Digital Commons Network^™

Research Note: Increased Lipid Accumulation Within Broiler Preadipocytes During Differentiation In Vitro At Atmospheric Oxygen Tension, Jessica Moraes Cruvinel, Elizabeth S. Greene, Rachel W. Read, Kichoon Lee, Sami Dridi, Paula R. Chen

Poultry Science Faculty Publications and Presentations

In the broiler industry, intensive genetic selection has been placed on muscle growth which has undesirably led to increased fat accretion. Models of chicken preadipocyte differentiation in vitro have conventionally used incubators without the ability to control oxygen (O₂) tension; thus, the cells are exposed to atmospheric (∼20-21%) O₂, which is supraphysiological compared to the O₂ tension within adipose tissue. The objective of this study was to investigate embryonic broiler preadipocyte differentiation at different O₂ tensions, including atmospheric (20%), physiological (5%), and hypoxic (1%). Culture at 1% O₂ resulted in increased …

Examining The Impact Of Early Literacy Interventions On Teachers’ And Parents’ Learning And Perceptions Of Early Literacy Development, Abigael Mary Hogarth Todd Miss

Theses and Dissertations (Comprehensive)

Parents and teachers play a vital role in fostering early literacy development; however, many require additional training to enhance their understanding of alphabet knowledge and phonological awareness. This study examined the effectiveness of two instructional videos—one on phonological awareness and one on evaluating alphabet books—in increasing teachers’ (n = 35) and parents’ (n = 34) perceptions about these domains and the practical application of information covered in the videos. The 69 participants viewed each video, and results indicated a general decrease in confidence following exposure to these videos, likely reflecting an increased awareness of the complexity of the …

Negotiated Cultural Identity And Belonging Of Self-Identified Indo-Guyanese Immigrant Women, Neta (Goomatee) Deonarain-Gear

Theses and Dissertations (Comprehensive)

This dissertation examines how young, self-identified Indo-Guyanese women who immigrated to Southwestern Ontario in the 1970s negotiate cultural identity and belonging. Utilizing a bio-ethnographic bricolage narrative methodology, the study explores the impact of postcolonial diaspora and social displacement on these women’s experiences within the "third space" or borderlands. Grounded in relativist ontology and constructivist epistemology, storytelling serves as the primary data collection method through a critical theory lens. Interviews with 12 participants were analyzed thematically and reflexively, revealing how participants construct meaning and navigate cultural identities. The analysis, conducted through feminist, decolonial, and trauma-informed perspectives, offers insights into "psychological homelessness" …

Neighbourhood Resilience Planning With Renters In Hamilton, Ontario, Canada, Anna Do

Theses and Dissertations (Comprehensive)

This sequential mixed-methods study demonstrates the co-production of knowledge between academic researchers and local communities. Guided by the resilience planning framework, the study engaged 48 renters from the Beasley neighbourhood of Hamilton, Ontario, Canada in identifying stressful and supportive locations using a participatory mapping tool called the “Place Report.” A total of 74 Place Reports were submitted, with most reporting supportive places in or near Beasley. Thematic analysis revealed three overarching domains, and 13 themes related to the use and function of these locations. Places pertaining to food, housing, and physical activity emerged as the most frequently discussed topics. The …

Limiting H1n1 Replication Via The Dsrnai Pathway Using Sequence-Specific Ldsrna, Shawn Marie Sharon Carr, Stephanie Dewitte-Orr

Theses and Dissertations (Comprehensive)

The seasonal influenza virus causes a common respiratory illness that can be life threatening to the immunocompromised, the very young, and the elderly. The current strategies for avoiding a serious influenza virus infection are good hygiene practices and the annual influenza vaccine. Unfortunately, last year’s influenza virus vaccine effectiveness ranged between 32-60% for children and adolescents and 46-54% for adults. These low efficacy rates are due to the vaccine often targeting hemagglutinin, a highly variable surface protein. This thesis seeks to create a prophylactic treatment via the RNA interference (RNAi) response that targets the virus’s conserved genes that are integral …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

Introduction: Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wild-type controls.

Methods: The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low

Faculty, Staff and Students Publications

Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FRβ). Because FRβ does not bind folate until the monocyte/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FRβ might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FRβ knockout mice. We observe that FRβ knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) …

Diagnostic And Prognostic Value Of Cystatin C In Acute Coronary Syndrome: An Up-To-Date Meta-Analysis, Michal Pruc, Damian Swieczkowski, Basar Cander, Milosz J Jaguszewski, Sagar Galwankar, Salvatore Di Somma, Fatimah Lateef, Indrani Sardesai, Ayman El-Menyar, Michal Zembala, Jacek Kubica, Togay Evrin, Burak Katipoglu, Zubaid Rafique, Frank William Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

Background: The role of Cystatin C (CysC) in the diagnosis and prognosis of cardiovascular disease, particularly acute coronary syndrome (ACS), is increasingly significant. The goal of this meta-analysis was to assess the diagnostic and prognostic value of CysC in patients with ACS, as well as its association with major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction, heart failure, and stroke.

Methods: The present study is a systematic review and meta-analysis. Using PubMed, Web of Science, Cochrane Library, and Embase, a literature review of cohort and case control studies reporting MACE and using the terms ACS and Cystatin C …

Prognostic Value Of The Monocyte-To-High-Density Lipoprotein-Cholesterol Ratio In Acute Coronary Syndrome Patients: A Systematic Review And Meta-Analysis, Michał Pruc, Jacek Kubica, Maciej Banach, Damian Świeczkowski, Zubaid Rafique, William Frank Peacock, Zbigniew Siudak, Stanisław Surma, Prabath Nanayakkara, Krzysztof Kurek, Anne Lepetit, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Globally, diseases of the cardiovascular system stand as principal contributors to mortality and are expected to show an upward trajectory. The occurrence of acute coronary syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS.

Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients.

Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses published before February 26, …

Toward Precision Longevity: Aging Interventions In The Single-Cell Atlas Era, Jason B Chen, Miranda C Wang, Shangyu Gong, Hongjie Li

Faculty, Staff and Students Publications

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type–specific aging patterns and molecular …

Efficacy Of Nampt Inhibition In T-Cell Acute Lymphoblastic Leukemia, Chelsea Vrana, Matthew Zhang, Max Rochette, Michelle Alozie, Hailey Oviedo, Alan Gonzalez, Jaden Sherman, Barry Zorman, Pavel Sumazin, Karen R Rabin, Jacob J Junco

Faculty, Staff and Students Publications

Novel agents targeting upregulated signaling pathways are needed to improve outcomes in T-cell acute lymphoblastic leukemia (T-ALL), since conventional cytotoxic chemotherapy regimens have reached the limits of tolerability. We identified upregulated, targetable signaling pathways common to both human T-ALL samples and a KrasLSL-G12D/+.Mb1Cre/+ murine model of T-ALL. We found the NAMPT inhibitor FK866 had the greatest cytotoxicity of a panel of small molecule inhibitors tested in human and mouse T-ALL cell lines, and in patient derived xenograft (PDX)-expanded T-ALL patient samples. We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the …

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …

Stent Thrombosis: A Contemporary Guide To Definitions, Risk Factors, And Management, Ambre Flowers, Bernard Evenhuis, Benjamin Gabanic, Allison Weiss, Scott Eisenberg, Riyan Siddiqui, Affan Rizwan, Iqra Riaz, Hafeez Ul Hassan Virk, Mahboob Alam, Muzamil Khawaja, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Stent thrombosis remains a major complication following percutaneous coronary intervention, with significant morbidity and mortality implications. Despite advancements in drug-eluting stents and optimized pharmacotherapy, real-world registry data indicate that definite or probable stent thrombosis occurs in approximately 0.5% of percutaneous coronary intervention cases, with a 30-day mortality rate approaching 25% and a long-term risk exceeding 30% at 10 years. Stent thrombosis is classified based on timing into acute, subacute, late, and very late thrombosis, with subacute and very late stent thrombosis being the most prevalent. Clinical consequences include myocardial infarction, emergent revascularization, and heightened cardiovascular risk, necessitating timely recognition and …

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: Jacc: Cardiovascular Imaging Position Statement, Gilbert H L Tang, Syed Zaid, Rebecca T Hahn, Vratika Aggarwal, Mohamad Alkhouli, Edris Aman, Sergio Berti, Y S Chandrashekhar, Scott M Chadderdon, Andreina D'Agostino, Neil P Fam, Edwin C Ho, Chad Kliger, Susheel K Kodali, Parasuram Krishnamoorthy, Azeem Latib, Stamatios Lerakis, D Scott Lim, Vaikom S Mahadevan, Devi G Nair, Jagat Narula, Patrick T O'Gara, Douglas L Packer, Fabien Praz, Jason H Rogers, Tobias F Ruf, Carlos E Sanchez, Alok Sharma, Gagan D Singh, Nicolas M Van Mieghem, Mani A Vannan, Pradeep K Yadav, Lina Ya'qoub, Firas E Zahr, Ralph Stephan Von Bardeleben

Faculty, Staff and Students Publications

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure …

Genetic Associations Among Inflammation, White Matter Architecture, And Extracellular Free Water, Amanda L. Rodrigue, Emma M. Knowles, Josephine Mollon, Samuel R. Mathias, Juan M. Peralta, Ana C. Leandro, Peter T. Fox, Peter Kochunov, Rene L. Olvera, Laura Almasy, Joanne E. Curran, John Blangero, David C. Glahn

School of Medicine Publications

Phenotypic and genetic relationships between white matter microstructure (i.e., fractional anisotropy [FA]) and peripheral inflammatory responses (i.e., circulating cytokines) have important implications for health and disease. However, it is unclear whether previously discovered genetic correlations between the two traits are due to tissue‐specific white matter architecture or increased free water in the extracellular space. We applied a two‐compartment model to diffusion tensor imaging (DTI) data and estimated tissue‐specific white matter microstructure (FAT) and free water volume (FW). We then quantified their heritability and their genetic correlations with two peripherally circulating proinflammatory cytokines (IL‐8 and TNFα), and compared these correlations to …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Clinical Criteria For Limbic-Predominant Age-Related Tdp-43 Encephalopathy, David A. Wolk, Peter T. Nelson, Liana Apostolova, Konstantinos Arfanakis, Patricia A. Boyle, Cynthia M. Carlsson, Nick Corriveau-Lecavalier, Penny Dacks, Bradford C. Dickerson, Gladys E. Maestre

School of Medicine Publications

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of …

Towards A Map Of The Immune System Manipulation Network By Trypanosoma Cruzi, Juan Cruz Gamba, Ana Rosa Pérez, Carolina Verónica Poncini, Cristina Poveda, Iván Marcipar, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Ai-Based Detection Of Coronary Artery Occlusion Using Acoustic Biomarkers Before And After Stent Placement, David Anderson Lloyd, Andrei Dragomir, Bulent Ozpolat, Biykem Bozkurt, Yasemin Akay, Metin Akay

Faculty, Staff and Students Publications

No abstract provided.

Recognition And Management Of Persistent Chylomicronemia: A Joint Expert Clinical Consensus By The National Lipid Association And The American Society For Preventive Cardiology, Seyedmohammad Saadatagah, Miriam Larouche, Mohammadreza Naderian, Vijay Nambi, Diane Brisson, Iftikhar J Kullo, P Barton Duell, Erin D Michos, Michael D Shapiro, Gerald F Watts, Daniel Gaudet, Christie M Ballantyne

Faculty, Staff and Students Publications

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia (PC)" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for …

Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim

Faculty, Staff and Students Publications

Finite element modeling (FEM) is a critical tool in biomechanics and biomedical engineering, offering valuable insights where in vivo or ex vivo investigations are not possible. This review specifically highlights the diverse applications of FEM within obstetrics and gynecology through a comprehensive analysis of the literature. We explore the past use of FEM in analyzing complications affecting pelvic floor structures, urinary continence, and reproduction. The potential contributions of FEM in addressing these challenges are summarized and future directions for its application in obstetrics and gynecology are highlighted.

A Murine Model Of Gestational Diabetes Reveals Masld Risk And Alterations In Markers Of Hepatic Mitochondrial Metabolism, Grace E Shryack, Alexa A Krause, Simone Hernandez Ruano, Laura C Schulz, Kathleen A Pennington, R Scott Rector

Faculty, Staff and Students Publications

Introduction: Gestational Diabetes Mellitus (GDM) impacts roughly 1 in 7 pregnancies and results in metabolic dysfunction-associated steatotic liver disease (MASLD) in 30% of these women. Nonetheless, there exists a dearth of investigation into the relationship between GDM and MASLD. Here, we sought to investigate the potential role of hepatic mitochondrial function in GDM and MASLD.

Methods: One week prior to conception and throughout pregnancy, mice were fed either a low-fat control diet (CD) or a high-fat, high-sucrose (HFHS) diet to induce an established model of GDM. Maternal livers were collected at day 0, 6.5, 13.5 and 17.5 of pregnancy. Hepatic …

Poststroke Impulsivity: A Narrative Review, Melissa B Jones, Dakota E Broadway, Malena Gimenez-Zapiola, Ricardo E Jorge

Faculty, Staff and Students Publications

In this narrative review, the authors examine the multidimensional nature and presentations of impulsivity after stroke. Impulsivity manifests as immediate or premature responses, impaired delayed gratification, perseverance despite punishment, and other displays of impaired emotional and behavioral regulation. The literature on the assessments, outcomes, and treatment of patients with these various manifestations after a cerebrovascular injury is reviewed. Findings from case reports indicate that poststroke impulsivity may manifest across neurobehavioral syndromes that are not well defined in the psychiatric nomenclature, such as alien hand syndrome and atypical impulse control disorders. Overall, impulse control disorders appear to be rare poststroke. Therapeutic …

Targeting The Exonic Circular Ogt Rna/O-Glcnac Transferase/Forkhead Box C1 Axis Inhibits Asparagine- And Alanine-Mediated Ferroptosis Repression In Neuroblastoma Progression, Qilan Li, Yang Cheng, Chunhui Yang, Minxiu Tian, Xiaojing Wang, Dan Li, Xinyue Li, Jiaying Qu, Shunchen Zhou, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

The disruption of ferroptosis, an emerging form of programmed cell death, is crucial in the development and aggressiveness of tumors. Meanwhile, the mechanisms and treatments that control ferroptosis in neuroblastoma (NB), a prevalent extracranial cancer in children, are still unknown. In this study, forkhead box C1 (FOXC1) and O-GlcNAc transferase (OGT) are identified as regulators of asparagine- and alanine-mediated ferroptosis repression in NB. Mechanistically, OGT facilitates FOXC1 stabilization via inducing O-GlcNAcylation in liquid condensates to increase the expression of asparagine synthetase (ASNS) and glutamate pyruvate transaminase 2 (GPT2), resulting in asparagine and alanine biogenesis, and subsequent …

Nanoparticle Contrast-Enhanced Computed Tomography Of Sporadic Aortic Aneurysm And Dissection: Effect Of Nanoparticle Size And Contrast Agent Dose, Laxman Devkota, Chen Zhang, Deborah Vela, Poonam Sarkar, Prajwal Bhandari, Zbigniew Starosolski, Renuka Menon, Dianna M Milewicz, Ying H Shen, Scott A Lemaire, Ketan B Ghaghada

Faculty, Staff and Students Publications

Background: Aortopathies, such as aortic aneurysm and dissection (AAD), are associated with enhanced aortic wall permeability and endothelial dysfunction. We previously demonstrated that nanoparticle contrast-enhanced computed tomography (nCECT), which detects enhanced aortic wall permeability, could enable non-invasive detection of early AAD before its progresses to fatal aortic rupture. This study investigated the effect of nanoparticle contrast agent (NPCA) size and dose on detection of aortopathy by nCECT.

Methods: In vivo studies were performed in a mouse model of sporadic AAD induced by challenging animals with high fat diet (5 weeks) and angiotensin II infusion (last one week). The effects …

Assessing The Cardioprotective Effects Of Exercise In Apoe Mouse Models Using Deep Learning And Photon-Counting Micro-Ct, Alex J Allphin, Rohan Nadkarni, Zay Y Han, Darin P Clark, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: The allelic variations of the apolipoprotein E (APOE) gene play a critical role in regulating lipid metabolism and significantly impact cardiovascular disease risk (CVD). This study aimed to evaluate the impact of exercise on cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT) and deep learning-based segmentation.

Methods: A total of 140 mice were grouped based on APOE genotype (APOE2, APOE3, APOE4), sex, and exercise regimen. All mice were maintained on a controlled diet to isolate the effects of exercise. Low dose cardiac photon counting micro-CT imaging with intrinsic gating was performed …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund

Faculty, Staff and Students Publications

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat‐to‐neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan‐extending lipid chaperone, lipid binding protein‐3 (LBP‐3), which shuttles dihomo‐γ‐linolenic (DGLA) acid from intestinal fat to neurons. We present the first high‐resolution crystal structure of LBP‐3, which reveals a classic iLBP fold with an unexpected and unique homodimeric …