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Expression And Purification Of Prohibitin Proteins And Investigation Of Their Interaction With Mycobacterium Tuberculosis’S Virulence Factors, Zeina Rhaim

Open Access Theses & Dissertations

Prohibitin (PHB) is a highly conserved mitochondrial protein involved in cell cycle regulation, apoptosis, mitochondrial integrity, macrophage activation, cytokine production and many other critical cell functions. The prohibitin complex, formed by Prohibitin-1 (PHB1) and Prohibitin-2 (PHB2), functions as a mitochondrial membrane-associated receptor. Cancer, neurodegenerative disorders, and renal conditions were found to be linked to an irregular PHB expression. Emerging evidence has also highlighted a significant role for PHB in tuberculosis (TB), particularly through its interactions with Mycobacterium tuberculosis (Mtb) virulence determinants. The molecular mechanisms by which PHB influences TB pathogenesis remain poorly understood. Our preliminary studies showed that PHB1 was …

Ode To The Infomercial, Edward Wade

Open Access Theses & Dissertations

'Ode to the Infomercial' is a poetry collection in five sections which explores themes of contemporary American life, parenthood, and the media landscape. While primarily written in a narrative voice, the poetic approach is as diverse as the content. Interwoven throughout the collection is religious imagery and political posturing accompanied by healthy doses of self-criticism and humor.

Separating The Control Of Moving And Holding In Human Post-Stroke Arm Paresis, Alkis M. Hadjiosif, Kahori Kita, Scott T. Albert, Robert A. Scheidt, Reza Shadmehr, John W. Krakauer

Biomedical Engineering Faculty Research and Publications

Moving and holding-still (holding) have been posited to be separately controlled. The paretic arm after stroke exhibits different abnormalities during rest vs. movement, providing an opportunity to ask whether control of these behaviors is independently affected in stroke. We quantified resting postural abnormalities in human stroke patients by measuring their biases in force production as they held their hand still in various locations in a planar workspace and then assessed whether these resting force biases influenced reaching in the same workspace. Patients displayed marked resting force biases at each location, even when the arm was supported. However, these …

Now You See It: Evaluating A Small Object Detection Model For Uncrewed Surface Vehicle Operations, Jenna Ehnot

Master's Theses and Capstones

As Uncrewed Surface Vehicle (USV) operations scale in size, distance, and complexity, they increasingly rely on artificial intelligence (AI) algorithms to maintain situational awareness, and operators must understand how algorithm performance may change as camera configuration is adjusted to meet operational needs. This thesis proposes distance-based evaluation strategies that characterize object detection performance in terms directly applicable to USV operations. In this research, a YOLOv5s model was trained to detect small maritime obstacles, focusing on aids to navigation, and the lobster pot floats common in the Gulf of Maine. Three test videos were collected, each capturing a buoy approaching the …

Quantifying Contributions Of Sonar Systems On Marine Soundscapes: A Statistical And Machine Learning Analysis, Reilly Jacob Lessard

Master's Theses and Capstones

A variety of elements are used to characterize marine soundscapes, including natural and anthropogenic sound. One anthropogenic activity that potentially contributes to marine soundscapes, but is not sufficiently understood, is the use of different types of ocean-mapping sonar systems. Sonar systems are used abundantly in marine environments for purposes such as ocean floor mapping and military security purposes [Ryu et al., 2023] [Marszal and Salamon, 2013]. The systems used to conduct this research are the Kongsberg TOPAS PS40 sub-bottom profiler and the RESON SeaBat T51-R multibeam echosounder, along with SoundTrap recorders, which were deployed in the Gulf of Maine. Periods …

“War Is God” And “Unguessed Kinships”: Blood Meridian And Cormac Mccarthy’S “Border Tetralogy”, Seth Reeves

Electronic Theses and Dissertations

This thesis applies the metaphysics of philosopher Gilles Deleuze to Cormac McCarthy’s novel Blood Meridian, arguing that the novel initiates a thread of immanent subjectivity that unfolds throughout the Border Trilogy that follows it. Against a hierarchical metaphysics of transcendence, specifically an inverted Platonic Idealism, Blood Meridian dramatizes an immanent world of “optical democracy,” a prose style that levels the human and nonhuman and eludes subject and object categories. The kid’s autonomy from Judge Holden’s violent domination marks the truncated beginning of a Deleuzian subjectivity of becoming-other and immanent kinship. This incomplete gesture continues in the Border Trilogy, where …

Assessing Native Tallgrass Prairie Species As Main Roadside Vegetation In Arkansas, Sarah Paschal

Graduate Theses and Dissertations

Tallgrass prairies are among the most endangered ecosystems in North America, with Arkansas having lost over 99% of its native grasslands. This research evaluated the potential for using native tallgrass prairie species in Arkansas roadside vegetation. Two field experiments were conducted from 2022 to 2024. The first assessed seven native seed mixtures at three roadside locations (Clarksville, Huntsville, and Newport). Seed mixture composition significantly influenced establishment outcomes, with early-establishing forbs such as black-eyed Susan, partridge pea, and Illinois bundleflower performing well, though establishment varied by location. A second trial compared planting date (Autumn, Winter, Spring) and planting method (broadcast, drill …

Synthetic Dataset For Understanding Negation In Text-Guided Image Editing, Nhat-Tan Bui

Graduate Theses and Dissertations

Negation is a fundamental linguistic concept used by humans to convey information that they do not desire. Despite this, minimal research has focused on negation within text-guided image editing. This lack of research means that vision-language models (VLMs) for image editing may struggle to understand negation, implying that they struggle to provide accurate results. One barrier to achieving human-level intelligence is the lack of a standard collection by which research into negation can be evaluated. This thesis presents the first large-scale dataset, Negative Instruction (NeIn), for studying negation within instruction-based image editing. Our dataset comprises 366,957 quintuplets, i.e., source image, …

Hiring Expectations For New And Future Workers In Animal Genetics Careers, Meghan C. Wulster-Radcliffe, James N. Macleod, Robert J. Coleman, John S. Radcliffe, Rebekah B. Epps, Carol D. Hanley, Cheyenne S. Summers, Steven A. Zinn, Sarah A. Reed

Animal and Food Sciences Faculty Publications

To better align educational outcomes with workforce demands in animal and equine genetics, this study surveyed 65 industry professionals on entry-level competencies, hiring trends, and graduate preparedness of undergraduate students. The survey assessed employer ratings on the importance and perceived proficiency of seven core competencies: critical thinking, communication, teamwork, leadership, professionalism, career/self-development, and equity/inclusion, as well as technical knowledge and broader skills relevant to animal breeding and genetics. Results revealed oral communication, teamwork, and work ethic were rated as the most critical transferable skills, though notable proficiency gaps persist, particularly in leadership and professionalism. Foundational technical knowledge in genetics, molecular …

Protein Structural Modeling Explains Rapid Oxidation In Poultry And Fish Myoglobins Compared To Livestock Myoglobins, Greeshma Sreejesh, Surendranath P. Suman, Gretchen G. Mafi, Morgan M. Pfeiffer, Ranjith Ramanathan

Animal and Food Sciences Faculty Publications

Background: This study aimed to investigate rapid oxidation in poultry and fish myoglobin compared to livestock myoglobin using protein structural differences and bioinformatics tools. Methods: Myoglobins from beef (Bos taurus), bison (Bos bison), sheep (Ovis aries), goat (Capra hircus), red deer (Cervus elaphus), pork (Sus scrofa), chicken (Gallus gallus), turkey (Meleagris gallopavo), yellowfin tuna (Thunnus albacares), and tilapia (Oreochromis niloticus) were analyzed to understand differences in structure and function that may influence oxidative behavior. Results: Fish and poultry had shorter or absent D-helix in their myoglobin structure than other species. Tilapia showed the largest heme cavity surface area, indicating significant …

Seasonal And Diurnal Variation In Forage Nutritive Value Of Cool-Season Grasses As Predicted By Near-Infrared Reflectance Spectroscopy (Nirs), Ann Marie C. Riley, Isabelle A. Kagan, Brittany E. Davis, Laurie M. Lawrence, Chris D. Teutsch, S. Ray Smith

Animal and Food Sciences Faculty Publications

A better understanding of seasonal and diurnal variation in forage nutritive value may help to maximize protein intake and digestibility for grazing livestock. Forage nutritive value was evaluated in four cool-season grasses common to Kentucky pastures: orchardgrass (Dactylis glomerata L.; OG), perennial ryegrass (Lolium perenne L. ssp. perenne; PRG), Kentucky bluegrass (Poa pratensis L.; KBG), and tall fescue [Schedonorus arundinaceus (Schreb.) Dumort.; TF]. In 2015 and 2017, 10 cool-season grass cultivars representing four species, planted in quadruplicate (40 plots) in central Kentucky, were maintained vegetatively with 2–4 week mowing and sampled in the morning and the afternoon at the same …

A Secret Society Of Readers: College-Age Mentors’ Literacy Experiences With Young Adolescent Mentees, Lindsay Persohn, Dulcey B. Hunter, Chelsea Rivera, Karyn Z. Mendez, Cheryl R. Ellerbrock, Lucy Monette

Journal of Global Education and Research

This study occurred within Year One and Year Two of an ongoing literacy initiative designed to build reader identities among underserved middle school students. Using a near-peer mentoring model, mentees were paired with college-student mentors to interact weekly around books and reading. Reader interests and identities are influenced by affective and relational approaches through mentored reading experiences and a variety of texts. This qualitative case study (n = 11 of 24 Year One and n = 13 of 37 Year Two mentors) aimed to identify the ways mentor/mentee relationships affect reader interests, attitudes, and skills, and to evaluate the …

The Transition Zone Hypothesis On Biodiversity Of The Indian River Lagoon System, Florida, Richard L. Turner

Ocean Engineering and Marine Sciences Faculty Publications

The Indian River Lagoon System (IRL) is regarded as having a high level of biodiversity. The level of biodiversity is often attributed in part to the 2-degree latitudinal span (251 km) of the IRL and to its position in a transitional zone between tropical and temperate biotic provinces. This hypothesis was tested for submerged aquatic vegetation (SAV) based on a recent treatise (Littler, Littler, and Hanisak, 2008). Five of seven species of seagrass are tropical, and two have either a broad or very narrow latitudinal distribution; the transition-zone hypothesis does not hold for seagrasses. Most macroalgae (131 spp.) are tropical/subtropical; …

Evaluation Of Ramp Instead Of Forage During Grain Adaptation And Different Sorghum Varieties On Enteric Methane Production From Cattle, Jack T. Fort

Department of Animal Science: Dissertations, Theses, and Student Research

Two experiments were conducted to evaluate the use of RAMP (Cargill Corn Milling, Blair, Nebraska) compared with traditional forage-based adaptations on methane (CH₄) and carbon dioxide (CO₂) emissions, performance, and carcass characteristics. Experiment 1, 64 yearling British × Continental steers (initial BW = 423 ± 6 kg) were adapted using 100% RAMP (RAMP) or a traditional forage diet (CON; 43% forage) before transitioning 22 d to a common finishing diet containing 65.6% steam-flaked corn. Emissions were measured in paired replications using a two-chamber indirect calorimetry barn. During adaptation RAMP did not affect CH₄ production (g/d; …

Impact Of Constant Versus Variable Inclusions Of Modified Distillers Grains Plus Solubles On Feedlot Cattle Performance And Carcass Characteristics And Impact Of The Frequency Of Varying Modified Distillers Grains Plus Solubles Inclusions In Feedlot Diets On Performance, Carcass Characteristics, Feeding Behavior, And Ruminal Ph Of Finishing Steers, Paige M. Madison

Department of Animal Science: Dissertations, Theses, and Student Research

Inconsistent availability or supply of distillers grains (DGS) can cause more variation in DGS inclusions throughout the feeding period. Two feedlot experiments evaluated the effects of varying inclusions of modified distillers grains plus solubles (MDGS) in feedlot diets. Beef steers (n = 400; initial BW = 287) were used in a 2 × 2 + 1 factorial experiment with treatments including: control with no MDGS compared to 2 inclusions (10% and 25%) of MDGS diet inclusions fed consistently or variably. No interactions were observed between MDGS consistency and inclusion for any performance or carcass characteristics (P > 0.10), so …

Integrating Innovative Sensing And Ground Measurements For Forage Mass Estimation In Rye Pasture, Pedro Henrique Jota Fernandes

Department of Animal Science: Dissertations, Theses, and Student Research

The United States beef industry relies on forages to provide up to 80% of total lifetime dry matter intake, making accurate forage mass estimation essential for determining stocking rates, improving grazing efficiency, and supporting economic sustainability. Traditional methods to quantify forage mass, however, are time-consuming and labor-intensive. This thesis presents research efforts to achieve accurate forage mass estimation in cereal rye pasture by integrating novel sensing technologies.

Chapter 1 reviews the importance and evolution of forage mass estimation methods, from destructive clipping to indirect approaches based on canopy measurements. It then introduces remote sensing, from proximal tools to drone- and …

Investigation Of Changes In Exotic Bird Serum Vitamin D Levels Between Indoor And Outdoor Housing, Alexander J. Marley

Department of Animal Science: Dissertations, Theses, and Student Research

Vitamin D is a fat-soluble vitamin that is directly related to sunlight and is involved in multiple physiological processes including calcium metabolism, feather quality, and chick development. Most vertebrate species are capable of both absorption of exogenous vitamin D and internal synthesis of vitamin D, with vitamin D3 (cholecalciferol), being more accessible and bioactive in bird species. In exotic bird species, dietary requirements for vitamin D3 are largely unknown, and the ability to maintain adequate serum concentrations of vitamin D3 metabolites without direct sunlight exposure also requires evaluation. Concerns arise in situations where individuals may be housed indoors for extended …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Reviewing Vascular Influences On Neuronal Migration, Cortical Development, And Neurodevelopmental Disorders: Focus On Autism, Adhd And Schizophrenia, Lalit K Ahirwar, Spiros L Blackburn, Devin W Mcbride, Peeyush Kumar T

Faculty, Staff and Student Publications

During cortical development, newly born neurons migrate radially or tangentially from their origin to expand the cortex. Simultaneously, neuron-derived factors support angiogenesis, and an elaborate network of blood cerebral vessels develops in the cortex. Traditionally, blood cerebral vessels were considered to support the growing cortex or migrating neurons by providing nutrients and oxygen. However, recent studies have shed light on Endothelial cells' influence on cortical development; they guide neuronal migration by providing molecular cues and structural support. Here, we review the current understanding of how CNS cerebral vessels support neurogenesis, neuronal migration, and the formation of the six-layer cortical structure …

Evaluation Of Renal Masses With Cest Mri: Protocol Optimization And Preliminary Results, Xiaojing Wang, Jochen Keupp, Ivan E Dimitrov, Ananth Madhuranthakam, Durga Udayakumar, Mahsa Taherzadeh, Emin Albayrak, Orson W Moe, Payal Kapur, Robert E Lenkinski, Ivan Pedrosa, Elena Vinogradov

Faculty, Staff and Student Publications

Purpose: This study investigates the application of CEST MRI in human kidneys, with the overarching goal of developing CEST MRI for renal mass characterization. Here, the focus is on the development of a protocol and the proof-of-principle evaluation of CEST for the characterization of clear cell renal cell carcinoma (ccRCC).

Methods: Ten healthy volunteers and five patients diagnosed with ccRCC underwent CEST MRI scans at 3 T. The sequence performance was characterized in healthy volunteers and tested using three saturation power levels, B1rms = 0.7, 1.2, and 1.6 μT. We compared the magnetization transfer ratio asymmetry (MTRasym) values at 1.0, …

Smart Spatial Omics (S2-Omics) Optimizes Region Of Interest Selection To Capture Molecular Heterogeneity In Diverse Tissues, Musu Yuan, Kaitian Jin, Hanying Yan, Amelia Schroeder, Chunyu Luo, Sicong Yao, Bernhard Dumoulin, Jonathan Levinsohn, Tianhao Luo, Jean R Clemenceau, Inyeop Jang, Minji Kim, Yunhe Liu, Minghua Deng, Emma E Furth, Parker Wilson, Anupma Nayak, Idania Lubo, Luisa Maren Solis Soto, Linghua Wang, Jeong Hwan Park, Katalin Susztak, Tae Hyun Hwang, Mingyao Li

Faculty, Staff and Student Publications

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here we …

Differential Effects Of Murine Stroke Models On Dopaminergic Neurons, Glial Responses, And Neurobehavioral Outcomes, Sidra Tabassum, Heng Hu, Silin Wu, Shuning Huang, Bosco Seong Kyu Yang, Chang-Hun Lee, Aaron W Gusdon, Xuefang S Ren

Faculty, Staff and Student Publications

Stroke is a leading cause of disability worldwide, often resulting in persistent motor, cognitive, and emotional impairments. While the hippocampus and amygdala play critical roles in post-stroke behavioral changes, specific neuronal alterations and prolonged glial responses within these regions across different stroke types remain unclear. This study investigates the behavioral, neuronal, and glial effects of subarachnoid hemorrhage (SAH), transient middle cerebral artery occlusion (tMCAO), and photothrombotic stimulation (PTS) in mice. SAH and tMCAO models exhibited significant motor deficits, spatial and recognition memory impairments, and increased anxiety- and depressive-like behaviors, whereas the PTS model showed similar motor and cognitive impairments but …

Inhibiting Monocyte Migration Reduces Arterial Thrombosis And Facilitates Thrombolysis, Hee Jeong Jang, Jiwon Kim, Ha Kim, Taesu Kim, Jinyong Chung, Sebastian Cremer, Marvin Krohn-Grimberghe, Eo Jin Kim, Dawid Schellingerhout, Matthias Nahrendorf, Dong-Eog Kim

Faculty, Staff and Student Publications

Background: Monocytes contribute to the initiation and propagation of venous thrombosis. Little is known about the roles monocytes play in arterial thrombosis, the cause of stroke and myocardial infarction.

Methods: We investigated how CCR2 (CC chemokine receptor 2) knockout (-/-)-mediated monocyte deficiency affects platelet function, blood coagulation, thrombus volume, and thrombolytic susceptibility in 666 male mice with FeCl3-mediated carotid arterial thrombosis, including 365 C57BL/6 wild type (WT) mice, 295 CCR2-/- mice, and 6 CX3CR1-GFP (CX3C chemokine receptor 1-green fluorescent protein) mice.

Results: Intravital microscopy and flow cytometry showed that both neutrophils and monocytes were recruited to the acute arterial thrombus, …

Profiling The Preclinical Pharmacokinetics And Biodistribution Of A Platinum(Iv)-Based Oxaliplatin Prodrug Oxalitex And Their Significance To Antitumor Response, Guangan He, Gregory D Thiabaud, Kathryn A Shelton, Luke J Segura, Jonathan F Arambula, Jonathan L Sessler, Rick A Finch, Zahid H Siddik

Faculty, Staff and Student Publications

OxaliTEX (NOVO-111) is a novel gadolinium(III) texaphyrin-platinum(IV) complex that is under development for clinical trials. It was designed as a prodrug of oxaliplatin (1,2-diaminocyclohexane-platinum(II) oxalate) tethered to a tumor-affinic texaphyrin moiety to improve drug delivery to the tumor. However, oxaliTEX was not only more effective as an antitumor agent but also better tolerated in mice. To appreciate this higher therapeutic index and advance its preclinical development, studies were undertaken to profile its plasma pharmacokinetics, distribution to tumor and normal tissues, and pharmacodynamics of the p53/p21 molecular pathway. Nude mice, with or without a subcutaneous colorectal HCT-116 xenograft harboring a phenotypically …

Decoding Fibrosis In Nonresolvable Covid-19: A Role For Myeloid-Specific Hif1a Deletion, Kemly Philip, Hannah P Thompson, Scott D Collum, Isabella Lefebvre, Bindu Akkanti, Bihong Zhao, Rahat Hussain, Manish Patel, Michael R Blackburn, Tingting W Mills, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

A complication of viral lung infections is the development of pulmonary fibrosis. This phenomenon is most evident in patients with COVID-19, where in its most aggressive form patients developed nonresolvable (NR) COVID-19 requiring lung transplantation. NR-COVID-19 was characterized by the presentation of a fulminant fibrotic lung injury that progressed rapidly, even in patients with limited comorbidities. However, the mechanisms that led to this rapidly progressing form of fibrosis are not fully understood. A common clinical manifestation in the most severe cases of COVID-19 was the presence of "silent" hypoxemia. Thus, we hypothesized that a dysfunctional hypoxic response may result in …

The Role Of Neutrophils In Vasospasm And Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Is It Time For A Sah Clinical Trial Targeting Neutrophils?, William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence …