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Current Concepts In Hip And Core Assessment To Reduce The Risk Of Acl Injury, Jeremy M. Burnham, Anthony T. Drazick, Ghislain Aminake, Darren L. Johnson, Mary Lloyd Ireland, Brian W. Noehren

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: Hip and trunk (“core”) muscle dysfunction has emerged as a modifiable contributor to lower-limb biomechanics linked with non-contact anterior cruciate ligament (ACL) injuries. Clinicians increasingly target core stability and control during injury-prevention screening and post-operative rehabilitation programs; however, the literature lacks a focused synthesis of core-directed strategies for ACL injury mitigation. The purpose of this current concepts review is to synthesize current evidence on hip- and core-focused assessment and rehabilitation strategies that may mitigate ACL injury risk.

Design: Current Concepts Review.

Methods: A narrative search of PubMed and Google Scholar (January 2000 – April 2025) identified biomechanical, prospective, interventional, …

Candidate Interaction Partners Of Calpain-5 Suggest Clues To Its Involvement In Neovascular Inflammatory Vitreoretinopathy, Jozsef Gal, Vimala Bondada, Rachel Crasta, Dorothy E. Croall, Calvin P. Vary, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

Although calpain-5/CAPN5 is widely expressed in mammals, little is known regarding its functions. Pathogenic mutations of CAPN5 are causal for a devastating autoimmune eye disease, neovascular inflammatory vitreoretinopathy (NIV). To provide insight into both the physiological and pathological roles of CAPN5, it is essential to identify candidate interaction partners and possible substrates. Human SH-SY5Y neuroblastoma cells, transfected with full-length catalytically dead (Cys81Ala) CAPN5-3×FLAG, were used for anti-FLAG co-immunoprecipitation (co-IP) and quantitative proteomics using Sequential Window Acquisition of all THeoretical mass spectra (SWATH-MS). Fifty-one proteins were enriched at least four-fold, p < 0.01, relative to cells transfected with an empty FLAG vector. A high proportion (24/51) of candidate CAPN5 interaction partners are associated with protein quality control, including components of the chaperonin, chaperone, and ubiquitin–proteasome systems. Additional candidate interactors include tubulins, kinases, phosphatases, G proteins, and mitochondrial proteins. CAPN5 interactions for 14 of the candidate proteins were confirmed by co-IP and immunoblotting. Of these 14 proteins, 11 exhibited in vitro calcium-induced proteolysis following co-IP with WT CAPN5-3×FLAG. Impaired calcium-induced proteolysis of co-IP proteins was observed for the pathogenic CAPN5 variants R243L and R289W. Further studies are needed to validate the association of candidate CAPN5 interactors with proteins and complexes suggested by the SWATH-MS and co-IP results, and the possible role of CAPN5 within such complexes. The possible involvement of CAPN5 in protein quality control is relevant to NIV, as defects in protein quality control have been implicated in inherited retinal disorders. Proteomic data are available via ProteomeXchange with identifier PXD068008.

Difficult-To-Treat Rheumatoid Arthritis With Concomitant Yao Syndrome With Response To Dual-Inhibitor Therapy, Nawar Aljundi, Paramarajan Piranavan

Internal Medicine Faculty Publications

No abstract provided.

An Unbiased Molecular Characterization Of Peripartum Cardiomyopathy Hearts Identifies Mast Cell Chymase As A New Diagnostic Candidate, J. F. Mulvey, C. Sailer, J. S. Achter, Gregory Nathaniel Milburn, R. C. Bretherton, K. Kahnert, S. Erbil Bilir, H. Hvid, C. Pyke, F. Gustafsson, L. Adamo, Kenneth S. Campbell, K. M. Herum, A. Lundby

Internal Medicine Faculty Publications

Peripartum cardiomyopathy (PPCM) is a rare form of acute heart failure that develops in women toward the end of pregnancy or early postpartum. No effective, specific treatment for PPCM is available and heart transplantation or mechanical circulatory support may be required in severe cases where drug treatment for heart failure is insufficient. The mechanisms through which the disease progresses are not well understood, and despite similar clinical characteristics to dilated cardiomyopathy of other etiologies (nonperipartum cardiomyopathy; NPCM) it is not known how the molecular remodeling differs between these groups. We aimed to provide insight into the human PPCM heart using …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

Social Engagement Moderates The Relationship Between Cognitive Functioning, Depressive Symptoms, And Restless Sleep In Older Black Adults, Sunkanmi Folorunsho, Olufunmilola Abraham, Darlingtina K. Esiaka

Pharmacy Practice and Science Faculty Publications

INTRODUCTION: Older Black adults face higher dementia risk, but it is unclear whether social engagement offsets the effects of depression and restless sleep.

METHODS: We analyzed 1,905 Black adults aged 50+ from the 2016-2020 Health and Retirement Study (HRS). Linear mixed-effects models tested how depressive symptoms, restless sleep, and social engagement predicted baseline cognition and cognitive decline.

RESULTS: Higher depressive symptoms and restless sleep were associated with lower baseline cognition (about 0.2 and 0.5 points lower) and faster decline (β×time ≈ −0.07 and −0.05). Greater social engagement predicted higher baseline cognition (about 0.6 points higher) and slower decline (β×time ≈ …

Dino-Lg: Enhancing Vision Transformers With Label Guidance For Coronary Artery Calcium Detection, Mahmut Selman Gokmen, Caner Ozcan, Moneera N. Haque, Steve W. Leung, Seth Parker, Brent Seales, Cody Bumgardner

Biomedical Engineering Faculty Publications

Coronary artery disease (CAD), one of the leading causes of mortality worldwide, necessitates effective risk assessment strategies, with coronary artery calcium (CAC) scoring via computed tomography (CT) being a key method for prevention. Traditional methods, primarily based on UNET architectures implemented on pre-built models, face challenges like the scarcity of annotated CT scans containing CAC and imbalanced datasets, leading to reduced performance in segmentation and scoring tasks. In this study, we address these limitations by introducing DINO-LG, a novel label-guided extension of DINO (self-distillation with no labels) that incorporates targeted augmentation on annotated calcified regions during self-supervised pre-training. Our three-stage …

Validity And Reliability Of Force Insoles To Measure Center Of Pressure During Return-To-Sport Testing, Delaney Mcneese, Charles Eisner, Rachel Todd, Brian W. Noehren, Meredith K. Owen

Biomedical Engineering Faculty Publications

Center of pressure is a valuable biomechanical variable, predicting joint loading contributions during movement and giving insight into compensatory patterns. The purpose of this study was to assess the validity and reliability of force insoles in calculating vertical ground reaction force and center of pressure during return-to-sport jump testing. Ten healthy individuals performed double- and single-leg vertical and horizontal jumps on an instrumented treadmill while wearing instrumented force insoles. Vertical ground reaction force and anterior–posterior and medial–lateral center of pressure were collected at peak vertical ground reaction force from both devices. Repeat testing occurred 7 ± 5 days following the …

Non-Contact Optical Spectroscopy For Metabolic And Vascular Characterizations Of Orthotopic Tongue Cancer Models In Vivo, Md Zahid Hasan, Jing Yan, Sumit Sarker, Pranto Soumik Saha, Caigang Zhu

Biomedical Engineering Faculty Publications

Most tissue optical spectroscopy platforms use a fiber probe for light delivery and collection, while the inconsistent probe-sample contact could induce significant distortions in the measured optical signals, which consequently bring analysis errors. Moreover, it will be practically difficult to use a fiber probe for measurements in some cases such as oral cancer investigations using small animal models. To address the critical challenge, we report a portable, lens-based, optical spectroscopy device capable of quantifying key vascular and metabolic parameters in vivo without probe-sample contact. We combined lenses based diffuse reflectance and fluorescence spectroscopy into one portable platform to enable multi-parametric …

Combined Autofluorescence And Diffuse Reflectance Spectroscopy For Rapid Metabolic And Vascular Characterizations Of Orthotopic Tongue Tumors In Vivo, Pranto Soumik Saha, Jing Yan, Sumit Sarker, Zahid Hasan, Caigang Zhu

Biomedical Engineering Faculty Publications

Precise label-free quantification of tissue metabolic and vascular dynamics in vivo represents a critical challenge for cancer therapy prediction and longitudinal treatment assessment. In this study, we demonstrated a portable autofluorescence and diffuse reflectance spectroscopy device along with novel spectroscopic algorithms to quantify tissue vascular and metabolic parameters of orthotopic head and neck cancer models in vivo. Tissue-mimicking phantom studies were used to verify the dual-modal optical spectroscopy and easy-to-use spectroscopic algorithms for rapid and accurate estimation of tissue oxygen saturation, total hemoglobin contents, and intrinsic optical redox ratio. Animal studies were conducted to demonstrate the feasibility of our …

Noninvasive Diffuse Optical Monitoring Of Cerebral Blood Flow And Oxygenation Responses To Intermittent Hypoxia In Neonatal Rats, Pegah Safavi, Mehrana Mohtasebi, Chowdhury Azimul Haque, Faezeh Akbari, Xuhui Liu, Yiqi Yuan, Li Chen, Lei Chen, Guoqiang Yu

Biomedical Engineering Faculty Publications

Significance: Intermittent hypoxia (IH) is common in preterm neonates and can cause hypoxic–ischemic brain injury. Simultaneous monitoring of cerebral blood flow (CBF) and oxygenation is essential to detect oxygen delivery-extraction mismatches and guide intervention.

Aim: We aimed to adapt and test an innovative diffuse speckle contrast flow oximetry (DSCFO) system for continuous monitoring of cerebral hemodynamics during IH in neonatal rats, a model approximating human neonates.

Approach: Two compact laser diodes and a miniature CMOS camera were integrated into a fiber-free probe for continuous monitoring of changes in relative CBF (rCBF) and oxy- and deoxy-hemoglobin concentrations (Δ[HbO₂] and …

Comparative Evaluation Of R134a And Hfo‐1234ze Cryogen Spray Cooling Using A Mouse Model With Controllable Epidermal Pigmentation, Wangcun Jia, Yurie Jeong, Crystal Huynh, Oswald Lai, Emily Nguyen, Grant Swajian, Jade Niu, Ayana Kashikar, Joshua Khaw, Hong Pu, Bernard Choi, John August D'Orazio, J. Stuart Nelson, Bahman Anvari

Pediatrics Faculty Publications

Objectives: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance.

Methods: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1r^e/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold …

Metabolomics Driven Discovery Of Bioactive Natural Products Leads From Marine And Terrestrial Sources For The Development Of Analgesics, Sahar Mofidi Tabatabaei

University of Kentucky Doctoral Dissertations

Natural products remain a rich source of structurally diverse bioactive compounds for drug discovery, particularly for pain therapeutics. However, the chemical complexity of natural product extracts presents significant challenges for the efficient identification and prioritization of bioactive metabolites. This dissertation integrates untargeted LC-MS/MS-based metabolomics, molecular networking, classical natural products chemistry, and neurobiological assays to accelerate the discovery of analgesic lead compounds targeting the emerging pain-associated receptor σ₂R/TMEM97.

An untargeted metabolomics workflow was developed to systematically profile complex biological extracts and guide bioactive compound isolation. High-resolution LC-MS/MS data were analyzed using molecular networking (GNPS/GNPS2) to visualize chemical space, dereplicate known metabolites, …

Discovering Naturally Occurring Antifreeze Peptides From Microbiome By Integrating Protein Language Models And Molecular Dynamics Simulation, Ibrahim A. Imam, Trevor Morey, Yuexu Jiang, Duolin Wang, Dong Xu, Qing Shao

Chemical and Materials Engineering Faculty Publications

Antifreeze peptides inhibit ice crystal growth and recrystallization, and are promising components of cryoprotective formulations for cell, tissue, and food preservation, as well as anti-icing surface coatings. However, the discovery of new antifreeze peptides has been hindered by their sequence diversity and the limited scalability of experimental screening. In this study, we identify novel antifreeze peptide candidates from a microbiome-derived sequence library using ensemble machine learning and molecular dynamics (MD) simulations. We developed an ensemble classifier composed of 10 adapter-tuned protein-language models and a random forest meta-learner. After training on a curated dataset of 73 766 sequences, we applied this …

Functionalization Of Microfiltration Media Towards Catalytic Hydrogenation Of Selected Halo-Organics From Water, Subrajit Bosu, Samuel S. Thompson, Doo Young Kim, Noah D. Meeks, Dibakar Bhattacharyya

Chemical and Materials Engineering Faculty Publications

Contaminated water detoxification remains difficult due to the presence of persistent halo-organic contaminants, such as perfluorooctanoic acid (PFOA) and chlorophenols, which are chemically stable and resist conventional purification methods. Functionalized membrane-based separation and decontamination have garnered immense attention in recent years. Commercially available microfiltration membrane (PVDF) and polymeric non-woven fiber filters (glass and composite) are functionalized with poly(methacrylic acid) (PMAA) that shows outstanding pH-responsive performance and tunable water permeability under ambient conditions perfect for environmental applications. Polymer loading based on weight gain measurements on PMAA–microglass composite fibers (137%) and microglass fibers (116%) confirmed their extent of functionalization, which was significantly …

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

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 …

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 …

Dennd5b Disruption Results In Reduced Body Fat And Increased Intestinal Fatty Acid Oxidation By Activation Of Autophagy, Khaga R. Neupane, Alexander Karakashian, Maura Mobilia, Olivia Hage, Patrick Tso, Min Liu, Laurent Vergnes, Karen Reue, Scott M. Gordon

Physiology Faculty Publications

Intestinal absorption of dietary lipid is essential for systemic lipid homeostasis; however, elevated postprandial plasma lipid levels are associated with obesity and increased risk for atherosclerotic cardiovascular disease. In humans and rodents, biological sex impacts dietary triglyceride absorption, and males tend to have higher postprandial triglyceride levels compared to females, but the physiological basis for this is not well understood. Here, we show that the gene DENND5B is associated with body composition in humans and mice and that genetic deletion of Dennd5b in mice prevents postprandial plasma triglyceride elevations in both sexes. Our findings establish a role for this protein …

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

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 (Apc^Min/+) 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

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 …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G. Clina, Brian C. Helsel, Sigan L. Hartley, David A. White, Victoria L. Fleming-Batayneh, Benjamin Handen, Bradley Christian, Elizabeth Head, Mark Mapstone, Christy L. Hom, Beau Ances, Jeffrey Burns, H. Diana Rosas, Florence Lai, Sharon Krinsky Mchale, Joseph H. Lee, Frederick A. Schmitt, Jordan Harp, Ira T. Lott, Shahid Zaman, Lauren T. Ptomey

Neurology Faculty Publications

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS. METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (n = 82, mean age = 39.9 ± 8.5 years, 97.6% White race) were age- and sex-matched to participants without CHD (n = 82, mean age = 40.5 ± 8.1 years, 98.8% White race). Cognitive assessments and Centiloid load (CL) (positron …

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 …

Decoding The Human Pbmc Isonome, Patricia Hayes Doyle, Madeline L. Page, J. Anthony Brandon, Bernardo Aguzzoli Heberle, Brendan J. White, Ann Marie Stowe, Mark T.W. Ebbert

Neurology Faculty Publications

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at a level difficult to resolve with bulk or short-read methods. This approach enables isoform-level investigation of cellular diversity and disease mechanisms and definition of cell-types, rather than using genes alone. Using a modified, microfluidic-free PIPseq workflow and computational pipeline adapted for Oxford Nanopore long-read sequencing, we generated the largest long-read single-cell dataset of human peripheral blood mononuclear cells (PBMCs) from a single donor to date, the first with sufficient cell numbers to detect megakaryocytes. This study profiled isoform usage across immune cells, integrating marker expression and …

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 …

Autosiq, Liming Zhou, Talukder Z. Jubery, Baskar Ganapathysubramanian, Thomas Lübberstedt, Siddique I. Aboobucker

Plant and Soil Sciences Faculty Publications

Doubled haploid (DH) technology can fast-track crop breeding.Haploid induction yields haploids with only one set of genomes, which are usually sterile.Haploid fertility (HF) is the ability of haploid plants to set seed, and it is a critical bottleneck in DH pipelines.Genetic mechanisms to restore HF hold immense potential in DH crop breeding, yet its phenotyping remains manual, destructive, and inconsistent.While recent advances in imaging and machine learning have improved throughput for general plant traits, no curated image dataset exists for Arabidopsis thaliana that explicitly represents HF.Here, we present AutoSiQ, a dataset and baseline deep learning pipeline for automated HF quantification.AutoSiQ …

Proposal Of Metagenomic-Origin Lra-5 As A Precursor Of Active Β-Lactamases Through Tyr69gln And Val166glu Amino Acid Substitutions, Gabriela D'Amico González, María Margarita Rodríguez, Pedro Penzotti, Florencia Brunetti, Barbara Ghiglione, Luke A. Moe, Daniela Centrón, Gabriel Gutkind, Lin Gao, Shozeb Haider, Rachel A. Powers, Sebastián Klinke, Pablo Power

Plant and Soil Sciences Faculty Publications

Wild-type LRA-5, recovered from Alaskan soil samples, shares no more than 33% amino acid sequence identity with enzymes from pathogens like PER β-lactamases. Recombinant E. coli expressing wild-type LRA-5 and its engineered variants LRA-5^Y69Q and LRA-5^V166E showed MIC values equivalent to control strains. However, LRA-5^Y69Q/V166E displayed MICs above the resistant breakpoint for some β-lactams. Kinetic parameters correlated with the MICs, showing that the catalytic efficiency of LRA-5^Y69Q/V166E was comparable to those from class A β-lactamases, such as CTX-M-15, PER-2, and KPC-2. LRA-5^Y69Q/V166E exhibited k_cat/K_m values up to 11,000-fold higher compared to wild-type …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …