Digital Commons Network^™

Space Agriculture: A Comprehensive Systems-Level Review Of Challenges And Opportunities, Hassan Fazayeli, Aaron Lee M. Daigh, Cassandra Palmer, Santosh Pitla, David Jones, Yufeng Ge

Biological Engineering Faculty Publications

As humanity prepares for prolonged space missions and future extraterrestrial settlements, developing reliable and resilient food-production systems is becoming a critical priority. Space agriculture, the cultivation of plants beyond Earth (particularly on the Moon and Mars), faces a constellation of interdependent environmental, biological, and engineering challenges. These include limited solar radiation, elevated ionizing radiation, large thermal variability, non-Earth atmospheric pressures, reduced gravity, regolith substrates with low nutrient-holding capacity, high-CO₂/low-O₂ atmospheres, pervasive dust, constrained water and nutrient availability, altered plant physiology, and the overarching need for closed-loop, resource-efficient systems. These stressors create an exceptionally challenging environment for plant …

Imaging Reactive Oxygen Species With L-012 Reveals Neutrophil Extracellular Trap Formation In Pancreatic Ductal Adenocarcinoma, Angisha Basnet, Kaitlyn M Landreth, Michael Sestito, Kristen Ranson, Seth T Gammon, David Piwnica-Worms, Brian A Boone, Tracy W Liu

Faculty, Staff and Student Publications

Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed …

Precise Diagnosis Of Small Invasive Pulmonary Nodules Driven By Single-Cell Immune Signatures In Peripheral Blood, Yang Xia, Yin Zhu, Sai Zhang, Mo Zhou, Jiaqi Zhou, Guanxin Xu, Baiqin Zhao, Guofei Zhang, Qiyuan Wang, Bin Wang, Zexin Chen, Hongyu Shi, Xiuning Le, Tony Mok, Wei Chen, Junqiang Fan, Weiwei Yin, Wen Li

Faculty, Staff and Student Publications

Early detection of lung cancer is crucial for improving patient outcomes. However, accurately diagnosing invasive pulmonary nodules and predicting tumor invasiveness remain major clinical challenges. Given the established role of immune dysfunction in cancer development, we hypothesize that peripheral immune profiling could provide a strategy for managing pulmonary nodules. In this multi-center, prospective study, we combine peripheral immune profiling via mass cytometry with machine learning algorithms to develop an integrated pulmonary nodule management platform. This platform accurately distinguishes invasive from non-invasive pulmonary nodules (AUC = 0.952), outperforming established clinical and radiomics-based models. Furthermore, it effectively predicts tumor invasiveness, differentiating minimally …

Harnessing Blueberry Flower Chemistry And Morphology To Boost Pollination And Bee Health, Monica Borghi

Funded Research Records

No abstract provided.

Thriving Hives: The Apiary - Beekeeping Essentials, Joseph Okoh, Andree' Walker Bravo

All Current Publications

This fact sheet is designed to help honey bee producers optimize their beekeeping practices and improve management systems. It offers essential guidance on selecting an ideal apiary location, choosing the right beehive, and ensuring efficient colony management. Additionally, this document serves as a valuable training resource for aspiring beekeepers.

Spike Timing Depended Plasticity Produces Unsupervised Learning Of Synergistic Muscle Feedback In A Synthetical Neural Network, Mark Allen Pupkiewicz

Dissertations and Theses

This study investigates how type Ia feedback from muscle spindles can be organized into groups representing agonistic muscle pairs through Spike Timing Dependent Plasticity (STDP). A single degree of freedom joint is actuated with four biologically modeled muscles forming two agonistic pairs. In order to emulate the sensory dynamics of biological muscle spindles, sensors in the model record the active length and velocity states of each muscle, the two primary factors eliciting type Ia afferent responses. In biological networks, synapses from Ia sensory neurons frequently activate interneurons representing agonistic muscle sources. This research investigates whether this organization can emerge in …

Epidemiology, Presentation, And Diagnosis Of Type 2 Diabetes Mellitus In Children And Adolescents, Bisher Alsabbagh, Whard Alsabbagh

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents has increased substantially over recent decades, paralleling rising rates of pediatric obesity and metabolic risk. Youth-onset T2DM is characterized by significant insulin resistance accompanied by an inadequate compensatory insulin response, resulting in progressive hyperglycemia and early beta-cell dysfunction. Incidence varies widely among racial and ethnic groups, with the highest rates observed in non-Hispanic Black, Hispanic, Native American, Asian American, and Pacific Islander youth. Risk factors include obesity, family history, high-risk ethnicity, pubertal insulin resistance, prenatal metabolic exposures, and comorbid conditions such as polycystic ovary syndrome. Clinical presentation ranges …

Investigating Factors That Affect Total Ige Antibody Levels Of A Canine Population In Louisville, Ky, Iris N. Gillespie

Undergraduate Theses

Canine atopic dermatitis (CAD) is a genetically predisposed condition that causes inflammatory and pruritic (itchy) skin reactions in response to environmental and food allergens. The main purpose of this study is to determine if there is a correlation between pollen counts and total canine IgE antibody levels of dogs living in Louisville, KY. Additionally, data is analyzed to look for trends documented in previous studies related to the impacts of sex, age, and allergic symptoms on total IgE count. In collaboration with the Downtown Animal Hospital, blood samples were drawn from 16 dogs at one point in February (when pollen …

Bayesian Learning To Reduce Cardiac Risk Of Patients With Locally Advanced Non-Small Cell Lung Cancer Based On Personalized Radiation Therapy Prescription, Ruitao Lin, Mei Chen, Xiaodong Zhang, Tianlin Xu, Ting Xu, Rachel C Maguire, Kelsey L Corrigan, Efstratios Koutroumpakis, Joe Y Chang, Steven H Lin, Aileen B Chen, Quynh-Nhu Nguyen, Saumil J Gandhi, Matthew S Ning, Julianna Bronk, Stephen Chun, Ali Ajdari, Joshua S Niedzielski, Jinzhong Yang, Xinru Chen, Tinsu Pan, Qing H Meng, Anne S Tsao, Anita Deswal, Radhe Mohan, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Radiation-induced heart damage is a significant concern in the treatment of non-small cell lung cancer (NSCLC) that can have debilitating or life-threatening consequences. Current strategies focus on minimizing heart exposure, but individual susceptibility varies. Existing evidence also suggests that a uniform "one-size-fits-all" dosimetric constraint for the heart may not be optimal for all patients.

Methods and materials: We developed a prospective study using Bayesian continuous learning and adaptation to develop a framework for personalized adaptive radiation treatment (PART) to reduce cardiovascular adverse events among patients with locally advanced NSCLC. The trial includes a Bayesian personalized risk prediction model to …

Health-Related Quality Of Life In The Era Of Immune Checkpoint Blockade: What Do Patient-Reported Outcomes Reveal?, Alexandra M Dunker, Neha Malik, Kathryn J Krause, Emily Z Keung, Jason B Liu, Elise F Nassif Haddad, Neeta Somaiah, Heather G Lyu, Christina L Roland

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical.

Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken …

A Review Of Recent And Developing Studies Regarding Percutaneous Coronary Intervention (Pci): A Narrative Review, Bisher Alsabbagh, Azeez Shala, Joshua Rupert, Abdallah Elsayed

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

This comprehensive literature review synthesizes the most recent evidence and evolving clinical guidelines concerning percutaneous coronary intervention (PCI) from 2015 to 2025. The study integrates findings from 42 peer-reviewed trials, meta-analyses, registries, and international guideline statements issued by the American College of Cardiology/American Heart Association (ACC/AHA), European Society of Cardiology (ESC), and related societies. Results reveal a decade-long evolution in PCI practice marked by a shift from anatomy-driven to physiology and imaging-guided decision-making, supported by tools such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). Modern guidelines emphasize individualized, team-based revascularization …

Measuring Levels Of Ultrashort-Chain Per- And Polyfluoroalkyl Substances In Blood Collection Tubes, Alina M. Dziembowski

Discovery Undergraduate Interdisciplinary Research Internship

Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals that are now ubiquitous in the environment. Due to PFAS stability leading to its environmental persistence, there is concern regarding potential long-term health effects as PFAS accumulation occurs in humans from dietary and inhalation exposure routes. Chronic exposure may lead to adverse effects such as fertility issues or liver damage. Although a wide range of PFAS have been found in human samples, specifically human serum, there remains data gaps for what PFAS are present in human blood. Recent innovation in detection technology has led to the ability to more accurately …

An Updated Annotated Checklist Of The Mammals Of The Crane Trust, Hall County, Nebraska, Bethany L. Ostrom, Amanda H. Medaries, Andrew J. Caven, Jenna M. Malzahn, Alexa Rojas, Matthew R. Schaaf, David M. Baasch, Thomas E. Labedz, Greg D. Wright

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

The Crane Trust is a regional nonprofit conservation organization that has protected land in the biologically important Central Platte River Valley for over four decades. A mammal inventory was conducted on the Crane Trust’s main habitat complex in 1980. Since, a variety of environmental conditions have shifted locally, regionally, and globally. An analysis of the mammal community was conducted using past and recent data to determine how species composition and relative abundance have shifted categorically from 1980 to 2021. We used all available data to categorize relative abundance during two distinct time periods per a modified “DAFOR” scale including 7 …

Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P Whelton, Catherine H Marshall, Michael J Blaha, Peter Durda, Xiuqing Guo, Craig W Johnson, Henry J Lin, Kent D Taylor, Russell P Tracy, Ronit I Yarden, Ani W Manichaikul, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Peter Ganz, Lang Wu

Faculty, Staff and Student Publications

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls …

Actin Dysregulation Induces Neuroendocrine Plasticity And Immune Evasion: A Vulnerability Of Small Cell Lung Cancer, Yoojeong Seo, Shengzhe Zhang, Jinho Jang, Kyung-Pil Ko, Kee-Beom Kim, Yuanjian Huang, Dong-Wook Kim, Bongjun Kim, Gengyi Zou, Jie Zhang, Sohee Jun, Wonhong Chu, Nicole A Kirk, Ye Eun Hwang, Young Ho Ban, Shilpa S Dhar, Joseph M Chan, Min Gyu Lee, Charles M Rudin, Kwon-Sik Park, Jae-Il Park

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. Capping protein inhibiting regulator of actin dynamics (CRACD) that promotes actin polymerization, is frequently inactivated in SCLC. However, the role of CRACD loss in SCLC is unknown. Here we show that CRACD depletion drives neuroendocrine (NE) cell plasticity and immune evasion in SCLC. Mechanistically, CRACD inactivation disrupts actin organization, leading to suppression of Yap1-NOTCH signaling and subsequent NE gene upregulation. Simultaneously, CRACD loss drives EZH2-mediated histone methylation via nuclear actin disruption, leading to repression of MHC-I genes and depletion of CD8⁺ T cells. Consequently, CRACD-downregulated tumors exhibit …

From Collision To Coexistence: Data-Driven Approaches To Reducing Wildlife Rehabilitation Center Intakes, Alice Anastos

Honors Projects

This project investigates the primary anthropogenic drivers of wildlife admissions at Lake Erie Nature and Science Center using a quantitative analysis of 10,172 intake records from the WILD-ONe database. Window collisions were by far the leading cause of admission, accounting for 54% of all intakes. Orphaning represented 12%, followed by vehicle collisions (5%) and domestic cat attacks (4%). By integrating findings from current wildlife rehabilitation research, this study identifies evidence-based strategies, such as bird-safe window treatments, public education on natural animal behavior, and targeted urban planning, that can substantially reduce preventable injuries. These results underscore the need for context-specific outreach …

Plant Vs. Animal Protein: Effect On Recovery, Performance, And Long-Term Health, Claudia Stachura

Honors Theses

Protein plays a fundamental role in muscle repair, growth, and athletic performance, which has led to increased interest in how different protein sources compare, particularly as plant-based diets become more common among athletes and physically active individuals. The debate surrounding plant-based versus animal-based protein sources primarily focuses on differences in protein quality, amino acid composition, digestibility, and potential long-term health implications. This paper examines current evidence comparing the effectiveness of plant and animal protein sources in supporting muscle protein synthesis (MPS), resistance training adaptations, recovery, and performance, while also considering broader health and environmental outcomes.

Protein supports muscle growth by …

Unveiling The Genomic Blueprint Of Two Pantoea Agglomerans Phages: Lia And Yaegar As Emerging Members Of The Chaseviridae Family, Leslie M. Ewool

Theses and Dissertations

Bacteriophages represent an essential component of microbial ecosystems and a promising resource for biocontrol. This study presents a comprehensive comparative genomic and evolutionary characterization of two novel bacteriophages that infect Pantoea agglomerans, Lia and Yaegar, belonging to the Loessnervirus genus within the Chaseviridae family. Both Lia and Yaegar possess double-stranded DNA genomes of approximately 54 kb with 44.4% GC content and 82 predicted open reading frames (ORFs). Functional annotation revealed distinct modules for replication, structural assembly, and lysis, but no genes associated with lysogeny, antibiotic resistance, or virulence. Average nucleotide identity (ANI) analysis indicated over 96% similarity between Lia, Yaegar, …

Effect Of Various Lactobacillus Probiotic Strains On Oral Antihypertensive Drug Response: A Systematic Review, Khoirunnisa Ramadhani, Keri Lestari

Pharmacology and Clinical Pharmacy Research

Hypertension is a major risk factor for cardiovascular disease, and the effectiveness of antihypertensive therapy can be influenced by metabolic and systemic inflammatory factors associated with gut microbiota conditions. Probiotic strains from the genus Lactobacillus have been reported to modulate antihypertensive effects through complex biological mechanisms. This article evaluates experimental evidence from seven in vivo studies on the influence of Lactobacillus strains on the response to antihypertensive drugs, including pharmacodynamic mechanisms and drug–probiotic interactions. The combination of Lactiplantibacillus plantarum with amlodipine enhanced nitric oxide production, increased eNOS expression, reduced IL-6 levels, and improved drug bioavailability, leading to greater blood pressure …

Optimization Of Guava Leaf Extract Cream Formulation Through Variations Of Xanthan Gum And Stearic Acid For Wound Cure In Rats, Ayudia Cipta Khairani, Mia Ariasti

Pharmacology and Clinical Pharmacy Research

Cuts are among the most common skin injuries caused by sharp objects and can lead to infection if not properly treated. Natural ingredients such as guava leaves have been widely investigated for their wound-healing potential. Guava leaves contain bioactive compounds including flavonoids, saponins, alkaloids, and tannins, which contribute to anti-inflammatory, antibacterial, and tissue regeneration processes. This study aimed to formulate and evaluate the physical properties and wound-healing effectiveness of guava leaf ethanol extract cream with varying concentrations of xanthan gum and stearic acid as emulsifiers. The extract was obtained by maceration using 70% ethanol and formulated into four cream formulas …

Drug-Related Problems In Hemodialysis Patients With Chronic Kidney Disease: A Study At X Hospital (January–May 2022), Muhammad Refki Abrari, Jatmiko Susilo

Pharmacology and Clinical Pharmacy Research

The prevalence of chronic kidney disease (CKD) in Indonesia has increased from 2.0 ‰in 2013 to 3.8 ‰in 2018. The presence of complex comorbidities associated with CKD causes varied therapy regimens (poly-pharmacy), leading to an increased risk of drug-related problems (DRPs). To overcome these complications, dialysis is often used to remove metabolic waste and rebalance electrolytes to maintain life in patients experiencing rapid loss of kidney function. This study aims to evaluate drugs consumed as well as DRPs experienced by patients diagnosed with CKD undergoing hemodialysis at X Hospital from January to May 2022. The study procedures were carried out …

What Is The Hospital Pharmaceutical Care? Perceptions And Expectations Of Doctors In Interprofessional Collaboration In 2 Types Of Indonesia Hospitals, Anisyah Achmad, Savvy Augustin Tirta, Titi Annisa Bella, Ratna Kurnia Illahi, Bambang Sidharta, Valentina Yurina, Wara Rejeki

Pharmacology and Clinical Pharmacy Research

Hospital Pharmaceutical Care (HPC) is the pharmacist’s direct responsibility to aim for patient safety and quality of life. HPC is a means of avoiding medication and human errors. Carrying out a HPC requires a good collaboration between doctors and pharmacists in treatment management. The aim of the research was to determine the relationship between doctors’ perceptions and expectations of clinical pharmacists at HPC. This research is descriptive quantitative observational with a cross-sectional approach. The data were collected using purposive sampling (type A hospital) and total sampling (type C hospital) through interviews using perception and expectations questionnaires on doctors’ to pharmacists …

Β-Glucan As A Potential Modulator Of Tgf-Β Signaling And Emt-Driven Resistance In Triple-Negative Breast Cancer, Hanifa Dinda Hayati, Riezki Amalia, Gemilang Lara Utama, Dika Pramita Destiani

Pharmacology and Clinical Pharmacy Research

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks expression of estrogen, progesterone, and HER2 receptors, limiting the effectiveness of targeted therapies and making chemotherapy the primary treatment option. However, resistance to chemotherapy remains a major clinical challenge, often driven by dysregulation of the transforming growth factor-β (TGF-β) signaling pathway. TGF-β plays a dual role in cancer, initially acting as a tumor suppressor but later promoting tumor progression through mechanisms such as epithelial–mesenchymal transition (EMT), immune evasion, and the establishment of cancer stemness. This review aims to explore the role of TGF-β signaling and EMT …

Environmental Risk Assessment Of Textile Waste From Bio-Engineered Fibers In The Fashion Industry, Aayush Pankaj Agarwal, Harshit Soral, Irmak Aktan, Karol Montserrat Gonzalez Saad, Maria Daniela Saa Espinosa, Sheetal Suhas Dhanuka, Yi Yang

Harrisburg University Dissertations and Theses

The global fashion industry generates over 92 million tons of textile waste annually, a figure projected to increase significantly by 2030. Bio-engineered fibers, including bacterial cellulose, mycelium-based leather, and recombinant protein textiles emerge as sustainable alternatives to conventional fibers. Despite their promise, recent evidence suggests that these fibers may pose environmental risks at the end-of-life stage, such as incomplete biodegradation in landfills, microfiber shedding, and chemical leaching from dyes and coatings. The purpose of this study is to examine how these risks are represented through scientific literature, corporate sustainability reports, and policy frameworks, and to identify strategies for integrating risk …

Perceived Effects Of Verbal Orders On In-Patient Medication Reconciliation And Safety: A Multi-Center Cross-Sectional Study, Yahaya Jafaru, Abubakar K. Sahabi, Mohammed M. Sani

Pharmacology and Clinical Pharmacy Research

Medication reconciliation presents significant challenges for healthcare professionals, particularly due to communication gaps that contribute to patient safety incidents. The aim of the study was to investigate the perceived effect of verbal orders on in-patient medication reconciliation and safety. The study was a cross-sectional survey with nurse employees of the three tertiary hospitals in Kebbi State, Nigeria as population of the study. The instrument for the data collection was a 21-items researcher-constructed self-administered questionnaire. Chi-square and binomial regression analysis were used in data analysis. Over two-thirds (70.7%) of the respondents reported a negative perceived effect on the patient’s compliance. The …

Crosstalk Between Gut Microbiota And Antihypertensive Drugs: A Systematic Review, Dhiya'ul Haq, Keri Lestari

Pharmacology and Clinical Pharmacy Research

Hypertension is a multifactorial condition characterized by persistently elevated blood pressure. In addition to genetic and environmental factors, recent studies suggest that the gut microbiota contributes to the development of hypertension and modulates the response to antihypertensive therapy. This review aims to summarize the latest knowledge on the bidirectional interaction between gut microbiota and antihypertensive drugs. Original studies published up to May 2025 on this topic were collected from two online databases: PubMed and Scopus. A total of 220 articles were identified, and 9 articles met the inclusion criteria for further discussion. Three of these included articles discussed how gut …

Anti-Inflammatory Actions Of Trigonella Foenum-Graecum L. In Acute And Chronic Inflammation: Insights From Preclinical Studies, Angel Christella, Dzava P. F. Ismail, Eli Halimah

Pharmacology and Clinical Pharmacy Research

Chronic inflammation is a major factor in various degenerative diseases. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often the main choice, but long-term side effects such as gastrointestinal irritation and nephrotoxicity limit their use. Therefore, natural alternatives such as Trigonella foenum-graecum (fenugreek) have attracted attention due to their bioactive compound contents with anti-inflammatory properties. This narrative review was conducted through a systematic search of articles from the last 10 years in PubMed and Scopus. Keywords used a combination of MeSH and free terms related to fenugreek and anti-inflammatory agents. In vitro and in vivo studies evaluating the anti-inflammatory effects …

Racial And Ethnic Disparities In Neoadjuvant Chemotherapy Patterns And Outcomes In Early-Stage Her2-Positive Breast Cancer, Inimfon Jackson, Xiudong Lei, Hui Zhao, Rashmi Murthy, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

We examined neoadjuvant chemotherapy (NACT) use, pathological complete response (pCR) and the association with overall survival (OS) among patients with early-stage HER2-positive breast cancer (BC). Patients ≥18 years with stage I-III HER2-positive BC from 2010-2022 who had surgery and chemotherapy were identified. Of 195,023 patients treated with chemotherapy, 37.7% received NACT. NACT use increased from 18.6% in 2010 to 63.4% in 2022 (p <  0.001) and pCR rates rose from 21% to 47.6% (p <  0.001). Black patients were less likely to receive NACT (aOR = 0.96;95%CI 0.93-0.99) or achieve pCR (aOR = 0.86;95%CI 0.82-0.90) than White patients. pCR was associated with a reduction in the risk of death (aHR = 0.45;95%CI 0.42-0.48). 3-year OS increased from 91% in 2010 to 95% in 2019 for patients without a pCR (p <  0.001), and from 97% to 99% for patients with pCR (p = 0.002). Further research is needed to understand and address racial and ethnic disparities in treatment access and outcomes.

Fgf13 Regulates Vgsc-Independent Cardiomyocyte Impulse Propagation Via Cx43 Trafficking, Lala Tanmoy Das, Mattia Malvezzi, Aravind R Gade, Maiko Matsui, Margaret Mckay, Eric Q Wei, Matea J Zelich, Keon Mazdisnian, Jared Kushner, Bi-Xing Chen, Isabella Distefano, Daniel Roybal, Lin Yang, Lisa Stoll, James C Lo, Marian Kalocsay, Fadi G Akar, Steven O Marx, Geoffrey S Pitt

Faculty, Staff and Student Publications

Background: FHF (fibroblast growth factor homologous factor) variants associate with arrhythmias. Although FHFs are best characterized as regulators of voltage-gated sodium channel (VGSC) gating, recent studies suggest broader, non-VGSC-related functions, including regulation of Cx43 (connexin 43) gap junctions and hemichannels, mechanisms that have generally been understudied or disregarded.

Methods: We assessed cardiac conduction and cardiomyocyte action potentials in mice with constitutive cardiac-specific Fgf13 ablation (cFgf13KO) while targeting Cx43 gap junctions and hemichannels pharmacologically. We characterized FGF13 regulation of Cx43 abundance and subcellular distribution. With proximity labeling proteomics, we investigated novel candidate mechanisms underlying FGF13 regulation of Cx43. …

Increased Intermembrane Space [Ca2+] Drives Mitochondrial Structural Damage In Cpvt, Shanna Hamilton, Radmila Terentyeva, Roland Veress, Fruzsina Perger, Zuzana Nichtova, Mark Bannister, Jinxi Wang, Sage Quiggle, Rachel Battershell, Matthew Gorr, Sandor Györke, Bum-Rak Choi, Christopher George, Andriy Belevych, György Csordás, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Mitochondrial dysfunction caused by abnormally high RyR2 (ryanodine receptor) activity is a common finding in cardiovascular diseases. Mechanisms linking RyR2 gain of function with mitochondrial remodeling remain elusive. We hypothesized that RyR2 hyperactivity in cardiac disease increases [Ca 2+ ] in the mitochondrial intermembrane space (IMS) and activates the Ca 2+ -sensitive protease calpain, driving remodeling of mitochondrial cristae architecture through cleavage of structural protein OPA1 (optic atrophy protein 1).

METHODS: We generated a highly arrhythmogenic rat model of catecholaminergic polymorphic ventricular tachycardia, induced by RyR2 gain-of-function mutation S2236L(Ser2336Leu)(+/-) . We created a new biosensor to measure IMS-[Ca2+ ] …