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Responses Of Skeletal Muscle To Mechanical Stimuli In Female Rats Following And During Muscle Disuse Atrophy, Alexander B. Sklivas, Zachary R. Hettinger, Sarah Rose, Alessandra Mantuano, Amy L. Confides, Sandra Rigsby, Frederick F. Peelor, Benjamin F. Miller, Timothy A. Butterfield, Esther E. Dupont-Versteegden Mar 2025

Responses Of Skeletal Muscle To Mechanical Stimuli In Female Rats Following And During Muscle Disuse Atrophy, Alexander B. Sklivas, Zachary R. Hettinger, Sarah Rose, Alessandra Mantuano, Amy L. Confides, Sandra Rigsby, Frederick F. Peelor, Benjamin F. Miller, Timothy A. Butterfield, Esther E. Dupont-Versteegden

Physiology Faculty Publications

The purpose of this study was to investigate the ability of mechanotherapy to enhance recovery or prevent loss of muscle size with disuse in female rats. Female F344/BN rats were assigned to weight bearing (WB), hindlimb suspended (HS) for 14 days with reambulation for 7 days without mechanotherapy or reambulation (RA) with mechanotherapy (RAM) (study 1), or to WB, HS for 7 days, with HS mechanotherapy (HSM) or without mechanotherapy (study 2) to gastrocnemius muscle. Muscle fiber cross-sectional area (CSA) and fiber type, collagen, satellite cell number, and protein synthesis (ksyn) and degradation (kdeg) were assessed. …


Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr. Mar 2025

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …


Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka Mar 2025

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …


Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley Mar 2025

Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.

Methods: We created a dataset ready for …


Characterization, Performance, And Toxicological Assessment Of Polysulfone-Sulfonated Polyether Ether Ketone Membranes For Water Separation Applications, Muhammad Usman Yousaf, Lucca Madeo Cortarelli, Nerissa I. Jebet, Jason M. Unrine, Nirupam Aich, Olga V. Tsyusko, Isabel C. Escobar Mar 2025

Characterization, Performance, And Toxicological Assessment Of Polysulfone-Sulfonated Polyether Ether Ketone Membranes For Water Separation Applications, Muhammad Usman Yousaf, Lucca Madeo Cortarelli, Nerissa I. Jebet, Jason M. Unrine, Nirupam Aich, Olga V. Tsyusko, Isabel C. Escobar

Markey Cancer Center Faculty Publications

The removal of small molecular weight charged compounds from aqueous solutions using membrane remains a challenge. In this study, polysulfone (PSf)- and sulfonated polyether ether ketone (SPEEK)-based membranes were fabricated via non- solvent induced phase separation process (NIPS) using N-Methyl-2-Pyrrolidone (NMP) as solvent and water as non-solvent. Membranes were characterized structurally and morphologically, followed by toxicity assessment conducted before and after filtration, both with and without annealing at various pH values to evaluate potential leaching of trapped solvent from the membrane pores. Additionally, membrane performance was characterized using binary mixtures of cationic and anionic dyes. The results demonstrated selective filtration …


Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li Mar 2025

Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li

Markey Cancer Center Faculty Publications

Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …


Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu Mar 2025

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …


Crystal Structure And Hirshfeld-Surface Analysis Of The Pesticide Etoxazole, Chaluvarangaiah Sowbhagya, Thaluru M.Mohan Kumar, Hemmige S. Yathirajan, Sean Parkin Mar 2025

Crystal Structure And Hirshfeld-Surface Analysis Of The Pesticide Etoxazole, Chaluvarangaiah Sowbhagya, Thaluru M.Mohan Kumar, Hemmige S. Yathirajan, Sean Parkin

Chemistry Faculty Publications

Etoxazole (C21H23F2NO2), systematic name 4-(4-tert-butyl-2-ethoxyphenyl)-2- (2,6-difluorophenyl)-4,5-dihydro-1,3-oxazole, is a fluorinated insecticide and acaricide that inhibits chitin biosynthesis, disrupting insect development by preventing proper exoskeleton formation. Widely used in agriculture since 1998, it is readily absorbed by plant tissues and translocates within leaves. Metabolic studies have identified several oxidative degradation products, while toxicological assessments have examined potential effects, including oxidative stress. This study presents a detailed crystallographic and Hirshfeld surface analysis of etoxazole. The molecule consists of a central dihydro-oxazole ring flanked by 2,6-difluorophenyl and 4-tert-butyl-2-ethoxyphenyl groups, each twisted relative to the oxazole core. The dihydro-oxazole ring is nearly planar, with the …


Atp-Sensitive Potassium Channels Alter Glycolytic Flux To Modulate Cortical Activity And Sleep, Nicholas J. Constantino, Caitlin M. Carroll, Holden C. Williams, Hemendra J. Vekaria, Carla M. Yuede, Kai Saito, Patrick W. Sheehan, J. Andy Snipes, Marcus E. Raichle, Erik S. Musiek, Patrick G. Sullivan, Josh M. Morganti, Lance A. Johnson, Shannon L. Macauley Feb 2025

Atp-Sensitive Potassium Channels Alter Glycolytic Flux To Modulate Cortical Activity And Sleep, Nicholas J. Constantino, Caitlin M. Carroll, Holden C. Williams, Hemendra J. Vekaria, Carla M. Yuede, Kai Saito, Patrick W. Sheehan, J. Andy Snipes, Marcus E. Raichle, Erik S. Musiek, Patrick G. Sullivan, Josh M. Morganti, Lance A. Johnson, Shannon L. Macauley

Physiology Faculty Publications

Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are associated with wakefulness and decreased ISF lactate is required for sleep. ATP-sensitive potassium (KATP) channels couple glucose-lactate metabolism with excitability. Using mice lacking KATP channel activity (e.g., Kir6.2−/− mice), we explored how changes in glucose utilization affect cortical electroencephalography (EEG) activity and sleep/wake homeostasis. In the brain, Kir6.2−/− mice shunt glucose toward glycolysis, reducing neurotransmitter biosynthesis and dampening cortical EEG activity. Kir6.2−/− mice spent more time …


Media Through The Lens Of Scientific Reductionism: The Gene-Ius Of Genetic Determinism In Gattaca, Asmita Lehther Feb 2025

Media Through The Lens Of Scientific Reductionism: The Gene-Ius Of Genetic Determinism In Gattaca, Asmita Lehther

Kentucky Undergraduate Journal for the Health Humanities

This essay examines the construct of scientific reductionism within the framework established by Andrew Niccol’s film Gattaca, illustrating how genetic determinism shapes social hierarchies and opportunities. By analyzing Vincent's struggle as an "in-valid" in a society that equates genetic superiority with worth, the essay critiques the reduction of individual potential to biological labels, revealing the oppressive nature of such systems.


Sowing The Seeds Of Confusion To Reap Content Mastery, Rebecca Mcgrail Feb 2025

Sowing The Seeds Of Confusion To Reap Content Mastery, Rebecca Mcgrail

Greater Faculties: A Review of Teaching and Learning

No abstract provided.


The Core Circadian Clock Factor, Bmal1, Transduces Sex-Specific Differences In Both Rhythmic And Nonrhythmic Gene Expression In The Mouse Heart, Xiping Zhang, Spencer B. Procopio, Haocheng Ding, Maya G. Semel, Elizabeth A. Schroder, Mark R. Viggars, Tanya S. Seward, Ping Du, Kevin Wu, Sidney R. Johnson, Abhilash Prabhat, David J. Schneider, Isabel G. Stumpf, Ezekiel R. Rozmus, Zhiguang Huo, Brian P. Delisle, Karyn A. Esser Feb 2025

The Core Circadian Clock Factor, Bmal1, Transduces Sex-Specific Differences In Both Rhythmic And Nonrhythmic Gene Expression In The Mouse Heart, Xiping Zhang, Spencer B. Procopio, Haocheng Ding, Maya G. Semel, Elizabeth A. Schroder, Mark R. Viggars, Tanya S. Seward, Ping Du, Kevin Wu, Sidney R. Johnson, Abhilash Prabhat, David J. Schneider, Isabel G. Stumpf, Ezekiel R. Rozmus, Zhiguang Huo, Brian P. Delisle, Karyn A. Esser

Physiology Faculty Publications

No abstract provided.


Dysregulated Alveolar Epithelial Cell Progenitor Function And Identity In Hermansky-Pudlak Syndrome, Joanna Y. Wang, Sylvia N. Michki, Sneha Sitaraman, Brandon J. Banaschewski, Reshma Jamal, Jason J. Gokey, Susan M. Lin, Jeremy B. Katzen, Maria C. Basil, Edward Cantu, Jonathan A. Kropski, Jarod A. Zepp, David B. Frank, Lisa R. Young Feb 2025

Dysregulated Alveolar Epithelial Cell Progenitor Function And Identity In Hermansky-Pudlak Syndrome, Joanna Y. Wang, Sylvia N. Michki, Sneha Sitaraman, Brandon J. Banaschewski, Reshma Jamal, Jason J. Gokey, Susan M. Lin, Jeremy B. Katzen, Maria C. Basil, Edward Cantu, Jonathan A. Kropski, Jarod A. Zepp, David B. Frank, Lisa R. Young

Surgery Faculty Publications

Hermansky-Pudlak syndrome (HPS) is a genetic disorder of endosomal protein trafficking associated with pulmonary fibrosis in specific subtypes, including HPS-1 and HPS-2. Single-mutant HPS1 and HPS2 mice display increased fibrotic sensitivity while double-mutant HPS1/2 mice exhibit spontaneous fibrosis with aging, which has been attributed to HPS mutations in alveolar epithelial type II (AT2) cells. We utilized HPS mouse models and human lung tissue to investigate mechanisms of AT2 cell dysfunction driving fibrotic remodeling in HPS. Starting at 8 weeks of age, HPS mice exhibited progressive loss of AT2 cell numbers. HPS AT2 cell function was impaired ex vivo and in …


Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya Feb 2025

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …


Amyloid-Β Predominant Alzheimer’S Disease Neuropathologic Change, Gabor G. Kovacs, Yuriko Katsumata, Xian Wu, Khine Zin Aung, David Fardo, Shelley L. Forrest, Peter T. Nelson Feb 2025

Amyloid-Β Predominant Alzheimer’S Disease Neuropathologic Change, Gabor G. Kovacs, Yuriko Katsumata, Xian Wu, Khine Zin Aung, David Fardo, Shelley L. Forrest, Peter T. Nelson

Neurology Faculty Publications

Different subsets of Alzheimer’s disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer’s Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies.


Males Differ More Between Developmental Stages Than Females, And Plasticity To Light Is Stage-Dependent In The Tropical Plant Marchantia Inflexa, Jonathan D. Moore, D. Nicholas Mcletchie Feb 2025

Males Differ More Between Developmental Stages Than Females, And Plasticity To Light Is Stage-Dependent In The Tropical Plant Marchantia Inflexa, Jonathan D. Moore, D. Nicholas Mcletchie

Biology Faculty Publications

Plants have evolved strategies to maintain photosynthesis and mitigate tissue-damaging high light. In some dioecious seed plants, these strategies are sexually dimorphic and are linked to spatial segregation of the sexes (SSS) along light gradients. In vascular tissue-free plants (bryophytes) with separate sexes, SSS is common, but how light gradients, sexual dimorphisms, and SSS correlate is not well understood. To test if sexual dimorphisms in vegetative or sexual stages lead to light-associated SSS in bryophytes, we used Marchantia inflexa whose males occupy a wider range of light conditions, including higher light conditions, than females. We also tested if changes in …


Ear Pinna Growth And Differentiation Is Conserved In Murids And Requires Bmp Signaling For Chondrocyte Proliferation, Robyn S. Allen, Shishir K. Biswas, Ashley W. Seifert Feb 2025

Ear Pinna Growth And Differentiation Is Conserved In Murids And Requires Bmp Signaling For Chondrocyte Proliferation, Robyn S. Allen, Shishir K. Biswas, Ashley W. Seifert

Biology Faculty Publications

Despite being a major target of reconstructive surgery, development of the ear pinna remains poorly studied. Here, we provide a cellular characterization of late gestational and postnatal ear pinna development in two rodents and investigate the role of BMP5 in expansion and differentiation of auricular elastic cartilage. We find that ear pinna development is largely conserved between Mus musculus and the highly regenerative Acomys dimidiatus. The pattern of pre-cartilaginous cells is established early in development. These cells are specified into chondroblasts before ear unfolding and then undergo extensive proliferation before maturation. The elastic cartilage, connective tissue fibroblasts, dermal papilla and …


Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing Feb 2025

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …


Long-Term Agricultural Management Reduces Abundance And Alters Community Structure Of Ground Beetles (Coleoptera: Carabidae), Cynthia M. Fiser, Nathan L. Haan, Douglas A. Landis Feb 2025

Long-Term Agricultural Management Reduces Abundance And Alters Community Structure Of Ground Beetles (Coleoptera: Carabidae), Cynthia M. Fiser, Nathan L. Haan, Douglas A. Landis

Entomology Faculty Publications

Carabid beetles (Coleoptera: Carabidae) are beneficial predators and bioindicators of ground-dwelling arthropod diversity in agricultural landscapes. We studied changes in community composition, activity density, and diversity of carabids in a long-term agroecosystem study spanning 30 years in the US Midwest. We contrasted carabid community metrics measured by pitfall trap sampling in two conservation-oriented treatments in a corn-soybean-wheat rotation. One treatment uses conventional practices but with reduced agrochemical inputs (Reduced Input), while the other has no synthetic inputs (Biologically Based). Since a 1994–95 study on the same site, in 2019 overall carabid activity density had declined a minimum of 58–76 % …


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell Feb 2025

A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell

Markey Cancer Center Faculty Publications

The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 + T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8+ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8 + T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based …


Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich Feb 2025

Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich

Markey Cancer Center Faculty Publications

Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase …


The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn Feb 2025

The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in …


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


Recurrent Selection For Partial Resistance To Anthracnose Disease In Shrubby Stylo (Stylosanthes Scabra), D F. Cameron, R A. Boland, S Chakraborty, B Jamieson, J.A G. Irwin Jan 2025

Recurrent Selection For Partial Resistance To Anthracnose Disease In Shrubby Stylo (Stylosanthes Scabra), D F. Cameron, R A. Boland, S Chakraborty, B Jamieson, J.A G. Irwin

IGC Proceedings (1977-2023)

Three cycles of crossing have been completed in a recurrent selection programme for partial resistance to anthracnose disease of shrubby stylo (Stylosanthes scabra) In a field study of a subset of 40 F2 populations from the first cycle, highly significant differences (P<0.001) in anthracnose resistance were found for both male and female effects and for the female x male interaction, In a subsequent F3 progeny test of 99 families selected for disease resistance and yield, 92 of the families were resistant to highly resistant with leaf damage <1% (cf, >50% damage for the susceptible cultivar, Fitzroy). Strong discrimination for resistance was also obtained in a second subset of 23 F2 populations using combined glasshouse and field selection for resistance. Further improvement in anthracnose resistance was achieved in the second and third cycles of recurrent selection. The broadly based resistance of selections from the third cycle …


Calliandra Calothyrsus - A Potential New Shrub Legume For Tropical Animal Production?, B Palmer, R A. Bray, T M. Ibrahim Jan 2025

Calliandra Calothyrsus - A Potential New Shrub Legume For Tropical Animal Production?, B Palmer, R A. Bray, T M. Ibrahim

IGC Proceedings (1977-2023)

Calliandra calothyrsus outyielded leucaena in cutting experiments at 2 sites in northern Australia and I in Indonesia. Drying significantly depressed the voluntary intake and digestibility of leaf, possibly due to the presence of tannin. Calliandra has the potential as a supplement for the low quality grass common to the tropics both ln grazing and cut-and-carry systems.


Glycine Latifolia- A Potentially Useful Native Legume For Clay Soils In Tropical And Subtropical Australia, M C. Rees, R M. Jones, A.H D. Brown, J N. Coote Jan 2025

Glycine Latifolia- A Potentially Useful Native Legume For Clay Soils In Tropical And Subtropical Australia, M C. Rees, R M. Jones, A.H D. Brown, J N. Coote

IGC Proceedings (1977-2023)

In tropical and subtropical Australia, more than 5 million ha of heavy-textured soils receive adequate rainfall for cropping or pasture improvement. Glycine latifolla, a perennial legume native to these areas, shows promise for permanent pastures or long term leys. It occurs from latitudes 22"8 to 31 •s on heavy textured soils in the 500-1200 mm rainfall zone. It is a prostrate plant that roots from stolons and sets seed under grazing, It is drought tolerant, frost resistant, and produces dry matter yields comparable to those from the introduced legumes Desmanthus virgatus and Indigofera schimperi, There is a need to …


Development Of Rhizoma Peanut For Forage In Lower South, Usa, Gordon M. Prine, Edwin C. French Jan 2025

Development Of Rhizoma Peanut For Forage In Lower South, Usa, Gordon M. Prine, Edwin C. French

IGC Proceedings (1977-2023)

Rhizoma (perennial) peanut (Arachiis glabrata Benth.) (RP) is n perennial, warm-season legume, adapted to well-drained soils of humid tropics and subtropics. It is grown in Florida and warmer portions of the south-eastern USA up to about 32°N. Cultivar Florigraze was released in 1978 and cv. Arbrook in 1986. Commercial hectarage of RP has increased about 40% annually to approximately 2000 ha in 1992. Propagated vegetatively from rhizomes, RP Is slow to establish. Rhizoma peanut is drought-tolerant, persistent, grows well on droughty, low-fertility soils, requires moderate to excessive soil drainage and requires no N and usually no P fertiliser. It …


Effects Of Cutting Heights And Cutting Frequencies On The Annual Yield Of Leucaena And Calliandra Hedges, O Ncamihigo, P Brandelard Jan 2025

Effects Of Cutting Heights And Cutting Frequencies On The Annual Yield Of Leucaena And Calliandra Hedges, O Ncamihigo, P Brandelard

IGC Proceedings (1977-2023)

A 3-year study was conducted in Burundi to examine the effects of 3 cutting heights (0, 50 and 100 cm) and 3 cutting frequencies (3, 4 and 6 months) on the total annual biomass yield and leaf production of 3 shrub legumes, Leucaena diverslfolia cv, Buitenzorg, L. leucocephala cv, Peruvian and Calliandra calothyrsus. Highest annual biomass and leaf production were obtained at the 100 cm cutting hejght, There was no significant effect of cutting interval on L. leucocephala but for Calliandra calothyrsus, leaf production was highest at the 4- month cutting frequency. Both biomass production and leaf production …


Performance Of Desmanthus Virgatus Accessions In The Caribbean, M B. Adjei, K Albrecht Jan 2025

Performance Of Desmanthus Virgatus Accessions In The Caribbean, M B. Adjei, K Albrecht

IGC Proceedings (1977-2023)

Twenty-three Desmanthus virgatus accessions, established on a mildly alkaline clay soil (Typic Rendoll Mollisol), were repeatedly harvested to 10 cm stubble over a 2-year period whenever regrowths reached the early-pod stage of maturity to determine forage yield, leaf/stem proportions, forage quality and stand persistence. Differences were observed in seasonal growth distribution and annual forage yield of accessions. Collections from Venezeula and Mexico were among the most productive (8-11 t dry matter/ha/year) and from the Dominican Republic, the least productive (<6 t/ha/year) accessions. Most accessions perissted well under the lenient garvesting regime imposed. The proportion of leaf in dry forage ranged from 34 to 43% with average leaf crude protein (CP) content in vitro organic matter digestibility (IVOMD) of 19.2% and 83.4%, respectively. The average stem CP and IVOMD were 7.4% and 48.9%, respectively, and were not affected by accessions. Leaf samples of all Desmanthus accessions contained high levels of tannins (26-31 g tannic acid equivalent s/kg DM). However, unlike fibre fractions, leaf IVOMD was only weakly correlated with leaf tannin content (r-0.38).