Medicine and Health Sciences Commons^™

Attenuation Of Relapsing Fever Neuroborreliosis In Mice By Il-17a Blockade, Meihui Cheng, Jingwen Xu, Kaiyun Ding, Jing Zhang, Wei Lu, Jiansheng Liu, Jiahong Gao, Kishore R Alugupalli, Hongqi Liu

Department of Microbiology and Immunology Faculty Papers

Relapsing fever due to Borrelia hermsiiis characterized by recurrent bacteremia episodes. However, infection of B. hermsii, if not treated early, can spread to various organs including the central nervous system (CNS). CNS disease manifestations are commonly referred to as relapsing fever neuroborreliosis (RFNB). In the mouse model of B. hermsiiinfection, we have previously shown that the development of RFNB requires innate immune cells as well as T cells. Here, we found that prior to the onset of RFNB, an increase in the systemic proinflammatory cytokine response followed by sustained levels of IP-10 concurrent with the CNS disease phase. RNA sequencing …

Viral Small Terminase: A Divergent Structural Framework For A Conserved Biological Function., Ravi K. Lokareddy, Chun-Feng David Hou, Fenglin Li, Ruoyu Yang, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The genome packaging motor of bacteriophages and herpesviruses is built by two terminase subunits, known as large (TerL) and small (TerS), both essential for viral genome packaging. TerL structure, composition, and assembly to an empty capsid, as well as the mechanisms of ATP-dependent DNA packaging, have been studied in depth, shedding light on the chemo-mechanical coupling between ATP hydrolysis and DNA translocation. Instead, significantly less is known about the small terminase subunit, TerS, which is dispensable or even inhibitory in vitro, but essential in vivo. By taking advantage of the recent revolution in cryo-electron microscopy (cryo-EM) and building upon a …

A Critical Review Of Medication Adherence In Hypertension: Barriers And Facilitators Clinicians Should Consider, Seyed Mehrdad Hamrahian, Omar H. Maarouf, Tibor Fülöp

Department of Medicine Faculty Papers

Hypertension is a global public health problem, and its prevalence is increasing worldwide. Impacting all human societies and socioeconomic strata, it remains the major modifiable risk factor for global burden of cardiovascular disease all-cause mortality and the leading cause of loss of disability-adjusted life years. Despite increased awareness, the rate of blood pressure control remains unsatisfactory, particularly in low-to middle-income countries. Apparent treatment-resistant hypertension is associated with worse adverse health outcomes. It includes both true resistant and pseudo-resistant hypertension, which requires out-of-office blood pressure monitoring to exclude white-coat effect and confirmation of adherence to the agreed recommended antihypertensive therapy. The …

The Role Of Ubiquitination In Spinal And Bulbar Muscular Atrophy, Medha Sengupta, Anna Pluciennik, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative and neuromuscular genetic disease caused by the expansion of a polyglutamine-encoding CAG tract in the androgen receptor (AR) gene. The AR is an important transcriptional regulator of the nuclear hormone receptor superfamily; its levels are regulated in many ways including by ubiquitin-dependent degradation. Ubiquitination is a post-translational modification (PTM) which plays a key role in both AR transcriptional activity and its degradation. Moreover, the ubiquitin-proteasome system (UPS) is a fundamental component of cellular functioning and has been implicated in diseases of protein misfolding and aggregation, including polyglutamine (polyQ) repeat expansion diseases …

Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto

Department of Cancer Biology Faculty Papers

Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …

Tunable Action Potential Repolarization Governed By Kv3.4 Channels In Dorsal Root Ganglion Neurons., Tyler D. Alexander, Tanziyah Muqeem, Lianteng Zhi, Stephen R. Tymanskyj, Manuel Covarrubias

Department of Neuroscience Faculty Papers

The Kv3.4 channel regulates action potential (AP) repolarization in nociceptors and excitatory synaptic transmission in the spinal cord. We hypothesize that this is a tunable role governed by protein kinase-C-dependent phosphorylation of the Kv3.4 cytoplasmic N-terminal inactivation domain (NTID) at four nonequivalent sites. However, there is a paucity of causation evidence linking the phosphorylation status of Kv3.4 to the properties of the AP. To establish this link, we used adeno-associated viral vectors to specifically manipulate the expression and the effective phosphorylation status of Kv3.4 in cultured dorsal root ganglion (DRG) neurons from mixed-sex rat embryos at embryonic day 18. These …

Young Transposable Elements Rewired Gene Regulatory Networks In Human And Chimpanzee Hippocampal Intermediate Progenitors, Sruti Patoori, Samantha M Barnada, Christopher Large, John I Murray, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs …

D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak

Department of Medicine Faculty Papers

Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. …

Enhanced Membrane Binding Of Oncogenic G Protein Αqq209l Confers Resistance To Inhibitor Ym-254890, Clinita E. Randolph, Morgan B. Dwyer, Jenna L. Aumiller, Alethia J. Dixon, Asuka Inoue, Patrick Osei-Owusu, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins couple activated G protein-coupled receptors (GPCRs) to intracellular signaling pathways. They can also function independently of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling, as occurs with the αqQ209L mutation in uveal melanoma. YM-254890 (YM) can inhibit signaling by both GPCR-activated WT αq and GPCR-independent αqQ209L. Although YM inhibits WT αq by binding to αq-GDP and preventing GDP/GTP exchange, the mechanism of YM inhibition of cellular αqQ209L remains to be fully understood. Here, we show that YM promotes a subcellular redistribution of αqQ209L from the plasma membrane (PM) to the cytoplasm. …

Epigenetic Dysregulations In Arsenic-Induced Carcinogenesis, Ranakul Islam, Lei Zhao, Yifang Wang, Grace Lu-Yao, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced …

Breakdown Of The Central Synapses In C9orf72-Linked Als/Ftd, Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler, Brigid K Jensen

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease that leads to the death of motor and cortical neurons. The clinical manifestations of ALS are heterogenous, and efficacious treatments to significantly slow the progression of the disease are lacking. Cortical hyper-excitability is observed pre-symptomatically across disease-causative genetic variants, as well as in the early stages of sporadic ALS, and typically precedes motor neuron involvement and overt neurodegeneration. The causes of cortical hyper-excitability are not yet fully understood but is mainly agreed to be an early event. The identification of the nucleotide repeat expansion (GGGGCC)n in the C9ORF72 gene has …

Dataset Of Middle Cerebral Artery Blood Flow Stability In Response To High-Definition Transcranial Electrical Stimulation, Luiz H. Stefano, Diandra B. Favoretto, Diego C. Nascimento, Luan R.A. Santos, Marom Bikson, Joao P. Leite, Octavio M. Pontes-Neto, Dylan J. Edwards, Taiza G.S. Edwards

Moss-Magee Rehabilitation Papers

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA. Participants received three electrical stimulation conditions (anode center, cathode center, and …

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

Gut Permeability May Be Associated With Periprosthetic Joint Infection After Total Hip And Knee Arthroplasty, Emanuele Chisari, Jeongeun Cho, Marjan Wouthuyzen-Bakker, Javad Parvizi

Rothman Institute Faculty Papers

A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system function and ultimately affecting the outcome of interventions. We hypothesized that the loss of mucosal barrier in the gut may be associatedto acute and chronic periprosthetic joint infections (PJI). Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) were tested in plasma as part of …

Isc10, An Inhibitor Of The Smk1 Mapk, Prevents Activation Loop Autophosphorylation And Substrate Phosphorylation Through Separate Mechanisms, Abhimannyu Rimal, Thomas M Swayne, Zeal P Kamdar, Madison A Tewey, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Many eukaryotic protein kinases are activated by the intramolecular autophosphorylation of activation loop residues. Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that autophosphorylates its activation loop tyrosine and thereby upregulates catalytic output. This reaction is controlled by an inhibitor, Isc10, that binds the MAPK during meiosis I and an activator, Ssp2, that binds Smk1/Isc10 during meiosis II. Upon completion of the meiotic divisions, Isc10 is degraded, and Smk1 undergoes autophosphorylation to generate the high activity form of the MAPK that controls spore formation. How Isc10 inhibits Smk1 is not clear. Here, we use a bacterial coexpression/reconstitution system …

Pre-Exposure To Mrna-Lnp Inhibits Adaptive Immune Responses And Alters Innate Immune Fitness In An Inheritable Fashion, Zhen Qin, Aurélie Bouteau, Christopher Herbst, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which …

Is Strongyloides Stercoralis Hyperinfection Induced By Gglucocorticoids A Result Of Both Suppressed Host Immunity And Altered Parasite Genetics?, De'broski R Herbert, Jonathan D C Stoltzfus, Heather L Rossi, David Abraham

Department of Microbiology and Immunology Faculty Papers

The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of S.s. infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How …

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 …

Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …

G Protein-Coupled Receptor Kinase 6 (Grk6) Regulates Insulin Processing And Secretion Via Effects On Proinsulin Conversion To Insulin, Matthew J Varney, Wouter Steyaert, Paul J Coucke, Joris R Delanghe, David E Uehling, Babu Joseph, Richard Marcellus, Rima Al-Awar, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Recent studies identified a missense mutation in the gene coding for G protein-coupled receptor kinase 6 (GRK6) that segregates with type 2 diabetes (T2D). To better understand how GRK6 might be involved in T2D, we used pharmacological inhibition and genetic knockdown in the mouse β-cell line, MIN6, to determine whether GRK6 regulates insulin dynamics. We show inhibition of GRK5 and GRK6 increased insulin secretion but reduced insulin processing while GRK6 knockdown revealed these same processing defects with reduced levels of cellular insulin. GRK6 knockdown cells also had attenuated insulin secretion but enhanced proinsulin secretion consistent with decreased processing. In support …

The Pro-Fibrotic Response To Lens Injury Is Signaled In A Pi3k Isoform-Specific Manner, A. Sue Menko, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Notes From An Epicenter: Navigating Behavioral Clinical Trials On Autism Spectrum Disorder Amid The Covid-19 Pandemic In The Bronx, Alaina S Berruti, Roseann C Schaaf, Emily A Jones, Elizabeth Ridgway, Rachel L. Dumont, Benjamin E Leiby, Catherine Sancimino, Misung Yi, Sophie Molholm

Department of Occupational Therapy Faculty Papers

Background: The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children.

Main text: In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly …

A Genome-Wide Screen Identifies Pdpk1 As A Target To Enhance The Efficacy Of Mek1/2 Inhibitors, Weijia Cai, Nicole A. Wilski, Timothy J. Purwin, Megane Vernon, Manoela Tiago, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Melanomas frequently harbor activating NRAS mutations. However, limited advance has been made in developing targeted therapy options for NRAS mutant melanoma patients. MEK inhibitors (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of Phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacological and molecular approaches. Combined PDPK1 inhibitors (PDPK1i) with MEKi suppressed NRAS mutant xenograft growth and induced gasdermin E-associated pyroptosis. In an immune-competent …

Ondansetron To Reduce Neonatal Opioid Withdrawal Severity: A Randomized Clinical Trial, Gary Peltz, Lauren M. Jansson, Susan Adeniyi-Jones, Carol Cohane, David Drover, Steven Shafer, Meiyue Wang, Manhong Wu, Balaji Govindaswami, Priya Jegatheesan, Cynthia Argani, Salwa Kahn, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Objective
To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS).

Study Design
A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days.

Results
Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p>0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p=0.02). A non-significant trend was noted for the duration of …

Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …

The Health Effects Of A Plant-Based Diet On The Human Gut Microbiome, Bryant T. Bell

Student Papers, Posters & Projects

The popularity of a plant-based diet is sweeping the western world. Markets and social media influencers are promoting and encouraging this dietary lifestyle. With people switching diets, research is needed to see how one’s gut microbiome and health are affected. In this review article, the health effect of a plant-based diet on the gut microbiota is evaluate. Over 15 articles contained research on the physiology of the gastrointestinal system, microbes in the gut, nutrition, and diets affecting health issues. It is concluded that a plant-based diet promotes good health and gut microbiome; however, there are some nutritional deficiencies that may …

Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion, Ruihe Lin, Zi-Xuan Wang, Elizabeth Cottrill, Nitika Badjatia, Stacey Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Next-generation sequencing (NGS) analysis of thyroid samples aids in risk stratification of cytologically indeterminate nodules and contributes to our understanding of molecular mechanisms in thyroid neoplasia. Several genes, including BRAF, RAS, and EIF1AX, are known to play a role in thyroid tumorigenesis. Here we report a case of papillary thyroid carcinoma (PTC) in which a single lesion harbored a novel YWHAG-BRAF fusion and EIF1AX mutation and displayed mixed morphological findings. The patient is a 74-year-old female with multiple incidentally discovered thyroid nodules, two of which were sampled by ultrasound-guided fine needle aspiration (FNA). Cytologic diagnosis for both nodules was suspicious …

Human Hepatocyte 4-Acetoxy- N, N-Diisopropyltryptamine Metabolite Profiling By Reversed-Phase Liquid Chromatography Coupled With High-Resolution Tandem Mass Spectrometry, Sara Malaca, Marilyn A Huestis, Leonardo Lattanzio, Luigi T Marsella, Adriano Tagliabracci, Jeremy Carlier, Francesco P Busardò

College of Health Professions Faculty Papers

Tryptamine intoxications and fatalities are increasing, although these novel psychoactive substances (NPS) are not controlled in most countries. There are few data on the metabolic pathways and enzymes involved in tryptamine biotransformation. 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT) is a synthetic tryptamine related to 4-hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT), 4-acetyloxy-N,N-dipropyltryptamine (4-AcO-DPT), and 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT). The aim of this study was to determine the best 4-AcO-DiPT metabolites to identify 4-AcO-DiPT consumption through human hepatocyte metabolism and high-resolution mass spectrometry. 4-AcO-DiPT metabolites were predicted in silico with GLORYx freeware to assist in metabolite identification. 4-AcO-DiPT was incubated with 10-donor-pooled human hepatocytes and sample analysis was performed with reversed-phase liquid …

Altered Genome-Wide Hippocampal Gene Expression Profiles Following Early Life Lead Exposure And Their Potential For Reversal By Environmental Enrichment, Garima Singh, V Singh, T Kim, A Ertel, W Fu, J S Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Early life lead (Pb) exposure is detrimental to neurobehavioral development. The quality of the environment can modify negative influences from Pb exposure, impacting the developmental trajectory following Pb exposure. Little is known about the molecular underpinnings in the brain of the interaction between Pb and the quality of the environment. We examined relationships between early life Pb exposure and living in an enriched versus a non-enriched postnatal environment on genome-wide transcription profiles in hippocampus CA1. RNA-seq identified differences in the transcriptome of enriched vs. non-enriched Pb-exposed animals. Most of the gene expression changes associated with Pb exposure were reversed by …