop as phenotypic females, skewing sex ratios and promoting symbiont spread. Despite this, Wolbachia 1 persists at intermediate frequencies in wild populations. We hypothesised that elevated temperatures might reduce penetration of …


Evolutionary Transitions In Social Behavior Are Associated With Convergent And Partially Reversible Expansions Of Transcription Factor Binding Sites, Savanna G. Ploessl, Beryl M. Jones Jan 2026

Evolutionary Transitions In Social Behavior Are Associated With Convergent And Partially Reversible Expansions Of Transcription Factor Binding Sites, Savanna G. Ploessl, Beryl M. Jones

Entomology Faculty Publications

The evolution of sociality involves shifts in physiology and behavior, most notably the emergence of a reproductive division of labor. Within social colonies, these distinct behavioral phenotypes arise from differential regulation of a shared genome. Changes in transcription factor (TF) binding motifs are one potential mechanism underpinning this plasticity, with prior studies suggesting that social species exhibit expansions in TF binding sites. However, it remains unclear whether motif expansions are reversed when sociality is lost. Here we analyze predicted TF motif occurrences across gene promoters in 42 bee species spanning millions of years of evolutionary divergence and multiple independent gains …


Variability In Mountain Pine Beetle (Coleoptera: Curculionidae) Gene Expression In Response To Increasing Concentrations Of Species-Specific Double-Stranded Rna, Kylie J. Bickler, Zachary Bragg, Flávia Pampolini, Bethany R. Kyre, Lynne K. Rieske Jan 2026

Variability In Mountain Pine Beetle (Coleoptera: Curculionidae) Gene Expression In Response To Increasing Concentrations Of Species-Specific Double-Stranded Rna, Kylie J. Bickler, Zachary Bragg, Flávia Pampolini, Bethany R. Kyre, Lynne K. Rieske

Entomology Faculty Publications

Sensitivity to double-stranded RNA (dsRNA)-induced gene silencing has been observed in multiple coleopterans. Initial work with mountain pine beetle, Dendroctonus ponderosae Hopkins, determined that specific ubiquitously expressed essential genes can cause mortality when silenced by carefully designed dsRNAs. However, current dsRNA production methods are not economically feasible for production at scale. Therefore, identifying the minimum efficacious dose is a critical step to deployment. To investigate the relationship between dsRNA dose and subsequent gene expression, adult mountain pine beetles were fed either a target or control dsRNA across a gradient of concentrations, including 2.5, 1.0, 0.25, and 0.025µg/µl, and relative gene …


Anuran Occupancy Of Created Wetlands Within Reforested Legacy Surface Mines In Kentucky And West Virginia, Jillian C. Newman, Steve Price, Jacquelyn C. Guzy, Joshua Castle, John J. Cox, Jeffery L. Larkin, Christopher D. Barton Jan 2026

Anuran Occupancy Of Created Wetlands Within Reforested Legacy Surface Mines In Kentucky And West Virginia, Jillian C. Newman, Steve Price, Jacquelyn C. Guzy, Joshua Castle, John J. Cox, Jeffery L. Larkin, Christopher D. Barton

Forestry and Natural Resources Faculty Publications

Restoration of habitat is an important component of wildlife management. Surface coal mining has altered forest cover in the Central Appalachians, and most reclamation activities on previously mined lands result in non-native grasslands or shrub lands. The Forestry Reclamation Approach (FRA), which emphasizes non-native vegetation removal, soil decompaction, planting of native trees and shrubs, and, in some cases, wetland creation represents an alternative to grassland-based reclamation that may promote forest-associated wildlife on legacy surface mines. We used automated recording units to evaluate the response of anurans to created wetlands and the FRA in Kentucky and West Virginia, USA. We used …


Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt Jan 2026

Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt

Theses and Dissertations--Physiology

APOE exists as three common alleles (APOE2, APOE3, APOE4) that encode their corresponding protein isoforms (apoE2, apoE3, apoE4). Despite differing by only one or two single-amino acid substitutions, each APOE allele confers a distinct AD risk profile with APOE4 increasing risk by 28% and APOE2 decreasing risk by 14% compared to the most commonly expressed APOE3 allele. While traditionally considered “neutral,” APOE3 still accounts for ~36% of AD cases while APOE4 contributes ~57%, indicating that the majority of AD cases would not occur in the absence of the APOE3 and APOE4 alleles. Microglia, the resident phagocytic immune cells …


Fiber-Reinforced Composites For Vaginal Tissue Engineering Applications, Samyuktha S. Kolluru, Abir Hamdaoui, Annabella M. Mascot, Siobhan S. Sutcliffe, Jerry L. Lowder, Michelle L. Oyen, Samantha G. Zambuto Jan 2026

Fiber-Reinforced Composites For Vaginal Tissue Engineering Applications, Samyuktha S. Kolluru, Abir Hamdaoui, Annabella M. Mascot, Siobhan S. Sutcliffe, Jerry L. Lowder, Michelle L. Oyen, Samantha G. Zambuto

Mechanical Engineering Faculty Publications

The vagina is a fibromuscular tube-shaped organ that plays critical roles in menstruation, pregnancy, and female sexual health. Vaginal tissue constituents, including cells and extracellular matrix components, contribute to tissue structure, function, and prevention of injury and pathology. However, much microstructural function remains unknown, including how the fiber-cell and cell–cell interactions influence macromechanical properties. A deeper understanding of these interactions will provide critical information needed to reduce and prevent vaginal pathologies. Our objective for this work is to design a novel tissue-mimicking biomaterial for vaginal tissue engineering, and characterize its biological and mechanical performance in the vaginal microenvironment. We successfully …


Evolution Of A Client‐Level Dataset: 20 Years Of National Child Traumatic Stress Network Data Collection, C. A. Purbeck, A. N. Cooke, L. J. Liang, C. Smith, J. Staten, J. Epstein, H. B. Hodgdon, Jessica Eslinger, A. Wells, J. Goodrich, T. H. Bethel, K. Willett, Y. C. Fu, J. A. Fairbank, E. C. Briggs Jan 2026

Evolution Of A Client‐Level Dataset: 20 Years Of National Child Traumatic Stress Network Data Collection, C. A. Purbeck, A. N. Cooke, L. J. Liang, C. Smith, J. Staten, J. Epstein, H. B. Hodgdon, Jessica Eslinger, A. Wells, J. Goodrich, T. H. Bethel, K. Willett, Y. C. Fu, J. A. Fairbank, E. C. Briggs

Center on Trauma and Children Faculty Publications

Objectives: For 20 years, the National Child Traumatic Stress Network's (NCTSN) data collection efforts have been a central mechanism for Clinical Quality Improvement (ClQI). The NCTSN is a federally funded initiative in the United States composed of programs dedicated to raising the standard of care and increasing access to services for children and families who have experienced traumatic events.

Methods: These efforts span three initiatives: the Core Data Set (CDS), the Clinical Improvement through Measurement Initiative (CIMI) Measurement Based Care (MBC), and CIMI Data Sharing (CIMI-DS) that collected and analyzed client-level data to improve care for children and families served …


A Method For Beginners Volume 1: The Intersection Of The Yaqui Tribe And Guitar Pedagogy, Daniel Preciado Arreola Jan 2026

A Method For Beginners Volume 1: The Intersection Of The Yaqui Tribe And Guitar Pedagogy, Daniel Preciado Arreola

Theses and Dissertations--Music

This dissertation is divided into four chapters. The first is an introduction explaining the project; the second describes the Yaqui Tribe's background, significance, and musical traditions, primarily based on three sources: the thesis Sones de Pascola by Cristian Salvador Islas Miranda, the biographical book El Viaje de Mechabili by Daniel Librado Luna, and the album Juya Ánia. The third chapter details the methodological framework and development process used to construct the guitar method presented in Chapter 4. This fourth chapter consists of the first volume of an ongoing multi-volume guitar method—authored by me—focused largely on the melodies from the aforementioned …


Cantate Fratres: Forming And Sustaining Traditional Catholic Music, Liturgy And Culture In The Institute Of Christ The King Sovereign Priest, Reyers P. Brusoe Jan 2026

Cantate Fratres: Forming And Sustaining Traditional Catholic Music, Liturgy And Culture In The Institute Of Christ The King Sovereign Priest, Reyers P. Brusoe

Theses and Dissertations--Music

The Institute of Christ the King Sovereign Priest is an understudied member of the Traditional Catholic and Latin Mass Communities whose unique approach to Catholic liturgy, culture, and formation offers a sustainable model for the Catholic Church's longevity and renewal. This study is the first of its kind, combining the theoretical positions of affect theory, ecomusicology/musical sustainability, and the musicology of religion to explore and explain the success of this growing classical community. This dissertation examines Church documents, theological literature, and multidisciplinary academic sources as a foundation for the study.             In studying the Institute of Christ the King Sovereign Priest, …


Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek Jan 2026

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …


Red Clover Isoflavones And Establishment In The Context Of Tall Fescue Toxicosis Mitigation In The Mid-South, Jonathan L. Stephens Jan 2026

Red Clover Isoflavones And Establishment In The Context Of Tall Fescue Toxicosis Mitigation In The Mid-South, Jonathan L. Stephens

Theses and Dissertations--Plant and Soil Sciences

Low levels of red clover (Trifolium pratense L.) have been shown to mitigate tall fescue (Lolium arundinaceum (Schreb.) toxicosis symptoms. This is because of the presence of plant-produced compounds known as isoflavones. Production of a red clover supplement on a commercial scale would require industrial-level processing of raw plant material into granules or pellets. The first study of this thesis evaluated the impact of drying temperature on bioavailability of isoflavones. Drying temperatures up to 104°C had minimal impact on isoflavone concentrations. Additionally, varietal differences in isoflavone concentrations were documented. The second study of this thesis evaluated optimal establishment …


C/Ebpα Is Essential For Gonadal But Not Inguinal White Adipose Tissue Formation In Mice, Krista Y. Hu, Yu-Lin Ma, Esme A. Dodge, Olivia A. B. Maguire, Caio V. Matias, Ryan K. Barney, Hector S. Himede, Juliana Gomez Pardo, Miriam Cepeda, Scott M. Gordon, Robert C. Bauer Jan 2026

C/Ebpα Is Essential For Gonadal But Not Inguinal White Adipose Tissue Formation In Mice, Krista Y. Hu, Yu-Lin Ma, Esme A. Dodge, Olivia A. B. Maguire, Caio V. Matias, Ryan K. Barney, Hector S. Himede, Juliana Gomez Pardo, Miriam Cepeda, Scott M. Gordon, Robert C. Bauer

Physiology Faculty Publications

Objective: The distribution of excess white adipose tissue (WAT) in obesity correlates with risk for comorbidities. Thus, understanding depot-specific WAT developmental mechanisms is translationally relevant. SNPs near the gene CEBPA associate with waist to hip ratio, and while C/EBPα is a recognized regulator of adipogenesis, there is no previously known role for C/EBPα in regulating adipose distribution.

Methods: We crossed Cebpa floxed mice to the AdipoQ-Cre transgenic mouse strain, generating mice with adipocyte-specific knockout of Cebpa (Cebpa_ASKO). Mice were phenotyped on a chow diet and after prolonged high-fat diet (HFD) feeding.

Results: Cebpa_ASKO mice almost entirely lack gonadal …


Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle Jan 2026

Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle

Physiology Faculty Publications

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. CAN is characterized by impaired cardiovascular autonomic control and is associated with increased mortality, especially among women with type 2 diabetes. Identifying environmental factors that exacerbate the CAN-associated phenotype may reveal modifiable strategies to reduce cardiovascular risk.

Nighttime light exposure is a novel cardiovascular risk factor. Among ∼90,000 individuals, greater nighttime light exposure correlated with increased atrial fibrillation and heart failure risk. Light at night disrupts sympathovagal balance and elevates nocturnal heart rate in humans. Dim light at night similarly disrupts autonomic regulation of heart rate in mice. We …


Early Microglial Response To Amyloid Plaques Drives Sleep Loss In Alzheimer’S Disease, Nicholas J. Constantino, Riley E. Irmen, Matthew J. Lanning, Sierra M. Turner, Clair C. Ashley, Caitlin M. Carroll, Evan M. Neary, Dave Rubinow, J. Andy Snipes, Shannon L. Macauley Jan 2026

Early Microglial Response To Amyloid Plaques Drives Sleep Loss In Alzheimer’S Disease, Nicholas J. Constantino, Riley E. Irmen, Matthew J. Lanning, Sierra M. Turner, Clair C. Ashley, Caitlin M. Carroll, Evan M. Neary, Dave Rubinow, J. Andy Snipes, Shannon L. Macauley

Physiology Faculty Publications

Introduction: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear.

Methods: Electroencephalography/electromyography (EEG/EMG) recordings, quantitative EEG analysis, and sleep deprivation were performed in APPswe/PSEN1dE9 (APP/PS1) mice at different stages of pathology relative to normal aging. Amyloid burden and microglial density were quantified with whole-brain light-sheet microscopy. CSF1R-mediated microglial depletion explored effects of microglia on sleep loss.

Results: Amyloid plaques caused non–rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with …


Pediatric Chop Chemotherapy Acutely Disrupts Satellite-Cell Dynamics And Blunts Muscle Mass In A Sex-Specific Manner, Jainil Daredia, Marc A. Magaña, Carla M.C. Nascimento, Jaden M. Wells, Nicholas T. Thomas, Yuan Wen, Savannah V. Rauschendorfer, Cory M. Dungan, Michael P. Wiggs Jan 2026

Pediatric Chop Chemotherapy Acutely Disrupts Satellite-Cell Dynamics And Blunts Muscle Mass In A Sex-Specific Manner, Jainil Daredia, Marc A. Magaña, Carla M.C. Nascimento, Jaden M. Wells, Nicholas T. Thomas, Yuan Wen, Savannah V. Rauschendorfer, Cory M. Dungan, Michael P. Wiggs

Physiology Faculty Publications

Pediatric cancer survival now exceeds 85% owing, in part, to advances and the use of combination chemotherapy treatments such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Despite its efficacy, CHOP may cause off-target effects during critical pediatric development periods such as impairments of skeletal muscle. We evaluated the acute effects of a CHOP administered to C57Bl/6J mice from postnatal day 28 to 48. CHOP slowed body-weight gain and led to a smaller gastrocnemius fiber cross-sectional area by ~25% in both sexes (n ¼ 11 or 12 males; n ¼ 8 or 9 females). RNA sequencing detected 214 differentially expressed genes …


Skeletal Muscle Methylome-Transcriptome Disruptions During The Onset And Progression Of Colorectal Cancer-Induced Cachexia, Ana Regina Cabrera, Ronald G. Jones, Eleanor R. Shrems, Francielly Morena, Yuan Wen, Tyrone A. Washington, Kevin A. Murach, Nicholas P. Greene Jan 2026

Skeletal Muscle Methylome-Transcriptome Disruptions During The Onset And Progression Of Colorectal Cancer-Induced Cachexia, Ana Regina Cabrera, Ronald G. Jones, Eleanor R. Shrems, Francielly Morena, Yuan Wen, Tyrone A. Washington, Kevin A. Murach, Nicholas P. Greene

Physiology Faculty Publications

Cancer cachexia is a wasting condition, primarily affecting skeletal muscle, impairing patients’ quality of life, prognosis, and survival. The molecular triggers are incompletely defined, but given prior evidence for epigenetic plasticity in muscle, we speculate that dysregulated DNA methylation plays a role in muscle transcriptional alterations mediating cachexia severity. We aimed to describe and integrate the cachexia methylome and transcriptome. We used a time course approach in a mild cachexia model (colon-26, C26) coupled with a severe cachexia genetic model (ApcMin/+) in both biological sexes to assess the methylome across degrees of cachexia pathology. The muscle methylome and …


Cytoprotective Role Of Octacosanol In Lipopolysaccharide-Induced Inflammation, Jingrong Tang, Zhi Hong Yang, Wenling Li, Huaitian Liu, Diego Lucero, Denis Sviridov, Olivia White, Julia Kun, Yoh Suke Mukouyama, Alan T. Remaley Jan 2026

Cytoprotective Role Of Octacosanol In Lipopolysaccharide-Induced Inflammation, Jingrong Tang, Zhi Hong Yang, Wenling Li, Huaitian Liu, Diego Lucero, Denis Sviridov, Olivia White, Julia Kun, Yoh Suke Mukouyama, Alan T. Remaley

Physiology Faculty Publications

Inflammation and endothelial dysfunction are key steps in the pathogenesis of atherosclerosis. Octacosanol (C28H58O, OCT), a very-long-chain saturated aliphatic alcohol (VLCA) with 28 carbons, is the main component of policosanol, a nutraceutical mixture of VLCAs (C20-C34) extracted from plants. Polycosanol in animal models is known to reduce atherosclerosis, but its mechanism of action remains unclear. This study investigates the pathways by which OCT alleviates LPS-induced inflammation in primary human aortic endothelial cells (HAECs). After overnight pretreatment with purified OCT, inflammation in HAECs was induced by lipopolysaccharide (LPS) at 100 ng/ml. The effects of OCT on the …


Hyperacute Interleukin-1Β Production And Neutrophil Extracellular Trap Formation In The Cerebral Circulation Of Stroke Patients With Large Vessel Occlusion, Justine Münsterberg, Caspar Brekenfeld, Hanna Englert, Marius Piepke, Regine J. Dress, Martin Oertel, Tina Fischer, Romy Hackbusch, Mingming Zha, Haodi Cai, Christian Casar, Ines S. Schädlich, Leo Winter, Alina Jander, Karoline Degenhardt, Maxim Bester, Fabian Flottmann, Uta Hanning, Brigitte Holst, Anna Worthman, Johanna Hiefner, Berenike Rutz, Eckhard Schlemm, Götz Thomalla, Bettina H. Clausen, Ann M. Stowe, Immo Prinz, Thiruma V. Arumugam, Markus Glatzel, Thomas Renné, Jens Fiehler, Eva Tolosa Jan 2026

Hyperacute Interleukin-1Β Production And Neutrophil Extracellular Trap Formation In The Cerebral Circulation Of Stroke Patients With Large Vessel Occlusion, Justine Münsterberg, Caspar Brekenfeld, Hanna Englert, Marius Piepke, Regine J. Dress, Martin Oertel, Tina Fischer, Romy Hackbusch, Mingming Zha, Haodi Cai, Christian Casar, Ines S. Schädlich, Leo Winter, Alina Jander, Karoline Degenhardt, Maxim Bester, Fabian Flottmann, Uta Hanning, Brigitte Holst, Anna Worthman, Johanna Hiefner, Berenike Rutz, Eckhard Schlemm, Götz Thomalla, Bettina H. Clausen, Ann M. Stowe, Immo Prinz, Thiruma V. Arumugam, Markus Glatzel, Thomas Renné, Jens Fiehler, Eva Tolosa

Neurology Faculty Publications

Objective: Cerebral ischemia remains a major cause of disability, and the contribution of the hyperacute immune response is increasingly recognized. The aim of this study was to investigate the local inflammatory response in the affected brain of stroke patients with large vessel occlusion during the hyperacute phase of stroke. Methods: To decipher the role of myeloid immune cells in stroke-induced inflammation, we performed an unsupervised multiomics analysis of innate immune pathways in ischemic blood obtained directly from the occluded middle cerebral artery in 54 patients undergoing mechanical recanalization. Paired nonischemic arterial blood served as an internal control. Results: Stroke triggered …


Climate Change Effects On Biomass And Greenhouse Gas Emissions Are Ameliorated By Nontoxic Endophytes In Southeastern Usa Transition Zone Tall Fescue Pastures, Rebecca Kay Mcgrail, Jonathan D. Moore, A. Elizabeth Carlisle, Jim A. Nelson, Rebecca L. Mcculley Jan 2026

Climate Change Effects On Biomass And Greenhouse Gas Emissions Are Ameliorated By Nontoxic Endophytes In Southeastern Usa Transition Zone Tall Fescue Pastures, Rebecca Kay Mcgrail, Jonathan D. Moore, A. Elizabeth Carlisle, Jim A. Nelson, Rebecca L. Mcculley

Plant and Soil Sciences Faculty Publications

Background: The plant–microbe interaction between tall fescue and its endophyte Epichloë coenophiala can affect ecosystem responses to changing rainfall patterns and increasing temperatures. Endophyte-infected (E+) stands often exhibit improved stress tolerance and differing soil greenhouse gas (GHG) emissions compared to endophyte-free (E−) stands. However, it is unknown if mammalian nontoxic endophyte (NTE) strains introduced into some tall fescue cultivars confer differing stress tolerances or reduce soil GHG emissions.

Methods: We quantified the impact of fescue-NTE symbioses in Jesup and Texoma on biomass and GHG emissions in response to increased temperature (+3°C) and altered precipitation (50% lengthened interval between events) using …


Separation Of Trichothecene Mycotoxins In A Matrix Of Hemp (Cannabis Sativa L.) Seed, And Quantification Of Deoxynivalenol In Hemp Grain Infected With Fusarium Graminearum, Isabelle A. Kagan, Magdalena Ricciardi, Henry S. Smith, Rachel R. Schendel, Robert Pearce, Nicole Gauthier Jan 2026

Separation Of Trichothecene Mycotoxins In A Matrix Of Hemp (Cannabis Sativa L.) Seed, And Quantification Of Deoxynivalenol In Hemp Grain Infected With Fusarium Graminearum, Isabelle A. Kagan, Magdalena Ricciardi, Henry S. Smith, Rachel R. Schendel, Robert Pearce, Nicole Gauthier

Plant and Soil Sciences Faculty Publications

Background: Fusarium graminearum, one of the causal agents of ear rot in maize and head blight of cereal grains, also infects hemp (Cannabis sativa L. containing a maximum of 0.3% tetrahydrocannabinol or THC). This fungal pathogen produces trichothecene mycotoxins when it infects maize and cereal grains, but little is known about its production of mycotoxins in hemp. A method was developed to separate mycotoxins deoxynivalenol (DON), 15-acetyldeoxynivalenol (15-ADON), and 3-acetyldeoxynivalenol (3-ADON) in commercial hemp seed and grain (harvested tissue), using high-performance liquid chromatography (HPLC) with ultraviolet detection. Results: In HPLC analysis of commercial hemp seed, DON was separated from matrix …