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Pd-L1 Translocation To The Plasma Membrane Enables Tumor Immune Evasion Through Mib2 Ubiquitination, Xinfang Yu, Wei Li, Haidan Liu, Xu Wang, Cristian Coarfa, Chao Cheng, Xinlian Yu, Zhaoyang Zeng, Ya Cao, Ken H Young, Yong Li Feb 2023

Pd-L1 Translocation To The Plasma Membrane Enables Tumor Immune Evasion Through Mib2 Ubiquitination, Xinfang Yu, Wei Li, Haidan Liu, Xu Wang, Cristian Coarfa, Chao Cheng, Xinlian Yu, Zhaoyang Zeng, Ya Cao, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, …


Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye Feb 2023

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …


Synthetic Assembly Dna Cloning To Build Plasmids For Multiplexed Transgenic Selection, Counterselection Or Any Other Genetic Strategies Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Alejandro Sarrion-Perdigones, Herman A Dierick Feb 2023

Synthetic Assembly Dna Cloning To Build Plasmids For Multiplexed Transgenic Selection, Counterselection Or Any Other Genetic Strategies Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Alejandro Sarrion-Perdigones, Herman A Dierick

Faculty, Staff and Students Publications

We recently described a drug-based selectable and counterselectable genetic platform for the animal model system Drosophila melanogaster, consisting of four resistance and two sensitivity markers that allow direct selection for, or counterselection against, a desired genotype. This platform eliminates the need to identify modified progeny by traditional laborious screening using dominant eye and body color markers, white+ and yellow+, respectively. The four resistance markers permit selection of animals using G418 sulfate, Puromycin HCl, Blasticidin S, or Hygromycin B, while the two sensitivity markers allow counterselection of animals against Ganciclovir or Acyclovir, and 5-Fluorocytosine. The six markers …


Modeling Ewing Sarcoma Lung Metastasis, Atreyi Dasgupta, Lyazat Kurenbekova, Tajhal D Patel, Kimal Rajapakshe, Gargi Ghosal, Bikesh Nirala, Cristian Coarfa, Jason Yustein Feb 2023

Modeling Ewing Sarcoma Lung Metastasis, Atreyi Dasgupta, Lyazat Kurenbekova, Tajhal D Patel, Kimal Rajapakshe, Gargi Ghosal, Bikesh Nirala, Cristian Coarfa, Jason Yustein

Faculty, Staff and Students Publications

Ewing Sarcoma (EwS) is the second most common malignant bone tumor in adolescents and young adults. The single-most powerful predictor of outcome in EwS is presence of metastatic burden at the time of diagnosis. Patients with metastatic Ewing Sarcoma have an abysmal 5-year survival rate of 10–25%, which has not changed over the past 30–40 years. Thus, unraveling underlying mechanisms of EwS metastasis are imperative for developing effective therapeutic measures. Investigations towards this goal are limited by the lack of reliable genetically engineered mouse models and specialized metastatic models. Using two established cell lines, A673 and TC71, we generated lung …


Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun Feb 2023

Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun

Faculty, Staff and Students Publications

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic …


Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li Feb 2023

Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li

Faculty, Staff and Student Publications

Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. …


Serial Recombineering Cloning To Build Selectable And Tagged Genomic P[Acman] Bac Clones For Selection Transgenesis And Functional Gene Analysis Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick Feb 2023

Serial Recombineering Cloning To Build Selectable And Tagged Genomic P[Acman] Bac Clones For Selection Transgenesis And Functional Gene Analysis Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick

Faculty, Staff and Students Publications

Transgenes with genomic DNA fragments that encompass genes of interest are the gold standard for complementing null alleles in rescue experiments in the fruit fly Drosophila melanogaster. Of particular interest are genomic DNA clones available as bacterial artificial chromosomes (BACs) or fosmids from publicly available genomic DNA libraries. Genes contained within BAC and fosmid clones can be easily modified by recombineering cloning to insert peptide or protein tags to localize, visualize, or manipulate gene products, and to create point mutations or deletions for structure-function analysis of the inserted genes. However, since transgenesis efficiency is inversely correlated with transgene size, obtaining …


Multiplexed Transgenic Selection And Counterselection Strategies To Expedite Genetic Manipulation Workflows Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick Feb 2023

Multiplexed Transgenic Selection And Counterselection Strategies To Expedite Genetic Manipulation Workflows Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick

Faculty, Staff and Students Publications

We recently described a set of four selectable and two counterselectable markers that provide resistance and sensitivity, respectively, against their corresponding drugs using the model organism Drosophila melanogaster. The four selectable markers provide animal resistance against G418 sulfate, Puromycin HCl, Blasticidin S, or Hygromycin B, while the two counterselection markers make animals sensitive to Ganciclovir/Acyclovir, or 5-Fluorocytosine. Unlike classical phenotypic markers, visual or fluorescent, which require extensive screening progeny of a genetic cross for desired genotypes, resistance and sensitivity markers eliminate this laborious procedure by directly selecting for, or counterselecting against, the desired genotypes. We demonstrated the usefulness of …


Molecular Mechanisms Regulating Wound Repair: Evidence For Paracrine Signaling From Corneal Epithelial Cells To Fibroblasts And Immune Cells Following Transient Epithelial Cell Treatment With Mitomycin C, Sonali Pal-Ghosh, Beverly A Karpinski, Himani Datta Majumdar, Trisha Ghosh, Julie Thomasian, Stephen R Brooks, Andrew P Sawaya, Maria I Morasso, Kaitlin K Scholand, Cintia S De Paiva, Jeremias G Galletti, Mary Ann Stepp Feb 2023

Molecular Mechanisms Regulating Wound Repair: Evidence For Paracrine Signaling From Corneal Epithelial Cells To Fibroblasts And Immune Cells Following Transient Epithelial Cell Treatment With Mitomycin C, Sonali Pal-Ghosh, Beverly A Karpinski, Himani Datta Majumdar, Trisha Ghosh, Julie Thomasian, Stephen R Brooks, Andrew P Sawaya, Maria I Morasso, Kaitlin K Scholand, Cintia S De Paiva, Jeremias G Galletti, Mary Ann Stepp

Faculty, Staff and Students Publications

In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show …


The Tetraspanin Transmembrane Protein Cd53 Mediates Dyslipidemia And Integrates Inflammatory And Metabolic Signaling In Hepatocytes, Cassandra B Higgins, Joshua A Adams, Matthew H Ward, Zev J Greenberg, Małgorzata Milewska, Jiameng Sun, Yiming Zhang, Luana Chiquetto Paracatu, Qian Dong, Samuel Ballentine, Weikai Li, Ilona Wandzik, Laura G Schuettpelz, Brian J Debosch Feb 2023

The Tetraspanin Transmembrane Protein Cd53 Mediates Dyslipidemia And Integrates Inflammatory And Metabolic Signaling In Hepatocytes, Cassandra B Higgins, Joshua A Adams, Matthew H Ward, Zev J Greenberg, Małgorzata Milewska, Jiameng Sun, Yiming Zhang, Luana Chiquetto Paracatu, Qian Dong, Samuel Ballentine, Weikai Li, Ilona Wandzik, Laura G Schuettpelz, Brian J Debosch

2020-Current year OA Pubs

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction …


In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel Feb 2023

In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel

2020-Current year OA Pubs

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought …


Analysis Of Freight Movements In The San Joaquin Valley, Aly Tawfik, Utsav Shah Feb 2023

Analysis Of Freight Movements In The San Joaquin Valley, Aly Tawfik, Utsav Shah

Mineta Transportation Institute

Freight transportation plays a primary role in supply chains, costs, and availability of goods and is a major part of the economy. This study identifies, assesses, and utilizes different data sources to uncover and understand the patterns and movements of different types of freight in the San Joaquin Valley’s (SJV's) different counties. The San Joaquin Valley region consists of eight counties: San Joaquin, Stanislaus, Merced, Madera, Fresno, Kings, and Tulare. This research explored some major datasets with freight information, such as Global Trade Atlas (GTA), Port Imports and Exports Reporting Systems (PIERS), and Streetlight data insights for the year 2019 …


Brainwave: A Flexible Method For Noninvasive Stimulation Of Brain Rhythms Across Species, Matthew K. Attokaren, Nuri Jeong, Lou Blanpain, Abigail L. Paulson, Kristie M. Garza, Ben Borron, Michael Walelign, Jon Willie, Annabelle C. Singer Feb 2023

Brainwave: A Flexible Method For Noninvasive Stimulation Of Brain Rhythms Across Species, Matthew K. Attokaren, Nuri Jeong, Lou Blanpain, Abigail L. Paulson, Kristie M. Garza, Ben Borron, Michael Walelign, Jon Willie, Annabelle C. Singer

2020-Current year OA Pubs

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are limited. Accordingly, we recently introduced a noninvasive stimulation approach using flickering lights and sounds ("flicker"). Flicker drives rhythmic activity in deep and superficial brain regions. Gamma flicker spurs immune function, clears pathogens, and rescues memory performance in mice with amyloid pathology. Here, we present substantial improvements to this approach that is flexible, user-friendly, and generalizable across multiple experimental settings and species. We present novel open-source …


Sex-Specific Hypnotic Effects Of The Neuroactive Steroid (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile Are Mediated By Peripheral Metabolism Into An Active Hypnotic Steroid, Francesca M Manzella, Omar H Cabrera, Davis Wilkey, Brier Fine-Raquet, Jelena Klawitter, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic Feb 2023

Sex-Specific Hypnotic Effects Of The Neuroactive Steroid (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile Are Mediated By Peripheral Metabolism Into An Active Hypnotic Steroid, Francesca M Manzella, Omar H Cabrera, Davis Wilkey, Brier Fine-Raquet, Jelena Klawitter, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

2020-Current year OA Pubs

BACKGROUND: The novel synthetic neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) blocks T-type calcium channels but does not directly modulate neuronal γ-aminobutyric acid type A (GABA

METHODS: We used a combination of behavioural loss of righting reflex, neuroendocrine, pharmacokinetic, in vitro patch-clamp electrophysiology, and in vivo electrophysiological approaches in wild-type mice and in genetic knockouts of the Ca

RESULTS: Adult male mice were less sensitive to the hypnotic effects of 3β-OH compared with female mice, and these differences appeared during development. Adult males had higher 3β-OH brain concentrations despite being less sensitive to its hypnotic effects. Females metabolised 3β-OH into the active GABA …


The Insurance Landscape For Implant- And Autologous-Based Breast Reconstruction In The United States, Louisa C. Boyd, Jason A. Greenfield, Sravya S. Ainapurapu, Rachel Skladman, Gary Skolnick, Durai Sundaramoorthi, Justin M. Sacks Feb 2023

The Insurance Landscape For Implant- And Autologous-Based Breast Reconstruction In The United States, Louisa C. Boyd, Jason A. Greenfield, Sravya S. Ainapurapu, Rachel Skladman, Gary Skolnick, Durai Sundaramoorthi, Justin M. Sacks

2020-Current year OA Pubs

UNLABELLED: Insurance coverage of postmastectomy breast reconstruction is mandated in America, regardless of reconstructive modality. Despite enhanced patient-reported outcomes, autologous reconstruction is utilized less than nonautologous reconstruction nationally. Lower reimbursement from Medicare and Medicaid may disincentivize autologous-based reconstruction. This study examines the impact of insurance and sociodemographic factors on breast reconstruction.

METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample Database from 2014 to 2017 was performed. International Classification of Diseases Clinical Modification and Procedure Coding System codes were used to identify patients for inclusion. De-identified sociodemographic and insurance data were analyzed using

RESULTS: In …


Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A Sue Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow Feb 2023

Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A Sue Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow

2020-Current year OA Pubs

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …


Forgotten Brother Reuben Lewis: Missouri River Fur Trader And Indian Agent For The Arkansas Cherokees, Jay H. Buckley, Deveney Reber Feb 2023

Forgotten Brother Reuben Lewis: Missouri River Fur Trader And Indian Agent For The Arkansas Cherokees, Jay H. Buckley, Deveney Reber

Faculty Publications

Reuben Lewis was born in 1777, the fourth and youngest child of William Lewis and Lucy Meriwether. Their oldest child, Jane, married and lived out her days at Locust Hill, the family estate in Virginia. The Lewis’ second child, baby Lucinda, died in infancy. Their third child, Meriwether – the closest in age and friendship to Reuben – became the famous first half of the Lewis and Clark Expedition which explored the uncharted West before he met his tragic and mysterious death on the Natchez Trace in Tennessee. While Reuben’s life has been rightly overshadowed by his older brother Meriwether’s …


Analysis Of Electrophysiological Markers And Correlated Components Of Neural Responses To Discourse Coherence, Kurt M. Masiello Feb 2023

Analysis Of Electrophysiological Markers And Correlated Components Of Neural Responses To Discourse Coherence, Kurt M. Masiello

Dissertations, Theses, and Capstone Projects

Constructing meaning from spoken language is invaluable for learning, social interaction, and communication. In clinical populations with developmental disorders of speech comprehension, the severity of disruption can persist and vary from limiting occupational opportunities to lower performance outcomes. Previous research has reported an event-related potential (ERP) neural positivity over right hemisphere lateral anterior sites in response to semantic and discourse processing. Although useful as a marker for clinical populations of autism spectrum disorder (ASD) and developmental language disorder (DLD), little is understood about the dynamics and neural sources of this biological marker. In addition to traditional methods of ERP analysis, …


Storytelling In Modernist Fiction: A “Method Of Presence”, Laura Malhotra Feb 2023

Storytelling In Modernist Fiction: A “Method Of Presence”, Laura Malhotra

Dissertations, Theses, and Capstone Projects

This dissertation explores the relationship between narrative modes in cinema and literature and adopts the lineage laid out by Lukács that connects the oral tradition and epic poetry to the novel. I attach art cinema to this lineage and seek to justify its position as an equally significant medium representative of the age in which it is produced. This study aims to correct one established view of film, put forth by the Frankfurt School, of its low value as an art form and as a site of meaning. I compare the birth of literary modernism in Britain to the emergence …


Student Awareness Of Models In First-Year Engineering Courses, Farshid Marbouti, Kelsey J. Rodgers, Angela K. Thompson, Matthew Verleger, Nicholas Hawkins Feb 2023

Student Awareness Of Models In First-Year Engineering Courses, Farshid Marbouti, Kelsey J. Rodgers, Angela K. Thompson, Matthew Verleger, Nicholas Hawkins

Faculty Research, Scholarly, and Creative Activity

Contribution: This study assesses more than 800 students' awareness of engineering model types before and after taking two first-year engineering courses across two semesters and evaluates the effect of each course. Background: All engineers must be able to apply and create models to be effective problem solvers, critical thinkers, and innovative designers. To help them develop these skills, as a first step, it is essential to assess how to increase students' awareness of engineering models. According to Bloom's taxonomy, the lower remember and understand levels, which encompass awareness, are necessary for achieving the higher levels, such as apply, analyze, evaluate, …


Origin And Evolution Of Marsupial-Specific Imprinting Clusters Through Lineage-Specific Gene Duplications And Acquisition Of Promoter Differential Methylation, Wenqi Cao, Kory C. Douglas, Paul B. Samollow, John Vandeberg, Xu Wang, Andrew G. Clark Feb 2023

Origin And Evolution Of Marsupial-Specific Imprinting Clusters Through Lineage-Specific Gene Duplications And Acquisition Of Promoter Differential Methylation, Wenqi Cao, Kory C. Douglas, Paul B. Samollow, John Vandeberg, Xu Wang, Andrew G. Clark

School of Medicine Publications

Genomic imprinting is a parent-of-origin-specific expression phenomenon that plays fundamental roles in many biological processes. In animals, imprinting is only observed in therian mammals, with ∼200 imprinted genes known in humans and mice. The imprinting pattern in marsupials has been minimally investigated by examining orthologs to known eutherian imprinted genes. To identify marsupial-specific imprinting in an unbiased way, we performed RNA-seq studies on samples of fetal brain and placenta from the reciprocal cross progeny of two laboratory opossum stocks. We inferred allele-specific expression for >3,000 expressed genes and discovered/validated 13 imprinted genes, including three previously known imprinted genes, Igf2r, Peg10, …


Toxin Induced Parkinsonism And Hospitalization Related Adverse Outcome Mitigation For Parkinson’S Disease: A Comprehensive Review, Kenneth R. Dalton, Charles J. Kidd, Nawaz Hack Feb 2023

Toxin Induced Parkinsonism And Hospitalization Related Adverse Outcome Mitigation For Parkinson’S Disease: A Comprehensive Review, Kenneth R. Dalton, Charles J. Kidd, Nawaz Hack

School of Medicine Publications

Patients with Parkinson’s disease admitted to the hospital have unique presentations. This unique subset of patients requires a multidisciplinary approach with a knowledge-based care team that can demonstrate awareness of complications specific to Parkinson’s disease to reduce critical care admissions, morbidity, and mortality. Early recognition of toxic exposures, medication withdrawals, or medication-induced symptoms can reduce morbidity and mortality. This review can assist in the critical assessment of new or exacerbating Parkinson’s disease symptoms.


A Molecular Signature Defining Exercise Adaptation With Ageing And In Vivo Partial Reprogramming In Skeletal Muscle, Ronald G. Jones Iii, Andrea Dimet-Wiley, Amin Haghani, Francielly Morena Da Silva, Camille R. Brightwell, Seongkyun Lim, Sabin Khadgi, Yuan Wen, Corey M. Dungan, Robert T. Brooke, Nicholas P. Greene, Charlotte A. Peterson, John J. Mccarthy, Steve Horvath, Stanley J. Watowich, Christopher S. Fry, Kevin A. Murach Feb 2023

A Molecular Signature Defining Exercise Adaptation With Ageing And In Vivo Partial Reprogramming In Skeletal Muscle, Ronald G. Jones Iii, Andrea Dimet-Wiley, Amin Haghani, Francielly Morena Da Silva, Camille R. Brightwell, Seongkyun Lim, Sabin Khadgi, Yuan Wen, Corey M. Dungan, Robert T. Brooke, Nicholas P. Greene, Charlotte A. Peterson, John J. Mccarthy, Steve Horvath, Stanley J. Watowich, Christopher S. Fry, Kevin A. Murach

Health, Human Performance and Recreation Faculty Publications and Presentations

Exercise promotes functional improvements in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown. Using transcriptome profiling from (1) a skeletal muscle-specific in vivo Oct3/4, Klf4, Sox2 and Myc (OKSM) reprogramming-factor expression murine model; (2) an in vivo inducible muscle-specific Myc induction murine model; (3) a translatable high-volume hypertrophic exercise training approach in aged mice; and (4) human exercise muscle biopsies, we collectively defined exercise-induced genes that are common to partial reprogramming. Late-life exercise training lowered murine DNA methylation age according to several contemporary muscle-specific clocks. A comparison of the murine soleus transcriptome …


The Known And Unknowns Of Aphid Biotypes, And Their Role In Mediating Host Plant Defenses, Neetu Khanal, Christopher Vitek, Rupesh Kariyat Feb 2023

The Known And Unknowns Of Aphid Biotypes, And Their Role In Mediating Host Plant Defenses, Neetu Khanal, Christopher Vitek, Rupesh Kariyat

Entomology and Plant Pathology Faculty Publications and Presentations

Insect species are subjected to disparate selection pressure due to various biotic and abiotic stresses. Management practices including the heavy use of chemical insecticides and introduction of insect-resistant plant cultivars have been found to accelerate these processes. Clearly, natural selection coupled with human intervention have led to insect adaptations that alter phenotypes and genetic structure over time, producing distinct individuals with specialized traits, within the populations, commonly defined as biotypes. Biotypes are commonly found to have better fitness in the new environment and, in the case of aphids, the most commonly studied system for biotypes, have the ability to successfully …


An Analysis Of The Effects Of Demographic Variables And Perceptions On The Safety Reporting Behavior In Collegiate Flight Programs, Daniel Kwasi Adjekum, Micah Walala, Julius Keller, Cody Christensen, Randal J. Demik, John P. Young, Gary J. Northam Jan 2023

An Analysis Of The Effects Of Demographic Variables And Perceptions On The Safety Reporting Behavior In Collegiate Flight Programs, Daniel Kwasi Adjekum, Micah Walala, Julius Keller, Cody Christensen, Randal J. Demik, John P. Young, Gary J. Northam

International Journal of Aviation Sciences (IJAS)

The purposes of this study were to assess the perceptions of respondents on scale items that measure safety culture in collegiate aviation programs in the United States (U.S.) and establish levels of interactions between demographic variables and safety reporting behavior. A convenience sample (n = 259) of flight students inclusive of those who are flight instructors from five collegiate aviation programs in the U.S. responded to scale items adopted from the Collegiate Aviation Perceptions of Safety Culture Assessment Survey (CAPSCAS) online. The highest perception mean score was on Safety Fundamentals (4.2) and the lowest perception mean score was on Safety …


Law Schools Under Siege: The Challenge To Enhance Knowledge,Creativity, And Skill Training, Robert I. Reis Jan 2023

Law Schools Under Siege: The Challenge To Enhance Knowledge,Creativity, And Skill Training, Robert I. Reis

Ohio Northern University Law Review

No abstract provided.


Comment On The Use Of “Cy Pres” In Class Actions In Ohio, Geoffrey J. Ritts Jan 2023

Comment On The Use Of “Cy Pres” In Class Actions In Ohio, Geoffrey J. Ritts

Ohio Northern University Law Review

No abstract provided.


Judges Gone Wild, Parker B. Potter Jr. Jan 2023

Judges Gone Wild, Parker B. Potter Jr.

Ohio Northern University Law Review

No abstract provided.


Who Are We Fighting? Conceptions Of The Enemy In The War Onterror, Lawrence Friedman Jan 2023

Who Are We Fighting? Conceptions Of The Enemy In The War Onterror, Lawrence Friedman

Ohio Northern University Law Review

No abstract provided.


Empathy And Experience In The Sotomayor Hearing, Kathryn Abrams Jan 2023

Empathy And Experience In The Sotomayor Hearing, Kathryn Abrams

Ohio Northern University Law Review

No abstract provided.