Digital Commons Network^™

Effects Of Energy Drinks On Crayfish Physiology, Melyna Sweeney

Williams Honors College, Honors Research Projects

Energy drinks have become the drink of choice among many college students due to the rush of energy it provides via the megadose of caffeine (Vercammen et al. 2019). Because of their newfound popularity, there is much research to be done about the effects on human physiology. Energy drinks are known to increase endurance in muscles of rat subjects (Imagawa et al. 2009) and stimulate enhanced “alertness” (Smit & Rogers, 2002). The purpose of this research was to uncover the potential effects that energy drinks have on metabolic rate and/or stress responses in crayfish (Procambarus clarkii), with the …

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Testosterone Acts Through The Membrane Protein Gprc6a To Cause Cardiac Edema In Zebrafish Embryos, Vahid Zadmajid, Shayan Shahriar, Daniel A Gorelick

Faculty, Staff and Students Publications

Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants …

Roles Of The Gut Microbiota In Human Neurodevelopment And Adult Brain Disorders, Rahul Mallick, Sanjay Basak, Ranjit Kumar Das, Antara Banerjee, Sujay Paul, Surajit Pathak, Asim K. Duttaroy

Health & Biomedical Sciences Faculty Publications

Growing evidence demonstrates the connection between gut microbiota, neurodevelopment, and adult brain function. Microbial colonization occurs before the maturation of neural systems and its association with brain development. The early microbiome interactions with the gut-brain axis evolved to stimulate cognitive activities. Gut dysbiosis can lead to impaired brain development, growth, and function. Docosahexaenoic acid (DHA) is critically required for brain structure and function, modulates gut microbiota, and impacts brain activity. This review explores how gut microbiota influences early brain development and adult functions, encompassing the modulation of neurotransmitter activity, neuroinflammation, and blood-brain barrier integrity. In addition, it highlights processes of …

Artificial Gravity: An Effective Countermeasure For Microgravity-Induced Headward Fluid Shift?, Larry A Kramer, Khader M Hasan, Xu Zhang, Edwin Mulder, Darius A Gerlach, Karina Marshall-Goebel, Brandon R Macias, Steven S Laurie, Gary Strangman, Raj Iyer, Eric M Bershad

Faculty, Staff and Student Publications

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine whether daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of 6° head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: no AG (control), daily 30-min intermittent AG (iAG), and daily 30-min continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA …

Therapeutic Targeting Of Hypoxia Inducible Factor In Acute Respiratory Distress Syndrome, Thu T Tran, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia-inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel-Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen-dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses …

Opportunities For Helicobacter Pylori Eradication Beyond Conventional Antibiotics, Camilia Metadea Aji Savitri, Kartika Afrida Fauzia, Ricky Indra Alfaray, Hafeza Aftab, Ari Fahrial Syam, Masrul Lubis, Yoshio Yamaoka, Muhammad Miftahussurur

Faculty, Staff and Students Publications

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics …

Germline Mutations In A G Protein Identify Signaling Cross-Talk In T Cells, Hyoungjun Ham, Huie Jing, Ian T Lamborn, Megan M Kober, Alexey Koval, Yamina A Berchiche, D Eric Anderson, Kirk M Druey, Judith N Mandl, Bertrand Isidor, Carlos R Ferreira, Alexandra F Freeman, Sundar Ganesan, Meliha Karsak, Peter J Mustillo, Juliana Teo, Zarazuela Zolkipli-Cunningham, Nicolas Chatron, François Lecoquierre, Andrew J Oler, Jana Pachlopnik Schmid, Douglas B Kuhns, Xuehua Xu, Fabian Hauck, Waleed Al-Herz, Matias Wagner, Paulien A Terhal, Mari Muurinen, Vincent Barlogis, Phillip Cruz, Jeffrey Danielson, Helen Stewart, Petra Loid, Sebastian Rading, Boris Keren, Rolph Pfundt, Kol A Zarember, Katharina Vill, Lorraine Potocki, Kenneth N Olivier, Gaetan Lesca, Laurence Faivre, Melanie Wong, Anne Puel, Janet Chou, Maud Tusseau, Niki M Moutsopoulos, Helen F Matthews, Cas Simons, Ryan J Taft, Ariane Soldatos, Etienne Masle-Farquhar, Stefania Pittaluga, Robert Brink, Danielle L Fink, Heidi H Kong, Juraj Kabat, Woo Sung Kim, Tatjana Bierhals, Kazuyuki Meguro, Amy P Hsu, Jingwen Gu, Jennifer Stoddard, Benito Banos-Pinero, Maria Slack, Giampaolo Trivellin, Benoît Mazel, Maarja Soomann, Samuel Li, Val J Watts, Constantine A Stratakis, Maria F Rodriguez-Quevedo, Ange-Line Bruel, Marita Lipsanen-Nyman, Paul Saultier, Rashmi Jain, Daphne Lehalle, Daniel Torres, Kathleen E Sullivan, Sébastien Barbarot, Axel Neu, Yannis Duffourd, Morgan Similuk, Kirsty Mcwalter, Pierre Blanc, Stéphane Bézieau, Tian Jin, Raif S Geha, Jean-Laurent Casanova, Outi M Makitie, Christian Kubisch, Patrick Edery, John Christodoulou, Ronald N Germain, Christopher C Goodnow, Thomas P Sakmar, Daniel D Billadeau, Sébastien Küry, Vladimir L Katanaev, Yu Zhang, Michael J Lenardo, Helen C Su

Center for Medical Ethics and Health Policy Staff Publications

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2, which encodes Gαi2, a key component in heterotrimeric G-protein signal transduction usually thought to regulate adenylyl cyclase-mediated cAMP production. Patients with activating Gαi2 mutations had clinical presentations that included impaired immunity. Mutant Gαi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant Gαi2 influenced TCR signaling by sequestering the GTPase-activating protein RASA2, thereby promoting RAS activation and increasing downstream ERK/MAPK and PI3K-AKT S6 signaling to drive cellular growth and proliferation.

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …

Loss Of Transient Receptor Potential Channel 5 Causes Obesity And Postpartum Depression, Yongxiang Li, Tessa M Cacciottolo, Na Yin, Yang He, Hesong Liu, Hailan Liu, Yuxue Yang, Elana Henning, Julia M Keogh, Katherine Lawler, Edson Mendes De Oliveira, Eugene J Gardner, Katherine A Kentistou, Panayiotis Laouris, Rebecca Bounds, Ken K Ong, John R B Perry, Inês Barroso, Longlong Tu, Jonathan C Bean, Meng Yu, Kristine M Conde, Mengjie Wang, Olivia Ginnard, Xing Fang, Lydia Tong, Junying Han, Tia Darwich, Kevin W Williams, Yongjie Yang, Chunmei Wang, Shelagh Joss, Helen V Firth, Yong Xu, I Sadaf Farooqi

Duncan NRI Faculty and Staff Publications

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of …

The Role Of An Ultraconserved Long Non-Coding Rna In B-Cell Lymphomagenesis, Swati Mohapatra

Dissertations and Theses (Open Access)

Ultraconserved regions (UCRs) are genomic segments with perfect (100%) conservation between the orthologous regions of human, rat, and mouse genomes. UCRs can be transcribed into mono-exonic long non-coding RNAs (lncRNAs) known as transcribed ultraconserved regions (T-UCRs). These regions, despite lacking protein-coding potential, are increasingly recognized for their regulatory roles in gene expression, including the modulation of non-coding RNA (ncRNA) transcripts. NcRNAs play crucial roles in cellular processes, including oncogenic transformation, with emerging evidence revealing their ability to encode small peptides known as ncRNA-encoded peptides (ncPEPs). These peptides, originating from small open reading frames (smORFs), contribute to diverse cellular functions and …

The Effects Of Non-Invasive Brain Stimulation On Excitability Of The Primary Motor Cortices And Complex Motor Task Learning, Erik Woodruff Wilkins

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are promising non-invasive brain stimulation techniques, particularly for clinical applications involving altered or impaired motor function, such as in stroke and Parkinson’s disease. Although tDCS and tACS are different modalities, both forms of stimulation operate on the same principle - weak electrical currents are delivered through electrodes placed on the scalp in specific configurations known as “montages”. The most commonly used montage for targeting the primary motor cortex (M1) is the M1-SO configuration. This montage leverages the established observation that cortical regions directly beneath the anode generally increase in …

Genetic Diversity Of 1,845 Rhesus Macaques Improves Genetic Variation Interpretation And Identifies Disease Models, Jun Wang, Meng Wang, Ala Moshiri, R Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H O'Connor, Zach Johnson, Melween Martinez, Michael J Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M Thomasy, Jeffrey Rogers, Rui Chen

Faculty, Staff and Students Publications

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which …

Towards An Interdisciplinary “Science Of The Mind”: A Call For Enhanced Collaboration Between Philosophy And Neuroscience, Alessandra Buccella, Uri Maoz, Liad Mudrik

Psychology Faculty Articles and Research

In recent decades, the neuroscientific community has moved from describing the neural underpinnings of mental phenomena—as characterized by experimental psychology and philosophy of mind—to attempting to redefine those mental phenomena based on neural findings. Nowadays, many are intrigued by the idea that neuroscience might provide the “missing piece” that would allow philosophers (and, to an extent, psychologists, too) to make important advances, generating new means that these disciplines lack to close knowledge gaps and answer questions like “What is Free Will?” and “Do humans have it?.” In this paper, we argue that instead of striving for neuroscience to replace philosophy …

Modeling Acute Myocardial Infarction And Cardiac Fibrosis Using Human Induced Pluripotent Stem Cell-Derived Multi-Cellular Heart Organoids, Myeongjin Song, Da Bin Choi, Jeong Suk Im, Ye Na Song, Ji Hyun Kim, Hanbyeol Lee, Jieun An, Ami Kim, Hwan Choi, Joon-Chul Kim, Choongseong Han, Young Keul Jeon, Sung Joon Kim, Dong-Hun Woo

Faculty, Staff and Student Publications

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating …

A Revamped Rat Reference Genome Improves The Discovery Of Genetic Diversity In Laboratory Rats, Tristan V De Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S Chitre, William Chow, Vincenza Colonna, Clifton L Dalgard, Wendy M Demos, Peter A Doris, Erik Garrison, Aron M Geurts, Hakan M Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin Howe, Jun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R Smith, Leah C Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D Murphy, Abraham A Palmer, Anne E Kwitek, Melinda R Dwinell, Robert W Williams, Jun Z Li, Hao Chen

Faculty, Staff and Student Publications

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites …

Colorectal Cancer Murine Models: Initiation To Metastasis, Ramesh Pothuraju, Imran Khan, Maneesh Jain, Michael Bouvet, Mokenge Malafa, Hemant K Roy, Sushil Kumar, Surinder K Batra

Faculty, Staff and Students Publications

Despite significant advancements in prevention and treatment, colorectal cancer (CRC) remains the third leading cause of cancer-related deaths. Animal models, including xenografts, syngeneic, and genetically engineered, have emerged as indispensable tools in cancer research. These models offer a valuable platform to address critical questions regarding molecular pathogenesis and test therapeutic interventions before moving on to clinical trials. Advancements in CRC animal models have also facilitated the advent of personalized and precision medicine. Patient-derived xenografts and genetically engineered mice that mirror features of human tumors allow for tailoring treatments to specific CRC subtypes, improving treatment outcomes and quality of life. To …

Icnirp Statement On Short Wavelength Light Exposure From Indoor Artificial Sources And Human Health, Sharon Miller, Christian Cajochen, Adele Green, John Hanifin, Anke Huss, Ken Karipidis, Sarah Loughran, Gunnhild Oftedal, John O'Hagan, David H Sliney, Rodney Croft, Eric Van Rongen, Nigel Cridland, Guglielmo D'Inzeo, Akimasa Hirata, Carmela Marino, Martin Röösli, Soichi Watanabe

Department of Neuroscience Faculty Papers

Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from …

Ethanol Leaf Extracts Of Anogeissus Leiocarpus In Antioxidants And Hepatotoxic Effects Of Escherichia Coli Infected Swiss Mice, Fred Coolborn Akharaiyi, Chioma Bertha Ehis-Eriakha, Peter Taiwo Olagbemide, Stephen Eromosele Akemu

BioMedicine

Introduction: Diseases caused by bacteria can be managed with medicinal plants with rightful dosage that will not affect body physiology and organs.

Aim: This research aimed to evaluate the antioxidants and the effects of Anogeisus leiocarpus on liver function.

Materials and Methods: Ethanol leaf extracts were processed for antioxidants and hepatotoxic effects using animal models. Group one (negative control) was given access to water and regular feed, group two (positive control) was dosed with 107 CFU/ml of Escherichia coli O157:H7, and groups 3-6 were dosed with 107 E. coli O157:H7 for 3 days and treated with extract concentrations of 12, …

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …

A Road Map For The Treatment Of Pediatric Diffuse Midline Glioma, Carl Koschmann, Wajd N Al-Holou, Marta M Alonso, Jamie Anastas, Pratiti Bandopadhayay, Tara Barron, Oren Becher, Rodrigo Cartaxo, Maria G Castro, Chan Chung, Madison Clausen, Derek Dang, Robert Doherty, Ryan Duchatel, Matthew Dun, Mariella Filbin, Andrea Franson, Stefanie Galban, Marc Garcia Moure, Hugh Garton, Pruthvi Gowda, Joana Graca Marques, Cynthia Hawkins, Allison Heath, Esther Hulleman, Sunjong Ji, Chris Jones, Lindsay Kilburn, Cassie Kline, Michael A Koldobskiy, Daniel Lim, Pedro R Lowenstein, Q Richard Lu, Joanna Lum, Stephen Mack, Suresh Magge, Bernard Marini, Donna Martin, Neena Marupudi, Dana Messinger, Rajen Mody, Meredith Morgan, Mateus Mota, Karin Muraszko, Sabine Mueller, Siva Kumar Natarajan, Javad Nazarian, Michael Niculcea, Nicholas Nuechterlein, Hideho Okada, Valerie Opipari, Manjunath P Pai, Sharmistha Pal, Erik Peterson, Timothy Phoenix, John R Prensner, Matthew Pun, G Praveen Raju, Zachary J Reitman, Adam Resnick, David Rogawski, Amanda Saratsis, Stefanie G Sbergio, Mark Souweidane, James M Stafford, Theophilos Tzaridis, Sujatha Venkataraman, Orazio Vittorio, Jack Wadden, Daniel Wahl, Robert J Wechsler-Reya, Viveka Nand Yadav, Xu Zhang, Qiang Zhang, Sriram Venneti

Faculty, Staff and Students Publications

Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring. We highlight the importance of comprehensive collaboration to advance the understanding, diagnostics, and therapeutics for DMGs.

Molecular Determinants Of Trp Channel Gating, Briar J. Bell

Theses and Dissertations (ETD)

Transient Receptor Potential (TRP) ion channels are a family of proteins that contribute to a myriad of physiological functions. They have been extensively studied since their discovery 35 years ago; however, there are still many questions regarding the mechanisms by which they function. This family of proteins is characterized by a generally shared structure: an intracellular N terminus featuring ankyrin repeats, six transmembrane helices including the pore domain, a re-entrant loop and TRP helix, and an intracellular C terminus with varying structure. Each of these regions has been implicated in the regular function of TRPs, while mutations that alter trafficking …

Advancing Kidney Xenotransplantation With Anesthesia And Surgery – Bridging Preclinical And Clinical Frontiers Challenges And Prospects, Xiaojian Zhang, Hailian Wang, Qin Xie, Yang Zhang, Yixin Yang, Man Yuan, Yuqi Cui, Si-Yuan Song, Jianzhen Lv, Yi Wang

Children’s Nutrition Research Center Staff Publications

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and …

Configuring Thermal Ablation Volumes For Treatment Of Distinct Tumor Shapes: A Repeatability Study Using A Robotic Approach, Milica Bulatović, Jan Hermann, Pascale Tinguely, Iwan Paolucci, Stefan Weber

Faculty, Staff and Student Publications

Objectives: In the current clinical practice of thermal ablation treatment for liver tumors, achieving consistent and effective clinical outcomes across tumors of varying shapes, sizes and locations remains challenging. The aim of this study was to evaluate the repeatability of a novel robotic approach for configurable ablation of distinct tumor shapes and compare it to the standard ablation technique for creating ellipsoidal ablation volumes.

Materials and methods: The repeatability was evaluated in terms of width variability in created ablation volumes. Using a robotic navigation platform, custom ablation profiles configured with power, time, and distance parameters were designed to create four …

Postmortem-Derived Ipsc Models In Substance Use Disorders Research, Emily Frances Mendez, Consuelo Walss-Bass

Faculty, Staff and Student Publications

No abstract provided.

Development Of 3d Cell Culture Model For Graves’ Ophthalmopathy, Rajit Chompoowong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Orbital tissue fibrosis and remodeling contribute to the development of exophthalmos, a hallmark symptom of Graves’ ophthalmopathy (GO). The central pathogenesis to this process are orbital fibroblasts (GOF), which express autoantigen, thyroid-stimulating hormone receptor (TSHR). However, there are limitations in preclinical models for studying the pathogenesis and drug discovery of GO, which poses challenges for developing effective treatment options. This study aimed to identify markers of GOF, explore epigenetic alteration, and develop a scaffold-free 3D cell culture model for GO. The novel results from immunohistochemical analysis showed that vimentin was uniquely expressed in GO but absent in control samples. Additionally, …

Meta-Analysis Of The Vmp-Like Sequences Of Lyme Disease Borrelia: Evidence For The Evolution Of An Elaborate Antigenic Variation System, Steven J Norris, Kalvis Brangulis

Faculty, Staff and Student Publications

VMP-like sequence (vls) antigenic variation systems are present in every Lyme disease Borrelia strain with complete genome sequences. The linear plasmid-encoded vls system consists of a single expression site (vlsE) and contiguous array(s) of silent cassettes that have ~90% identity with the central cassette region of the cognate vlsE gene; antigenic variation occurs through random, segmental, and unidirectional recombination of vls silent cassette sequences into the vlsE expression site. Automated annotation programs do not accurately recognize vls silent cassette sequences, so these regions are not correctly annotated in most genomic sequences. In this study, the vls …

Meta-Analysis Of Postoperative Myocardial Injury As A Predictor Of Mortality After Living Donor Liver Transplantation, Krzysztof Jankowski, Frank W Peacock, Michal Pruc, Teresa Malecka-Massalska, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to investigate postoperative myocardial injury, as expressed by the postoperative concentration of high-sensitivity cardiac troponin I (hs-cTnI) as a predictor of mortality among living donor liver transplantation (LDLT) patients.

METHODS: PubMed, Scopus, Embase and the Cochrane Library were searched through to September 1st 2022. The primary endpoint included in-hospital mortality. Secondary endpoints were 1-year mortality and re-transplantation occurrence. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I² test.

RESULTS: During the search, 2 studies were found …

The Maternal Gut Microbiome In Pregnancy: Implications For The Developing Immune System, Omry Koren, Liza Konnikova, Petter Brodin, Indira U Mysorekar, Maria Carmen Collado

Faculty, Staff and Students Publications

The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal …