Digital Commons Network^™

Astrovascular Decoupling In Awake 5×Fad Mice Is Associated With Reduced Astrocytic Calcium, Ruei-Lung Lin, Sophiya L. Sims, Nicholas A. Wright, Léopoldine B. Galopin, Blaine Weiss, Susan D. Kraner, Jacquelyn E. Rhinehart, Ting-Hsuan Lu, Pradoldej Sompol, Christopher M. Norris, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

INTRODUCTION

Evidence points to dysregulated Ca²⁺ in neurons and astrocytes in models of amyloidosis. While most of these data were obtained in vitro or in vivo under anesthesia, less work has investigated these variables in awake ambulating mice.

METHODS

Astrocytic Ca²⁺ fluctuations (GCaMP8f) were imaged concomitantly with vasoreactivity in S1 on a two-photon microscope during rest and ambulation. Single-cell resolution variables were extracted using continuous wavelet transform and traditional ΔF/F measures.

RESULTS

Along with increases in amyloid beta (Aβ) accumulation, we found significant reductions in measures of astrocyte functional connectivity, pairwise correlations, and network synchronicity in older 5×FAD …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

The Physiological Effects Of Anabolic Steroids On The Human Body, Aedan Kerr

Undergraduate Honors Theses

Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone used both medically and illicitly for their muscle-building and performance-enhancing properties. While clinically prescribed for conditions like hypogonadism, osteoporosis, and muscle-wasting diseases, AAS are frequently abused by athletes and recreational lifters seeking rapid physical gains. AAS increase muscle protein synthesis via androgen receptor-mediated gene transcription, but they also predispose users to tendon ruptures and various organ functions. AAS abuse is strongly associated with a host of side effects including gynecomastia, male-pattern hair loss, infertility, hepatotoxicity, erythrocytosis, dyslipidemia, insulin resistance, and hypogonadism. Cardiovascular complications such as left ventricular hypertrophy, cardiomyopathy, and myocardial infarctions …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

Neuropsychological Assessment Accuracy In Diagnosing Early-Onset Alzheimer’S Disease, Elise Thomas

Master's Theses and Doctoral Dissertations

Early-onset Alzheimer’s disease (EOAD), a progressive neurological condition, is often difficult to diagnose before substantial neuronal damage. Neuropsychological assessments offer a more cost-effective and accessible method for detecting early cognitive decline, yet limited research exists on optimal combinations for EOAD identification. This study analyzed data from 24 clinical studies to determine the diagnostic accuracy of FDA-approved EOAD assessments used in combination. No single combination was found to be superior across all diagnostic metrics. MMSE + MoCA + ADAS-Cog showed the highest sensitivity, MMSE + MoCA + RBANS the highest specificity, MMSE + RBANS the highest AUC value, and MMSE + …

The Influence Of Ultra-Widefield Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Nicole K Scripsema, Tala Al-Khaled, Amy Song, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan

Faculty, Staff and Students Publications

Purpose: To study the influence of ultra-widefield fluorescein angiography (FA) on the diagnosis and management of diabetic retinopathy (DR).

Methods: Ten experts in DR completed an online survey in which they were asked to diagnose and manage DR cases using different imaging modalities. Experts independently reviewed 20 cases of DR and provided a diagnosis and management plan for each case, first based on ultra-widefield color-free and red-free images alone and again with the corresponding ultra-widefield FA images. Experts were polled on their diagnostic confidence, use of FA in clinical practice, and opinions on the value of ultra-widefield FA. Based on …

Primary Polydipsia In A Case Of Genetic Behavioral Variant Frontotemporal Dementia, Yesenia Cantu, Taryn White, Gabriela Austgen, Christine Rizk, Olaoluwa O Okusaga, Melissa B Jones

Faculty, Staff and Students Publications

No abstract provided.

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

Distinct Contributions Of Cerebrospinal Fluid Biomarkers To Cognitive Impairment And Neuropsychiatric Symptoms In Young-Onset Dementia, Wei Hsuan Chiu, Anita M.Y. Goh, Dhamidhu Eratne, Charles B. Malpas, Matthew J.Y. Kang, Wendy Kelso, Mark Walterfang, Dennis Velakoulis, Samantha M. Loi

Research outputs 2022 to 2026

Objective: Young-onset dementia (YOD), defined by symptom onset before age 65, encompasses diverse aetiologies and presents with prominent neuropsychiatric symptoms (NPS) that often accompany or exacerbate cognitive decline. However, the pathological mechanisms linking NPS, cognition, and biomarkers remain unclear. It was hypothesised that relationships between NPS and cognition would be mediated or moderated by cerebrospinal fluid (CSF) biomarker levels in individuals with YOD. Methods: This retrospective, cross-sectional study included 46 participants with YOD (24 with Alzheimer's disease [AD], 22 with non-AD dementias) diagnosed at the Neuropsychiatry Centre, Royal Melbourne Hospital. NPS were measured using the Depression Anxiety and Stress Scale …

Functional And Traditional Medical Management Of Endometriosis: An Integrative Review, Madison G. Daniels

Senior Honors Theses

Endometriosis, a progressive disease that affects many women worldwide, has been managed primarily through hormonal medication, pain management and surgical intervention. However, there is a growing desire among women to use more natural and holistic methods to control the progression of this disease as well as effectively manage the severe symptoms that accompany it. This integrative review examines the efficacy of functional management as compared to traditional medical management. The pathophysiology of each treatment method and provide statistical evidence as to its efficacy. The progression of the disease, symptom management, and related side effects are all taken into consideration in …

The Effect Of Hypochlorous Acid On Cultured Osteoblast And Escherichia Coli, Cristina Flaquer Fusté

Graduate Theses/Dissertations

Hypochlorous acid (HOCl), a naturally occurring compound in neutrophils, has been used as an antimicrobial in wound treatment. Osteoblasts, bone-forming cells, within the bone tissue play a large role in bone fracture healing. Orthopedic infections are challenging to treat and highly morbid, including surgical site infection of arthroplasty procedures or infection in the setting of compound fractures. HOCl is being considered as a surgical antiseptic to decrease infections in orthopedic surgical procedures. This study therefore seeks to determine the effects of HOCl on osteoblasts and E. coli. Cultured osteoblasts were incubated with varying concentrations of HOCl to examine osteoblast …

Bolton’S Tooth Width Discrepancies Among Orthodontic Patients In A Tanzanian Population, Ferdinand Mabula Machibya, Eladius Laswai Daniel, Matilda Mtaya Mlangwa

Mansoura Journal of Dentistry

Aim: The aim of the current study was to assess the prevalence of intermaxillary teeth width discrepancy among orthodontic patients in a Tanzanian population. Methods: A cross sectional retrospective study was carried involving 204 orthodontic casts. Data collection involved mesio-distal teeth width measurement of all teeth anterior to second molars using a digital Vernier Caliper. Intermaxillary teeth width ratios between lower and upper teeth was then determined according to Bolton’s formula. Independent t test was used to assess whether anterior and overall intermaxillary teeth width ratios vary between males and females. The prevalence of Bolton’s teeth width discrepancies were determined …

Fracture Resistance Of Different Lithium Disilicate Restorations After Endodontic Access Cavity Preparation: Effect Of Repair Method, Hebah Agamal Abdulghafor, Essam A. Khedr, Nesma M. Elgohary, Walid A. Al-Zordk

Mansoura Journal of Dentistry

Objective: To evaluate the effect of different repair methods on the fracture resistance of lithium disilicate restorations after endodontic access cavity preparation. Materials and Methods: One hundred sixty sound human mandibular first molars were prepared and restored with four types of lithium disilicate–based crowns: IPS e.max CAD, GC Initial LiSi Block, Straumann n!ce, and CEREC Tessera (n = 40 each). Standardized endodontic access cavities were prepared in all specimens, then repaired using one of four techniques: (1) inlay restoration with Monobond Etch&Prime, (2) inlay restoration with IPS Ceramic Etching Gel + Monobond Plus, (3) direct composite with IPS Ceramic Etching …

Regulation Of Human Dna Mismatch Repair, Breanna Knicely

Theses and Dissertations--Toxicology and Cancer Biology

The DNA mismatch repair (MMR) pathway identifies and corrects misincorporations that arise during DNA replication. MMR is a pathway that is critical for maintaining genomic stability. Mutations within the MMR pathway, both germline and somatic, lead to the development of cancer. There are a variety of mechanisms that regulate the MMR pathway including protein-protein interactions, DNA damage response, and post-translational modifications. In this study, we aim to dive deeper into each of these mechanisms to obtain novel information regarding the mechanisms and regulation of human DNA MMR. In this study we generated hExo1 constructs mutating Exo1’s interactions with MSH2 and …

Heritability And Shared Environmental Effects Of Brain Diseases In 12,040 Extended Families, Janna I R Dijkstra, Marc Hulsman, Lisa Waterink, Henne Holstege, Charlotte E Teunissen, Wouter F L Christiaansen, Bryan A De Jong, Peter Kochunov, Brian Donohue, Marissa D Zwan, Anouk Den Braber, Lisa Vermunt, Sven J Van Der Lee

Faculty, Staff and Student Publications

Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h2) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h2 through bootstrapping; Alzheimer’s disease (AD) (h2 = …

Socket Preservation Using Autogenous Particulate Dentin In Combination With Liquid Platelet-Rich Fibrin Versus Bone Allografts After Surgical Extraction Of Impacted Lower Third Molar, Ali Mahmoud Mohamed Ali Elshafei, Wael Mohamed Ahmed Said Ahmed, Ziad Amr Elmissiry

Mansoura Journal of Dentistry

Objectives To evaluate and compare the efficacy of sticky tooth graft versus bone allografts used for socket preservation after the surgical extraction of horizontally impacted lower third molars. Materials and Methods Thirty patients with horizontally impacted lower third molars were randomly and equally divided into two groups; group I: 15 patients received dentin granules mixed with Liquid PRF (sticky tooth) in the socket after extraction, group II: 15 patients received bone allograft after extraction. Postoperative pain, edema and bone resorption were assessed. Bone resorption was evaluated using cone-beam computed tomography (CBCT) over a three-month period. Results There were statistically significant …

Comparing The Swallowing Dynamics Of Mandibular Implant Overdentures Retained With Different Attachment Systems: A Crossover Study, Nermeen Elsayed Mohamed Abdallah, Noha Hosny Elshaheed, Abdullah Mohammed Ibrahim Salem

Mansoura Journal of Dentistry

Objective This study's objective was to compare the swallowing dynamics for mandibular implant-retained overdentures with different attachment systems Materials and methods for this crossover study, 15 healthy patients were chosen from the outpatient clinic, Department of Removable Prosthodontics, Faculty of Dentistry. The patients already had 2 implants in the canine regions. New mandibular implant-retained overdentures with three different attachment systems (locator, ball, and bar) were constructed. Swallowing evaluation was done after 3 months of each implant overdenture insertion. Swallowing dynamics were evaluated by using the Test of Mastication and Swallowing Solids (TOMASS) and the Timed Water Swallow Test (TWST). ANOVA …

Evaluation Of Two- Implant Assisted Mandibular Overdentures Of Cobalt Chromium Vs. Peek Combined Denture Bases Regarding Occlusion And Patient Satisfaction: A Within-Subject Study, Khaled M. Diaa, Noha H. El-Shaheed, May A. Hagag, Fatma A. El-Waseef

Mansoura Journal of Dentistry

Objectives The purpose of this within-patient study was to compare two implant-assisted overdentures (IAOs) reinforced either with polyether-ether ketone (PEEK) or cobaltchromium (CO-CR) regarding the percentage of occlusal contact using a digital occlusion analysis system (Occlusense) and to assess patient satisfaction and Oral Health–Related Quality of Life (OHRQoL). Subjects and methods Ten complete edentulous subjects were eligible. All patients were delivered two mandibular implant-assisted overdentures with two reinforcement materials, CO-CR (group I) and PEEK (group II).The mandibular overdentures were retained to the underlying implant fixtures by ball and socket attachments. Patients were evaluated three months after each overdenture use. For …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Immune Pathway Modulation In Melanoma Using Chitosan Nanoparticle-Mediated Dsrna Delivery, Bethel C. Iwuji

Theses and Dissertations (Comprehensive)

Cancer is a group of diseases characterized by abnormal and uncontrolled cell division, which typically results in the formation of tumours. Even with advances in treatments, cancer remains one of the leading causes of death globally. Melanoma is an aggressive form of skin cancer which is highly malignant, develops in the pigment-producing cells of the skin, melanocytes, and in the late stages of the disease poses a significant challenge for therapeutic intervention due to its multidrug resistance. The innate immune system is the first line of defence against invading pathogens, including viruses, bacteria, and fungi, and can recognize and destroy …

Modeling Functional Connectivity With Learning And Memory In A Mouse Model Of Alzheimer’S Disease, Lindsay Fadel, Elizabeth Hipskind, Steen E Pedersen, Jonathan Romero, Caitlyn Ortiz, Eric Shin, Md Abul Hassan Samee, Robia G Pautler

Faculty, Staff and Students Publications

Introduction: Functional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.

Methods: We assessed the APP/PS1 mouse model of AD and wild-type controls …

Intraoperative Recognition And Anesthetic Management Of Myxedema Coma During Emergent Intertrochanteric Femur Fracture Repair, Arusa Macnojia, Marlene Lopez, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

Myxedema coma is a rare, life-threatening complication of severe, long-standing hypothyroidism, often precipitated by physiological stress such as infection, trauma, or surgery. Perioperative presentations of myxedema coma are especially uncommon. This case report describes a 71-year-old male with a history of poorly controlled hypothyroidism who underwent emergent surgical fixation of a traumatic left intertrochanteric femur fracture who developed intraoperative myxedema coma. Timely diagnosis and intervention—including intravenous thyroid hormone replacement, corticosteroids, hemodynamic support, and close anesthetic management were crucial to optimizing the patient’s outcome. This report highlights the critical role of anesthetic management in myxedema coma cases, emphasizing the importance of …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

Ancestry-Dependent Immunologic And Prognostic Effects Characterize The Prostate Cancer Urinary Proteome, Annie Ha, Jaron Arbet, Zhuyu Qiu, Amanda Khoo, Brian P. Main, Meinusha Govindarajan, Matthew Waas, Stanley K. Liu, O. John Semmes, Julius O. Nyalwidhe, Paul C. Boutros, Thomas Kislinger

Leroy T. Canoles Jr. Cancer Research Center Faculty Publications

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between …

Gait Variability As A Marker Of White Matter Integrity In Individuals With Down Syndrome, Elizabeth M. Leach, David K. Powell, Amanda C. Glueck, Elizabeth Head, Moaz W. Ibrahim, Amelia J. Anderson-Mooney, Kathryn L. Van Pelt, Jordan P. Harp, Frederick A. Schmitt, Ahmed A. Bahrani

Sanders-Brown Center on Aging Faculty Publications

Introduction: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS.

Methods: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years).

Results: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …