Digital Commons Network^™

Reciprocal Regulation Of Mitofusin 2-Mediated Mitophagy And Mitochondrial Fusion By Different Pink1 Phosphorylation Events, Jiajia Li, Xiawei Dang, Antonietta Franco, Gerald W Dorn

2020-Current year OA Pubs

Mitochondrial repair is essential to metabolic homeostasis. Outer mitochondrial membrane mitofusin (MFN) proteins orchestrate mitochondrial fusion that opposes mitochondrial degeneration caused by senescence. Depending upon physiological context, MFN2 can either mediate mitochondrial fusion or recruit cytosolic Parkin to initiate mitophagic elimination. Because it is not clear how these events are counter-regulated we engineered and expressed MFN2 mutants that mimic phosphorylated or non-phosphorylatable MFN2 at its PINK1 phosphorylation sites: T111, S378, and S442. By interrogating mitochondrial fusion, polarization status, and Parkin binding/mitophagy as a function of inferred MFN2 phosphorylation, we discovered that individual MFN2 phosphorylation events act as a biological "bar-code", …

Channa Reddy In Telangana Statehood Movement: Initiation, Intervention And Contribution, Jakkula Koteswar Rao, Ram Shepherd Bheenaveni

School of Social Work Faculty Publications

The present paper tries to explore some of the repeated accusations and half-truths against the Telangana leader – Dr. Marri Channa Reddy, who led the movement in 1969. It is believed that the leaders started the Telangana Statehood movement as a problem-solving movement against subregionalism. Dr. Reddy was a staunch opponent of Andhra’s internal colonization. This is not only absurd but also a parody of the truth. This is mainly due to the lack of original documents in an organized campaign for the separate state of Telangana. The print and electronic media reports speak of alarming national integration at the …

Towards A Model Of The Design Process For Games, John Healy, Charlie Cullen

Conference Papers

In this paper, we present an approach to studying the game design process by drawing upon general models of design to support research into the process of game design. Several general models of design exist to consider the processes through which designers work. Many of these fit within a structure of analysis, synthesis and evaluation that was first proposed by Christopher Jones in 1963 and later adapted by Bryan Lawson to account for the messy nature of design and the undertaking of these activities while negotiating between problem and solution. This paper proposes the adaptation of Lawson’s model of design …

Merging Modest With Complexity, Mark Garry

Doctoral

This thesis will enable a retrospective critical examination of aspects of my practice as an artist from 2005 - 2020. The research question addresses the implication of multiple forms of inter-reliance enabled in the practice. This will be enabled by opening a discursive space that retrospectively, integrates and critically examines the role and function of inter-reliance as a structural methodology and how this is implicated in the practice over this period.

This thesis will use term inter-reliance to define a play of relations where individual art works when viewed in isolation exist only in partial illumination as a form of …

Rosa Cornelia Veal Papers - Accession 1766, Rosa Cornelia Veal

Manuscript Collection

The Rosa Cornelia Veal Papers document the professional career, pedagogical philosophy, and personal life of Winthrop College Class of 1926 graduate Rosa Cornelia Veal (1904–1967), an educator whose work spanned elementary classroom instruction, teacher education, and curriculum development during the mid-twentieth century. The collection dates from 1904 to 1978, with the bulk of the materials concentrated between the 1930s and 1940s, corresponding to Veal’s tenure as an elementary school teacher and associate professor of elementary education at Ball State Teachers College.

The collection contains a substantial body of teaching materials that provide insight into classroom practices, instructional methods, and educational …

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …

Low Risk For Developing Diabetes Among The Offspring Of Individuals With Exceptional Longevity And Their Spouses, Iva Miljkovic, Ryan Cvejkus, Ping An, Bharat Thyagarajan, Kaare Christensen, Mary Wojczynski, Nicole Schupf, Joseph M Zmuda

2020-Current year OA Pubs

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean …

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

How Should We Define A Nociceptor In The Gut-Brain Axis?, Nick J Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu

2020-Current year OA Pubs

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, …

The Role Of Endogenous Opioid Neuropeptides In Neurostimulation-Driven Analgesia, Susan T Lubejko, Robert D Graham, Giulia Livrizzi, Robert Schaefer, Matthew R Banghart, Meaghan C Creed

2020-Current year OA Pubs

Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms …

Creating And Managing Eu Funded Research Networks: An Exploratory Case, Zeta Dooly, Aidan Duane, Aidan O'Driscoll

Articles

The collaborative European funded research and development landscape drives competitiveness among innovative organisations. Recently it has seen the rise of public private partnerships significantly impacting the dynamics of these networks. Thus, the complexity of managing research networks has intensified with the increased diversity of research network members. Additionally, the emergence of the academic entrepreneur has augmented the focus of educational institutions to include innovation and building start-up organisations. The impact of research is scalable if an optimum research network is created and managed effectively. This paper investigates network embeddedness; the nature of relationships, links and nodes within a research network, …

Advances In Our Clinical Understanding Of Autonomic Regulation Therapy Using Vagal Nerve Stimulation In Patients Living With Heart Failure, Marvin A Konstam, Douglas L Mann, John James E Udelson, Jeffrey L Ardell, Gaetano M De Ferrari, Martin R Cowie, Helmut U Klein, Douglas D Gregory, Joseph M Massaro, Imad Libbus, Lorenzo A Dicarlo, Javed Butler, John D Parker, John R Teerlink

2020-Current year OA Pubs

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to …

Influenza: Toward Understanding The Immune Response In The Young, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

Annually influenza causes a global epidemic resulting in 290,000 to 650,000 deaths and extracts a massive toll on healthcare and the economy. Infants and children are more susceptible to infection and have more severe symptoms than adults likely mitigated by differences in their innate and adaptive immune responses. While it is unclear the exact mechanisms with which the young combat influenza, it is increasingly understood that their immune responses differ from adults. Specifically, underproduction of IFN-γ and IL-12 by the innate immune system likely hampers viral clearance while upregulation of IL-6 may create excessive damaging inflammation. The infant's adaptive immune …

Classical And Γδ T Cells Are Each Independently Sufficient To Establish Protection Against A Classical Strain Of Klebsiella Pneumoniae, Joseph J Mackel, Catherine Morffy Smith, Rachel K Wasbotten, Joy Twentyman, David A Rosen

2020-Current year OA Pubs

Infections with classical strains of the Gram-negative bacterium

A Role For An Htlv-1 Vaccine?, Lee Ratner

2020-Current year OA Pubs

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, …

Four Decades Of Mapping And Quantifying Neuroreceptors At Work In Vivo By Positron Emission Tomography, Albert Gjedde, Dean F Wong

2020-Current year OA Pubs

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods …

Examining Virtual Driving Test Performance And Its Relationship To Individuals With Hiv-Associated Neurocognitive Disorders, David Grethlein, Vanessa Pirrone, Kathryn N Devlin, Will Dampier, Zsofia Szep, Flaura K Winston, Santiago Ontañón, Elizabeth A Walshe, Kim Malone, Shinika Tillman, Beau M Ances, Venk Kandadai, Dennis L Kolson, Brian Wigdahl

2020-Current year OA Pubs

SIGNIFICANCE: Existing screening tools for HIV-associated neurocognitive disorders (HAND) are often clinically impractical for detecting milder forms of impairment. The formal diagnosis of HAND requires an assessment of both cognition and impairment in activities of daily living (ADL). To address the critical need for identifying patients who may have disability associated with HAND, we implemented a low-cost screening tool, the Virtual Driving Test (VDT) platform, in a vulnerable cohort of people with HIV (PWH). The VDT presents an opportunity to cost-effectively screen for milder forms of impairment while providing practical guidance for a cognitively demanding ADL.

OBJECTIVES: We aimed to: …

Cd4+ T-Lymphocytes Exhibit Biphasic Kinetics Post-Myocardial Infarction, Vinay Kumar, Sumanth D Prabhu, Shyam S Bansal

2020-Current year OA Pubs

CD4

Cognitive And Brain Reserve Predict Decline In Adverse Driving Behaviors Among Cognitively Normal Older Adults, Samantha A Murphy, Ling Chen, Jason M Doherty, Prerana Acharyya, Noah Riley, Ann M Johnson, Alexis Walker, Hailee Domash, Maren Jorgensen, Sayeh Bayat, David B Carr, Beau M Ances, Ganesh M Babulal

2020-Current year OA Pubs

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain's adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer's …

Toward A Fully Implantable Ecosystem For Adaptive Neuromodulation In Humans: Preliminary Experience With The Cortec Braininterchange Device In A Canine Model, Gerwin Schalk, Samuel Worrell, Filip Mivalt, Alexander Belsten, Inyong Kim, Jonathan M Morris, Dora Hermes, Bryan T Klassen, Nathan P Staff, Steven Messina, Timothy Kaufmann, Jörn Rickert, Peter Brunner, Gregory A Worrell, Kai J Miller

2020-Current year OA Pubs

This article describes initial work toward an ecosystem for adaptive neuromodulation in humans by documenting the experience of implanting CorTec's BrainInterchange (BIC) device in a beagle canine and using the BCI2000 environment to interact with the BIC device. It begins with laying out the substantial opportunity presented by a useful, easy-to-use, and widely available hardware/software ecosystem in the current landscape of the field of adaptive neuromodulation, and then describes experience with implantation, software integration, and post-surgical validation of recording of brain signals and implant parameters. Initial experience suggests that the hardware capabilities of the BIC device are fully supported by …

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that

Islet Cilia And Glucose Homeostasis, Isabella Melena, Jing W Hughes

2020-Current year OA Pubs

Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin …

White Matter Abnormalities In The Hdc Knockout Mouse, A Model Of Tic And Ocd Pathophysiology, Kantiya Jindachomthong, Chengran Yang, Yuegao Huang, Daniel Coman, Maximiliano Rapanelli, Fahmeed Hyder, Joseph Dougherty, Luciana Frick, Christopher Pittenger

2020-Current year OA Pubs

INTRODUCTION: An inactivating mutation in the

MATERIALS AND METHODS: We performed exploratory RNA-seq to identify pathological alterations in several brain regions in

RESULTS: Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain

DISCUSSION: While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with …

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

Top-Down And Bottom-Up Propagation Of Disease In The Neuronal Ceroid Lipofuscinoses, John R Ostergaard, Hemanth R Nelvagal, Jonathan D Cooper

2020-Current year OA Pubs

BACKGROUND: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related diseases that share lipofuscin pathobiology as the common core feature, but otherwise distinguished by different a) initial anatomic location, and b) disease propagation.

METHODS: We have tested this hypothesis by comparing known differences in symptomatology and pathology of the CLN1 phenotype caused by complete loss of

RESULTS: Despite displaying similar pathological endpoints, the clinical phenotypes and the evidence of imaging and

DISCUSSION: The propagation of disease in these two …

Hemocytes Are Essential For Drosophila Melanogaster Post-Embryonic Development, Independent Of Control Of The Microbiota, Holly N. Stephenson, Robert Streeck, Florian Grüblinger, Christian Goosmann, Alf Herzig

Peninsula Medical School

ABSTRACT Proven roles for hemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the crucial role of hemocytes in post-embryonic development has long thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in hemocyte-ablation models under germ-free conditions. Here, we show that hemocytes have an essential role in post-embryonic development beyond their ability to control the microbiota. Using a newly generated strong hemocyte-specific driver line for the GAL4/UAS system, we show that specific ablation of hemocytes is early pupal lethal, even under axenic conditions. …

Modulation Of Mirisc-Mediated Gene Silencing In Eukaryotes, Courtney F Jungers, Sergej Djuranovic

2020-Current year OA Pubs

Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by various

Endogenous Opioid Systems Alterations In Pain And Opioid Use Disorder, Jessica A Higginbotham, Tamara Markovic, Nicolas Massaly, Jose A Morón

2020-Current year OA Pubs

Decades of research advances have established a central role for endogenous opioid systems in regulating reward processing, mood, motivation, learning and memory, gastrointestinal function, and pain relief. Endogenous opioid systems are present ubiquitously throughout the central and peripheral nervous system. They are composed of four families, namely the μ (MOPR), κ (KOPR), δ (DOPR), and nociceptin/orphanin FQ (NOPR) opioid receptors systems. These receptors signal through the action of their endogenous opioid peptides β-endorphins, dynorphins, enkephalins, and nociceptins, respectfully, to maintain homeostasis under normal physiological states. Due to their prominent role in pain regulation, exogenous opioids-primarily targeting the MOPR, have been …

The Human Myocardium Harbors A Population Of Naive B-Cells With A Distinctive Gene Expression Signature Conserved Across Species, Kevin C Bermea, Nicolas Kostelecky, Sylvie T Rousseau, Chieh-Yu Lin, Luigi Adamo

2020-Current year OA Pubs

INTRODUCTION: Cardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.

METHODS: We performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells …

Lively Emu Dialogues: Activating Feminist Common Worlding Pedagogies, Mindy Blaise, Catherine Hamm

Research outputs 2014 to 2021

This paper draws from a series of Place-thought walks that the authors took at an open-range zoo. It practices a feminist common worlds multispecies ethics to challenge the systems that maintain nature-culture divisions in early childhood education. Postdevelopmental perspectives (i.e., feminist environmental humanities, multispecies studies, Indigenous studies) are brought into conversation with early childhood education to consider how zoo-logics maintain binaries and hierarchical thinking. Zoo-logics are related to developmental, colonial, and Western ways of reasoning and being in the world. Two feminist approaches to ethics, (re)situating and dialoguing, are discussed and show how they are necessary for undermining binaries and …