Digital Commons Network^™

Functional Characterization Of Qt Interval Associated Scn5a Enhancer Variants Identify Combined Additive Effects, Lavanya Gunamalai, Parul Singh, Brian Berg, Leilei Shi, Ernesto Sanchez, Alexa Smith, Ghislain Breton, Mark T Bedford, Darius Balciunas, Ashish Kapoor

Faculty, Staff and Student Publications

Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from five SCN5A enhancers and their regulatory variants that are known to …

A Phase Ia Study Of A Novel Anti-Her2 Antibody-Drug Conjugate Gq1001 In Patients With Previously Treated Her2 Positive Advanced Solid Tumors, Chenfei Zhou, Bin Wang, Christina Teng, Hui Yang, Sarina A Piha-Paul, Gary Richardson, Ashanya Malalasekera, Yajun Sun, Wei Wang, Jieqiong Liu, Yan Shi, Xianbao Zhan, Charlotte Lemech

Faculty, Staff and Student Publications

Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.

Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary …

Alleviation Of Liver Fibrosis By Inhibiting A Non-Canonical Atf4-Regulated Enhancer Program In Hepatic Stellate Cells, Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng

Faculty, Staff and Student Publications

Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. …

Utah Producers And Soil Health: Statewide Survey Results, Peggy Petrzelka, Jessica Ulrich-Schad, Matt Yost, Jenae Dean, Earl Creech, Linda Schott, Tony Richards, Kristy Davis

All Current Publications

To gain soil health perspectives and actions from a representative sample of Utah farmers and ranchers, a mail and online survey of Utah producers was conducted in 2024, focused on those who indicated they produced crops in 2023. In this report, we provide an overview of the survey results, with a specific focus on producers’ views on soil health, indicators used for soil health, factors that influence soil health adoption, and information sources used for soil health.

Doing Doctorates Differently: The Parapedagogic Potentialities Of The Phd Process, Helen Bowstead, Ken Gale, Mary Catherine Garland, Claire Walsh

School of Law, Humanities and Social Sciences

Coming together in this conference collectivity, these are doctorates that in their doing – thinking, researching, writing, supervising, assessing, publishing – live by “no preexisting rules, processes, methods, categories or ‘determining judgement’.”1 They are doctorates that “cannot be taught or learned.”23 Such PhDs – thesis’ refusing to (con)form – in their ever probing, in-forming, stubborn curiousness of problematics living beyond solution driven research, lead to transformative moments in the act of learning, that in their difference are “...made sense of, not in terms of what [they] mean but in terms of what [they] do.”4Yet in their difference, doctorates working within …

Molecular Logic For Cellular Specializations That Initiate The Auditory Parallel Processing Pathways, Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, M Cecilia Ljungberg, Matthew J Mcginley, Laurence O Trussell, Xiaolong Jiang

Faculty, Staff and Students Publications

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the specialized cellular phenotypes in the CN. In particular, …

Tamm-Horsfall Protein Augments Neutrophil Netosis During Urinary Tract Infection, Vicki Mercado-Evans, Holly Branthoover, Claude Chew, Camille Serchejian, Alexander B Saltzman, Marlyd E Mejia, Jacob J Zulk, Ingrid Cornax, Victor Nizet, Kathryn A Patras

Faculty, Staff and Students Publications

Urinary neutrophils are a hallmark of urinary tract infection (UTI), yet the mechanisms governing their activation, function, and efficacy in controlling infection remain incompletely understood. Tamm-Horsfall glycoprotein (THP), the most abundant protein in urine, uses terminal sialic acids to bind an inhibitory receptor and dampen neutrophil inflammatory responses. We hypothesized that neutrophil modulation is an integral part of THP-mediated host protection. In a UTI model, THP-deficient mice showed elevated urinary tract bacterial burdens, increased neutrophil recruitment, and more severe tissue histopathological changes compared with WT mice. Furthermore, THP-deficient mice displayed impaired urinary NETosis during UTI. To investigate the effect of …

A Β-Hydroxybutyrate Shunt Pathway Generates Anti-Obesity Ketone Metabolites, Maria Dolores Moya-Garzon, Mengjie Wang, Veronica L Li, Xuchao Lyu, Wei Wei, Alan Sheng-Hwa Tung, Steffen H Raun, Meng Zhao, Laetitia Coassolo, Hashim Islam, Barbara Oliveira, Yuqin Dai, Jan Spaas, Antonio Delgado-Gonzalez, Kenyi Donoso, Aurora Alvarez-Buylla, Francisco Franco-Montalban, Anudari Letian, Catherine P Ward, Lichao Liu, Katrin J Svensson, Emily L Goldberg, Christopher D Gardner, Jonathan P Little, Steven M Banik, Yong Xu, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit …

Decreased Lipidated Apoe-Receptor Interactions Confer Protection Against Pathogenicity Of Apoe And Its Lipid Cargoes In Lysosomes, Jing L Guo, Alexandra Litvinchuk, David M Holtzman, Et Al.

2020-Current year OA Pubs

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation. Lipofuscin increased lysosomal accumulation of tau …

The Effect Of Transcutaneous Auricular Vagus Nerve Stimulation On Cardiovascular Function In Subarachnoid Hemorrhage Patients: A Randomized Trial, Gansheng Tan, Anna L Huguenard, Kara M Donovan, Phillip Demarest, Xiaoxuan Liu, Ziwei Li, Markus Adamek, Kory Lavine, Ananthv K Vellimana, Terrance T Kummer, Joshua W Osbun, Gregory J Zipfel, Peter Brunner, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this …

Full Issue, Volume 12, Number 3, Donna J. Peterson, Scott Cummings, Elizabeth Gregory North

Journal of Human Sciences and Extension

No abstract provided.

Untangling Memories Of Violence: The Khipu In El Rincón De Los Muertos (Alfredo Pita), Jonathan J. Oliveri

Living in Languages

This research proposes a structural reading of El rincón de los muertos to decode and trace echoes to the khipu which are embedded throughout the novel. Contrary to a graphic writing system, the Incan empire’s khipu (khipu) was a mnemotechnic system—a three-dimensional communicative device, an archive of memory that recorded information using different colored strings, and a system of knots. Our concept of mnemonics is different than that of the indigenous communities who relied on oral tradition and specifically for khipu a khipukamayuq (reader of khipu), in a narrative and discursive manner, to reconstruct the message the khipu contained. …

The Growing Rift Between Holocaust Scholars Over Israel/Palestine, Shira Klein

History Faculty Articles and Research

"A chasm has formed between Holocaust scholars concerning Israel/Palestine, deepening immeasurably since 7 October 2023. Unlike previous controversies in the field, the divide is not just historical or methodological; it revolves around academics’ role in the world today, particularly the public stand they choose to take on Palestine/Israel and Zionism. Two main camps have formed. Put reductively, one camp defends Israel, while the other defends Palestinians, although differences between individual scholars within each camp make for more of a spectrum than a clear-cut divide. How, despite a diversity of ideas and foci within each camp, did two academic-political antipodes solidify …

Remodeling Pedagogical Evaluation Tools To Incorporate Student Self-Efficacy And Sense Of Belonging In Scientific Research, Richelle L. Tanner, Nicholas P. Burnett, Emily E. King, Anne E. Todgham

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Curated undergraduate research experiences have been widely used at colleges and universities for decades to build student interest, technical preparation, and confidence in the pursuit of scientific careers. Educators often employ standardized survey instruments to evaluate learning outcomes for research experiences, but many of these assessments consider only technical skill development and career interests and are not rooted in discrete pedagogical theories. As higher education aims to create inclusive and equitable learning experiences for students, we argue that pedagogical assessment tools for undergraduate research experiences need to expand to consider outcomes such as increased science literacy, confidence in relational “soft” …

Effects Of Sex, Mating Status, And Genetic Background On Circadian Behavior In Drosophila, Oghenerukevwe Akpoghiran, Alexandra K. Strich, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Circadian rhythms play a crucial role in regulating behavior, physiology, and health. Sexual dimorphism, a widespread phenomenon across species, influences circadian behaviors. Additionally, post-mating physiological changes in females are known to modulate various behaviors, yet their effects on circadian rhythms remain underexplored. Here, using Drosophila melanogaster, a powerful model for studying circadian mechanisms, we systematically assessed the impact of sex and mating status on circadian behavior. We measured circadian period length and rhythm strength in virgin and mated males and females, including females mated to males lacking Sex Peptide (SP), a key mediator of post-mating changes. Across four wild-type and …

Office Of Equity And Inclusion Newsletter - January 2025, Office Of Equity And Inclusion, East Tennessee State University

Office of Equity and Inclusion Newsletters

No abstract provided.

Evaluating Elk Distribution And Conflict Under Proposed Management Alternatives At The National Elk Refuge In Jackson, Wyoming, Gavin G. Cotterill, Paul C. Cross, Eric K. Cole, Jonathan D. Cook, Margaret C. Mceachran, Tabitha A. Graves

Aspen Bibliography

We evaluated measurable attributes describing the current and future distribution of Cervus elaphus canadensis (elk) across a region surrounding Jackson, Wyoming, for five feedground management alternatives proposed by the U.S. Fish and Wildlife Service as a revision to 2007 "Bison and Elk Management Plan" of the National Elk Refuge. A resource selection function evaluated measurable attributes of interest to managers, including elk use of private property and sensitive habitat types at monthly timesteps and varying winter conditions. The study area boundaries were created through an expert elicitation process and consist of the Jackson Elk Herd Unit, Grand Teton National Park, …

Customized Feminine Hygiene Wash Containing Postbiotics From Lactobacillus Spp. To Treat Urinary Tract Infections (Uti), Veena G. Nair

Theses and Dissertations

Probiotics, which support host health by maintaining normal microbial flora, offer a promising approach for preventing recurrent infections. To evaluate the prophylactic potential of vaginal probiotics against urinary tract infections (UTIs), we conducted a study on 54 healthy South Indian women aged 18–40 who visited the Obstetrics and Gynaecology outpatient clinic at Trichy SRM Medical College and Research Centre between June and July 2022. Vaginal swabs were collected following ethical guidelines, and commensal microbiota were isolated for probiotic characterization, with the broader objective of developing a customized feminine hygiene wash enriched with vaginal postbiotics.

Lactobacilli cell-free supernatant (CFS) demonstrated potent …

Agri-Technology Transforming Farms And Ranches Across Nebraska, Shannon Sand

Cornhusker Economics

In summary, agri-tech is reducing the demand for traditional farm and ranch labor in Nebraska while creating new opportunities in technical, analytical, and management roles. As Nebraska maintains its leadership in agri-tech, there will be a growing need for a tech-savvy and versatile agricultural workforce.

Enhancing In Vitro Digestibility And Volatile Profile Of Sorghum Proteins Using Supercritical Carbon Dioxide Drying, Nafisa Sadaf, Arda Tuhanioglu, Safoura Ahmadzadeh, Ali Ubeyitogullari

Food Science Faculty Publications and Presentations

The goal of this research was to use supercritical carbon dioxide (SC-CO2) drying as a novel approach to generate sorghum protein concentrates with enhanced functional characteristics. Sorghum protein concentrates were extracted from white whole-grain sorghum flour and dried in two ways: freeze-drying and SC-CO2 drying. The dried proteins were characterized for their volatile compound content, in vitro digestibility, and amino acid composition. A more porous structure was observed for the SC-CO2-dried sorghum proteins compared with their freeze-dried counterparts. In the SC-CO2-dried samples, the levels of alcohols, esters, and organic acids were significantly lower than those in the freeze-dried ones, whereas …

Exploring The Lived Experiences Of Persons Living With Hiv Who Are Homebound Due To One Or More Comorbidities Within A Southern State Using Photovoice, Anthony Alyn "Deek" Cunningham

All ETDs from UAB

At the end of 2022, there were 1,109,418 adults and adolescents with HIV in the United States and the six dependent areas of American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, the Republic of Palau, and the US Virgin Islands (CDC, 2024). Due to ongoing advances in medications and treatments, people who have been diagnosed with HIV are living longer and healthier lives, making this a chronic health condition. Yet, there are gaps in the literature that focuses on this population growing older and aging in place. This dissertation investigated the lived experiences of individuals fifty years and older …

Exploring The Role Of Brain Angiogenesis Inhibitor 3 (Bai3) In Regulating Body Weight, Haifa Alsahrif

All ETDs from UAB

Obesity is a significant public health issue, strongly associated with various metabolic disorders, including type 2 diabetes and cardiovascular disease. Understanding the mechanisms that contribute to obesity is essential for developing effective interventions. One critical area of interest involves G-protein-coupled receptors (GPCRs), which are important in regulating metabolic health. These receptors are known to be involved in critical metabolic functions such as insulin secretion, lipid metabolism, and glucose uptake. The role of the GPCR, brain angiogenesis inhibitor-3 (BAI3), in metabolic regulation has not been fully explored. This dissertation focuses on the known functions of the BAI isoforms (BAI1-3) and presents …

Mergers And Acquisitions (M&As) In Pharmaceutical Markets: Associations With Market Concentration, Prices, Drug Quantity Sold, And Shortages, J. Daniel Mcgeeney M.S., Aylin Sertkaya Ph.D., Leah Ross M.A., Fred Ledley M.D., Cody Hyman Ph.D.

CISI Publication

In recent decades, the pharmaceutical industry has become increasingly concentrated in the United States, in part due to mergers and acquisitions (M&As) between drug manufacturers. This consolidation from M&As has been cited as a key factor affecting drug prices and drug shortages (U.S. Federal Trade Commission, 2022). In this study, we assessed trends in pharmaceutical M&As during 2010–2023 and evaluated the characteristics of drugs and companies involved in those M&As. We considered the effects of M&As on market concentration, drug prices, drug quantity sold, and drug shortages. We also considered how these associations vary by drug characteristics, including brand drugs …

Using Satellite Image Segmentation To Detect Trails, Jeremy Reynolds

Theses and Dissertations

This masters thesis proposes an innovative approach to satellite image segmentation by focusing on the detection and mapping of walking, hiking, and biking trails. The motivation behind this project comes from the underexplored area in segmentation techniques for trail identification and offers potential benefits for urban planning, environmental monitoring, and public health. The problem statement addresses the need for a model that can differentiate between various trail types and other natural or man-made elements. The project aims for efficiency and scalability in processing satellite imagery across different compute hardware. The work details several stages: researching existing segmentation techniques, specifically road …

Office Of Research, Economic Engagement And Outreach Update, January 8, 2025, Office Of Research, Economic Engagement And Outreach

Office of Research, Economic Engagement and Outreach

No abstract provided.

Divergent Bodyminds: Kin In The Difference, Ruth Churchill Dower, Claire Walsh

School of Law, Humanities and Social Sciences

In breaking the habit of ‘making sense’ typified by normative, neurotypical modes of engagement with the world, neurodiverse sociality performs a treachery in relation to prescriptive, dominating forms of normative reality. Within this conference paper, a modest site of resistance, a reconsideration of neurotypical normative reality takes place, extending beyond the boundaries underpinning neurotypical hegemonic discourse about ‘human’ reality, identity and existence: rescinding the neurotypical “normative standard for human experience” requiring the mapping of bodies in advance, to foreground bodies in excess, neurodiverse bodies subject to patterns and rhythms that defy stable or coherent identification. As bodies “always extending beyond …

Prdm16 Enhances Osteoblastogenic Runx2 Via Canonical Wnt10b/Β-Catenin Pathway In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Mia Prado, Virginia Fuenmayor Lopez, Georgia Colleluori, Lina Aguirre, Rui Chen, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

We previously reported that PRDM16 mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that Prdm16 regulates Runx2, an important osteoblastic transcription factor, expression and activity. However, the changes in PRDM16, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling …

Commensal-Pathogen Dynamics Structure Disease Outcomes During Clostridioides Difficile Colonization, Skye R S Fishbein, Anna L Deveaux, Sakshi Khanna, Aura L Ferreiro, James Liao, Wesley Agee, Jie Ning, Bejan Mahmud, Miranda J Wallace, Tiffany Hink, Kimberly A Reske, Candice Cass, Janaki Guruge, Sidh Leekha, Sunaina Rengarajan, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical outcomes. Microbiota humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clinically prevalent clade 1 lineages and identified candidate taxa, including Blautia, as markers of stable colonization. Using gnotobiotic mice engrafted with defined human microbiota, we validated strain-specific CDI severity across clade 1 strains isolated from patients. Mice engrafted …

Waste Clearance Shapes Aging Brain Health, Li-Feng Jiang-Xie, Antoine Drieu, Jonathan Kipnis

2020-Current year OA Pubs

Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer's and Parkinson's diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.

Tas 70th Annual Meeting Booklet, Tarrant County Archeological Society

North Texas Archeological Society Records

Information booklet about the 70th annual meeting