Medical Sciences Commons^™

Intouch Week Of April 24, 2023, New York Medical College

InTouch

• Leonard Newman, M.D. ’70 and Michael Gewitz, M.D., Honored for Decades of Service to NYMC
• SHSP Announces Reorganization and New Department of Rehabilitation Sciences
• D.P.T. Class of 2025 Honored at White Coat Ceremony, Prepares for Clinical Education
• Sari Koppel, SLP Class of 2023, Combines the Art and Science of Voice
• OISS Oversees Immigration Compliance for International Students and Scholars

Beneficial Actions Of Sglt2 Inhibition And H2s Therapy In Heart Failure With Preserved Ejection Fraction, Jake Doiron, Zhen Li, Huijing Xia, Kyle B. Lapenna, Timothy D. Allerton, Daniel R. Kapusta, David J. Lefer

School of Graduate Studies Faculty Publications

Association for Clinical and Translational Science, ACTS 2023, April 18 - 20, 2023, Washington DC

A Small Secreted Protein Nicol Regulates Lumicrine-Mediated Sperm Maturation And Male Fertility, Daiji Kiyozumi, Kentaro Shimada, Michael Chalick, Chihiro Emori, Mayo Kodani, Seiya Oura, Taichi Noda, Tsutomu Endo, Martin M Matzuk, Daniel H Wreschner, Masahito Ikawa

Faculty, Staff and Students Publications

The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the …

Candidate Variants In Dna Replication And Repair Genes In Early-Onset Renal Cell Carcinoma Patients Referred For Germline Testing, Elena V. Demidova, Ilya G. Serebriiskii, Ramilia Vlasenkova, Simon Kelow, Mark D. Andrake, Tiffiney R. Hartman, Tatiana Kent, James Virtucio, Gail L. Rosen, Richard T. Pomerantz, Roland L. Dunbrack, Erica A. Golemis, Michael J. Hall, David Y.T. Chen, Mary B. Daly, Sanjeevani Arora

Department of Biochemistry and Molecular Biology Faculty Papers

Background: Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined.

Methods: Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes.

Results: Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of …

Machine Learning Models For The Identification Of Prognostic And Predictive Cancer Biomarkers: A Systematic Review, Qasem Al-Tashi, Maliazurina B Saad, Amgad Muneer, Rizwan Qureshi, Seyedali Mirjalili, Ajay Sheshadri, Xiuning Le, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

The identification of biomarkers plays a crucial role in personalized medicine, both in the clinical and research settings. However, the contrast between predictive and prognostic biomarkers can be challenging due to the overlap between the two. A prognostic biomarker predicts the future outcome of cancer, regardless of treatment, and a predictive biomarker predicts the effectiveness of a therapeutic intervention. Misclassifying a prognostic biomarker as predictive (or vice versa) can have serious financial and personal consequences for patients. To address this issue, various statistical and machine learning approaches have been developed. The aim of this study is to present an in-depth …

Combined Inhibition Of Bcl-2 And Mcl-1 Overcomes Bax Deficiency-Mediated Resistance Of Tp53-Mutant Acute Myeloid Leukemia To Individual Bh3 Mimetics, Bing Z Carter, Po Yee Mak, Wenjing Tao, Edward Ayoub, Lauren B Ostermann, Xuelin Huang, Sanam Loghavi, Steffen Boettcher, Yuki Nishida, Vivian Ruvolo, Paul E Hughes, Phuong K Morrow, Torsten Haferlach, Steven Kornblau, Muharrem Muftuoglu, Michael Andreeff

Faculty, Staff and Student Publications

TP53-mutant acute myeloid leukemia (AML) respond poorly to currently available treatments, including venetoclax-based drug combinations and pose a major therapeutic challenge. Analyses of RNA sequencing and reverse phase protein array datasets revealed significantly lower BAX RNA and protein levels in TP53-mutant compared to TP53-wild-type (WT) AML, a finding confirmed in isogenic CRISPR-generated TP53-knockout and -mutant AML. The response to either BCL-2 (venetoclax) or MCL-1 (AMG176) inhibition was BAX-dependent and much reduced in TP53-mutant compared to TP53-WT cells, while the combination of two BH3 mimetics effectively activated BAX, circumventing survival mechanisms in cells treated with either BH3 mimetic, and synergistically induced …

Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch

Faculty, Staff and Student Publications

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening.

PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites.

METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites …

Developmental Exposure To Corn Grown On Lake Erie Dredged Material: A Preliminary Analysis, Kaylyn A. S. Flanigan, Madelyn I. Czuba, Victoria R. Riesgo, Megan A. Rúa, Louise M. Stevenson, Jari Willing

Biological Sciences Faculty Publications

While corn is considered to be a healthy food option, common agricultural practices, such as the application of soil amendments, might be introducing contaminants of concern (COC) into corn plants. The use of dredged material, which contain contaminants such as heavy metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), as a soil amendment is increasing. Contaminants from these amendments can accumulate in corn kernels harvested from plants grown on these sediments and potentially biomagnify in organisms that consume them. The extent to which secondary exposure to such contaminants in corn affect the mammalian central nervous system has been virtually …

Synaptic Scaling Of Corticostriatal Circuits Underlies Hyperactivity In Gaba Transporter-1 Deficient Mice, Yan-Jiao Wu, Xin Yi, Xue Gu, Qi Wang, Qin Jiang, Ying Li, Michael X Zhu, Jianqing Ding, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Homeostatic synaptic scaling entails adjustment of synaptic strength on a cell to prolonged changes of neuronal activity, which is postulated to participate in neuropsychiatric disorders in vivo. Here, we find that sustained elevation in ambient GABA levels, by either genetic deletion or pharmacological blockade of GABA transporter-1 (GAT1), leads to synaptic scaling up of corticostriatal pathways, which underlies locomotor hyperactivity. Meanwhile, medium spiny neurons of the dorsal striatum exhibit an aberrant increase in excitatory synaptic transmission and corresponding structural changes in dendritic spines. Mechanistically, GAT1 deficiency dampens the expression and function of metabotropic glutamate receptors (mGluRs) and endocannabinoid (eCB)-dependent …

Comparative Study Of Adenosine Analogs As Inhibitors Of Protein Arginine Methyltransferases And A Clostridioides Difficile- Specific Dna Adenine Methyltransferase, Jujun Zhou, Youchao Deng, Iredia D Iyamu, John R Horton, Dan Yu, Taraneh Hajian, Masoud Vedadi, Dante Rotili, Antonello Mai, Robert M Blumenthal, Xing Zhang, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

S-Adenosyl-l-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host–pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-ethyl moiety at the …

Synthetic Errα/Β/Γ Agonist Induces An Errα-Dependent Acute Aerobic Exercise Response And Enhances Exercise Capacity, Cyrielle Billon, Sadichha Sitaula, Subhashis Banerjee, Ryan Welch, Bahaa Elgendy, Lamees Hegazy, Tae Gyu Oh, Melissa Kazantzis, Arindam Chatterjee, John Chrivia, Matthew E Hayes, Weiyi Xu, Angelica Hamilton, Janice M Huss, Lilei Zhang, John K Walker, Michael Downes, Ronald M Evans, Thomas P Burris

Faculty, Staff and Students Publications

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that the orphan nuclear receptors estrogen receptor-related receptors (ERRs) play an important role in skeletal muscle exercise capacity. Three ERR subtypes exist (ERRα, β, and γ), and although ERRβ/γ agonists have been designed, there have been significant difficulties in designing compounds with ERRα agonist activity. Additionally, there are limited synthetic agonists that can be used to target ERRs in vivo. Here, we report the …

Increasing Colorectal Cancer Screening Uptake Among Hispanic/Latino Patients: A Quality Improvement Initiative, Erick Hernandez Campos, Elizabeth Morse, David Phillippi

DNP Projects

Background: In 2021, cancer (CRC) screening rates for Latino men (42%) and women (47.5%) remain well below the Health People 2020 target (70.5%). Extensive documentation of barriers for screening include language, insurance status, and other sociocultural barriers which contribute to delays in diagnosis and/or diagnosis at advanced stages of the disease, and worse health outcomes. Latinos need culturally and linguistically appropriate health promotion interventions aimed to increase CRC screening rates with any modality (FIT, Cologuard, or Colonoscopy).

Methods: The Donabedian Structure-Process-Outcome (S-P-O) Model for quality improvement was used to develop and target a provider-driven, language-concordant communication interventions for …

Identifying Signatures Of Ev Secretion In Metastatic Breast Cancer Through Functional Single-Cell Profiling, Mohsen Fathi, Melisa Martinez-Paniagua, Ali Rezvan, Melisa J Montalvo, Vakul Mohanty, Ken Chen, Sendurai A Mani, Navin Varadarajan

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecules. Despite extensive investigation, heterogeneity in EV secretion among cancer cells and the mechanisms that support EV secretion are not well characterized. We developed an integrated method to identify individual cells with differences in EV secretion and performed linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cells. Differential gene expression analyses identified a four-gene signature of breast cancer EV secretion: HSP90AA1, HSPH1, EIF5, and DIAPH3. We functionally validated this gene signature by testing it across cell lines with different metastatic potential …

Cross-Dataset Single-Cell Analysis Identifies Temporal Alterations In Cell Populations Of Primary Pancreatic Tumor And Liver Metastasis, Daowei Yang, Rohan Moniruzzaman, Hua Wang, Huamin Wang, Yang Chen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has a unique tumor microenvironment composed of various cell populations such as cancer cells, cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. Recently, single-cell RNA-sequencing analysis (scRNA-seq) has systemically revealed the genomic profiles of these cell populations in PDAC. However, the direct comparison of cell population composition and genomic profile between primary tumors (at both early- and late-stage) and metastatic tumors of PDAC is still lacking. In this study, we combined and analyzed recent scRNA-seq datasets of transgenic KPC mouse models with autochthonous PDAC and matched liver metastasis, revealing the unique tumor ecosystem and cell composition …

The Effects Of Exosomal Derived Tsg-6 On Microglia Activation, Jonathan A. Martinez, Rajashekhar Gangaraju Md

Longitudinal Scholar's Project

Following a traumatic brain injury, microglia become overactive for long periods and display pathologic behavior. We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (MSC-CCM) can suppress microglial activation. In this pilot study, we evaluated the efficacy of exosomes containing TNF-stimulated gene 6 (TSG6) derived from MSC-CCM on decreasing microglial activation in vitro via phagocytic activity and pro-inflammatory microglial gene expression.

Review Of Nighttime Temperature Effects On Long-Term Health Condition Through Sleep Studies, Sydnie Matkins

Modeling, Simulation and Visualization Student Capstone Conference

Over the past 40 years, there has been increasing interest in human sleep quality and duration. This nonsystematic review looked at over 80 peer-reviewed papers on the association among sleep, temperature, and long-term health conditions. Generally, warmer temperatures lend to poorer sleep quality, and poor sleep quality lend to mental illness and a higher risk of coronary heart disease and mortality. Future research should be to conduct a study that relies more on health records rather than questionnaires to accurately map current and future health quality.

Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6–6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to …

Mixed Depression In The Post-Covid-19 Syndrome: Correlation Between Excitatory Symptoms In Depression And Physical Burden After Covid-19, Alessio Simonetti, Evelina Bernardi, Stella Margoni, Antonello Catinari, Antonio Restaino, Valentina Ieritano, Marta Palazzetti, Federico Mastrantonio, Delfina Janiri, Matteo Tosato, Francesco Landi, Gabriele Sani

Faculty, Staff and Students Publications

The relationship between depression and post-COVID-19 disease syndrome (post-COVID-19 syndrome) is established. Nevertheless, few studies have investigated the association between post-COVID-19 syndrome and mixed depression, i.e., a specific sub-form of depression characterized by high level of excitatory symptoms. Aims of the present study are: (a) to compare the post-COVID-19 syndrome's burden in depressed and non-depressed patients, and (b) to investigate the correlation between post-COVID-19 syndrome's burden and the severity of mixed depression. One thousand and forty six (n = 1460) subjects with post-COVID-19 syndrome were assessed. Subjects were divided into those with (DEP) or without (CONT) depression. Sociodemographically, post-COVID-19 syndrome's …

Health Disparities In Multiple Sclerosis Among Hispanic And Black Populations In The United States, Michael Z Moore, Carlos A Pérez, George J Hutton, Hemali Patel, Fernando X Cuascut

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will …

Circadian Clock Control Of Mrtf/Srf Pathway Suppresses Beige Adipocyte Thermogenic Recruitment, Xuekai Xiong, Weini Li, Ruya Liu, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

The morphological transformation of adipogenic progenitors into mature adipocytes requires dissolution of actin cytoskeleton with loss of myocardin-related transcription factor (MRTF)/serum response factor (SRF) activity. Circadian clock confers temporal control in adipogenic differentiation, while the actin cytoskeleton-MRTF/SRF signaling transduces extracellular physical niche cues. Here, we define a novel circadian transcriptional control involved in actin cytoskeleton-MRTF/SRF signaling cascade that modulates beige fat thermogenic function. Key components of actin dynamic-MRTF/SRF pathway display circadian regulation in beige fat depot. The core clock regulator, brain and muscle arnt-like 1 (Bmal1), exerts direct transcriptional control of genes within the actin dynamic-MRTF/SRF cascade that impacts actin …

Ppgpp And Rna-Polymerase Backtracking Guide Antibiotic-Induced Mutable Gambler Cells, Yin Zhai, P J Minnick, John P Pribis, Libertad Garcia-Villada, P J Hastings, Christophe Herman, Susan M Rosenberg

Faculty, Staff and Students Publications

Antibiotic resistance is a global health threat and often results from new mutations. Antibiotics can induce mutations via mechanisms activated by stress responses, which both reveal environmental cues of mutagenesis and are weak links in mutagenesis networks. Network inhibition could slow the evolution of resistance during antibiotic therapies. Despite its pivotal importance, few identities and fewer functions of stress responses in mutagenesis are clear. Here, we identify the Escherichia coli stringent starvation response in fluoroquinolone-antibiotic ciprofloxacin-induced mutagenesis. Binding of response-activator ppGpp to RNA polymerase (RNAP) at two sites leads to an antibiotic-induced mutable gambler-cell subpopulation. Each activates a stress response …

Machine Learning-Based Routine Laboratory Tests Predict One-Year Cognitive And Functional Decline In A Population Aged 75+ Years, Karina Braga Gomes, Ramon Gonçalves Pereira, Alexandre Alberto Braga, Henrique Cerqueira Guimarães, Elisa De Paula França Resende, Antônio Lúcio Teixeira, Maira Tonidandel Barbosa, Wagner Meira Junior, Maria Das Graças Carvalho, Paulo Caramelli

Faculty, Staff and Student Publications

BACKGROUND: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study.

METHOD: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care …

Neoadjuvant Pembrolizumab In Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors, Kaysia Ludford, Won Jin Ho, Jane V Thomas, Kanwal P S Raghav, Mariela Blum Murphy, Nicole D Fleming, Michael S Lee, Brandon G Smaglo, Y Nancy You, Matthew M Tillman, Carlos Kamiya-Matsuoka, Selvi Thirumurthi, Craig Messick, Benny Johnson, Eduardo Vilar, Arvind Dasari, Sarah Shin, Alexei Hernandez, Xuan Yuan, Hongqui Yang, Wai Chin Foo, Wei Qiao, Dipen Maru, Scott Kopetz, Michael J Overman

Faculty, Staff and Student Publications

PURPOSE: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

METHODS: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response …

Development And Validation Of A Prediction Model For Kidney Failure In Long-Term Survivors Of Childhood Cancer, Natalie L Wu, Yan Chen, Bryan V Dieffenbach, Matthew J Ehrhardt, Sangeeta Hingorani, Rebecca M Howell, John L Jefferies, Daniel A Mulrooney, Kevin C Oeffinger, Leslie L Robison, Brent R Weil, Yan Yuan, Yutaka Yasui, Melissa M Hudson, Wendy M Leisenring, Gregory T Armstrong, Eric J Chow

Faculty, Staff and Student Publications

Purpose: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer.

Methods: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651, Robert I Haddad, Kevin Harrington, Makoto Tahara, Robert L Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Faculty, Staff and Student Publications

PURPOSE: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

METHODS: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration …

Consensus On The Ras Dimerization Hypothesis: Strong Evidence For Lipid-Mediated Clustering But Not For G-Domain-Mediated Interactions, Dhirendra K Simanshu, Mark R Philips, John F Hancock

Faculty, Staff and Student Publications

One of the open questions in RAS biology is the existence of RAS dimers and their role in RAF dimerization and activation. The idea of RAS dimers arose from the discovery that RAF kinases function as obligate dimers, which generated the hypothesis that RAF dimer formation might be nucleated by G-domain-mediated RAS dimerization. Here, we review the evidence for RAS dimerization and describe a recent discussion among RAS researchers that led to a consensus that the clustering of two or more RAS proteins is not due to the stable association of G-domains but, instead, is a consequence of RAS C-terminal …

An Altered Extracellular Matrix-Integrin Interface Contributes To Huntington’S Disease-Associated Cns Dysfunction In Glial And Vascular Cells, Sarah J Hernandez, Ryan G Lim, Tarik Onur, Mark A Dane, Rebecca Smith, Keona Wang, Grace En-Hway Jean, Andrea Reyes-Ortiz, Kaylyn Devlin, Ricardo Miramontes, Jie Wu, Malcolm Casale, David Kilburn, Laura M Heiser, James E Korkola, David Van Vactor, Juan Botas, Katherine L Thompson-Peer, Leslie M Thompson

Faculty, Staff and Students Publications

Astrocytes and brain endothelial cells are components of the neurovascular unit that comprises the blood-brain barrier (BBB) and their dysfunction contributes to pathogenesis in Huntington's disease (HD). Defining the contribution of these cells to disease can inform cell-type-specific effects and uncover new disease-modifying therapeutic targets. These cells express integrin (ITG) adhesion receptors that anchor the cells to the extracellular matrix (ECM) to maintain the integrity of the BBB. We used HD patient-derived induced pluripotent stem cell (iPSC) modeling to study the ECM-ITG interface in astrocytes and brain microvascular endothelial cells and found ECM-ITG dysregulation in human iPSC-derived cells that may …

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …

Redox And Nucleophilic Reactions Of Naphthoquinones With Small Thiols And Their Effects On Oxidization Of H2s To Inorganic And Organic Hydropolysulfides And Thiosulfate, Kenneth R Olson, Kasey J Clear, Yan Gao, Zhilin Ma, Nathaniel M Cieplik, Alyssa R Fiume, Dominic J Gaziano, Stephen M Kasko, Jennifer Luu, Ella Pfaff, Anthony Travlos, Cecilia Velander, Katherine J Wilson, Elizabeth D Edwards, Karl D Straub, Gang Wu

Faculty, Staff and Student Publications

Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; …

Education In The Emergency Department For Cardiac Conditions, Shelby Thomason

Nursing | Student Research Posters

In the United States 610,000 people die every year from coronary artery disease which equates to 1 in 4 deaths. Inequity in access to healthcare is a persistent issue that impact patient outcomes. Tracking adherence and patient outcomes can be challenging, especially for patients who may not have access to necessary resources or support. Nurses are often overworked and have limited time to provide in-depth education. Patients and their families often struggle to afford caregivers or other resources that can help manage these chronic cardiac conditions.