Digital Commons Network^™

Optimized Genomic Editing Of A Common Duchenne Muscular Dystrophy Mutation In Patient-Derived Muscle Cells And A New Humanized Mouse Model, Mateusz Z Durbacz, Yu Zhang, Hui Li, Takahiko Nishiyama, Efrain Sanchez- Ortiz, John R Mcanally, Damir Alzhanov, Ning Liu, Eric N Olson

Faculty, Staff and Student Publications

Duchenne muscular dystrophy (DMD) is a fatal X-linked, recessive disease caused by mutations in the DMD gene encoding dystrophin, a membrane-associated protein necessary for maintaining muscle structure and function. One of the common DMD mutations is the deletion of exon 52 (Δ52), which introduces a premature stop codon in exon 53, preventing the expression of functional dystrophin protein. Patients with this mutation could benefit from skipping or reframing exon 53 to restore the dystrophin open reading frame. In this study, we investigated the efficacy of single-cut CRISPR gene editing with Staphylococcus pyogenes Cas9 (SpCas9)-LRVQR to restore dystrophin expression …

Arid4b: An Orchestrator From Stem Cell Fate To Carcinogenesis, Rakhee Rathnam Kalari Kandy, Madan Kumar Arumugam, Mukesh Pratap Yadav, Bibhuti Bhusan Mishra, Jyotika Sharma

Faculty, Staff and Student Publications

All biological processes, from embryonic development to cancer, are tightly controlled by the interactions between genetics and epigenetics. An array of epigenetic modifications, such as DNA methylation, histone/chromatin modifications, and noncoding RNA-mediated targeting, are essential to regulate the heritable changes that occur during multiple cellular processes. A failure in proper regulation results in inappropriate gene expression that ultimately leads to pathological states. Groundbreaking advances in genomics and transcriptomics have revealed the potential involvement of epigenetics in various physiological and pathological states. The promising clinical and preclinical results shown by epigenetics drugs further underscore the central role of epigenetics in multiple …

Sickle Cell Disease Induces Chromatin Introversion And Ferroptosis In Cd8+ T Cells To Suppress Anti-Tumor Immunity, Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Jun Yao, Lanxin Bei, Yaohua Zhang, Pengju Gong, Lisa A Huang, Zhou Jiang, Jian Gao, Shuang Peng, Tina K Nguyen, Menuka Karki, Bora Lim, Cassian Yee, Jared K Burks, Qing Zhang, Li Ma, Jianjun Gao, Nizar M Tannir, Leng Han, Dihua Yu, Linghua Wang, Michael A Curran, Maria A Gubbiotti, Giannicola Genovese, Boyi Gan, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin

Faculty, Staff and Student Publications

Understanding how genetic disorders affect CD8

Determining Accurate Pore Structures Of Polypropylene Membrane For Ecmo Using Fe-Sem Under Optimized Conditions, Makoto Fukuda, Yoshiaki Nishite, Eri Murata, Koki Namekawa, Tomohiro Mori, Tsutomu Tanaka, Kiyotaka Sakai

Children’s Nutrition Research Center Staff Publications

Long-term ECMOs are expected to be put into practical use in order to prepare for the next emerging severe infectious diseases after the novel coronavirus pandemic in 2019-2023. While polypropylene (PP) and polymethylpentene (PMP) are currently the mainstream materials for the hollow fiber membranes of ECMO, the PP membrane coated with a silicone layer on the outer surface has also been commercialized. In this study, we sought a method to accurately observe the detailed pore morphologies of the PP membrane by suppressing irreversible changes in the morphology in SEM observation, which is a general-purpose observation with higher resolution. As a …

Voluntary Contractions Underestimate Peak Muscle Activity In Drop Jumps, David Alan Phillips, Skylar Paletta, Michael R. Perlet

Department of Kinesiology Scholarship and Creative Works

Maximal voluntary isometric contractions (MVIC) are a common method to normalize electromyographic amplitude into standardized units of %MVIC. However, in 60% of drop jump research using an MVIC in 2018–2023, supramaximal activation or activation greater than 100% MVIC occurred. Therefore, MVICs may not be representative of peak muscle activation, leading to erroneous interpretation of muscle activation. The purpose of this study is to quantify EMG normalization difference in drop jump landings. Sixteen (10 M, 6F) participants were recruited for the study. MVICs were recorded from nine lower extremity muscles and this activation compared to the maximal activation recorded from 10 …

Targeting Detoxifying Enzymes In The Lymphatic Filariasis Vector: An In Silico Study On Curcumin, Camphor, And Menthol, Rizal Subahar, Rawina Winita, Surya Dwira, Gulshan Fahmi El Bayani

Indonesian Journal of Medical Chemistry and Bioinformatics

Vector control remains a critical component in the prevention of lymphatic filariasis, a disease transmitted by insect vectors. Natural compounds such as curcumin, camphor, and menthol are being explored for their bio-insecticidal properties due to their potential to inhibit key detoxification and neurological enzymes in insects, including acetylcholinesterase (AChE), glutathione S-transferase (GST), and cytochrome P450 oxidases (CYP450). A molecular docking study using SwissDock was conducted to evaluate the interaction of curcumin, camphor, and menthol with AChE, GST, and CYP450 enzymes. Binding affinity (ΔG), hydrogen bonding, and active site interactions were analyzed to assess the inhibitory potential of each compound. Curcumin …

Specialized Insectivores Drive Differences In Avian Community Composition Between Primary And Secondary Forest In Central Africa, Eleanor M. Barrie, Billi A. Krochuk, Crinan Jarrett, Diogo F. Ferreira, Patricia F. Rodrigues, Susana Lin Mufumu, Silvestre Esteban Malanza, Agustin Ebana Nsue Akele, Cayetano Ebana Ebana Alene, Kristin Brzeski, Jacob C. Cooper, Jared Wolfe, Luke L. Powell

Michigan Tech Publications

The human population of sub-Saharan Africa is projected to triple by 2100, drastically increasing anthropogenic pressure on biodiversity. When rainforest is disturbed by anthropogenic drivers, species respond heterogeneously; these patterns have rarely been quantified for Congo rainforest fauna. Our objective was to understand how community composition changed with human disturbance—with particular interest in the guilds and species that indicate primary rainforest. At a long-term bird banding site on mainland Equatorial Guinea, we captured over 3200 birds across 6 field seasons in selectively logged secondary forest and in largely undisturbed primary forest. Our multivariate ordination indicated a significant split between primary …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Spatial And Multiomics Analysis Of Human And Mouse Lung Adenocarcinoma Precursors Reveals Tim-3 As A Putative Target For Precancer Interception, Bo Zhu, Pingjun Chen, Muhammad Aminu, Jian-Rong Li, Junya Fujimoto, Yanhua Tian, Lingzhi Hong, Hong Chen, Xin Hu, Chenyang Li, Natalie Vokes, Andre L Moreira, Don L Gibbons, Luisa M Solis Soto, Edwin Roger Parra Cuentas, Ou Shi, Songhui Diao, Jie Ye, Frank R Rojas, Eduardo Vilar, Anirban Maitra, Ken Chen, Nicolas Navin, Monique Nilsson, Beibei Huang, Simon Heeke, Jianhua Zhang, Cara L Haymaker, Vamsidhar Velcheti, Daniel H Sterman, Veena Kochat, William I Padron, Ludmil B Alexandrov, Zhubo Wei, Xiuning Le, Linghua Wang, Junya Fukuoka, J Jack Lee, Ignacio I Wistuba, Harvey I Pass, Mark Davis, Samir Hanash, Chao Cheng, Steven Dubinett, Avrum Spira, Kunal Rai, Scott M Lippman, P Andrew Futreal, John V Heymach, Alexandre Reuben, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, …

Identifying The Drivers Behind The Decline Of Douglas-Fir And True Fir Species In Sw Oregon, Alexander Bryant Bentley

Dissertations and Theses

Increased levels of Pseudotsuga menziesii (DF) and Abies species (TF) decline throughout dry forests in the Klamath Mountains and Western Cascades ecoregions have been recorded in recent years, with preliminary evidence suggesting that factors influenced by changing climatic conditions and encroachment from fire suppression policies are primarily to blame. Yet, the physiological and environmental mechanisms of drought-driven tree decline are poorly understood across biophysical and spatial gradients. Given the complex relations that drive decline, determining the degree of influence of specific drivers is difficult, creating unique challenges for modern forest management. To elucidate the most important factors driving DF and …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Effects Of Consuming Short-Form Videos On Young Adults’ Fine Motor Skills, Dragon Tanaghon Chew, Jerome Gabriel Gay, Hien Than, Zhi Qin Ko

Introduction to Research Methods RSCH 202

The composition of short-form video (SFV) consumption can affect cognitive abilities, including motor skills. This study addresses a potential concern due to the lack of data. By presenting two experimental designs, the study explores the impact of SFV consumption on the motor skills of young adults. The first experiment employs a between-subjects design, where 60 participants are randomly assigned to two groups, with one group exposed to 30 minutes of SFV content. The second experiment adopts a cross-sectional design based on self-reported historical SFV consumption, where motor skill is compared between groups with low (< 3 hours/day) and high (≥3 hours/day) SFV consumption. Typing performance is used as an indicator of motor skill for the first experiment and finger tapping test is used in the second. The results will compare pre- and post-intervention performance. The findings would enhance practical understanding and illustrate the relationship between social media and motor skills.

Key words: Short-form video, motor …

Influence Of Increasing Fires On Mixed Conifer Stand Dynamics In The U.S. Southwest, Simon D. Baker, Kristen M. Waring, David Auty, Nicholas Wilhelmi

Aspen Bibliography

(1) Stand-replacing fires may threaten the continued stability of mixed conifer forests in the U.S. Southwest. Increasing fire frequency and severity have made post-fire forest recovery trajectories uncertain for many coniferous species, potentially leading to long-term shifts in forest structure and composition. (2) The purpose of this study was to examine post-fire stand dynamics over a 10-year period, using a network of permanent plots established prior to wildfire events across Arizona and New Mexico. We assessed changes in over story composition, regeneration, and fuel loading across different fire severities. (3) High severity fire caused near-total over story mortality, with little …

Biological Control Of Pests In Insect Collections, Henry Townes

The Great Lakes Entomologist

No Abstract Available

Lighting Up The Cell: Developing A Luminescent Lanthanide Probe For Detecting Rnas, Jonathan Savell

Honors Projects

An anion detecting luminescent probe, Tb:DO2A-Cs124, was repurposed for use in RNA imaging. Potential RNA aptamers were identified for the molecule using Capture-SELEX and MinION sequencing. Fluorimetry data revealed these aptamers did not allow for the probe to luminesce in the presence of target RNAs due to adenosine monophosphate’s ability to quench the emission signal.

Colonization-Persistence Trade-Offs In The Human Microbiome, Liam F. Nokes

Environmental Studies Senior Theses

Understanding how diverse microbial taxa coexist in the human body without competitively excluding one another remains a key challenge in microbiome ecology. One proposed explanation is the colonization-persistence trade-off, where species with high colonization ability are poor persisters, and vice versa. We test for this trade-off across human associated microbial communities among many individuals and in multiple body sites using a large-scale participant-level meta-analysis of longitudinal microbiome datasets curated from the MGnify database. We applied island biogeography-based models to calculate effective colonization and persistence rates for microbial families and genera across 606 individuals over twenty-six studies. Regression of the log-transformed …

Exploring Muslim American Attitudes Toward Genetic Testing: Perceptions, Barriers, And Ethical Considerations, Hannah Mahmoud

University Honors Theses

This thesis explores perceptions and attitudes toward genetic testing within the Muslim American community, a group often underrepresented in genomic research and public health discourse. Using a community-distributed digital survey, data was collected from 50 self-identified Muslim Americans on their familiarity with genetic testing, reproductive and ethical considerations, and the influence of religious factors. While only 18% had undergone genetic testing themselves, many were familiar through family or friends, and most expressed cautious interest—especially when results could influence future family planning. Education level, age, and religious values shaped both comfort and understanding.

A key theme was the desire for culturally …

The Bone Is Not Alone: Skeletal Muscle Is A Novel Source Of Fibroblast Growth Factor 23, Kylie Heitman

All ETDs from UAB

Chronic kidney disease (CKD) is a major public health issue often accompanied by various pathologies. Hyperphosphatemia contributes to a range of complications, including vascular calcification, systemic inflammation, anemia, left ventricular hypertrophy, and skeletal muscle atrophy. Phosphate homeostasis is tightly regulated through a combination of renal excretion and its storage in bones, with fibroblast growth factor (FGF) 23 playing a central role in this regulation. Produced primarily by osteocytes in response to elevated serum phosphate, FGF23 helps maintain phosphate balance by promoting renal phosphate excretion and inhibiting the synthesis of vitamin D and parathyroid hormone. Dysregulation of FGF23 is associated both …

Enhancing Lutein And Anthocyanins Stability And Bioaccessibility Through Simultaneous Encapsulation Using Coaxial 3d Food Printing, Safoura Ahmadzadeh, Sorour Barekat, Ali Ubeyitogullari

Food Science Faculty Publications and Presentations

This study investigated the use of 3D printing to co-encapsulate, protect, and enhance the bioaccessibility of lutein and anthocyanins. Coaxial extrusion 3D printing in a spiral-cube geometry was utilized with lutein-loaded zein as the core material and anthocyanins-loaded corn starch paste as the shell material. The research examined various printing conditions, including starch concentrations of 10% and 11%, and printing temperatures ranging from 45 °C to 85 °C. A comprehensive analysis of the inks’ properties, such as printability, viscosity, microstructural characteristics, storage stability, and bioaccessibility of the encapsulated compounds, was conducted. Encapsulated lutein showed only a 29-55% degradation rate after …

Rewired M6a Of Promoter Antisense Rnas In Alzheimer’S Disease Regulates Neuronal Genes In 3d Nucleome, Benxia Hu, Yuqiang Shi, Feng Xiong, Yi-Ting Chen, Xiaoyu Zhu, Elisa Carrillo, Xingzhao Wen, Nathan Drolet, Chetan Singh Rajpurohit, Xiangmin Xu, Dung-Fang Lee, Claudio Soto, Sheng Zhong, Vasanthi Jayaraman, Hui Zheng, Wenbo Li

Faculty, Staff and Student Publications

N6-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs. Notably, many promoter-antisense RNAs (paRNAs) displayed cell-type-specific expression and changes in AD, including one produced adjacent to MAPT that encodes the Tau protein. MAPT-paRNA is highly expressed …

Develpoment Of Urchin-Like Gold Nanoparticles For Drug Delivery Of Glioblastoma And The Colorectal Cancer Cells, Joshua Ozougwu, Vinayak Shama, Bilal Javed Dr., Furong Tian Dr.

Level 3

No abstract provided.

Analysis Of Gold Nanoparticles To Develop The Rapid Antigen Biosensing Strips For Detection Of Toxins, Trang Nguyen Minh Long, Perveen Akhtar, Gayathree Thenuwara, Vinayak Sharma, Furong Tian Dr., Bilal Javed Dr.

Level 3

No abstract provided.

A Novel Approach To Treat Trastuzumab Resistant Her2+ Breast Cancer: Activation Pkcδ, Maria Grazia Mejia Monroy

Master's Theses

In the United States, approximately one in eight women will be diagnosed with invasive breast cancer in her lifetime and one in forty will die from breast cancer. From among all the different subtypes of breast cancer, HER2+ can be found in approximately 20% of breast cancer tumors. HER2 overexpression has been associated with an aggressive form of breast cancer, increasing the risk of metastasis or recurrent tumors in 50% of patients. The standard of care for HER2 positive breast cancer, trastuzumab, has been effective for some patients; however, others develop resistance over time, leading to disease progression and metastasis. …

Transition To Organic: Alfalfa Production In Utah, Earl Creech, Ryan Larsen, Marion Murray, Jennifer R. Reeve, Michele Schahczenski

All Current Publications

Transitioning to organic production may not require drastic operational changes on the part of the producer, as alfalfa production lends itself to more organic practices by default. Producers may decide to transition to certified organic production to capture organic price premiums, access niche market opportunities, reduce the use of synthetic inputs, meet growing consumer demand, enact personal values around environmental stewardship, and support soil and biodiversity conservation. Whatever a grower’s motivation, this fact sheet covers transitioning to organic production through understanding organic production systems, the National Organic Program (NOP) regulations, and crop-specific considerations.

Patterns Of Late Holocene And Historical Extinctions On Madagascar, Laurie R. Godfrey, Zachary S. Klukkert, Brooke E. Crowley, Robin R. Dawson, Peterson Faina, Benjamin Z. Freed, Evon Hekkala, Cortni Borgerson, Harimanjaka A. M. Rasolonjatovo, Patricia C. Wright, Stephen J. Burns

EKU Faculty and Staff Scholarship

Around 1000 years ago, Madagascar experienced the collapse of populations of large vertebrates that ultimately resulted in many species going extinct. The factors that led to this collapse appear to have differed regionally, but in some ways, key processes were similar across the island. This review evaluates four hypotheses that have been proposed to explain the loss of large vertebrates on Madagascar: Overkill, aridification, synergy, and subsistence shift. We explore regional differences in the paths to extinction and the significance of a prolonged extinction window across the island. The data suggest that people who arrived early and depended on hunting, …

Senescence Caused By Telomerase Inactivation In Myeloid, Mesenchymal, And Endothelial Cells Has Distinct Effects On Cancer Progression, Joseph Rupert, Zhanguo Gao, Yongmei Yu, Mikhail G Kolonin

Faculty, Staff and Student Publications

The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We generated genetic Tert knockout (KO) mice driven by the LysM promoter in myeloid cells, by the Pdgfra or Pdgfrb promoter in mesenchymal cells, and by the Tie2e promoter in endothelial cells. We compared the effect of the Tert KOs in syngeneic models of orthotopically grafted E0771 breast adenocarcinoma, RM1 prostate adenocarcinoma, and KPC pancreatic adenocarcinoma. Tumors in LysM-Tert …

Swi/Snf Atpase Silenced Hlf Potentiates Lung Metastasis In Solid Cancers, Jin Zhou, Austin Hepperla, Jeremy M Simon, Kangsan Kim, Qing Hu, Chuanhai Zhang, Lei Dong, Lianxin Hu, Cheng Zhang, Chengheng Liao, Alice Fang, Yayoi Adachi, Haoyong Fu, Tao Wang, Qian Liang, Fangzhou Zhao, Hongyi Liu, Masashi Takeda, Jun Fang, Hua Zhong, Peter Ly, Lu Wang, Payal Kapur, Lin Xu, Liwei Jia, Srinivas Malladi, James Brugarolas, M Celeste Simon, Bo Li, Qing Zhang

Faculty, Staff and Student Publications

Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Here, using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conduct an in vivo genome-wide CRISPR-Cas9 screen and identify HLF as a potent suppressor of lung metastasis. HLF depletion enhances ccRCC cell migration and lung metastasis, whereas HLF overexpression abrogates these effects. In ccRCC patients, HLF expression is reduced at metastatic sites and associates with epigenetic silencing mediated by the SWI/SNF ATPase subunit BRG1. HLF levels negatively correlate with migration potential in collagen. Mechanistically, HLF regulates LPXN expression, modulating the …

Development Of Antimicrobal Formulations From Natural Extracts And Silver Nanoparticles, Ellen Hoey, Lily Jaiswal, Shiv Shankar

Level 3

No abstract provided.

Ultrasound-Mediated Drug Uptake And Cytotocicity In Glioblastoma, Julianne Rogan, Janith Wanigasekera, Esen Efeoğlu

Level 3

No abstract provided.

The Golden Standard: Potential Of Gold Nanoparticles In Cancer Research And Therapy, Caoimhe Mcmanus, Shubhrima Ghosh Dr.

Level 3

No abstract provided.