Digital Commons Network^™

Sirt5 Inhibition Impairs Mitochondrial Metabolism And Enhances Venetoclax-Induced Elimination Of Acute Myeloid Leukemia Cells, Moran Wang, Ruiqi Zhu, Donald Small, Lan Lin, Li Li, Shengling Ma, Linghui Xia, Shanshan Luo, Wenjuan He, Jianming Yu, Junying Li, Ruowen Wei, Ao Zhang, Wei Shi, Yu Hu

Faculty, Staff and Students Publications

Metabolic reprogramming is a key focus of targeted therapies in acute myeloid leukemia (AML). The mitochondrial sirtuin SIRT5 removes succinyl groups from specific lysines and impacts cell metabolism, but its role in AML tumorigenesis has not been extensively explored. A recent study highlighted that SIRT5 regulates AML cell activity by modulating glutamine metabolism, but its molecular targets in AML remain unclear. This study aims to identify the substrates of SIRT5 in AML. It was found that a total of 83 proteins with 121 lysine (K) residues showed increased succinylation after SIRT5 knockdown, as determined by succinylome analysis of MOLM-13 cells. …

Contribution Of Pannexin Channels To Afterimage Signals In The Amphibian Retina, Yufei Liu, Nick Libian, Zheng Jiang, Wen Shen

Faculty, Staff and Students Publications

Pannexin 1 (Panx1) forms large-pore, single-membrane channels that connect the intracellular and extracellular environments, permitting the passage of ions and small molecules such as ATP. Panx1 channels are involved in diverse signaling pathways that contribute to various physiological processes, including sensory processing, although their precise mechanisms of action remain incompletely understood. This study reveals a Panx1-mediated mechanism regulating visual signal processing in the amphibian retina. Using immunolabeling and confocal imaging, we localized Panx1 channels in the cone-dominated On-bipolar cells, specifically at both somas and axon terminals. Whole-cell patch-clamp recordings showed that these channels have high permeability to Cl⁻ ions, which …

Community-Engaged Medical Student Elective To Improve Knowledge And Attitudes Toward Individuals With Intellectual And Developmental Disabilities, Kathryn J Kemere, Nital Appelbaum, Priya Chandan, Elisha Acosta

Faculty, Staff and Students Publications

Individuals with intellectual and developmental disabilities (IDD) face multiple barriers to inclusion throughout life. One barrier is the medical knowledge and biases of adult healthcare providers with diagnoses traditionally associated with childhood. Medical school curricula have limited content related to IDD, and students have limited opportunities to engage with community organizations during their clinical years. Methods: We created a one-month clinical elective to address medical students' attitudes and knowledge regarding individuals with IDD using experiential learning. Students saw adult patients in our primary care clinic with a variety of IDD diagnoses and spent 30% of their time at community sites …

Construct And Predictive Validity Of The Kansas City Cardiomyopathy Questionnaire In Adult Congenital Heart Disease, Ryan D Byrne, Ajith P Nair, Stephen J Dolgner, Swati Choudhry, Edward J Hickey, Alexis C Wood, Savitri Fedson, Biykem Bozkurt, Christopher R Broda

Faculty, Staff and Students Publications

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is an Food and Drug Administration-approved health status measure for patients with heart failure (HF) but has not been directly assessed in adult congenital heart disease (ACHD).

Objectives: This study evaluates construct and predictive validity of the KCCQ in ambulatory ACHD patients.

Methods: We performed cross-sectional and prospective cohort studies of ACHD patients who completed the KCCQ to assess construct and predictive validity, respectively. KCCQ scores were compared across ACHD complexity categories, disease characteristics and physiologic failure, and within 2 primary composite outcomes: death or all-cause hospitalization (DH) and death or interventional cardiac …

Effect Of Aerobic Or Resistance Exercise, Or Both On Insulin Secretion, Ciliary Neurotrophic Factor, And Insulin-Like Growth Factor-1 In Dieting Older Adults With Obesity, Georgia Colleluori, Viola Viola, Siresha Bathina, Reina Armamento-Villareal, Clifford Qualls, Antonio Giordano, Dennis T Villareal

Faculty, Staff and Students Publications

Background and aims: Obesity exacerbates age-related changes in metabolic and physical function. The effect of distinct exercise modalities combined with diet-induced weight loss on insulin secretion in older adults with obesity and frailty is unknown, and the potential mediators of the metabolic and functional improvements induced by lifestyle therapy still need to be identified. We aimed to assess the effects of various exercise therapies coupled with diet-induced weight loss on insulin secretion and sensitivity and on the levels of circulating Ciliary Neurotrophic Factor (CNTF), its receptor (CNTFRα), and Insulin-like Growth Factor-1 (IGF-1) in older adults with both obesity and frailty. …

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Mechanisms Underlying Atrial Fibrillation In Chronic Kidney Disease, Jose Alberto Navarro-Garcia, Joshua A Keefe, Jia Song, Na Li, Xander H T Wehrens

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is a serious and progressive worldwide health problem affecting 15 % of the global population. CKD is associated with higher mortality rates due to secondary complications such as cardiovascular disease. Common cardiovascular complications found in CKD patients include left ventricular hypertrophy, heart failure, and cardiac arrhythmias. The most common type of cardiac arrhythmia in CKD patients is atrial fibrillation (AF). Proper management of AF is important due to its high risk of cardiovascular complications and stroke. The incidence of AF remains higher in CKD patients than in the healthy population, highlighting the need to improve our …

The Eleventh Annual Meeting Of The Southeastern Association Of Shared Resources (Seasr) Nashville, Tn, Usa June 12-14, 2024, Jenny C Schafer, Lyra M Griffiths, Tania E Mesa, Deidre Daria, Daniel Kraushaar, Kristen V Massey, Edith M Sampson, Laura Fox-Goharioon, Laxminarayanan Krishnan, Stacie Woolard, Aaron Pitre

Faculty, Staff and Students Publications

No abstract provided.

Total Aortic Arch Replacement Using The Thoraflex Hybrid Device: Evolution From Investigational To Federally Approved Use In The United States, Vicente Orozco-Sevilla, Joseph S Coselli, Susan Y Green, Veronica A Glover, Ricardo De Jesus Avendaño Garnica, Anna H Xue, Lauren K Barron, Marc R Moon

Faculty, Staff and Students Publications

Background: After the US Food and Drug Administration (FDA) approved the Thoraflex Hybrid device in April 2022, hybrid devices to facilitate total arch replacement (TAR) became commercially available in the United States. However, little is known about how the Thoraflex device has been used since then. We present our experience (2016-2025) with this device.

Methods: At our practice, 62 patients [median age, 65 (54-73) years] underwent frozen elephant trunk (FET) TAR with the Thoraflex device: 14 under an investigational device exemption (IDE) (2016-2018) and 48 after FDA approval (2022-2025). Both Ante-Flo (straight) and Plexus (branched) models were used.

Results: Patients …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Dietary Lipids Induce Ppard And Bcl6 To Repress Macrophage Il-23 Induction After Intestinal Injury And Lps Exposure, Ashleigh M Gil, Daniel F Zegarra-Ruiz, Wan-Jung Wu, Kendra Norwood, Adrien Assie, Buck S Samuel, Angela M Major, Gretchen E Diehl, Andrea A Hill Mcalester

Faculty, Staff and Students Publications

Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage Il23a induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the …

Improving Door-In-Door-Out Times For Stemi Transfer Patients: Impact Of A Protocolized Autolaunch Process, Hashim Zaidi, Waleed Kayani, Eric Power, Hei Kit Chan, Sini Eapen, Benjamin Karfunkle

Faculty, Staff and Students Publications

Background: The timely transfer of patients with ST-segment elevation myocardial infarction (STEMI) to percutaneous coronary intervention-capable centers is critical for improving outcomes. Although the American Heart Association recommends a door-in-door-out (DIDO) time of ≤30 minutes, national compliance remains low.

Project rationale: At Harris Health, no patients with STEMI met this benchmark before 2022. We implemented a quality improvement (QI) initiative, including an "Autolaunch" process, to expedite STEMI transfers.

Project summary: During 2022-2023, we introduced QI initiatives, including the Autolaunch protocol, for patients with unequivocal STEMI. This process included rapid emergency medical services activation, direct catheterization laboratory transfer, and prearrival cardiologist …

Constitutive Il-7 Signaling Promotes Car-Nk Cell Survival In The Solid Tumor Microenvironment But Impairs Tumor Control, Matthew Dysthe, Ishwar Navin, Dayenne Van Leeuwen, Josue Pineda, Corrine Baumgartner, Cliona M Rooney, Robin Parihar

Faculty, Staff and Students Publications

Background: Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches. However, current cytokine strategies have limitations, including systemic toxicities, exogenous dependencies, and unwanted TME bystander effects. Here, we aimed to overcome these limitations by modifying CAR-NK cells to express a constitutively active interleukin (IL)-7 receptor, termed C7R, capable of providing intrinsic CAR-NK cell activation that does …

Potential Biological And Genetic Links Between Dementia And Osteoporosis: A Scoping Review, Abayomi N Ogunwale, Paul E Schulz, Jude K Des Bordes, Florent Elefteriou, Nahid J Rianon

Faculty, Staff and Students Publications

Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions.

Methods: Studies selected (1) involved clinical research investigating genetic factors or biomarkers associated with dementia or osteoporosis, and (2) were published in English in a peer-reviewed journal between July 1993 and March 2025. We searched Medline Ovid, Embase, PsycINFO, the Cochrane Library, the Web of Science databases, Google Scholar, and the reference lists of studies following the guidelines for …

Mouse Metastable Epialleles Are Extremely Rare, Chathura J Gunasekara, Uditha Maduranga, Taylor Zhang, Jonathan N Wells, Maria S Baker, Eleonora Laritsky, Yumei Li, Cristian Coarfa, Yi Zhu, Robert A Waterland

Faculty, Staff and Students Publications

Metastable epialleles (MEs) are genomic loci at which epigenetic marks are established stochastically during early embryonic development and maintained during subsequent differentiation and throughout life, leading to stable epigenetic and phenotypic variation among genetically identical individuals. Although MEs were first described in mice over 20 years ago, the extent of epigenetic metastability in the mouse genome remains unknown. We present the first unbiased genome-wide screen for MEs in mice. Using deep whole-genome bisulfite sequencing across tissues derived from the three embryonic germ layers in isogenic C57BL/6J mice, we identified only 29 MEs, precisely localizing them and documenting their rarity. Consistent …

Sensing The Stiffness: Cellular Mechano-Sensing At The Implant Interface, Patricia S Pardo, Delia Danila, Raja Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms …

Elimination Of Hiv Reservoirs Harboring Intact Proviruses, Min Li, Khanghy Truong, Suman Sharma, Baichao Sun, Min Chen, Jason T Kimata, Jin Wang

Faculty, Staff and Students Publications

Background: Human immunodeficiency virus (HIV) establishes persistent infection by integrating its proviral DNA into the host genome. While most integrated proviruses are defective, a small portion of proviruses are intact that represent a major obstacle to achieving an HIV cure. We have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. However, the effects of SECH on the dynamics of intact and defective HIV provirus remain unclear.

Methods: We isolated DNA from HIV-infected samples after SECH treatments. We analyzed HIV-1 proviruses in these samples by intact …

Spase: Spatially Resolved Pathology Scores Using Optimal Transport On Spatial Transcriptomics Data, Mohammad Nuwaisir Rahman, Mohammed Abid Abrar, Vikram Rakesh Shaw, James F Martin, M Saifur Rahman, Md Abul Hassan Samee

Faculty, Staff and Students Publications

Pathological events often impact tissue regions in a spatial variable manner, making it challenging to identify therapeutic targets. Spatial transcriptomics (ST) is a powerful technology to map spatially variable molecular mechanisms, yet suitable analytical methods have been lacking. We introduce SPaSE (Spatially-resolved Pathology ScorE), an optimal transport-based algorithm to compare ST data from diseased and control tissues. SPaSE computes a “pathology score” for each spot in the diseased sample, quantifying the pathological impact at that spot. In post-MI (myocardial infarction) mouse hearts, these scores delineated zones that matched independent expert annotations. Modeling pathology scores from gene expression revealed signatures predictive …

Altered Patterning Of Neural Activity In A Neuropathology, Clarissa Hoffman, Jingheng Cheng, Rodrigo Morales, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

The dynamics of neural circuits and their role in mediating cellular and organismal phenomena remain poorly understood, despite numerous efforts to dissect these processes through precise instantaneous measurements or longer-time averages and approximations. We use an alternative approach: we investigate these dynamics at the system's mesoscale by analyzing spike trains and waveforms. These extended activity patterns carry robust, tractable information, are highly responsive to physiological specifics, and enable detailed tracking of circuit behavior. In particular, this methodology allows for characterizing the functionality of tau-pathology-afflicted hippocampal circuits and identifying circuit-level abnormalities that are missed by through traditional analyses. In healthy mice, …

Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Lianlei Wang, Xinyu Yang, Sen Zhao, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Disco Study Group (Deciphering Disorders Involving Scoliosis & Comorbidities), Shiro Ikegawa, James R Lupski, Jonathan J Rios, Carol A Wise, Jianguo T Zhang, Chengtian Zhao, Nan Wu

Faculty, Staff and Students Publications

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we first reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited …

Exogenous Arginine Differentially Regulates Inflammatory Cytokine And Inducible Nitric Oxide Synthase Expression In Macrophages, Kelsey Stayer, Saliha Pathan, Aalekhya Biswas, Huiqiao Li, Yi Zhu, Fong Wilson Lam, Juan Marini, Sundararajah Thevananther

Faculty, Staff and Students Publications

Immune dysfunction and late mortality from multiorgan failure are hallmarks of severe sepsis. Arginine, a semi-essential amino acid important for protein synthesis, immune response, and circulatory regulation, is deficient in sepsis. However, arginine supplementation in sepsis remains controversial due to the potential to upregulate inducible nitric oxide synthase (iNOS)-mediated excessive nitric oxide (NO) generation in macrophages, leading to vasodilation and hemodynamic catastrophe. Citrulline supplementation has been considered an alternative to replenishing arginine via de novo synthesis, orchestrated by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). However, the functional relevance of the ASS1-ASL pathway in macrophages after endotoxin stimulation is …

Ovochymase 2 Is A Key Regulatory Factor Modulating Proteolytic Pathways And Sperm Maturation In The Mammalian Epididymis, Katarzyna Kent, Kaori Nozawa, Antrix Jain, Anna Malovannaya, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

Spermatozoa acquire fertilizing competence during epididymal transit through proteolytic, chaperone-mediated, and post-translational modifications. Ovochymase 2, an epididymis-specific trypsin-like serine protease, has emerged as a central regulator of this maturation process. Here, we integrate targeted gene disruption, comprehensive proteomic profiling, and affinity-based proteome enrichment to delineate how Ovochymase 2 influences sperm functionality. Deletion of Ovochymase 2 disrupts the proteome of epididymal sperm, resulting in diminished levels of core fertility-related factors-including a disintegrin and metalloprotease domain 3, β-defensins, and protease-inhibitor complexes-while inducing compensatory upregulation of alternate proteases and chaperones. Interaction assays confirm direct or indirect associations between Ovochymase 2 and sperm surface …

A Mouse Model Engineered To Spatiotemporally Control Cre Expression In Progesterone Receptor Positive Cells†, Elvis Quiroz, Ryan M Marquardt, Shu-Yun Li, Artiom Gruzdev, David Cunefare, Charan Ganta, San-Pin Wu, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

The Cre/loxP system is widely used for site-specific genetic manipulation in mice. The PgrCre mouse model, where Cre recombinase is driven by the progesterone receptor promoter, is commonly used for gene ablation in Pgr-positive uterine cells. However, the PgrCre is active in the neonatal uterus and does not allow temporal control. To enhance the functionality of the PgrCre mouse, we generated and characterized an inducible PgriCreERT2 mouse, in which iCreERT2 is inserted downstream of the endogenous Pgr promoter. PgriCreERT2 mice crossed with Rosa26-CAG-LSL-Sun1-sfGFP-myc reporter mice demonstrated tamoxifen-dependent recombination in uterine stromal fibroblasts and a subset of epithelial cells. Tamoxifen-induced ablation …

Impact Of Sanitation System Types On Residential And Environmental Presence Of Human Waste And Parasites In Alabama, Brandon Hunter, Catherine Coleman Flowers, Rojelio Mejia, Marc Arnold Deshusses

Faculty, Staff and Students Publications

Lowndes County is a predominantly Black rural county in Alabama, in the United States, which has a historical and current legacy of racial discrimination, creating inequitable infrastructure access and adverse health impacts. Over 80% rely on on-site sanitation infrastructure and most are failing. A community assessment of exposure to untreated sewage was conducted using samples from residential drinking water, surface swabs, and soil combined with environmental water and soil samples using culture-based and quantitative polymerase chain reaction (qPCR) methods. Testing varied slightly across samples, due to difficulty of access or availability. Of 43 households, 68% and 55% of houses had …

Oral Dosing Of The Nucleoside Analog Obeldesivir Is Efficacious Against Rsv Infection In African Green Monkeys, Jared Pitts, J Lizbeth Reyes Zamora, Savrina Manhas, Thomas Aeschbacher, Josolyn Chan, Vincent Cutillas, Varsha Nair, Nicholas C Riola, Arya Vijjapurapu, Meghan S Vermillion, Stacey Eng, Christopher Richards, Dong Han, Jason K Perry, Subhra Chaudhuri, Szu-Wen Liu, Clarissa Martinez, Nadine Peinovich, Kai-Hui Sun, Arthur Cai, Ross Martin, Jasmine Moshiri, Charlotte Hedskog, Darius Babusis, Dustin S Siegel, Rao Kalla, Vasanthi Avadhanula, Pedro A Piedra, Kim Stobbelaar, Peter L Delputte, Caleb Marceau, Roberto Mateo, Evguenia Maiorova, Hongmei Mo, Raju Subramanian, Richard L Mackman, Tomas Cihlar, Simon P Fletcher, John P Bilello

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with …

Global Diversity Of Soil-Transmitted Helminths Reveals Population-Biased Genetic Variation That Impacts Diagnostic Targets, Marina Papaiakovou, Andrea Waeschenbach, Olumide Ajibola, Sitara Sr Ajjampur, Roy M Anderson, Robin Bailey, Jade Benjamin-Chung, Maria Cambra-Pellejà, Nicolas R Caro, David Chaima, Rubén O Cimino, Piet Cools, Anélsio Cossa, Julia Dunn, Sean Galagan, Javier Gandasegui, Berta Grau-Pujol, Emma L Houlder, Moudachirou Ibikounlé, Timothy P Jenkins, Khumbo Kalua, Eyrun F Kjetland, Alejandro J Krolewiecki, Bruno Levecke, Adrian Jf Luty, Andrew S Macdonald, Inácio Mandomando, Malathi Manuel, Maria Martínez-Valladares, Rojelio Mejia, Zeleke Mekonnen, Augusto Messa, Harriet Mpairwe, Osvaldo Muchisse, Jose Muñoz, Pauline Mwinzi, Valdemiro Novela, Maurice R Odiere, Charfudin Sacoor, Judd L Walson, Steven A Williams, Stefan Witek-Mcmanus, D Timothy J Littlewood, Cinzia Cantacessi, Stephen R Doyle

Faculty, Staff and Students Publications

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We …

Innovations In Tavr: The Latest In Device Technology, Omar Sheikh, Errol Moras, Lorraine Mascarenhas, Sahar Samimi, Waleed T Kayani, Syed Zaid

Faculty, Staff and Students Publications

Aortic stenosis is the most prevalent valvular disease globally. Transcatheter aortic valve replacement (TAVR) has become a well-established treatment for aortic stenosis, offering outcomes comparable to surgical aortic valve replacement (SAVR). Its use has expanded to include younger, lower-risk patients and those with more complex anatomies. Recent advancements in TAVR include the increased adoption of transfemoral access, prosthesis designs optimized for challenging anatomies, enhanced delivery systems with repositioning capabilities, and outer skirts to minimize paravalvular leaks. Despite these innovations, several challenges remain. This review highlights recent updates in transcatheter heart valve (THV) systems, leaflet modification devices, and the current limitations …

Genome Report: Whole-Genome Assembly Of The Relapsing Fever Tick Ornithodoros Turicata Dugès (Acari: Argasidae), Mackenzie Tietjen, Amanda R Stahlke, David Luecke, Perot Saelao, Sheina B Sim, Scott M Geib, Brian E Scheffler, Anna K Childers, Alexander R Kneubehl, Pete D Teel, Job E Lopez

Faculty, Staff and Students Publications

The soft tick family Argasidae contains vectors of medical and veterinary importance, but few molecular resources are available compared to hard ticks (Ixodidae). One example is Ornithodoros turicata, a recognized vector of Borrelia turicatae, causal agent of human relapsing fever, and a putative vector of African swine fever virus. To address the current lack of molecular resources for the Argasidae, we generated a chromosome-level genome assembly for O. turicata using PacBio sequencing in conjunction with an Illumina Hi-C library. The resulting reference genome has a total of 1.1 Gb in length and was assembled into 10 chromosomes and 368 unplaced …