Digital Commons Network^™

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Scalable Biosynthesis And Recovery Of Poly-3-Hydroxybutyrate Produced From Cotton-Derived Glucose By Cupriavidus Necator, Ashley M. Clark, Lucia E. Gargano, Gabriella M. Fioravanti, Hannah M. Schapiro, Ron G. Kander

School of Design and Engineering Papers

To combat the growing issue of petroleum plastic waste, alternative bio-based polymers are being developed. Many of these biopolymers are made from bio-derived materials, or are biodegradable, but the most promising polymers fall in both categories. Polyhydroxyalkanoates (PHAs) are one such class of polymers, and poly-3-hydroxybutyrate (P3HB), the most popular PHA, has shown great potential. This study utilized two types of cotton-derived glucose, alongside commercial glucose, as a feedstock for the biosynthesis of P3HB by Cupriavidus necator (also known as Ralstonia eutropha). The fermentation took place in a 2-L bioreactor, showing potential for scale-up. A single-solvent extraction method was …

Yx0798 Is A Highly Potent, Selective, And Orally Effective Cdk9 Inhibitor For Treating Aggressive Lymphoma, Vivian Jiang, Yu Xue, Hong Kim, Qingsong Cai, Tianci Zhang, Lei Nie, Joseph Mcintosh, Yang Liu, Haiying Chen, Jia Zhou, Michael Wang

Faculty, Staff and Student Publications

Nongenetic transcription evolution has been increasingly explored and recognized to drive tumor cell progression and therapeutic resistance. As the regulation hub of transcription machinery, cyclin-dependent kinase 9 (CDK9) is the gatekeeper of RNA polymerase II transcription, and CDK9 dysfunction results in transcriptomic reprogramming and tumor cell progression. We recently reported that the heat shock protein 90 (HSP90)-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma (MCL) through transcriptomic reprogramming. We also showed that targeting CDK9 by AZD4573 and enitociclib is a safe and effective treatment in preclinical Mantle Cell Lymphoma (MCL) models, supporting CDK9 as a valid therapeutic target for …

Quantifying Interest In And Sentiment Of Online Media About Greenhouse Gas Emissions From Cattle Production In The United States, Michael L. Smith, Jinho Jung, Nicole Olynk Widmar, Danielle J. Ufer, Maria Berikou, Jayson Lusk

Department of Agricultural Economics Faculty Publications

The public is paying increased attention to the environmental impacts associated with cattle production systems in the US. Thus, cattle producers are increasingly exploring ways to communicate their efforts to reduce those environmental and climate impacts. This study uses online and social media data from 2018 to 2022 to examine public interest in and sentiment about beef and dairy cattle production when discussed within the context of greenhouse gas (GHG) emissions. Variation in mentions and net sentiment over the reporting period is quantified and analyzed. Over the period of data collection, which was interrupted by the COVID-19 pandemic, we find …

Needs Analysis Of Interactive Learning Media For Teachingheat Transfer In Physics: Students’ And Teachers’Perspectives, Rizki Eka Shintya, Ika Mustika Sari, Ida Kaniawati

Jurnal Pendidikan Sains

Heat transfer material in physics is known to be abstract. This study specifically analyzes the conceptual difficulties, and visualization needs specific to this material, which is different from the analysis of physics needs in general. This analysis does not only look for the need for traditional media but explicitly looks for the need for interactive media (simulation, animation, virtual laboratory). Therefore, this study aims to identify the need for interactive learning media in physics education, specifically in the teaching of heat transfer, from the perspective of students and teachers in West Java, Indonesia. Using a quantitative descriptive survey, data were …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …

Inhibition Of Osteosarcoma Lung Metastases By Β-Glucan And Cd40 Agonist Is Mediated By Activation Of Macrophages And Nk Cells, Pradeep Shrestha, Rejeena Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: Osteosarcoma (OS) lung metastases remain a significant therapeutic challenge. Innate immune activation is a promising therapeutic approach. Innate immune agonists can modulate the tumor immune microenvironment and improve therapeutic response.

Methods: Using an experimental syngeneic OS lung metastasis BALB/c mouse model with K7M3-luc OS cells, we evaluated the antitumor effects of yeast-derived particulate β-glucan in prevention and therapeutic settings. We then assessed whether the CD40 agonist (CD40a) in combination with β-glucan increased therapeutic response in two different immune-competent mouse models of OS lung tumor burden.

Results: In the pretreatment settings, mice treated with β-glucan prior to OS cell infusion …

Managing Chickens From Chicks To Peak Egg Production, Joseph Okoh, Essence Perry

All Current Publications

Chickens were first domesticated for cultural purposes, but selective breeding has focused on egg production. Choosing the right breeds and good management practices are essential for farmers to maximize egg yield, quality, and safety. This fact sheet covers poultry history, top egg-laying breeds, egg anatomy, nutrition, and practical tips to help farmers improve productivity and run successful egg production ventures.

A Farmer's Guide To Egg Quality, Safety, And Flock Health, Joseph Okoh, Essence Perry

All Current Publications

Eggs are a valuable source of nutrition and income for many backyard and smallholder farmers. To ensure a steady supply of high-quality eggs, it's essential to understand the key factors that influence hens’ health and productivity. From proper nutrition to effective lighting and disease prevention, each decision you make affects your flock’s performance. This guide offers practical advice to help you raise resilient, high-laying hens and build a successful small-scale egg production system, no matter your level of experience.

Genetic Engineering Of Esophageal Organoids: Crispr-Based Knock-In For Cell Lineage Tracing, Kyung-Pil Ko, Jae-Il Park

Faculty, Staff and Student Publications

Esophageal organoids serve as powerful systems to study epithelial lineage hierarchies and cancer biology. Gene manipulation in these organoids has traditionally involved overexpression or knockout strategies. However, CRISPR-/Cas9-based knock-in (KI) approaches now enable precise cell lineage tracing and live imaging. Here, we describe protocols to generate fluorescent KI organoids from murine esophageal epithelium by tagging Krt13 (BFP) and Sox2 (mNeon). These dual-reporter organoids allow direct monitoring of growth dynamics and differentiation trajectories. We outline CRISPR/Cas9 design, donor construction using homology-independent approaches (CRISPaint), delivery into organoid cells, enrichment and single-clone isolation, and validation by fluorescence. For organoids, homology-directed repair (HDR) can …

Re-Survey Of Blastocystis Infection In Free-Living Birds From Urban Xinxiang City, Xuehan Liu, Yingying Cao, Di An, Chengshui Liao, Ruibiao Wang, Bo Wen, Chunling Zhu, Huarun Sun, Longfei Zhang, Baoliang Qin, Yanhui Wang, Jianhe Hu, Yueyu Bai, Ke Ding, Lei Wang

The Thai Journal of Veterinary Medicine

Blastocystis is the most ubiquitous intestinal protozoan parasite found in humans and animals worldwide. Commonly, ST7 and ST6 are the major Blastocystis subtypes reported in birds, and their frequencies fluctuate greatly with various factors. However, little literature is available on the prevalence and subtype characteristics of this parasite in free-living wild birds in the same city. For this purpose, a total of 114 fresh fecal specimens were collected from wild free-living birds in urban districts of Xinxiang city and tested for Blastocystis using PCR of the barcoding region of the small subunit ribosomal RNA (SSU rRNA) gene. The positive isolates …

Evaluation Of Different Design Standards For The Design Of Axial Loaded Concrete Filled Steel Tube Columns Under Fire, Ebtsam Youssef Ibrahim Abd El Ghaffar, Nabil Said Mahmoud, Fikry A. Salem, Mohammed. M. Ghannam

Mansoura Engineering Journal

This paper compares various codes and standards for the behavior of “Concrete-Filled Steel Tubes” (CFST) columns under fire and axial load. The codes evaluated include European standards (EC4.2 and EC3.2), the American standard (AISC 360), and the Australian standard (AS/NZS 2327). The fire resistance of Concrete-Filled Steel Tubular (CFST) and steel hollow (SH) columns was assessed using a computer program developed with Visual Studio .NET. The program's results were compared with previous experimental data to evaluate the accuracy of various codes and standards in predicting the behavior of these columns under fire conditions. This study highlights the importance of selecting …

Targeting The Bcl2 Family: Advances And Challenges In Bh3 Mimetic-Based Therapies, Nabanita Mukherjee, James Sheetz, Yiqun Shellman

Student Papers, Posters & Projects

The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved significant clinical success, particularly in hematologic malignancies. However, several challenges remain, including resistance mechanisms, toxicity (such as MCL1 inhibitor-associated cardiotoxicity), and the intricate balance between apoptotic and non-apoptotic functions. This review provides a comprehensive overview of BCL2 family biology, the development and clinical application and outcomes of BH3 mimetics, and the emerging resistance mechanism known as double-bolt …

Factors Influencing Plant Community Structure And Composition Of Restored Tamaulipan Thornscrub Forests, Jerald T. Garrett, Audrey J. Hicks, Christopher A. Gabler

School of Earth, Environmental, & Marine Sciences Faculty Publications

The Lower Rio Grande Valley (LRGV) of Texas is a biodiversity hotspot due to its high alpha, beta, and gamma diversity and high regional endemism, which are at high risk of degradation. The region has lost 95% of its native thornforest habitat primarily due to agricultural and urban expansion. This study aims to evaluate the current vegetative structure and composition of restored thornforest sites located in the LRGV to identify restoration methods and site characteristics that affect forest restoration outcomes. Twelve restored thornforest sites were selected for this study that varied in time since restoration, patch size, degree of isolation, …

Interview With Orca Award Winner Donald Weeks; Unl Biochemistry; Biotechnology, Mark Griep, Donald Weeks

UNL ORCA Interview Series

Emeritus Professor Donald Paul Weeks was awarded the ORCA in 2014, a year before he retired. He grew up in a small farm south of Terre Haute, Indiana. In his youth, he participated in 4-H programs that must have sparked an interest in science because he earned his bachelor's degree from Purdue University in 1963. Purdue is about 90 miles north of Terre Haute. Don's doctoral work was at the University of Illinois in Champaign-Urbana for a project about protein synthesis during maize germination. Next, he did postdoctoral work at the Fox Chase Cancer Center in Philadelphia, where his research …

Comprehensive Analysis Of The Tumor Targeting Efficiency Of Functionalized Nanoparticles In An Immunocompetent Environment, Nolan Jackson, Nasry Bouzeineddine, Daniel Cecchi, Safara Holder, Katrina Gee, Wayne Beckham, Sameh Basta, Sunil Krishnan, Devika B Chithrani

Faculty, Staff and Student Publications

The success of nanoparticle-based cancer therapeutics relies on their efficient tumor uptake and retention. Given this, improving nanoparticle localization in tumors is paramount to maximize their therapeutic potential. A common approach to achieve this is to functionalize nanoparticles with active targeting moieties that bind to specific tumor-associated receptors. Among these, arginine-glycine-aspartic acid (RGD) peptides have shown a potential to promote tumor accumulation by targeting the ανβ3 integrin receptor, a receptor commonly overexpressed by tumors owing to its role in promoting angiogenesis, metastasis and proliferation. Yet, its efficacy is commonly assessed using immunocompromised mice models. While useful, these models do not …

Geogenie: A Deep Learning Approach To Predict Geographic Provenance Of Biodiversity Samples From Genomic Snps, Bradley T. Martin, Zachery D. Zbinden, Michael E. Douglas, Marlis R. Douglas, Tyler K. Chafin

Biological Sciences Faculty Publications and Presentations

Motivation

Determining geographic origin of samples is a common objective in wildlife management, forensics, and conservation. Current methods often assume evolutionary models or require extensive reference datasets, which are costly and difficult to develop, that perform poorly with uneven or biased sampling. Supervised deep learning offers a promising alternative by learning complex patterns without prior model specifications. Combined with novel geo-genetic data augmentation and preprocessing techniques, it can reduce reference panel demands and improve performance across diverse sampling schemes, broadening accurate provenance determination to more study systems. Results

We present GeoGenIE, an open-source software package powered by PyTorch for geographic …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Polychlorinated Biphenyls Alter Estrogen Receptor Β-Mediated Epigenetic Regulation, Promoting Endometriosis, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John P Lydon, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a pathological condition characterized by the ectopic growth of endometrial cells, leading to chronic pelvic pain and infertility. Epidemiological studies have associated exposure to dioxin-like polychlorinated biphenyls, particularly PCB126, with an increased risk of endometriosis. However, the underlying mechanisms of this association remain poorly understood. We utilized a surgically induced endometriosis mouse model and human endometrial cell lines to assess the impact of PCB126 on endometriosis progression. Mice were exposed to environmentally relevant doses of PCB126. Endometriotic lesion growth, estrogen receptor signaling, receptor tyrosine kinase activity, and gene expression changes induced by PCB126-mediated elevation of DNA methyltransferase 3A …

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

Bacillus Sp. Sw14 Isolated From Arid Mangroves Sediments Enhances Tomato Plant Growth: Insights From Genome Analysis And Greenhouse Evaluation, Balamurugan Sadaiappan, Qurban Ali, Mahideen Afridi, Munawwar Ali Khan, Sunil Mundra

All Works

Mangroves grow in arid regions with high temperatures, low precipitation, and evaporation. Despite low humidity and high salt concentration, these arid mangroves support diverse microorganisms, including salt-and temperature tolerant. The bacteria isolated from these arid mangroves have potential applications in arid agronomy, which alleviate plant stress and enhance plant growth. In this study, we characterize the genome of previously reported PGP and stress-tolerating bacteria, Bacillus sp. SW14, isolated from mangrove sediments of Umm Al Quwain, United Arab Emirates. Further, we investigated its effects on tomato seed germination and plant growth. Genome size of the strain SW14 is 4.25 MB, with …

A Neuroimmune Cerebral Assembloid Model To Study The Pathophysiology Of Familial Alzheimer's Disease, Andrea Becerra-Calixto, Anik Banerjee, Huihui Fan, Chunfeng Tan, Eunyoung Lee, Louise D Mccullough, Juneyoung Lee

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading cause of dementia globally. The accumulation of amyloid and tau proteins, neuronal cell death and neuroinflammation are seen with AD progression, resulting in memory and cognitive impairment. Microglia are crucial for AD progression as they engage with neural cells and protein aggregates to regulate amyloid pathology and neuroinflammation. Recent studies indicate that microglia contribute to the propagation of amyloid beta (Aβ) via their immunomodulatory functions including Aβ phagocytosis and inflammatory cytokine production. Three-dimensional cell culture techniques provide the opportunity to study pathophysiological changes in AD in human-derived samples that are difficult to recapitulate in …

Synaptic Transmission Promotes Brain Metastatic Outgrowth In Breast Cancer, Jayanta Mondal, Patrick Nylund, Prit Benny Malgulwar, William E Johnson, Jason T Huse

Faculty, Staff and Student Publications

This work demonstrates that normal neuron-to-neuron signaling machinery is hijacked by metastasizing cancer cells during their outgrowth in the central nervous system.

Quiescent Oxphos-High Triple-Negative Breast Cancer Cells That Persist After Chemotherapy Depend On Bcl-Xl For Survival, Slawomir Andrzejewski, Marie Winter, Leandro Encarnacao Garcia, Olusiji Akinrinmade, Francisco Madeira Marques, Emmanouil Zacharioudakis, Anna Skwarska, Julio Aguirre-Ghiso, Marina Konopleva, Guangrong Zheng, Susan A Fineberg, Daohong Zhou, Evripidis Gavathiotis, Tao Wang, Eugen Dhimolea

Faculty, Staff and Student Publications

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function ("OXPHOS-high" cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, …

A Preliminary, Photography-Based Assessment Of Bee Diversity At The Finca Botánica Organic Farm In The Central Pacific Coast Of Ecuador, Joseph S. Wilson, Tyler M. Wilson, Chris Packer, Orlando Pacheco

Biology Faculty Publications

Understanding wild bee diversity is critical for pollinator conservation, particularly in understudied tropical regions like coastal Ecuador. This preliminary study provides a photography-based assessment of bee diversity at Finca Botánica, an organic and regenerative farm on Ecuador’s central Pacific coast. Over a 10-day survey in December 2024, researchers documented 51 bee species across four families, with Apidae being the most represented. The study highlights a predominance of solitary, ground-nesting bees and a lower-than-expected diversity of Meliponini (stingless bees) and Euglossini (orchid bees) compared to other regions of Ecuador. Many species were found in forest patches, ecological corridors, and cover-cropped maize …

Enhanced Piezo1 Function Contributes To The Pathogenesis Of Sickle Cell Disease, Luis O Romero, Manisha Bade, Laila Elsherif, Jada D Williams, Xiangmei Kong, Adebowale Adebiyi, Kenneth I Ataga, Shang Ma, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, leading to anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions that restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a nonselective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte …

A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration In Pulmonary Arterial Hypertension, Tamanna Islam, Jacob Hooper, Xiaojun Zhang, Clarissa Garcia, Md Mahedi Hasan, David H Drewry, Mohammad Anwar Hossain, Taslim A Al-Hilal

Faculty, Staff and Student Publications

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules. Here, for the first time, we …

Multicenter Stroke Preclinical Assessment Network Analysis Of Cardiovascular Risk Factor Subgroups Treated With The Poly(Adp-Ribose) Polymerase Inhibitor Veliparib, Raymond C Koehler, Karni Bedirian, Mu-Hsun Chen, Yanrong Shi, Suyi Cao, Brooklyn D Avery, Senthilkumar S Karuppagounder, Kazi Akhter, Adnan Bibic, Valina L Dawson, Ted M Dawson, Márcio A Diniz, Jessica Lamb, Karisma A Nagarkatti, Anjali Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Andreia Lopes De Morais, Xuyan Jin, Cenk Ayata, Mariia Kumskova, Rakesh B Patel, Anil K Chauhan, Enrique C Leira, Pradip K Kamat, Mohammad B Khan, Krishnan M Dhandapani, David C Hess, Ligia S B Boisserand, Basavaraju G Sanganahalli, Lauren H Sansing, Patrick D Lyden

Faculty, Staff and Student Publications

Background: The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1 month. The PARP (poly(ADP-ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (n=231 …