Digital Commons Network^™

Profiling The Molecular And Clinical Landscape Of Glioblastoma Utilizing The Oncology Research Information Exchange Network Brain Cancer Database, Alexandra N. Demetriou, Frances Chow, David W. Craig, Michelle G. Webb, D. Ryan Ormond, James Battiste, Arnab Chakravarti, Howard Colman, John L. Villano, Bryan P. Schneider, James K. C. Liu, Michelle L. Churchman, Gabriel Zada

Markey Cancer Center Faculty Publications

Background. Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked var- iability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glio- blastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.

Methods. Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses util- ized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test …

Impact Of Tiered Implementation Of Clinical Decision Support System For Acute Kidney Injury And Nephrotoxin Exposure In Cardiac Surgery Patients, Christopher M. Justice Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Nephrotoxin exposure may worsen kidney injury and impair kidney recovery if continued in patients with acute kidney injury (AKI).

Objective: To determine if tiered implementation of a clinical decision support system (CDSS) would reduce nephrotoxin use in cardiac surgery patients with AKI.

Methods: We assessed patients admitted to the cardiac surgery intensive care unit at a tertiary care center from January 2020 to December 2021, and August 2022 to September 2023. A passive electronic AKI alert was activated in Jul 2020, followed by an electronic nephrotoxin alert in March 2023. In this alert, active nephrotoxic medication orders resulted in …

Implementing A Nurse-Driven Clostridium Difficile Screening Protocol, Sandrela Magnuson

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

Background: Clostridium difficile infection (CDI) is a prevalent infection often contracted in hospitals. CDI is also increasingly originating from community settings. In addition to the health risks associated with CDI, diagnosis of a hospital-acquired CDI can have a significant financial impact on hospital systems. When hospital acquired, hospital systems are no longer reimbursed by payers. Secondary to the increasing prevalence of community-acquired CDI, mechanisms for early detection and isolation are warranted.

Local Problem: J.W. Ruby Memorial Hospital has an integrated Clostridium difficile (C. difficile) electronic health record (EHR) screening questionnaire that requires updating to align with current guidelines.

Purpose: …

Translational Approaches To Address The Metastatic/Resistant (Mr) Phenotype Of Non-Small Cell Lung Cancer Brain Metastases, Kent L. Marshall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains the most frequently diagnosed malignant neoplasm shared in men and women worldwide, second only to the sexually dimorphic prostate cancer in men and breast cancer in women. Overall, lung cancer was responsible for 12.5% of new cancer cases globally in the year 2022. Of these cases, 80-85% are non-small cell lung cancer (NSCLC), a highly genotypically diverse sub-type of lung cancer. Over the past three decades, extraordinary improvement in screening, smoking cessation, early diagnosis and targeted therapy have been made, improving NSCLC survival markedly. However, as patients are surviving their primary disease better, there is a temporal …

Receipt Of Follow‑Up Care Plans On Colorectal Cancer Screening Among Breast, Prostate, And Lung Cancer Survivors, Meng-Han Tsai, Malcolm S. Bevel, Sydney E. Andrzejak, Justin X. Moore

Behavioral Science Faculty Publications

Purpose Our study aimed to examine whether receipt of follow-up care plans is associated with greater guideline-concordant CRC screening stratified by breast, prostate, and lung cancer survivors.

Methods We used data from years 2016, 2018, and 2020 of the Behavioral Risk Factor Surveillance System on 3339 eligible treatment-utilizing cancer survivors with complete treatment. We performed descriptive statistics and multivariable logistic regression to examine the mentioned association.

Results We observed that 83.9% of breast and 88.2% of prostate cancer survivors with follow-care plans received CRC screening (p-value < 0.001). The lowest CRC screening use was observed among lung cancer (70.8%). In multivariable analysis, receipt of follow-up care plans was strongly associated with greater odds of receiving CRC screening in breast (OR, 2.67; 95% CI: 1.71–4.16) and prostate (OR, 3.81; 95% CI: 2.30–6.31) cancer survivors. Regardless of provider type, 84 to 88% reduced likelihood of receipt of CRC screening when they received follow-up care plans among lung cancer survivors. Among those without follow-up care plans, breast (OR, 0.29; 95% CI: 0.09–0.92) and lung (OR, 0.05; 95% CI: 0.01–0.25) cancer survivors who received care from general practices were less likely to receive CRC screening compared to those who received care from non-general practices.

Conclusions Receipt of follow-up care plans was associated with greater CRC screening use in …

Periodontal Regeneration Related To Periodontitis Treated By Garden Cress And Ozone Therapy. (Randomized Clinical &Experimental Study), Zienab S. Farid, Doaa Adel Habba, Gihan Adel Balbola, Noura Mohammed Bakr

Journal of Medicine in Scientific Research

Objective: In this article, garden cress and ozone were evaluated for their potential therapeutic properties of PDL and resorption of alveolar bone in the periodontal tissues based on rats' experimental periodontitis and to assess the clinical effectiveness of local application of garden cress and ozone for treatment and management of periodontitis patients using scaling and root planing. Methodology: Thirty mature Wistar male albino rats. Three groups of rats were formed; periodontitis without treatment, periodontitis with garden cress, and periodontitis plus ozone therapy. The present study also included thirty periodontitis Patients were randomly allocated to one of three groups of ten …

The Rage Gene Crucial Function In The Etiology And Consequences Of Type I Diabetes, Amal A. Mohamed, Mohamed O. Mahmoud, Gamil M. Abdallah, Nada S. Ali, Mona Abdelmotaleb Abdelfatah Hussein, Ibrahim T. Ibrahim

Journal of Medicine in Scientific Research

Type I Diabetes, among the ten greatest causes of mortality worldwide, is estimated to afflict 642 million individuals by 2040. It is an auto-immune illness brought on by an association of environmental and genetic variables. that cause T lymphocytes to destroy insulin-producing β-cells. Its prevalence continues to rise by 3-4% annually worldwide, enhancing the risk of mortality. So, the idea of diabetic kidney disease (DKD) is widely established, and systemic treatment is essential. RAGEs are linked to inflammatory disorders that exist in a variety of TID-related cells; especially T cells. Variations in circulating RAGE concentrations have been linked to a …

Oral Collagen Supplementation In 2nd Degree Burn And Chronic Pressure Ulcers, Wesam Ibrahem Homouda, Helmy Ahmed Soliman, Esayed Hussien Elmokadem

Journal of Medicine in Scientific Research

Background: Healing of wounds requires adequate intake of protein, iron, Vitamin-C and zinc. In case of deficiency in the dietary intake, supplements may be prescribed. Collagen-peptide supplements can enhance skin hydration, elasticity, and reduce wrinkles. Burns, caused by various agents, severely damage skin layers. Pressure ulcers occur when prolonged pressure on the skin leads to tissue ischaemia, disrupting nutrition and oxygen supply, resulting in tissue necrosis. Systematic reviews show that oral collagen, either intact or hydrolyzed, effectively improves skin health.

Objectives: This article aim to evaluate the effect of oral collagen intake as a healing promoting supplementation in management of …

Prediction Of Recurrent Lateral Ankle Sprain And Ankle Pain Using Applied Care Strategies And Patient-Reported Outcomes, Ryan S. Mccann, Elisabeth Ohrnberger, Kyle B. Kosik, Phillip A. Gribble

Rehabilitation Sciences Faculty Publications

Context

Patients with lateral ankle sprains (LASs) often have deficient patient-reported outcomes (PROs) at return to activity (RTA), potentially increasing risk for recurrent LAS and ankle pain. Additionally, applied care strategies are known to correct impairments, but their ability to mitigate risk for long-term consequences remains unknown.

Objective

To determine if applied care strategies and PRO scores at RTA and 6 months after RTA predict recurrent LAS and ankle pain 12 months after an acute LAS. DESIGN: Prospective cohort study.

Setting

Online survey.

Patients or Other Participants

We enrolled 63 individuals within 1 week of sustaining an acute LAS.

Main …

Laboratory Evaluation Of Essential Oils Extracted From Peppermint And Eucalyptus Plants Against The Rat Flea (Xynopsylla Cheopis) And Evaluate Their Effects On Some Vital Process In Albino Rat, Rasha Ragheb Hassan, Micheal William Mikhail

Journal of Medicine in Scientific Research

The effectiveness of peppermint and eucalyptus oils was examined in the current study to the rat fleas (Xenopsylla cheopis). The constituents of each oil were identified by GC-MS. The LC50 and LC90 for each essential oil were calculated after 1 and 24 hours exposure. The effect of peppermint and eucalyptus oils on some vital process in albino rat treated with 1/10 and 1/20 of LD50 were studied for the ALT, AST, Urea and creatinine levels. TNF-α and IL-6 levels also were studied. Data indicated that peppermint essential oil had more efficacy than that of eucalyptus for 1 and 24 hours …

Social Determinants Of Health: Evaluation Using Rates Of Vision Screening And Follow-Up Examinations, Madeline Dyer

Williams Honors College, Honors Research Projects

Vision care is essential to the quality of life of young children, impacting them over the course of their lives. Social Determinants of Health (SDOH) affect the likelihood of a child having access to appropriate care specified by the Bright Futures. The aim of this study was to assess the impact of SDOH on the completion of vision screening and the rate of follow-up with an eye care provider when applicable. In addition, rates of instrument-based vision screening and recommended ophthalmology follow-up were compared with COI, a metric assessing the quality of resources available and the conditions that matter for …

Degradable Staples And Delivery Device, Meha Elango, Jessica Cabrera, Makayla Scarpitti, Kareemat Melaiye

Williams Honors College, Honors Research Projects

The scope of this project is to design a method to secure skin grafts to healthy tissue. The ultimate goal for the proposed method is to be dissolvable in some form. Currently, skin grafts procedures utilize staples in most cases to hold a skin graft in place, but there are disadvantages that come with it. Staples are easy to place, but time consuming during the removal procedure. They also cause a lot of pain and discomfort for the patient. The goal of this project is to determine a way a secure skin grafts to healthy skin in order to reduce …

Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. …

Bet Inhibition Reforms The Immune Microenvironment And Alleviates T Cell Dysfunction In Chronic Lymphocytic Leukemia, Audrey L. Smith, Sydney A. Skupa, Alexandria P. Eiken, Timothy E. Reznicek, Elizabeth Schmitz, Nolan Williams, Dalia Y. Moore, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Eslam Mohamed, Anna R. Mahr, Paul W. Denton, Ben Powell, Gideon Bollag, M. Jordan Rowley, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eμ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer …

Editorial: Intersection Of Diet, Intestinal Microbiota, And Their Metabolites On Cancer Prevention, Nancy D. Turner, Tiffany L. Weir, Jacques Izard

Journal Articles: Internal Medicine

No abstract provided.

Search Strategies For "Characterizing Metastatic Anogenital Squamous Cell Carcinoma In Immunosuppressed Patients: A Systematic Review", Sierra Thomas, Molly Antonson, Megan Wackel, Cynthia M. Schmidt, Ashley Wysong

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.

Antagomir Treatment For Deep-Space Simulated Changes In The Liver Of Mice, Natalie P. Hayslip

Honors Undergraduate Theses

With the start of NASA’s Artemis program, astronauts will soon leave the protection of Earth’s magnetosphere. Previous studies have established a theme of liver dysregulation associated with the harmful radiation and microgravity experienced in deep space. MicroRNAs (miRNAs) are key regulators of many of the pathologies observed during and after spaceflight, including hepatic fibrosis, making them strong potential biomarkers and therapeutic targets. Therefore, in the present study we investigated the effects of simulated microgravity, galactic cosmic radiation (GCR), and solar particle events (SPE) on miRNAs and mRNAs involved in the TGF-β signaling pathway, a key regulator of fibrosis, senescence, and …

Assessment Of Forensic And Clinical Criteria Of Orbital Blowout Fractures For Use In Bioarchaeological Analysis, Dylan E. Ornot

Honors Undergraduate Theses

Orbital blowout fractures are a particular facial fracture occurring within the inner eye orbits of the face caused by blunt force trauma to the eyeball or the lower orbital rim. This fracture is common in modern clinical contexts due to physical assaults, but examining this fracture in skeletal material can also provide insights into the patterns of interpersonal violence within the fields of bioarchaeology and forensic anthropology. Issues with analyzing this fracture in skeletal material arise due to the clinical assessment practices of blowout fractures, where medical practitioners are highly focused on the soft tissue presentations of the fracture in …

Ketogenic Diet In Treating Sepsis-Related Acquired Weakness: Is It Friend Or Foe?, Yanmei Miao, Leiyu Xie, Shaolin Chen, Xiaoming Zhang, Wenjie Liu, Peng Xie

Faculty, Staff and Students Publications

Background: Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with …

Comparative Exploration Of Mammalian Deafness Gene Homologues In The Drosophila Auditory Organ Shows Genetic Correlation Between Insect And Vertebrate Hearing, Daniel C Sutton, Jonathan C Andrews, Dylan M Dolezal, Ye Jin Park, Hongjie Li, Daniel F Eberl, Shinya Yamamoto, Andrew K Groves

Faculty, Staff and Students Publications

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to …

Identification Of Constrained Sequence Elements Across 239 Primate Genomes, Lukas F K Kuderna, Jacob C Ulirsch, Sabrina Rashid, Mohamed Ameen, Laksshman Sundaram, Glenn Hickey, Anthony J Cox, Hong Gao, Arvind Kumar, Francois Aguet, Matthew J Christmas, Hiram Clawson, Maximilian Haeussler, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rouselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Ioannis Karakikes, Kevin C Wang, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Adam Siepel, Anshul Kundaje, Benedict Paten, Kerstin Lindblad-Toh, Jeffrey Rogers, Tomas Marques Bonet, Kyle Kai-How Farh

Faculty, Staff and Students Publications

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of …

Statins And The Risk Of Pancreatic Cancer: A Systematic Review And Meta-Analysis Of 2,797,186 Patients, Eryka Karbowska, Damian Swieczkowski, Aleksandra Gasecka, Michal Pruc, Kamil Safiejko, Jerzy R Ladny, Tomasz Kopiec, Milosz J Jaguszewski, Krzysztof J Filipiak, Zubaid Rafique, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: Statin use in many studies is related to the improvement of a patients' condition including reducing the risk of various malignancies. Herein, is a systematic review and meta-analysis to examine the evidence on the association between statin therapy and the risk of the occurrence of pancreatic cancer, mainly in terms of decreased risk of developing pancreatic cancer among patients using statin therapy in the long-term perspective.

METHODS: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to December 1st, 2021. Random effect models were used to estimate summary odds ratios …

Moving From Conventional To Adaptive Risk Stratification For Oropharyngeal Cancer, Vlad C Sandulache, R Parker Kirby, Stephen Y Lai

Faculty, Staff and Students Publications

Oropharyngeal cancer (OPC) poses a complex therapeutic dilemma for patients and oncologists alike, made worse by the epidemic increase in new cases associated with the oncogenic human papillomavirus (HPV). In a counterintuitive manner, the very thing which gives patients hope, the high response rate of HPV-associated OPC to conventional chemo-radiation strategies, has become one of the biggest challenges for the field as a whole. It has now become clear that for ~30-40% of patients, treatment intensity could be reduced without losing therapeutic efficacy, yet substantially diminishing the acute and lifelong morbidity resulting from conventional chemotherapy and radiation. At the same …

Generation And Characterization Of In Vitro Transcribed Mrna, Cristina Poveda, Yi-Lin Chen, Ulrich Strych

Faculty, Staff and Students Publications

Here we describe the in vitro preparation of mRNA from DNA templates, including setting up the transcription reaction, mRNA capping, and mRNA labeling. We then describe methods used for mRNA characterization, including UV and fluorescence spectrophotometry, as well as gel electrophoresis. Moreover, characterization of the in vitro transcribed RNA using the Bioanalyzer instrument is described, allowing a higher resolution analysis of the target molecules. For the in vitro testing of the mRNA molecules, we include protocols for the transfection of various primary cell cultures and the confirmation of translation by intracellular staining and western blotting.

Role Of Wave3 As An Actin Binding Protein In The Pathology Of Triple Negative Breast Cancer, Lamyae El Khalki, Khalid Sossey-Alaoui

Faculty Scholarship

Breast cancer, a prevalent global health concern, has sparked extensive research efforts, particularly focusing on triple negative breast cancer (TNBC), a subtype lacking estrogen receptor (ER), progesterone receptor, and epidermal growth factor receptor. TNBC's aggressive nature and resistance to hormone-based therapies heightens the risk of tumor progression and recurrence. Actin-binding proteins, specifically WAVE3 from the Wiskott–Aldrich syndrome protein (WASP) family, have emerged as major drivers in understanding TNBC biology. This review delves into the intricate molecular makeup of TNBC, shedding light on actin's fundamental role in cellular processes. Actin, a structural element in the cytoskeleton, regulates various cellular pathways essential …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …

Tyrp1 Is The Mendelian Determinant Of The Axolotl (Ambystoma Mexicanum) Copper Mutant, Raissa F. Cecil, Lloyd Strohl, Maddie K. Thomas, James L. Schwartz, Nataliya Timoshevskaya, Jeramiah J. Smith, S. Randal Voss

Markey Cancer Center Faculty Publications

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that …

Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr

Markey Cancer Center Faculty Publications

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age- associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident …

Pai-1 As A Critical Factor In The Resolution Of Sepsis And Acute Kidney Injury In Old Age, Maria E. C. Bruno, Sujata Mukherjee, Jamie L. Sturgill, Virgilius Cornea, Peng Yeh, Gregory S. Hawk, Hiroshi Saito, Marlene E. Starr

Markey Cancer Center Faculty Publications

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival …