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Complexity Of Progranulin Mechanisms Of Action In Mesothelioma, Elisa Ventura, Christopher Xie, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Antonio Giordano, Andrea Morrione 2022 Temple University

Complexity Of Progranulin Mechanisms Of Action In Mesothelioma, Elisa Ventura, Christopher Xie, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Mesothelioma is an aggressive disease with limited therapeutic options. The growth factor progranulin plays a critical role in several cancer models, where it regulates tumor initiation and progression. Recent data from our laboratories have demonstrated that progranulin and its receptor, EphA2, constitute an oncogenic pathway in bladder cancer by promoting motility, invasion and in vivo tumor formation. Progranulin and EphA2 are expressed in mesothelioma cells but their mechanisms of action are not well defined. In addition, there are no data establishing whether the progranulin/EphA2 axis is tumorigenic for mesothelioma cells.

Methods: The expression of progranulin in various mesothelioma cell …


Role Of Parp1 And Nad+ Bioavailability In Base Excision And Single-Strand Break Repair, Kate M. Saville 2022 University of South Alabama

Role Of Parp1 And Nad+ Bioavailability In Base Excision And Single-Strand Break Repair, Kate M. Saville

Theses and Dissertations

High-grade gliomas (HGGs) are malignant, highly metabolically active brain tumors. HGGs are associated with poor patient outcome, attributed to resistance to current therapies, with a survival rate between 12 to 15 months. Gliomas are highly complex tumors, making targeted therapy difficult, highlighting the need for novel approaches and new treatment options. In addition, a large percentage of HGGs are comprised of glioma stem cells (GSCs) that further contribute to therapeutic resistance. Notable characteristics of GSCs are a heightened DNA damage response (DDR) and elevated replication stress that could provide opportunities for therapeutic targeting. A notable feature of many glioma tumors …


Data Supporting The Roles Of Bap1, Sting, And Ifn-Β In Isgf3 Activation In Ccrcc, Lauren E Langbein, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Li Li, Joseph R Testa, Haifeng Yang 2022 Thomas Jefferson University

Data Supporting The Roles Of Bap1, Sting, And Ifn-Β In Isgf3 Activation In Ccrcc, Lauren E Langbein, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Li Li, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The data presented in this article are companion materials to our manuscript titled "BAP1 maintains HIF-dependent interferon beta induction to suppress tumor growth in clear cell renal cell carcinoma" (Langbein et al., 2022), where we investigated the downstream effects of BAP1 (BRCA1-associated protein 1) expression in clear cell renal cell carcinoma (ccRCC) cell lines and mouse xenograft models. In the manuscript, we showed that BAP1 upregulates STING (stimulator of interferon genes) expression and activity in ccRCC cells, leading to IFN-β transcription and activation of interferon stimulated gene factor 3 (ISGF3), the transcription factor that mediates the effects of type I …


Altered Expression Of Glycobiology-Related Genes In Parkinson’S Disease Brain, Jay S Schneider, Garima Singh 2022 Thomas Jefferson University

Altered Expression Of Glycobiology-Related Genes In Parkinson’S Disease Brain, Jay S Schneider, Garima Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The precise mechanisms initiating and perpetuating the cellular degeneration in Parkinson's disease (PD) remain unclear. There is decreased expression of the main brain gangliosides, and GM1 ganglioside in particular, in the PD brain along with decreased expression of the genes coding for the glycosyltranferase and the sialyltransferase responsible for the synthesis of these brain gangliosides. However, potentially important pathogenic mechanisms contributing to the neurodegeneration in PD may also include altered levels of expression of genes involved in glycosylation, sialylation and sphingolipid synthesis and metabolism. Although various studies have described pathological lipid and glycolipid changes in PD brain, there have been …


Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli 2022 Thomas Jefferson University

Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to …


Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman 2022 Thomas Jefferson University

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …


Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky 2022 Thomas Jefferson University

Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP3 receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca2+ coupling, IP3Rs …


Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker 2022 Thomas Jefferson University

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …


Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang 2022 Thomas Jefferson University

Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BRCA1-associated protein 1 (BAP1) is a deubiquitinase that is mutated in 10-15% of clear cell renal cell carcinomas (ccRCC). Despite the association between BAP1 loss and poor clinical outcome, the critical tumor suppressor function(s) of BAP1 in ccRCC remains unclear. Previously, we found that hypoxia-inducible factor 2α (HIF2α) and BAP1 activate interferon-stimulated gene factor 3 (ISGF3), a transcription factor activated by type I interferons and a tumor suppressor in ccRCC xenograft models. Here, we aimed to determine the mechanism(s) through which HIF and BAP1 regulate ISGF3. We found that in ccRCC cells, loss of the von Hippel-Lindau tumor suppressor (VHL) …


Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny 2022 Wright State University - Main Campus

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …


Activity Of Prefrontal Cortex Subpopulations During Operant Alcohol Selfadministration, Grant Collins, H. Mejia Gomez, Faith Maxwell, Jessica M. Patel, Michael Salling 2022 LSU Health Sciences Center- New Orleans

Activity Of Prefrontal Cortex Subpopulations During Operant Alcohol Selfadministration, Grant Collins, H. Mejia Gomez, Faith Maxwell, Jessica M. Patel, Michael Salling

Medical Research Day

The National Institute of Alcohol Abuse and Alcoholism states, ‘according to the 2019 [National Survey on Drug Use and Health], 14.5 million (nearly 15 million) people ages 12 and older1 (5.3 percent of this age group2 ) had [alcohol use disorder (AUD)].’ The DSM-5 criteria for AUD includes compulsive drinking behavior.3 The prefrontal cortex (PFC) has roles in decisionmaking, response inhibition, and drug seeking and likely plays a role in compulsive alcohol drinking. However, the specific circuitry involved is unknown. There are two PFC circuits implicated in response inhibition or ‘stop’ behavior: PFC projections to the dorsomedial striatum (DMS) and …


Relationship Between Depression And Cognitive Impairment In Patients With Multiple Sclerosis, Alexandra Nguyen, Yazmeen Allen, Natalie Thayer, Shannin Moody, Deidre Devier 2022 LSU Health Sciences Center- New Orleans

Relationship Between Depression And Cognitive Impairment In Patients With Multiple Sclerosis, Alexandra Nguyen, Yazmeen Allen, Natalie Thayer, Shannin Moody, Deidre Devier

Medical Research Day

Background: Multiple Sclerosis (MS) is an autoimmune, neurodegenerative disease characterized by chronic inflammation and demyelination of the brain and spinal cord. This deterioration of the central nervous system leads to a wide range of motor, cognitive, and neuropsychiatric symptoms. Each patient varies in symptom profile and disease course. However, cognitive impairment has been found in roughly half of all people with MS regardless of MS subtype. This may present as deficits in attention, information processing speed, executive function, and visuospatial perception. This impairment may interfere with basic and instrumental activities of daily living, vocational status, and social functioning; all of …


Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter 2022 Jacksonville State University

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …


Investigation Of Zinc Chloride & Caffeine And Their Ects On Bone Homeostasis In A 3d Bone Model, Pooja Shah 2022 Seton Hall University

Investigation Of Zinc Chloride & Caffeine And Their Ects On Bone Homeostasis In A 3d Bone Model, Pooja Shah

Seton Hall University Dissertations and Theses (ETDs)

Approximately fourteen percent of the human body is composed of bone. The adult human skeleton is made of 206 bones, which make up the internal framework of the body. Osteoblast and Osteoclast cells are essential in maintaining the structure and function of bone, for bone homeostasis to occur. Previous data shows that caffeine can potentially have a negative effect on bone homeostasis. Whereas, ZnCl2 has been found to have a positive effect on bone homeostasis in controlled doses. Published data for treatments of caffeine and ZnCl2 are inadequate. The goal of this study was to determine the optimal …


Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny 2022 Wright State University

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …


Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak 2022 Wright State University - Main Campus

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.


Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong 2022 Thomas Jefferson University

Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer's instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes …


Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak 2022 Western University

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas3, an excessive and/or prolonged immune response1, the activation and proliferation of fibrosis-inducing progenitor cells4, and a pro-fibrotic extra-cellular microenvironment5. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …


Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng 2022 Western University

Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng

Undergraduate Student Research Internships Conference

The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We …


Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib 2022 Western University

Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib

Undergraduate Student Research Internships Conference

Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …


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