Digital Commons Network^™

Cyclin G2, A Novel Target Of Sulindac To Inhibit Cell Cycle Progression In Colorectal Cancer, Hongyou Zhao, Bin Yi, Zhipin Liang, Ches'nique N. Phillips, Hui Yi Lin, Adam I. Riker, Yaguang Xi

School of Medicine Faculty Publications

Sulindac has shown significant clinical benefit in preventing colorectal cancer progression, but its mechanism of action has not been fully elucidated. We have found that sulindac sulfide (SS) is able to inhibit cell cycle progression in human colorectal cancer cells, particularly through G1 arrest. To understand the underlying mechanisms of sulindac inhibitory activity, we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substantially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor cells. MiR-182, an oncogenic microRNA known to inhibit FOXO3a gene expression, is also involved in the suppressive effect of SS …

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Research

Biological Sciences; Physiology; Molecular Biology; Cell Biology

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

Blood N-3 Fatty Acid Levels And Total And Cause-Specific Mortality From 17 Prospective Studies, William S Harris, Nathan L Tintle, Fumiaki Imamura, Frank Qian, Andres V Ardisson Korat, Matti Marklund, Luc Djoussé, Julie K Bassett, Pierre-Hugues Carmichael, Yun-Yu Chen, Yoichiro Hirakawa, Leanne K Küpers, Federica Laguzzi, Maria Lankinen, Rachel A Murphy, Cécilia Samieri, Mackenzie K Senn, Peilin Shi, Jyrki K Virtanen, Ingeborg A Brouwer, Kuo-Liong Chien, Gudny Eiriksdottir, Nita G Forouhi, Johanna M Geleijnse, Graham G Giles, Vilmundur Gudnason, Catherine Helmer, Allison Hodge, Rebecca Jackson, Kay-Tee Khaw, Markku Laakso, Heidi Lai, Danielle Laurin, Karin Leander, Joan Lindsay, Renata Micha, Jaako Mursu, Toshiharu Ninomiya, Wendy Post, Bruce M Psaty, Ulf Risérus, Jennifer G Robinson, Aladdin H Shadyab, Linda Snetselaar, Aleix Sala-Vila, Yangbo Sun, Lyn M Steffen, Michael Y Tsai, Nicholas J Wareham, Alexis C Wood, Jason H Y Wu, Frank Hu, Qi Sun, David S Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian, Fatty Acids And Outcomes Research Consortium (Force)

Children’s Nutrition Research Center Staff Publications

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Impaired 26s Proteasome Assembly Precedes Neuronal Loss In Mutant Ubqln2 Rats., Wenjuan Zhang, Bo Huang, Limo Gao, Cao Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteasomal dysfunction is known to be associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). Our previous reports have shown that a mutant form of ubiquilin-2 (UBQLN2) linked to ALS/FTD leads to neurodegeneration accompanied by accumulations of the proteasome subunit Rpt1 in transgenic rats, but the precise pathogenic mechanisms of how this mutation impairs the proteasome remains to be elucidated. Here, we reveal that this UBQLN2 mutation in rats disrupted the proteasome integrity prior to neurodegeneration, that it dissociated the 26S proteasome in vitro, and that its depletion did not affect 26S proteasome assembly. During both disease progression and in …

Decade-Long Nationwide Trends And Disparities In Use Of Comfort Care Interventions For Patients With Ischemic Stroke, Kristie M Chu, Erica M Jones, Jennifer R Meeks, Alan P Pan, Kathryn L Agarwal, George E Taffet, Farhaan S Vahidy

Faculty, Staff and Students Publications

Background Stroke remains one of the leading causes of disability and death in the United States. We characterized 10-year nationwide trends in use of comfort care interventions (CCIs) among patients with ischemic stroke, particularly pertaining to acute thrombolytic therapy with intravenous tissue-type plasminogen activator and endovascular thrombectomy, and describe in-hospital outcomes and costs. Methods and Results We analyzed the National Inpatient Sample from 2006 to 2015 and identified adult patients with ischemic stroke with or without thrombolytic therapy and CCIs using validated

Somatic Cag Expansion In Huntington's Disease Is Dependent On The Mlh3 Endonuclease Domain, Which Can Be Excluded Via Splice Redirection, Jennie C.L. Roy, Antonia Vitalo, Marissa A. Andrew, Eduarda Mota-Silva, Marina Kovalenko, Zoe Burch, Anh M. Nhu, Paula E. Cohen, Ed Grabczyk, Vanessa C. Wheeler, Ricardo Mouro Pinto

School of Medicine Faculty Publications

Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD …

Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz

Publications

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of …

Activation Of The Cognitive Control Network Associated With Information Uncertainty, Tingting Wu, Kurt P. Schulz, Jin Fan

Publications and Research

The cognitive control network (CCN) that comprises regions of the frontoparietal network, the cingulo-opercular network, and other sub-cortical regions as core structures is commonly activated by events with an increase in information uncertainty. However, it is not clear whether this CCN activation is associated with both information entropy that represents the information conveyed by the context formed by a sequence of events and the surprise that quantifies the information conveyed by a specific type of event in the context. We manipulated entropy and surprise in this functional magnetic resonance imaging study by varying the probability of occurrence of two types …

Dexmedetomidine Or Propofol For Sedation In Mechanically Ventilated Adults With Sepsis, Christopher G Hughes, Patrick T Mailloux, John W Devlin, Joshua T Swan, Robert D Sanders, Antonio Anzueto, James C Jackson, Aimee S Hoskins, Brenda T Pun, Onur M Orun, Rameela Raman, Joanna L Stollings, Amy L Kiehl, Matthew S Duprey, Lan N Bui, Hollis R O'Neal, Allison Snyder, Michael A Gropper, Kalpalatha K Guntupalli, Gregg J Stashenko, Mayur B Patel, Nathan E Brummel, Timothy D Girard, Robert S Dittus, Gordon R Bernard, E Wesley Ely, Pratik P Pandharipande, Mends2 Study Investigators

Faculty, Staff and Students Publications

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale …

Conditional Survival Among Patients With Oropharyngeal Cancer Treated With Radiation Therapy And Alive Without Recurrence 5 Years After Diagnosis, Kristina R Dahlstrom, Juhee Song, Peter F Thall, Clifton D Fuller, Katherine A Hutcheson, Faye M Johnson, G Brandon Gunn, Jack Phan, Steven J Frank, William H Morrison, Renata Ferrarotto, David I Rosenthal, Erich M Sturgis, Adam S Garden

Faculty, Staff and Students Publications

BACKGROUND: Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis.

METHODS: This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and …

Medical School To Residency: How Can We Trust The Process?, Gary L Beck Dallaghan, Irene Alexandraki, Jennifer Christner, Meg Keeley, Sorabh Khandelwal, Beat Steiner, Paul A Hemmer

Faculty, Staff and Students Publications

Background To say that the transition from undergraduate medical education (UME) to graduate medical education (GME) is under scrutiny would be an understatement. Findings from a panel discussion at the 2018 Association of American Medical Colleges Annual meeting entitled, "Pass-Fail in Medical School and the Residency Application Process and Graduate Medical Education Transition" addressed what and when information should be shared with residency programs, and how and when that information should be shared. Materials and Methods Over 250 participants representing UME and GME (e.g. leadership, faculty, medical students) completed worksheets addressing these questions. During report-back times, verbal comments were transcribed …

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

Differences In The Genital Microbiota In Women Who Naturally Clear Chlamydia Trachomatis Infection Compared To Women Who Do Not Clear; A Pilot Study, Patricia Dehon Mott, Christopher M. Taylor, Rebecca A. Lillis, Caleb M. Ardizzone, Hannah L. Albritton, Meng Luo, Kaitlyn G. Calabresi, David H. Martin, Leann Myers, Alison J. Quayle

School of Graduate Studies Faculty Publications

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that …

Proteogenomic And Metabolomic Characterization Of Human Glioblastoma, Liang-Bo Wang, Alla Karpova, Marina A Gritsenko, Jennifer E Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H Rothstein, Runyu Hong, Vasileios Stathias, Macintosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia-Feng Tsai, Vladislav A Petyuk, Jamie Moon, Weiping Ma, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Matthew E Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A Wyczalkowski, Joshua F Mcmichael, Brittany L Henderson, Caleb M Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G Stratton, Lisa M Bramer, Erika Zink, Sneha P Couvillion, Kent J Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M Boca, Stephan Schürer, Feng Chen, Maciej Wiznerowicz, Karen A Ketchum, Emily S Boja, Christopher R Kinsinger, Ana I Robles, Tara Hiltke, Mathangi Thiagarajan, Alexey I Nesvizhskii, Bing Zhang, D R Mani, Michele Ceccarelli, Xi S Chen, Sandra L Cottingham, Qing Kay Li, Albert H Kim, David Fenyö, Kelly V Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel H Payne, Adam C Resnick, Pei Wang, Richard D Smith, Antonio Iavarone, Milan G Chheda, Jill S Barnholtz-Sloan, Karin D Rodland, Tao Liu, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM …

Obstructive Sleep Apnea And Dementia-Common Gene Associations Through Network-Based Identification Of Common Driver Genes, Hyun-Hwan Jeong, Arvind Chandrakantan, Adam C Adler

Faculty, Staff and Students Publications

BACKGROUND: Obstructive Sleep Apnea (OSA) occurs in 7% of the adult population. The relationship between neurodegenerative diseases such as dementia and sleep disorders have long attracted clinical attention; however, no comprehensive data exists elucidating common gene expression between the two diseases. The objective of this study was to (1) demonstrate the practicability and feasibility of utilizing a systems biology approach called network-based identification of common driver genes (NICD) to identify common genomic features between two associated diseases and (2) utilize this approach to identify genes associated with both OSA and dementia.

METHODS: This study utilized 2 public databases (PCNet, DisGeNET) …

Non-Dental Oral Cavity Findings In Gastroesophageal Reflux Disease: A Systematic Review And Meta-Analysis, Madalina-Gabriela Indre, Darius Sampelean, Vlad Taru, Angela Cozma, Dorel Sampelean, Mircea Vasile Milaciu, Olga Hilda Orasan

Journal of Mind and Medical Sciences

Gastroesophageal reflux disease (GERD) is known as the most prevalent gastrointestinal disorder in the United States, leading to substantial morbidity, although associated mortality is rare. Based on the appearance of esophageal mucosa on upper endoscopy, GERD is divided into erosive esophagitis (ERD) and nonerosive reflux disease (NERD). Heartburn and acid regurgitation are the typical symptoms of the disease, although some patients may present atypical manifestations such as epigastric pain, nausea, asthma, chronic cough, pharyngitis, laryngitis, sleep disturbances, otitis, and sinusitis. Other signs, such as oral mucosal lesions may result from GERD by direct acid or acidic vapor contact in the …

Linking The Brain And Bone Through Fat, Elisabeta Malinici, Anca Sirbu, Miruna Popa, Simona Fica

Journal of Mind and Medical Sciences

Over the past years, bone and adipose tissue have gained interest from researchers in the light of their secretory profiles, being able to produce active molecules, with the final effect of regulating energy homeostasis. Both adipocytes and osteoblasts originate in the pluripotent mesenchymal stem cell and this common origin has been proposed as the core of the fat-bone relationship. The central nervous system might be the third player in this association, capable of integrating signals. Numerous adipose tissue secreted factors that influence energy homeostasis and bone have been described: leptin, adiponectin, lipocalin 2, and inflammatory cytokines (e.g. IL-1, IL-6 and …

Save The Rich, Connor Harris

English Department: Research for Change - Wicked Problems in Our World

The problem of medication pricing and lobbying in the healthcare industry has caused millions of people within the United States to not be able to afford medications essential to their lives. Pharmaceutical companies are taking advantage of the need people have for certain drugs by setting the sale price far higher than it costs to produce. My suggested solution is to make lobbying illegal in the United States so that pharmaceutical companies would not have control over government officials who pass laws to help or hurt the issue of medication pricing. Illegalizing government lobbying will take away the incentive politicians …

Physician Burnout: Stress Within The Health Care System, Aidan Hauser

English Department: Research for Change - Wicked Problems in Our World

As our nation’s healthcare system expands, more stress and responsibility are placed on our physicians and frontline healthcare workers. The pressures of the daily job often prove extremely damaging to the employee’s mental and physical health. Physician and worker burnout is a growing epidemic that is damaging our care providers more and more every day. Burnout effects not only workers, but all of those surrounding them as well. This plague is not going to be repaired by one single change, but it is clear that many adjustments must be made to reform our healthcare system.

A Stress-Free Strategy To Correct Point Mutations In Patient Ips Cells, Jingli Cai, Elizabeth Kropf, Ya-Ming Hou, Lorraine Iacovitti

Department of Biochemistry and Molecular Biology Faculty Papers

When studying patient specific induced pluripotent stem cells (iPS cells) as a disease model, the ideal control is an isogenic line that has corrected the point mutation, instead of iPS cells from siblings or other healthy subjects. However, repairing a point mutation in iPS cells even with the newly developed CRISPR-Cas9 technique remains difficult and time-consuming. Here we report a strategy that makes the Cas9 “knock-in” methodology both hassle-free and error-free. Instead of selecting a Cas9 recognition site close to the point mutation, we chose a site located in the nearest intron. We constructed a donor template with the fragment …

Sirt3 Is Required For Liver Regeneration But Not For The Beneficial Effect Of Nicotinamide Riboside, Sarmistha Mukherjee, James Mo, Lauren M Paolella, Caroline E Perry, Jade Toth, Mindy M Hugo, Qingwei Chu, Qiang Tong, Karthikeyani Chellappa, Joseph A Baur

Children’s Nutrition Research Center Staff Publications

Liver regeneration is critical to survival after traumatic injuries, exposure to hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of the mitochondrial deacetylase SIRT3 drastically impairs regeneration and worsens mitochondrial function after partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed that the NAD precursor nicotinamide riboside (NR) promotes liver regeneration, but whether this involves sirtuins has not been tested. Here, we show that despite their NAD dependence and critical roles in regeneration, neither SIRT3 nor its nuclear counterpart SIRT1 is required for …

Zno Nucleation Into Trititanate Nanotubes By Ald Equipment Techniques, A New Way To Functionalize Layered Metal Oxides, Mabel Moreno, Miryam Arredondo, Quentin M Ramasse, Matthew Mclaren, Philine Stötzner, Stefan Förster, Eglantina Benavente, Caterina Salgado, Sindy Devis, Paula Solar, Luis Velasquez, Guillermo González

Faculty, Staff and Students Publications

In this contribution, we explore the potential of atomic layer deposition (ALD) techniques for developing new semiconductor metal oxide composites. Specifically, we investigate the functionalization of multi-wall trititanate nanotubes, H2Ti3O7 NTs (sample T1) with zinc oxide employing two different ALD approaches: vapor phase metalation (VPM) using diethylzinc (Zn(C2H5)2, DEZ) as a unique ALD precursor, and multiple pulsed vapor phase infiltration (MPI) using DEZ and water as precursors. We obtained two different types of tubular H2Ti3O7 species containing ZnO in their structures. Multi-wall trititanate nanotubes with ZnO intercalated inside the tube wall sheets were the main products from the VPM infiltration …

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …

Regional Variations In Heart Failure Quality And Outcomes: Get With The Guidelines-Heart Failure Registry, Luke C Cunningham, Gregg C Fonarow, Clyde W Yancy, Shubin Sheng, Roland A Matsouaka, Adam D Devore, Hani Jneid, Anita Deswal

Faculty, Staff and Students Publications

Background

Regional patient characteristics, care quality, and outcomes may differ based on a variety of factors among patients hospitalized for heart failure (HF). Regional disparities in outcomes of cardiovascular disease have been suggested across various regions in the United States. This study examined whether there are significant differences by region in quality of care and short‐term outcomes of hospitalized patients with HF across the United States.

Methods and Results

We examined regional demographics, quality measures, and short‐term outcomes across 4 US Census Bureau regions in patients hospitalized with HF and enrolled in the GWTG‐HF (Get With The Guidelines–Heart Failure) registry …

Late Gadolinium Enhancement Magnetic Resonance Imaging Evaluation Of Post-Atrial Fibrillation Ablation Esophageal Thermal Injury Across The Spectrum Of Severity, Qussay Marashly, Chaitra Gopinath, Alex Baher, Madan Acharya, Mobin Kheirkhahan, Benjamin Hardisty, Mossab Aljuaid, Ibrahim Tawhari, Mark Ibrahim, Alan K Morris, Eugene G Kholmovski, Brent D Wilson, Nassir F Marrouche, Mihail G Chelu

Faculty, Staff and Students Publications

Background Esophageal thermal injury (ETI) is a byproduct of atrial fibrillation (AF) ablation using thermal sources. The most severe form of ETI is represented by atrioesophageal fistula, which has a high mortality rate. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows identification of ETI. Hence, we sought to evaluate the utility of LGE-MRI as a method to identify ETI across the entire spectrum of severity. Methods and Results All AF radiofrequency ablations performed at the University of Utah between January 2009 and December 2017 were reviewed. Patients with LGE-MRI within 24 hours following AF ablation as well as patients …

Oxidative Stress And Dna Damage As Promoting Factors Of Hpv Integration, Meghri Katerji

Loma Linda University Electronic Theses, Dissertations & Projects

Human papillomaviruses (HPVs) cause virtually all cervical cancer cases and are also associated with other types of anogenital and oropharyngeal cancers. HPV-mediated carcinogenesis typically begins with the HPV episome integrating into the human genome. Unfortunately, the factors that promote this key process are not well defined. Since viral integration requires breaks in both viral and human genomes, DNA damage is likely a key determinant. The latter is primarily caused by an overproduction of reactive oxygen species (ROS). Therefore, high levels of background ROS in host cells, which may result from genetic/epigenetic factors together with exogenous influences, in principle, have the …

A Timeline Of Down Syndrome, Christian Guese, Kristina Mcinnes, Kimberly Miranda

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of Down Syndrome (DS) to discover absence of knowledge, discuss the bioethics in prenatal screening and develop a public health message. Our method of research was literature-based. DS is one of the most common aneuploidy disorders in the United States. There are three genetic variations of DS, Trisomy 21, a third copy of chromosome 21, accounts for 95% of cases. DS causes intellectual disability, developmental delays, facial dysmorphia, and low muscle tone. DS also leads to an increased risk for congenital heart defects and Alzheimer’s disease later in …

Temporal Dynamics Of Functional Brain States Underlie Cognitive Performance, Hong Gu, Kurt P. Schulz, Jin Fan, Yihong Yang

Publications and Research

The functional organization of the human brain adapts dynamically in response to a rapidly changing environment. However, the relation of these rapid changes in functional organization to cognitive functioning is not well understood. This study used a graph-based time-frame modularity analysis approach to identify temporally recurrent functional configuration patterns in neural responses to an n-back working memory task during fMRI. Working memory load was manipulated to investigate the functional relevance of the identified brain states. Four distinct brain states were defined by the predominant patterns of activation in the task-positive, default-mode, sensorimotor, and visual networks. Associated with escalating working memory …