Medicine and Health Sciences Commons^™

Angiotensinogen In Sex And Hypertension: New Insights From The Multi-Ethnic Study Of Atherosclerosis (Mesa), Alan Daugherty, Hong S. Lu, George L. Bakris

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.

Post-Intensive Care Syndrome And Pulmonary Fibrosis In Patients Surviving Ards-Pneumonia Of Covid-19 And Non-Covid-19 Etiologies, Jamie L. Sturgill, Kirby Mayer, Anna G. Kalema, Kinjal Dave, Stephanie Mora, Alborz Kalantar, David J. Carter, Ashley A. Montgomery-Yates, Peter E. Morris

Markey Cancer Center Faculty Publications

The purpose was to examine patient‑centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia‑related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19‑related ARDS and non‑COVID‑related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID‑19 and non‑COVID etiologies. Ninety‑four patients with mean age 53 ± 13 and 51% …

A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1a (CK1a) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1a enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1a phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of …

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K. Russell, Chad J. Creighton, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box–binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small- molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic …

Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated …

Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss

Markey Cancer Center Faculty Publications

The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …

In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun

Markey Cancer Center Faculty Publications

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …

Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng

Markey Cancer Center Faculty Publications

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both …

Adult Asthma Associated With Roadway Density And Housing In Rural Appalachia: The Mountain Air Project (Map)., W Jay Christian, John Flunker, Beverly May, Susan Westneat, Wayne T Sanderson, Nancy Schoenberg, Steven R Browning

UK CARES Faculty Publications

BACKGROUND: Appalachian Kentucky is a rural area with a high prevalence of asthma among adults. The relative contribution of environmental exposures in the etiology of adult asthma in these populations has been understudied.

OBJECTIVE: This manuscript describes the aims, study design, methods, and characteristics of participants for the Mountain Air Project (MAP), and focuses on associations between small area environmental exposures, including roadways and mining operations, and lifetime and current asthma in adults.

METHODS: A cohort of residents, aged 21 and older, in two Kentucky counties, was enrolled in a community-based, cross-sectional study. Stratified cluster sampling was used to select …

The Association Between Comorbidities And Self-Care Of Heart Failure: A Cross-Sectional Study, Kyoung Suk Lee, Debra K. Moser, Kathleen Dracup

Nursing Faculty Publications

Background Because heart failure (HF) is a debilitating chronic cardiac condition and increases with age, most patients with HF experience a broad range of coexisting chronic morbidities. Comorbidities present challenges for patients with HF to successfully perform self-care, but it is unknown what types and number of comorbidities influence HF patients’ self-care. The purpose of this study was to explore whether the number of cardiovascular and non-cardiovascular conditions are associated with HF self-care.

Methods Secondary data analysis was performed with 590 patients with HF. The number of cardiovascular and noncardiovascular conditions was calculated using the list of conditions in the …

Global Dna Adenine Methylation In Caenorhabditis Elegans After Multigenerational Exposure To Silver Nanoparticles And Silver Nitrate, Anye Wamucho, Jason M. Unrine, John May, Olga V. Tsyusko

UK CARES Faculty Publications

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO3 ). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-20 -deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO₃ . Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F₀) after two generations of exposure (F₂) and two generations of …

Child Traumatic Stress And Covid-19: The Impact Of The Pandemic On A Clinical Sample Of Children In Trauma Treatment, Ginny Sprang, Jessica G. Eslinger, Adrienne Whitt-Woosley, Stephanie Gusler, Tracy Clemans

Psychiatry Faculty Publications

Given the scope and duration of the COVID-19 pandemic, it is not surprising that research has documented negative effects to youth’s mental health. Yet, there is negligible research on the impact of the pandemic among clinical samples of youth receiving treatment for pre-existing trauma exposure and symptoms. The current study investigates COVID-19 as an index trauma, and if prior traumatic stress scores mediate the relationship between pandemic-related exposure and subsequent traumatic stress. Methods: This is a study of 130 youth ages 7–18 receiving trauma treatment at an academic medical center. The University of California Los Angeles Post-traumatic Stress Disorder-Reaction Index …

Participant Engagement To Develop Report-Back Materials For Personal Air Monitoring, Patrick H. Ryan, Chris Wolfe, Allison Parsons, Cole Brokamp, Ashley Turner, Erin N. Haynes

Epidemiology and Environmental Health Faculty Publications

Background: Studies that measure environmental exposures in biological samples frequently provide participants their results. In contrast, studies using personal air monitors do not typically provide participants their monitoring results. The objective of this study was to engage adolescents who completed personal air sampling and their caregivers to develop understandable and actionable report-back documents containing the results of their personal air sampling.

Methods: Adolescents and their caregivers who previously completed personal air sampling participated in focus groups to guide the development of report-back materials. We conducted thematic analyses of focus group data to guide the design of the report-back …

Measuring Ground Surface Elevation Changes In A Slow-Moving Colluvial Landslide Using Combinations Of Regional Airborne Lidar, Uav Lidar And Uav Photogrammetric Surveys, Sarah E. Johnson, William C. Haneberg, L. Sebastian Bryson, Matthew M. Crawford

UK CARES Faculty Publications

Slow-moving, chronically destructive landslides are projected to grow in number globally in response to precipitation increases from climate change, and land disturbances from wildfire, mining and construction. In the Cincinnati and northern Kentucky metropolitan area, USA, landslides develop in colluvium that covers the steep slopes along the Ohio River and its tributaries. Here we quantify elevation changes in a slow-moving colluvial landslide over 14 years using county- wide lidar, uncrewed aerial vehicle (UAV) structure-from-motion (SfM) surveys and a UAV lidar survey. Because the technology and quality differ between surveys, the challenge was to calculate a threshold of detectable change for …

A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo

UK CARES Faculty Publications

Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …

Effect Of Lifestyle-Based Lipid Lowering Interventions On The Relationship Between Circulating Levels Of Per-And Polyfluoroalkyl Substances And Serum Cholesterol, Stephanie Morgan, M. Abdul Mottaleb, Maria P. Kraemer, Debra K. Moser, Jessica Worley, Andrew J. Morris, Michael C. Petriello

UK CARES Faculty Publications

Exposure to certain per-and polyfluoroalkyl substances (PFAS) has been shown to be positively associated with total and/or low-density lipoprotein cholesterol. Examining this association in lipid lowering interventions may provide additional evidence linking PFAS to cardiovascular risk. We examined the relationship of 6 PFAS with cholesterol in a 6-month lifestyle-based intervention. We quantitated PFAS in 350 individuals at baseline and post intervention and examined associations of PFAS with cholesterol before and after intervention. Food frequency questionnaires and GIS analyses were used to investigate PFAS hotspots and possible exposure routes. Cholesterol significantly decreased following intervention and in parallel, PFOS, PFOA, PFHxS, and …

Impact Of In Utero Drug Exposure On Neonates Requiring Ecmo: A Retrospective Cohort Study, Hallie Walther, Aric Schadler, Karen Garlitz, John Anthony Bauer, Lindsay Kohler, Erika Waldsmith, Hubert O. Ballard

UK CARES Faculty Publications

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children’s Hospital. A total of 56 neonatal patients were placed on ECMO …

Hpv Vaccination And Cervical Cancer Screening Promotion Among Black Individuals: Social Ecological Perspectives From Key Informants Interviews, Adebola Adegboyega, Desmennu Adeyimika, Obielodan Omoadoni, Dignan Mark

UK CARES Faculty Publications

Objectives: Rates of HPV infection and HPV-related cancers are elevated in the Black population of the US. Efforts to promote HPV vaccination and cervical cancer screening are important to reducing the cancer burden among Black populations. The purpose of this qualitative descriptive study guided by social ecological model (SEM) was to describe from the perspective of key informants, the challenges and opportunities for HPV vaccination and cervical cancer screening promotion among Black adults.

Design: Twenty-three key informants participated in individual interviews over zoom video conferencing. The sessions were audio- recorded, transcribed verbatim, and checked for accuracy prior to data analysis. …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

Magnetic Nanocomposites For The Remote Activation Of Sulfate Radicals For The Removal Of Rhodamine B, Pranto Paul, Marissa Nicholson, J. Zach Hilt

UK CARES Faculty Publications

The widespread presence of numerous organic contaminants in water poses a threat to the ecological environment and human health. Magnetic nanocomposites exposed to an alternating magnetic field (AMF) have a unique ability for magnetically mediated energy delivery (MagMED) resulting from the embedded magnetic nanoparticles; this localized energy delivery and associated chemical and thermal effects are a potential method for removing contaminants from water. This work developed a novel magnetic nanocomposite—a polyacrylamide-based hydrogel loaded with iron oxide nanoparticles. For this magnetic nanocomposite, persulfate activation and the contamination removal in water were investigated. Magnetic nanocomposites were exposed to AMF with a model …

Association Of Symptoms And Mode Of Transportation To Emergency Department In Patients With Acute Coronary Syndrome, Leslie L. Davis, Thomas P. Mccoy, Barbara Riegel, Sharon Mckinley, Lynn V. Doering, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with acute coronary syndrome (ACS) with symptoms matching their expectations of a heart attack are more likely to use emergency medical services (EMS) than not.

Objective: To determine whether presenting symptom clusters are associated with EMS use in ACS patients and if EMS use or symptom clusters are associated with prehospital delay.

Methods: This secondary analysis used data from the PROMOTION trial, a randomized clinical trial that enrolled 3522 subjects with a history of or at risk for ACS from 5 sites in the United States, Australia, and New Zealand. Subjects were randomized to usual care or an …

Body Mass Index Percentiles Versus Body Composition Assessments: Challenges For Disease Risk Classifications In Children, Jody L. Clasey, Elizabeth Ann Easley, Margaret O'Bryan Murphy, Stefan G. Kiessling, Arnold Stromberg, Aric Schadler, Hong Huang, John A. Bauer

UK CARES Faculty Publications

Background: Identifying at-risk children with optimal specificity and sensitivity to allow for the appropriate intervention strategies to be implemented is crucial to improving the health and well-being of children. We determined relationships of body mass indexes for age and sex percentile (BMI%) classifications to actual body composition using validated and convenient methodologies and compared fat and non-fat mass estimates to normative cut-off reference values to determine guideline reliability. We hypothesized that we would achieve an improved ability to identify at-risk children using simple, non-invasive body composition and index measures.

Methods: Cross-sectional study of a volunteer convenience sample of 1,064 (537 …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany Breon Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 μmole PCB126 per kg of body weight via oral gavage on postnatal …

Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1, Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong, Ying Liang

Markey Cancer Center Faculty Publications

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/- male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of micro- RNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male …

Chronic Environmental Circadian Disruption Increases Atherosclerosis And Dyslipidemia In Female, But Not Male, Apolipoproteine-Deficient Mice, Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast

Saha Cardiovascular Research Center Faculty Publications

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D …

Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain

Saha Cardiovascular Research Center Faculty Publications

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration In Humans, Sean D. Regnier, William W. Stoops, Joshua A. Lile, Joseph L. Alcorn Iii, B. Levi Bolin, Anna R. Reynolds, Lon R. Hays, Abner O. Rayapati, Craig R. Rush

Behavioral Science Faculty Publications

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder.

Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/ day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, …

An Improved Germline Genome Assembly For The Sea Lamprey Petromyzon Marinus Illuminates The Evolution Of Germline-Specific Chromosomes, Nataliya Timoshevskaya, Kaan İ. Eşkut, Vladimir A. Timoshevskiy, Sofia M.C. Robb, Carson Holt, Jon E. Hess, Hugo J. Parker, Cindy F. Baker, Allison K. Miller, Cody Saraceno, Mark Yandell, Robb Krumlauf, Shawn R. Narum, Ralph T. Lampman, Neil J. Gemmell, Jacquelyn Mountcastle, Bettina Haase, Jennifer R. Balacco, Giulio Formenti, Sarah Pelan, Ying Sims, Kerstin Howe, Olivier Fedrigo, Erich D. Jarvis, Jeramiah James Smith

Markey Cancer Center Faculty Publications

Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically …