Digital Commons Network^™

Cxcl17 Is A Specific Diagnostic Biomarker For Severe Pandemic Influenza A(H1n1) That Predicts Poor Clinical Outcome, Jose Alberto Choreño-Parra, Shabaana A Khader, Et Al

Open Access Publications

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The …

Response To Ibudilast Treatment According To Progressive Multiple Sclerosis Disease Phenotype, Andrew D Goodman, Janel K Fedler, Jon Yankey, Elizabeth A Klingner, Dixie J Ecklund, Christopher V Goebel, Robert A Bermel, Marianne Chase, Christopher S Coffey, Eric C Klawiter, Robert T Naismith, Robert J Fox, Sprint-Ms Investigators

Open Access Publications

OBJECTIVE: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis.

BACKGROUND: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown.

DESIGN/METHODS: SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for …

Rna-Seq Identifies Genes Whose Proteins Are Upregulated During Syncytia Development In Murine C2c12 Myoblasts And Human Bewo Trophoblasts, Christopher Azar, Mark C Valentine, Julie Trausch-Azar, Lisa Rois, Moe Mahjoub, D Michael Nelson, Alan L Schwartz

Open Access Publications

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development.

Immunological Findings And Clinical Outcomes Of Infants With Positive Newborn Screening For Severe Combined Immunodeficiency From A Tertiary Care Center In The U.S., Vasudha Mantravadi, Jeffrey J Bednarski, Michelle A Ritter, Hongjie Gu, Ana L Kolicheski, Caroline Horner, Megan A Cooper, Maleewan Kitcharoensakkul

Open Access Publications

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in

Antigen Presenting Cells Link The Female Genital Tract Microbiome To Mucosal Inflammation, With Hormonal Contraception As An Additional Modulator Of Inflammatory Signatures, Elizabeth H Byrne, Barry L Hykes, Scott A Handley, Et Al

Open Access Publications

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low

Targeting Host Glycolysis As A Strategy For Antimalarial Development, Andrew J Jezewski, Yu-Hsi Lin, Julie A Reisz, Rachel Culp-Hill, Yasaman Barekatain, Victoria C Yan, Angelo D'Alessandro, Florian L Muller, Audrey R Odom John

Open Access Publications

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather …

Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott

Open Access Publications

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

METHODS: MRE was collected at two imaging sites …

Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging For Coronavirus Disease 2019, Freimut D Juengling, Antonio Maldonado, Frank Wuest, Thomas H Schindler

Open Access Publications

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering

Comprehensive Assessment Of A Nationwide Simulation-Based Course For Artificial Life Support, Mateusz Puslecki, Ahmed S Said, Et Al

Open Access Publications

BACKGROUND: Successful implementation of medical technologies applied in life-threatening conditions, including extracorporeal membrane oxygenation (ECMO) requires appropriate preparation and training of medical personnel. The pandemic has accelerated the creation of new ECMO centers and has highlighted continuous training in adapting to new pandemic standards. To reach high standards of patients' care, we created the first of its kind, National Education Centre for Artificial Life Support (NEC-ALS) in 40 million inhabitants' country in the Central and Eastern Europe (CEE). The role of the Center is to test and promote the novel or commonly used procedures as well as to develop staff …

Mortality In Hemodialysis Patients With Covid-19, The Effect Of Paricalcitol Or Calcimimetics, María Dolores Arenas Jimenez, Adriana S Dusso, Et Al

Open Access Publications

BACKGROUND: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. …

Sequence- And Structure-Specific Cytosine-5 Mrna Methylation By Nsun6, Tommaso Selmi, Shobbir Hussain, Sabine Dietmann, Matthias Heiß, Kayla Borland, Sophia Flad, Jean-Michel Carter, Rebecca Dennison, Ya-Lin Huang, Stefanie Kellner, Susanne Bornelöv, Michaela Frye

Open Access Publications

The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3'UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation …

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …

Joseph Smith’S Translation: The Words And Worlds Of Early Mormonism, Samuel Morris Brown, Kent P. Jackson, Reviewer

BYU Studies

Samuel Morris Brown’s Joseph Smith’s Translation: The Words and Worlds of Early Mormonism announces a sweeping objective: to place all of Joseph Smith’s prophetic projects under a single heading: translation. The thesis of the book is that “translation as a source of scriptural texts” is mirrored in “translation as a process by which humans became assimilable to the divine presence” (ix). “Translation was about more than words and sentences. Translation was also concerned with the transformation of human beings and the worlds they were capable of inhabiting. These twin senses of translation run together in early Latter-day Saint thought” (4).

Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brain's structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for …

Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al

Open Access Publications

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing …

Validity Of A Four-Item Household Water Insecurity Experiences Scale For Assessing Water Issues Related To Health And Well-Being, Sera L. Young, Joshua D. Miller, Edward A. Frongillo Jr., Godfred O. Boateng, Zeina Jamaluddine, Torsten B. Neilands

Faculty Publications

We sought to determine whether a shortened version of the 12-item Household Water Insecurity Experiences (HWISE) Scale, which measures water insecurity equivalently in low- and middle-income countries (LMICs), is valid for broad use. Using data from 9,261 households in 25 LMICs, subsets of candidate items were evaluated on their predictive accuracy, criterion validity, and sensitivity-specificity. A subset with items assessing "worry," "changing plans," "limited drinking water," and "inability to wash hands" because of problems with water (range: 0-12) were highly correlated with full HWISE Scale scores (correlation coefficient: 0.949-0.980) and introduced minimal additional error (root mean square error: 2.13-2.68). Criterion …

Effective Dose Of Intravenous Oxycodone Depending On Sex And Age For Attenuation Ofintubation-Related Hemodynamic Responses, Keum Young So, Ki Tae Jung, Bo Hyun Jang, Sang Hun Kim

Turkish Journal of Medical Sciences

Background/aim: Preoperative intravenous oxycodone may help to prevent or attenuate intubation-related hemodynamic responses (IRHRs), but its pharmacokinetics differs according to age and sex. Therefore, we investigated the 95% effective dose (ED95) of intravenous oxycodone for attenuating all IRHRs, depending on the age and sex of the study population. Materials and methods: All patients were allocated to one of 6 groups: 1) 20-40 year old males, 2) 41-65yearold males, 3) 66-80 year old males, 4) 20-40 year old females, 5) 41-65yearold females, and 6) 66-80 year old females (groups YM, OM, EM, YF, OF, and EF, respectively). Using Dixon's up-and-down method, …

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Patient-Derived Induced Pluripotent Stem Cell Models For Phenotypic Screening In The Neuronal Ceroid Lipofuscinoses, Ahmed Morsy, Angelica V. Carmona, Paul C. Trippier

Journal Articles: Pharmaceutical Sciences

Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare, fatal, inherited neurodegenerative lysosomal storage disorders. Numerous genes (CLN1-CLN8, CLN10-CLN14) were identified in which mutations can lead to NCL; however, the underlying pathophysiology remains elusive. Despite this, the NCLs share some of the same features and symptoms but vary in respect to severity and onset of symptoms by age. Some common symptoms include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and in the rare adult-onset, dementia. Currently, all forms of NCL are fatal, and no curative treatments are available. Induced pluripotent stem …

Science Dialogue Mapping Of Knowledge And Knowledge Gaps Related To The Effects Of Dairy Intake On Human Cardiovascular Health And Disease, Andrew W Brown, Kathryn A Kaiser, Andrew Keitt, Kevin Fontaine, Madeline Gibson, Barbara A Gower, James M Shikany, Colby J Vorland, Donald C Beitz, Dennis M Bier, J Thomas Brenna, David R Jacobs, Penny Kris-Etherton, Kevin Maki, Michael Miller, Marie-Pierre St-Onge, Margarita Teran-Garcia, David B Allison

Children’s Nutrition Research Center Staff Publications

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products, 1) should be …

Wearable Activity Tracking Device Use In An Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial, Kanika Bowen-Jallow, Omar Nunez-Lopez, Alex Wright, Erika Fuchs, Mollie Ahn, Elizabeth Lyons, Daniel Jupiter, Lindsey Berry, Oscar Suman, Ravi S Radhakrishnan, Andrea M Glaser, Deborah I Thompson

Children’s Nutrition Research Center Staff Publications

Background: The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity.

Methods: Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, …

Gut Microbiota Profiles Of Young South Indian Children: Child Sex-Specific Relations With Growth, Nirupama Shivakumar, Ambily Sivadas, Sarita Devi, Farook Jahoor, John Mclaughlin, Craig P Smith, Anura V Kurpad, Arpita Mukhopadhyay

Children’s Nutrition Research Center Staff Publications

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with …

A Standardized Protocol For The Comprehensive Assessment Of Dental Hygiene Work, Shawn C Roll, Mark E Hardison, Jane L Forrest, Nikki L Colclazier, Joyce Y Sumi, Nancy A Baker

Pediatrics Research and Scholarship

BACKGROUND: Work-related musculoskeletal disorders are prevalent in dental hygienists. Although engineering controls and ergonomic training is available, it is unclear why this intransigent problem continues. One possible barrier is that a comprehensive, standardized protocol for evaluating dental hygiene work does not exist.

OBJECTIVE: This study aimed to generate a valid and reliable observational protocol for the assessment of dental hygiene work.

METHODS: An iterative process was used to establish and refine an ecologically valid video acquisition and observation protocol to assess key activities, tasks, and performance components of dental hygiene work.

RESULTS: Good inter-rater reliability was achieved across all variables …

Is Left-Behind A Real Reason For Children's Social Cognition Deficit? An Fnirs Study On The Effect Of Social Interaction On Left-Behind Preschooler's Prefrontal Activation, Keya Ding, Chuanjiang Li, Huibin Jia, Mingming Zhang, Dongchuan Yu

Open Access Publications

The left-behind phenomenon, caused by parent out-migration, has become a common social issue and might lead to long-term and potential risks for children in rural areas of China. It is important to investigate the effect of social interaction on prefrontal activation of left-behind children in China because of possible effects of parent out-migration on children's social cognition. We recruited 81 rural Chinese preschoolers aged 52-76 months (mean = 64.98 ± 6.321 months) preschoolers with three different statuses of parental out-migration (including non-, partially, and completely left-behind children). Using functional Near-Infrared Spectroscopy (fNIRS), we compared behavior and brain activation and in …

Clinical Prediction Rule For Sars-Cov-2 Infection From 116 U.S. Emergency Departments 2-22-2021, Jeffrey A. Kline, Stacey House, Et Al.

Open Access Publications

OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.

METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records …

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …

A Voxel-Wise Assessment Of Growth Differences In Infants Developing Autism Spectrum Disorder, A Cárdenas-De-La-Parra, J D Lewis, V S Fonov, K N Botteron, R C Mckinstry, G Gerig, J R Pruett Jr, S R Dager, J T Elison, M A Styner, A C Evans, J Piven, D L Collins, Ibis Network

Open Access Publications

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry …

Multi-Modal Biomarkers Of Low Back Pain: A Machine Learning Approach, Bidhan Lamichhane, Dinal Jayasekera, Rachel Jakes, Matthew F Glasser, Justin Zhang, Chunhui Yang, Derayvia Grimes, Tyler L Frank, Wilson Z Ray, Eric C Leuthardt, Ammar H Hawasli

Open Access Publications

Chronic low back pain (LBP) is a very common health problem worldwide and a major cause of disability. Yet, the lack of quantifiable metrics on which to base clinical decisions leads to imprecise treatments, unnecessary surgery and reduced patient outcomes. Although, the focus of LBP has largely focused on the spine, the literature demonstrates a robust reorganization of the human brain in the setting of LBP. Brain neuroimaging holds promise for the discovery of biomarkers that will improve the treatment of chronic LBP. In this study, we report on morphological changes in cerebral cortical thickness (CT) and resting-state functional connectivity …

Inhibitor Of Growth Protein 3 Epigenetically Silences Endogenous Retroviral Elements And Prevents Innate Immune Activation, Yanhua Song, Gaopeng Hou, Jonathan Diep, Yaw Shin Ooi, Natalia S. Akopyants, Stephen M. Beverley, Jan E. Carette, Harry B. Greenberg, Siyuan Ding

Open Access Publications

Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important …