Medical Specialties Commons^™

Discovery And Fine-Mapping Of Height Loci Via High-Density Imputation Of Gwass In Individuals Of African Ancestry, Mariaelisa Graff, Anne E Justice, Kristin L Young, Eirini Marouli, Xinruo Zhang, Rebecca S Fine, Elise Lim, Victoria Buchanan, Kristin Rand, Mary F Feitosa, Mary K Wojczynski, Lisa R Yanek, Yaming Shao, Rebecca Rohde, Adebowale A Adeyemo, Melinda C Aldrich, Matthew A Allison, Christine B Ambrosone, Stefan Ambs, Christopher Amos, Donna K Arnett, Larry Atwood, Elisa V Bandera, Traci Bartz, Diane M Becker, Sonja I Berndt, Leslie Bernstein, Lawrence F Bielak, William J Blot, Erwin P Bottinger, Donald W Bowden, Jonathan P Bradfield, Jennifer A Brody, Ulrich Broeckel, Gregory Burke, Brian E Cade, Qiuyin Cai, Neil Caporaso, Chris Carlson, John Carpten, Graham Casey, Stephen J Chanock, Guanjie Chen, Minhui Chen, Yii-Der I Chen, Wei-Min Chen, Alessandra Chesi, Charleston W K Chiang, Lisa Chu, Gerry A Coetzee, David V Conti, Richard S Cooper, Mary Cushman, Ellen Demerath, Sandra L Deming, Latchezar Dimitrov, Jingzhong Ding, W Ryan Diver, Qing Duan, Michele K Evans, Adeyinka G Falusi, Jessica D Faul, Myriam Fornage, Caroline Fox, Barry I Freedman, Melissa Garcia, Elizabeth M Gillanders, Phyllis Goodman, Omri Gottesman, Struan F A Grant, Xiuqing Guo, Hakon Hakonarson, Talin Haritunians, Tamara B Harris, Curtis C Harris, Brian E Henderson, Anselm Hennis, Dena G Hernandez, Joel N Hirschhorn, Lorna Haughton Mcneill, Timothy D Howard, Barbara Howard, Ann W Hsing, Yu-Han H Hsu, Jennifer J Hu, Chad D Huff, Dezheng Huo, Sue A Ingles, Marguerite R Irvin, Esther M John, Karen C Johnson, Joanne M Jordan, Edmond K Kabagambe, Sun J Kang, Sharon L Kardia, Brendan J Keating, Rick A Kittles, Eric A Klein, Suzanne Kolb, Laurence N Kolonel, Charles Kooperberg, Lewis Kuller, Abdullah Kutlar, Leslie Lange, Carl D Langefeld, Loic Le Marchand, Hampton Leonard, Guillaume Lettre, Albert M Levin, Yun Li, Jin Li, Yongmei Liu, Youfang Liu, Simin Liu, Kurt Lohman, Vaneet Lotay, Yingchang Lu, William Maixner, Joann E Manson, Barbara Mcknight, Yan Meng, Keri L Monda, Kris Monroe, Jason H Moore, Thomas H Mosley, Poorva Mudgal, Adam B Murphy, Rajiv Nadukuru, Mike A Nalls, Katherine L Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Christine Neslund-Dudas, Marian L Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Temidayo O Ogundiran, Adesola Ogunniyi, Oladosu Ojengbede, Hayrettin Okut, Olufunmilayo I Olopade, Andrew Olshan, Badri Padhukasahasram, Julie Palmer, Cameron D Palmer, Nicholette D Palmer, George Papanicolaou, Sanjay R Patel, Curtis A Pettaway, Patricia A Peyser, Michael F Press, D C Rao, Laura J Rasmussen-Torvik, Susan Redline, Alex P Reiner, Suhn K Rhie, Jorge L Rodriguez-Gil, Charles N Rotimi, Jerome I Rotter, Edward A Ruiz-Narvaez, Benjamin A Rybicki, Babatunde Salako, Michele M Sale, Maureen Sanderson, Eric Schadt, Pamela J Schreiner, Claudia Schurmann, Ann G Schwartz, Daniel A Shriner, Lisa B Signorello, Andrew B Singleton, David S Siscovick, Jennifer A Smith, Shad Smith, Elizabeth Speliotes, Margaret Spitz, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Lara Sucheston, Yan V Sun, Salman M Tajuddin, Herman Taylor, Kira Taylor, Bamidele O Tayo, Michael J Thun, Margaret A Tucker, Dhananjay Vaidya, David J Van Den Berg, Sailaja Vedantam, Mara Vitolins, Zhaoming Wang, Erin B Ware, Sylvia Wassertheil-Smoller, David R Weir, John K Wiencke, Scott M Williams, L Keoki Williams, James G Wilson, John S Witte, Margaret Wrensch, Xifeng Wu, Jie Yao, Neil Zakai, Krista Zanetti, Babette S Zemel, Wei Zhao, Jing Hua Zhao, Wei Zheng, Degui Zhi, Jie Zhou, Xiaofeng Zhu, Regina G Ziegler, Joe Zmuda, Alan B Zonderman, Bruce M Psaty, Ingrid B Borecki, L Adrienne Cupples, Ching-Ti Liu, Christopher A Haiman, Ruth Loos, Maggie C Y Ng, Kari E North

Faculty, Staff and Student Publications

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two …

A Phase Ii Study Of Autologous Mesenchymal Stromal Cells And C-Kit Positive Cardiac Cells, Alone Or In Combination, In Patients With Ischaemic Heart Failure: The Cctrn Concert-Hf Trial, Roberto Bolli, Raul D Mitrani, Joshua M Hare, Carl J Pepine, Emerson C Perin, James T Willerson, Jay H Traverse, Timothy D Henry, Phillip C Yang, Michael P Murphy, Keith L March, Ivonne H Schulman, Sohail Ikram, David P Lee, Connor O'Brien, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Gregory Lewis, Aisha Khan, Ketty Bacallao, Krystalenia Valasaki, Bangon Longsomboon, Adrian P Gee, Sara Richman, Doris A Taylor, Dejian Lai, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara Simpson, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Faculty, Staff and Student Publications

AIMS: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.

METHODS AND RESULTS: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association …

Resident Immune Cells Of The Avascular Lens: Mediators Of The Injury And Fibrotic Response Of The Lens., A. Menko, Jodirae Dedreu, Caitlin M. Logan, Heather Paulson, Alex V Levin, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen

Faculty, Staff and Students Publications

To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced in vitro models that combine ex vivo, stem cell-derived "organoid" cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem …

Sars-Cov-2 Infects Human Engineered Heart Tissues And Models Covid-19 Myocarditis, Adam L Bailey, Oleksandr Dmytrenko, Lina Greenberg, Andrea L Bredemeyer, Pan Ma, Jing Liu, Vinay Penna, Emma S Winkler, Sanja Sviben, Erin Brooks, Ajith P Nair, Kent A Heck, Aniket S Rali, Leo Simpson, Mehrdad Saririan, Dan Hobohm, W Tom Stump, James A Fitzpatrick, Xuping Xie, Xianwen Zhang, Pei-Yong Shi, J Travis Hinson, Weng-Tein Gi, Constanze Schmidt, Florian Leuschner, Chieh-Yu Lin, Michael S Diamond, Michael J Greenberg, Kory J Lavine

Faculty, Staff and Student Publications

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology …

Single-Cell Transcriptomics Identifies Limbal Stem Cell Population And Cell Types Mapping Its Differentiation Trajectory In Limbal Basal Epithelium Of Human Cornea, De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu, Yumei Li, Stephen C Pflugfelder, Hongyu Miao, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

METHODS: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

RESULTS: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. …

Mechanisms, Diagnosis, Prevention And Management Of Perioperative Opioid-Induced Hyperalgesia, Sylvia H Wilson, Kevin M Hellman, Dominika James, Adam C Adler, Arvind Chandrakantan

Faculty, Staff and Students Publications

Opioid-induced hyperalgesia (OIH) occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate. To address a lack of perioperative awareness, we present an educational review of clinically relevant aspects of the disorder. Although the mechanisms of OIH are thought to primarily involve medullary descending pathways, it is likely multifactorial with several relevant therapeutic targets. We provide a suggested clinical definition and directions for clinical differentiation of OIH from other diagnoses, as this may be confusing but is germane to appropriate management. Finally, we discuss prevention including patient education and analgesic management choices. As prevention may serve as the …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

Clinical And Economic Burden Of Stroke Among Young, Midlife, And Older Adults In The United States, 2002-2017, Safi U Khan, Muhammad Zia Khan, Muhammad U Khan, Muhammad Shahzeb Khan, Mamas A Mamas, Muhammad Rashid, Ron Blankstein, Salim S Virani, Michelle C Johansen, Michael D Shapiro, Michael J Blaha, Miguel Cainzos-Achirica, Farhaan S Vahidy, Khurram Nasir

Faculty, Staff and Students Publications

OBJECTIVE: To assess trends of stroke hospitalization rates, inpatient mortality, and health care resource use in young (aged ≤44 years), midlife (aged 45-64 years), and older (aged ≥65 years) adults.

PATIENTS AND METHODS: We studied the National Inpatient Sample database (January 1, 2002 to December 31, 2017) to analyze stroke-related hospitalizations. We identified data using the

RESULTS: Of 11,381,390 strokes, 79% (n=9,009,007) were ischemic and 21% (n=2,372,383) were hemorrhagic. Chronic diseases were more frequent in older adults; smoking, alcoholism, and migraine were more prevalent in midlife adults; and coagulopathy and intravenous drug abuse were more common in young patients with …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

The Impact Of Covid-19 On Kidney Transplantation And The Kidney Transplant Recipient – One Year Into The Pandemic, Pascale Khairallah, Nidhi Aggarwal, Ahmed A Awan, Chandan Vangala, Medha Airy, Jenny S Pan, Bhamidipati V R Murthy, Wolfgang C Winkelmayer, Venkat Ramanathan

Faculty, Staff and Students Publications

The COVID‐19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses …

Nmr Methods For Determining Lipid Turnover Via Stable Isotope Resolved Metabolomics, Penghui Lin, Li Dai, Daniel R. Crooks, Leonard M. Neckers, Richard M. Higashi, Teresa W.-M. Fan, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Lipids comprise diverse classes of compounds that are important for the structure and properties of membranes, as high-energy fuel sources and as signaling molecules. Therefore, the turnover rates of these varied classes of lipids are fundamental to cellular function. However, their enormous chemical diversity and dynamic range in cells makes detailed analysis very complex. Furthermore, although stable isotope tracers enable the determination of synthesis and degradation of complex lipids, the numbers of distinguishable molecules increase enormously, which exacerbates the problem. Although LC-MS-MS (Liquid Chromatography-Tandem Mass Spectrometry) is the standard for lipidomics, NMR can add value in global lipid analysis and …

Metabolism And Oncology: The Role Of Nutrition In Improving Cancer Outcomes, Michael A. Chapek

University Honors Theses

Despite significant advances in oncologic treatment, underlying cancer-associated metabolic derangements and nutritional needs remain largely neglected in cancer care. Cancer cachexia and protective metabolic changes exhibited by cancerous cells continue to pose formidable barriers to improving therapeutic outcomes and quality of life for patients. Cancer has traditionally been viewed as a proliferative disease caused by genetic mutations, but newer perspectives suggest that it is primarily a metabolic disease. The present paper discusses the etiology of cachexia and sarcopenia, and nutritional interventions that can be offered to patients suffering from these wasting disorders. The role of inflammation in cancer and the …

Loss Of Bone Morphogenetic Protein-Binding Endothelial Regulator Causes Insulin Resistance, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Huaizhu Wu, Christie M Ballantyne, Sean M Hartig, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that …

Serial Block-Face Scanning Electron Microscopy (Sbf-Sem) Of Biological Tissue Samples, Justin A Courson, Paul T Landry, Thao Do, Eric Spehlmann, Pascal J Lafontant, Nimesh Patel, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

Serial block-face scanning electron microscopy (SBF-SEM) allows for the collection of hundreds to thousands of serially-registered ultrastructural images, offering an unprecedented three-dimensional view of tissue microanatomy. While SBF-SEM has seen an exponential increase in use in recent years, technical aspects such as proper tissue preparation and imaging parameters are paramount for the success of this imaging modality. This imaging system benefits from the automated nature of the device, allowing one to leave the microscope unattended during the imaging process, with the automated collection of hundreds of images possible in a single day. However, without appropriate tissue preparation cellular ultrastructure can …

Myd88 L265p Elicits Mutation-Specific Ubiquitination To Drive Nf-Κb Activation And Lymphomagenesis, Xinfang Yu, Wei Li, Qipan Deng, Haidan Liu, Xu Wang, Hui Hu, Ya Cao, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Zhongxin Lu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate …

James's Choice: Treating An Infant With Craniosacral Therapy (Cst), Veronica Quarry

Journal of Transformative Touch

No abstract provided.

Space-Occupying Brain Lesions, Trauma-Related Tau Astrogliopathy, And Artag: A Report Of Two Cases And A Literature Review, Adam D. Bachstetter, Filip G. Garrett, Gregory A. Jicha, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age-affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the …

An Arabidopsis Oxalyl-Coa Decarboxylase, Atoxc, Is Important For Oxalate Catabolism In Plants, Justin Foster, Ninghui Cheng, Vincent Paris, Lingfei Wang, Jin Wang, Xiaoqiang Wang, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well-studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, acyl-activating enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. This enzyme has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Since this initial discovery, this enzyme and proposed pathway have been found to be important to other plants …

A Principal Components Analysis Of Factors Associated With Successful Implementation Of An Lvad Decision Support Tool, Kristin M Kostick, Meredith Trejo, Arvind Bhimaraj, Andrew Civitello, Jonathan Grinstein, Douglas Horstmanshof, Ulrich P Jorde, Matthias Loebe, Mandeep R Mehra, Nasir Z Sulemanjee, Vinay Thohan, Barry H Trachtenberg, Nir Uriel, Robert J Volk, Jerry D Estep, J S Blumenthal-Barby

Faculty, Staff and Students Publications

BACKGROUND: A central goal among researchers and policy makers seeking to implement clinical interventions is to identify key facilitators and barriers that contribute to implementation success. Despite calls from a number of scholars, empirical insights into the complex structural and cultural predictors of why decision aids (DAs) become routinely embedded in health care settings remains limited and highly variable across implementation contexts.

METHODS: We examined associations between "reach", a widely used indicator (from the RE-AIM model) of implementation success, and multi-level site characteristics of nine LVAD clinics engaged over 18 months in implementation and dissemination of a decision aid for …

Single-Cell Rna-Seq Analysis Reveals Compartment-Specific Heterogeneity And Plasticity Of Microglia, Junying Zheng, Wenjuan Ru, Jay R Adolacion, Michael S Spurgat, Xin Liu, Subo Yuan, Rommel X Liang, Jianli Dong, Andrew S Potter, S Steven Potter, Ken Chen, Rui Chen, Navin Varadarajan, Shao-Jun Tang

Faculty, Staff and Students Publications

Microglia are ubiquitous central nervous system (CNS)-resident macrophages that maintain homeostasis of neural tissues and protect them from pathogen attacks. Yet, their differentiation in different compartments remains elusive. We performed single-cell RNA-seq to compare microglial subtypes in the cortex and the spinal cord. A multi-way comparative analysis was carried out on samples from C57/BL and HIV gp120 transgenic mice at two, four, and eight months of age. The results revealed overlapping but distinct microglial populations in the cortex and the spinal cord. The differential heterogeneity of microglia in these CNS regions was further suggested by their disparity of plasticity in …

Stakeholder Perspectives And Sustainability Of An Integrated Care Model For The Prevention And Management Of Obesity: The Childhood Obesity Research Demonstration (Cord) Project, Rebecca E Lee, Nathan H Parker, Allen M Hallett, Dennis Kao, Maria J Modelska, Hanadi S Rifai, Erica G Soltero, Daniel P O'Connor

Children’s Nutrition Research Center Staff Publications

Although reliable strategies exist to promote healthy habits that reduce childhood obesity, the sustainability of these strategies remains an ongoing public health challenge. This study aimed to identify factors experienced in a large, multisite project aimed at reducing childhood obesity that might contribute to project sustainability. Hypothesized constructs underpinning sustainability included replicability, continuation of benefits, institutionalization, and community capacity. Key informants (n = 27) completed 60 min, in-depth interviews, which were audio recorded and transcribed. Transcripts were first coded using a combined deductive and inductive approach. Four major themes emerged (with numerous subthemes): developing partnerships, challenges to the sustainability …

The Mwtab Python Library For Restful Access And Enhanced Quality Control, Deposition, And Curation Of The Metabolomics Workbench Data Repository, Christian D. Powell, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

The Metabolomics Workbench (MW) is a public scientific data repository consisting of experimental data and metadata from metabolomics studies collected with mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. MW has been constantly evolving; updating its ‘mwTab’ text file format, adding a JavaScript Object Notation (JSON) file format, implementing a REpresentational State Transfer (REST) interface, and nearly quadrupling the number of datasets hosted on the repository within the last three years. In order to keep up with the quickly evolving state of the MW repository, the ‘mwtab’ Python library and package have been continuously updated to mirror the changes …

Prior Sleep Problems And Adverse Post-Traumatic Neuropsychiatric Sequelae Of Motor Vehicle Collision In The Aurora Study, Thomas C Neylan, Ronald C Kessler, Kerry J Ressler, Gari Clifford, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Sarah D Linnstaedt, Laura T Germine, Sophia Sheikh, Alan B Storrow, Brittany E Punches, Kamran Mohiuddin, Nina T Gentile, Meghan E Mcgrath, Sanne J H Van Rooij, John P Haran, David A Peak, Robert M Domeier, Claire Pearson, Leon D Sanchez, Niels K Rathlev, William F Peacock, Steven E Bruce, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Steven E Harte, James M Elliott, Irving Hwang, Maria V Petukhova, Nancy A Sampson, Karestan C Koenen, Samuel A Mclean

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes.

METHODS: A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were …

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

Integrative Network Analyses Of Transcriptomics Data Reveal Potential Drug Targets For Acute Radiation Syndrome, Robert Moore, Bhanwar Lal Puniya, Robert Powers, Chittibabu Guda, Kenneth W. Bayles, David B. Berkowitz, Tomáš Helikar

Journal Articles: Pathology and Microbiology

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, …

The Chromosome-Level Genome Of Dragon Fruit Reveals Whole-Genome Duplication And Chromosomal Co-Localization Of Betacyanin Biosynthetic Genes, Jinfang Zheng, Lyndel W. Meinhardt, Ricardo Goenaga, Dapeng Zhang, Yanbin Yin

Food for Health: Publications

Dragon fruits are tropical fruits economically important for agricultural industries. As members of the family of Cactaceae, they have evolved to adapt to the arid environment. Here we report the draft genome of Hylocereus undatus, commercially known as the white-fleshed dragon fruit. The chromosomal level genome assembly contains 11 longest scaffolds corresponding to the 11 chromosomes of H. undatus. Genome annotation of H. undatus found ~29,000 protein-coding genes, similar to Carnegiea gigantea (saguaro). Whole-genome duplication (WGD) analysis revealed a WGD event in the last common ancestor of Cactaceae followed by extensive genome rearrangements. The divergence …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Nih Funding For Vaccine Readiness Before The Covid-19 Pandemic, Anthony E. Kiszewski, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000–2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000–2019. During this period, NIH funding for published vaccine research against specific pandemic threats …