Digital Commons Network^™

3d-Bioprinting Of Patient-Derived Cardiac Tissue Models For Studying Congenital Heart Disease., Jayne T Wolfe, Wei He, Min-Su Kim, Huan-Ling Liang, Akankshya Shradhanjali, Hilda Jurkiewicz, Bonnie P Freudinger, Andrew S Greene, John F Ladisa, Lobat Tayebi, Michael E Mitchell, Aoy Tomita-Mitchell, Brandon J Tefft

Faculty Research 2023

INTRODUCTION: Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies.

METHODS: To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521.

RESULTS: Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including …

Functional Analysis Of Collagen 17a1: A Genetic Modifier Of Junctional Epidermolysis Bullosa In Mice., Thomas J. Sproule, Robert Y Wilpan, Benjamin E. Low, Kathleen A Silva, Deepak Reyon, J Keith Joung, Michael V. Wiles, Derry C. Roopenian, John P Sundberg

Faculty Research 2023

Previous work strongly implicated Collagen 17a1 (Col17a1) as a potent genetic modifier of junctional epidermolysis bullosa (JEB) caused by a hypomorphic mutation (Lamc2jeb) in mice. The importance of the noncollagenous domain (NC4) of COLXVII was suggested by use of a congenic reduction approach that restricted the modifier effect to 2-3 neighboring amino acid changes in that domain. The current study utilizes TALEN and CRISPR/Cas9 induced amino acid replacements and in-frame indels nested to NC4 to further investigate the role of this and adjoining COLXVII domains both as modifiers and primary risk effectors. We confirm the importance of COLXVI AA 1275 …

Clathrin Light Chain-Conjugated Drug Delivery For Cancer., Sungwook Jung, Liwei Jiang, Jing Zhao, Leonard D. Shultz, Dale L Greiner, Munhyung Bae, Xiaofei Li, Farideh Ordikhani, Rui Kuai, John Joseph, Vivek Kasinath, David R Elmaleh, Reza Abdi

Faculty Research 2023

Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer-melanoma, breast cancer, and lung cancer-with CLC-PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free …

Open Drug Discovery In Alzheimer's Disease., Alison D Axtman, Paul E Brennan, Tristan Frappier-Brinton, Ranjita Betarbet, Gregory W. Carter, Haian Fu, Opher Gileadi, Anna K Greenwood, Karina Leal, Frank M Longo, Lara M Mangravite, Aled M Edwards, Allan I Levey, The Emory-Sage-Sgc Treat-Ad Center.

Faculty Research 2023

Alzheimer's disease (AD) drug discovery has focused on a set of highly studied therapeutic hypotheses, with limited success. The heterogeneous nature of AD processes suggests that a more diverse, systems-integrated strategy may identify new therapeutic hypotheses. Although many target hypotheses have arisen from systems-level modeling of human disease, in practice and for many reasons, it has proven challenging to translate them into drug discovery pipelines. First, many hypotheses implicate protein targets and/or biological mechanisms that are under-studied, meaning there is a paucity of evidence to inform experimental strategies as well as high-quality reagents to perform them. Second, systems-level targets are …

Cry1 Expression During Postnatal Development Is Critical For The Establishment Of Normal Circadian Period, Aaron E Schirmer, Vivek Kumar, Andrew Schook, Eun Joo Song, Michael S Marshall, Joseph S Takahashi

Faculty Research 2023

The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, Period1 (Per1), Period2 (Per2), Cryptochrome1 (Cry1), and Cryptochrome2 (Cry2), regulate the negative feedback within this loop. Although these proteins have distinct roles within the core circadian mechanism, their individual functions are poorly understood. Here, we used a tetracycline trans-activator system (tTA) to examine the role of transcriptional oscillations in Cry1 and Cry2 in the persistence of circadian activity rhythms. We demonstrate that rhythmic Cry1 expression is an important regulator of circadian period. We then define a critical period from birth to postnatal day …

Evaluation Of Tarsal Injuries In C57bl/6j Male Mice., Brenda Kick, Laura C. Anderson, Rosalinda A. Doty, Christine Wooley, Meaghan E Dyer, Torrian L Green, Veronica Knickerbocker, Zoe Brown, Samantha Loeber, Janine M Wotton, Bonnie L. Lyons, Linda L Waterman, Zoë Bichler

Faculty Research 2023

Tarsal joint abnormalities have been observed in aged male mice on a C57BL background. This joint disease consists of calcaneal displacement, inflammation, and proliferation of car- tilage and connective tissue, that can progress to ankylosis of the joint. While tarsal pathol- ogy has been described previously in C57BL/6N substrains, as well as in STR/ort and B10. BR strain, no current literature describes this disease occurring in C57BL/6J mice. More importantly the behavioral features that may result from such a change to the joint have yet to be evaluated. This condition was observed in older male mice of the C57BL/6J lineage, …

Seven Naturally Variant Loci Serve As Genetic Modifiers Of Lamc2jeb Induced Non-Herlitz Junctional Epidermolysis Bullosa In Mice., Thomas J. Sproule, Vivek M. Philip, Nabig A Chaudhry, Derry C. Roopenian, John P Sundberg

Faculty Research 2023

Epidermolysis Bullosa (EB) is a group of rare genetic disorders that compromise the structural integrity of the skin such that blisters and subsequent erosions occur after minor trauma. While primary genetic risk of all subforms of EB adhere to Mendelian patterns of inheritance, their clinical presentations and severities can vary greatly, implying genetic modifiers. The Lamc2jeb mouse model of non-Herlitz junctional EB (JEB-nH) demonstrated that genetic modifiers can contribute substantially to the phenotypic variability of JEB and likely other forms of EB. The innocuous changes in an 'EB related gene', Col17a1, have shown it to be a dominant modifier of …

Bridging The Rodent To Human Translational Gap: Marmosets As Model Systems For The Study Of Alzheimer's Disease., Stacey J Sukoff Rizzo, Gregg Homanics, David J Schaeffer, Lauren Schaeffer, Jung Eun Park, Julia Oluoch, Tingting Zhang, Annat Haber, Nicholas T Seyfried, Benedict Paten, Anna Greenwood, Takeshi Murai, Sang Ho Choi, Hasi Huhe, Julia Kofler, Peter L Strick, Gregory W. Carter, Afonso C Silva

Faculty Research 2023

INTRODUCTION: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer's disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD.

METHODS: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets …

Metabolic Responses Of Normal Rat Kidneys To A High Salt Intake., Satoshi Shimada, Brian Hoffmann, Chun Yang, Theresa Kurth, Andrew S Greene, Mingyu Liang, Ranjan K Dash, Allen W Cowley

Faculty Research 2023

In this study, novel methods were developed, which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague–Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch …

Alterations In C:N Ratio To Understand Plant Metabolic Pathways In Response To Pressure From Goat Grazing In The Invasive Species: Rhamnus Cathartica, Vivian Marchan

Ignite the Spark Outstanding Undergraduate Research and Scholarship

The high fecundity and high germination rates of Rhamus cathartica serves the species to out-compete regional plant native species. Its high abundance in deciduous forest ecosystems forces species that are unable to utilize R. cathartica as a food source to migrate to areas of lower density, further contributing to the decline in regional biodiversity. Bare soil conditions left as the result of the high concentration of Nitrogen in senesced leaves and leaf litter, cause further amplification of the migration of non-plant species to areas of lower R. cathartica density. Nitrogen is essential to primary and secondary metabolism, thus minimizing the …

Dystonin Modifiers Of Junctional Epidermolysis Bullosa And Models Of Epidermolysis Bullosa Simplex Without Dystonia Musculorum., Thomas J. Sproule, Robert Y Wilpan, John J Wilson, Benjamin E. Low, Yudai Kabata, Tatsuo Ushiki, Riichiro Abe, Michael V. Wiles, Derry C. Roopenian, John P Sundberg

Faculty Research 2023

The Lamc2jeb junctional epidermolysis bullosa (EB) mouse model has been used to demonstrate that significant genetic modification of EB symptoms is possible, identifying as modifiers Col17a1 and six other quantitative trait loci, several with strong candidate genes including dystonin (Dst/Bpag1). Here, CRISPR/Cas9 was used to alter exon 23 in mouse skin specific isoform Dst-e (Ensembl GRCm38 transcript name Dst-213, transcript ID ENSMUST00000183302.5, protein size 2639AA) and validate a proposed arginine/glutamine difference at amino acid p1226 in B6 versus 129 mice as a modifier of EB. Frame shift deletions (FSD) in mouse Dst-e exon 23 (Dst-eFSD/FSD) were also identified that cause …

Genetic Background Influences The 5xfad Alzheimer's Disease Mouse Model Brain Proteome., Cheyenne D Hurst, Amy R Dunn, Eric B Dammer, Duc M Duong, Sarah M Shapley, Nicholas T Seyfried, Catherine Kaczorowski, Erik C B Johnson

Faculty Research 2023

There is an urgent need to improve the translational validity of Alzheimer’s disease (AD) mouse models. Introducing genetic background diversity in AD mouse models has been proposed as a way to increase validity and enable the discovery of previously uncharacterized genetic contributions to AD susceptibility or resilience. However, the extent to which genetic background influences the mouse brain proteome and its perturbation in AD mouse models is unknown. In this study, we crossed the 5XFAD AD mouse model on a C57BL/6J (B6) inbred background with the DBA/2J (D2) inbred background and analyzed the effects of genetic background variation on the …

Mate Recognition In Genetically Distinct Populations Of The Eastern Red-Backed Salamander (Plethodon Cinereus), Courtney Thomas

Masters Theses

Lineages that have undergone genetic divergence and subsequently experience secondary contact present fascinating situations related to the potential for reproductive isolation. Within species hybrid zones provide unique opportunities to test the strength of reproductive barriers through behavioral experiments when genetic relatedness between groups is established. Among the complex interactions that operate to maintain species boundaries, mate recognition and mate choice are two behaviors that serve to promote evolutionary independence across diverse taxonomic lineages. I explored mate recognition in genetically distinct populations of the Eastern Red-backed Salamander, Plethodon cinereus, a small, abundant, terrestrial salamander with a widespread distribution throughout northeastern United …

Annual Report Of The Town Of Wolfeboro, New Hampshire For The Year Ending December 31, 2022 With Proposed Budget, Warrant Articles, And Other Information For 2023., Wolfeboro Town Representatives

Wolfeboro, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Town Of Weare, New Hampshire 2022 Annual Report, Reports Of The Selectmen, Treasurer, Town Clerk, Trustees, Departments, Boards, Committees, And Commissions For The Year Ending December 31, 2022., Weare Town Representatives

Weare, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Doctrine And Covenants 21: Metanarrative Of The Restoration, Steve L. Olsen

Interpreter: A Journal of Latter-day Saint Faith and Scholarship

Joseph Smith dictated Doctrine and Covenants 21 at the inaugural meeting of the Church of Jesus Christ on April 6, 1830. The present study examines the literary craftsmanship of the revelation to plumb the depths of its role in the restoration of the gospel of Jesus Christ. The analysis explores the meaning of patterns of usage in the text from the most specific (diction, syntax, figures of speech) to the most general (tone, rhetoric, and structural logic). The hypothesis of this study is that Doctrine and Covenants 21 provides a metanarrative of the Restoration — that is, a set of …

2023 Spring And Winter - Schedule Of Classes, Office Of The Registrar, East Tennessee State University

Registration Resources

No abstract provided.

Gattonrx Magazine - 2023, Bill Gatton College Of Pharmacy, East Tennessee State University

GattonRX Magazine

No abstract provided.

2023-2024 - Quillen College Of Medicine Operating Budget (October), Budget And Financial Planning, East Tennessee State University

College of Medicine Operating Budgets and Analysis

No abstract provided.

2023-2024 - Quillen College Of Medicine Operating Budget (July), Budget And Financial Planning, East Tennessee State University

College of Medicine Operating Budgets and Analysis

No abstract provided.

2023-2024 - Etsu General Academic Operating Budget (October), Budget And Financial Planning, East Tennessee State University

ETSU General Academic Operating Budgets and Analysis

No abstract provided.

Investigating Sources Of Microplastics And Effects Of Plastic Pollution On Biofilm Function In The Huron River, Sadie Baker

Master's Theses and Doctoral Dissertations

Plastics are a global environmental threat due to mass production and the many unknowns regarding the long-term effects of plastic pollution in the environment. Microplastics (MPs) are plastic particles less than 5 mm in size, and they have become ubiquitous in aquatic ecosystems. MPs enter aquatic ecosystems through non-point sources such as urbanization, runoff, or atmospheric fallout or through point-sources such as wastewater treatment plants (WWTPs). To determine MP sources in the Huron River, we evaluated MP load (MPs/day) upstream and downstream from urban centers (Ann Arbor and Ypsilanti) and the Ann Arbor WWTP. The average MP load among sample …

Pinchas Dov - (2023), Esther Janowski

Florida Middle and High School Holocaust Reflection Contest

No abstract provided.

Guide To The Ageing Of Explosive Ordnance In The Environment, Geneva International Centre For Humanitarian Demining

Global CWD Repository

The aim of this guide is to give an overview of what is currently known about the ageing of explosive ordnance and the changes in risk that this presents to EOD operators. Analysis of ageing requires internal examination of the ordnance, a highly technical process sometimes referred to as ‘exploitation’. A brief introduction to exploitation is given in Chapter 1. Different explosive ordnance with differing designs have different predispositions to ageing; this is explained in Chapter 2. How various environmental factors affect the components of explosive ordnance is covered in Chapter 3, more specific changes are detailed in Chapter 4. …

2023-2024 Factbook, Tennessee. General Assembly

Factbook

This Fact Book provides an overview of the state's budget for the fiscal year.

Afterword

Tennessee Law Review

No abstract provided.

Mandatory Judging, Douglas R. Richmond

Loyola University Chicago Law Journal

As a matter of judicial ethics, judges must disqualify themselves in matters in which their impartiality may reasonably be questioned. This key principle implicates two additional aspects of judicial ethics: the duty to sit and the rule of necessity. The duty to sit basically describes a judge’s duty to preside over a case unless disqualified as a matter of judicial ethics. Or, phrased another way, a judge must hear a case if her impartiality cannot reasonably be questioned. Recognition of the duty to sit means that judges may not disqualify themselves based on their unease with cases, personal or professional …

Doctrinal Destruction And Chevron's Extinction Debt, James Ming Chen

Florida State University Law Review

Chevron, the landmark Supreme Court case urging judicial deference to reasonable agency interpretations of vague or ambiguous statutes, has dominated federal administrative law since 1984. The sudden rise of the major questions doctrine, however, has destroyed Chevron’s jurisprudential habitat. Conservation biology suggests that habitat destruction is most devastating to dominant species, often imposing a biological “debt” that must be repaid through extinction. As with biology, so with law: “Major questions” having displaced agency deference, Chevron is doomed.

Black Quarterback, White Masks: A Critical Analysis Of The Nfl Anthem Protests, Cody Walizer

Electronic Theses and Dissertations

The NFL anthem protests were and are an important cultural moment and social movement. The widespread emulation of the protest, and the adoption of the kneel as a symbol of unity, reverence, and silent objection demonstrates the protests’ continued relevance. This dissertation critically analyzes Colin Kaepernick’s protest through the lens of racial rhetorical criticism (Flores, 2016) and Fanonian communication studies (Towns, 2020). Through the case studies of David Brooks, Lee Siegel, and Colin Fleming, and their New York Times opinion pieces on Kaepernick from 2016-17, this study argues that the common discourses surrounding the protest exist within the strategic rhetoric …

Reconstructing The Past And Our Reconstruction Present: The Long Struggle To Teach Divisive Concepts - Panel 3, Robert D. Bland

Tennessee Law Review

"In our present moment, as we see just as many signs of a Third 'Redemption,' as we see of a Third Reconstruction, it is important to remember the previous struggles over history and memory ..."