Digital Commons Network^™

Active Dna Demethylation Upstream Of Rod-Photoreceptor Fate Determination Is Required For Retinal Development, Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G. Harding, Shiming Chen, Meelad M. Dawlaty, Philip A. Ruzycki, John R. Edwards, Brian S. Clark

2020-Current year OA Pubs

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, …

Left Atrial And Ventricular Remodeling In Chronic Mitral Regurgitation, Jack J Yi, Martha Mcgilvray, Tari-Ann Yates, Samantha Procasky, Jakraphan Yu, Caleb Berberet, Nicholas Banull, Jie Zheng, Jonathan K Zoller, Matthew R Schill, Christian Zemlin, Ralph J Damiano Jr

2020-Current year OA Pubs

OBJECTIVE: This study describes the structural and mechanical changes in the left atrium and left ventricle in a canine model of chronic mitral regurgitation in an attempt to identify markers linked to the onset of atrial tachyarrhythmias or left ventricle dysfunction.

METHODS: Animals underwent baseline and terminal echocardiography and cardiac magnetic resonance imaging. Under echocardiographic guidance, chordae tendinae were avulsed until there was severe mitral regurgitation, defined by regurgitant jet area to left atrium area more than 70%. At terminal surgery, rapid atrial pacing was performed to test inducibility of atrial tachyarrhythmias.

RESULTS: Twelve canines underwent mitral valve chordae avulsion …

Validation Of The Brugia Test Plus To Detect Igg4 Antibodies In Individuals From Belitung Timur, A Brugia Malayi Endemic Area In Indonesia, Taniawati Supali, Elisa Iskandar, Noviani Sugianto, Yenny Djuardi, Katherine Gass, Jean M. Saunders, Peter U. Fischer, Marco A. Biamonte

2020-Current year OA Pubs

The Brugia Test Plus (BT+) is a new rapid diagnostic test for Brugia species which detects human IgG4 antibodies specific for the immunogenic Brugia protein BmR1. The aim of this study was to evaluate the BT+ assay with several types of sample-matrices: whole blood, plasma, and dried blood spots (DBS) from individuals living in Belitung Timur, a Brugia malayi endemic area in Indonesia. Night blood was collected from residents living in four presumed endemic villages, while DBS were collected from schoolchildren living in those four villages. The sensitivity of BT+ was measured by comparing the BT+ results to microscopic examination …

Longer Scans Boost Prediction And Cut Costs In Brain-Wide Association Studies, Leon Qi Rong Ooi, Scott Marek, Nico U F Dosenbach, Timothy O Laumann, Evan M Gordon, Et Al.

2020-Current year OA Pubs

A pervasive dilemma in brain-wide association studies

Comparing Machine Learning Techniques For Neonatal Mortality Prediction: Insights From A Modeling Competition, Brynne A Sullivan, Alvaro G Moreira, Ryan M Mcadams, Lindsey A Knake, Ameena Husain, Jiaxing Qiu, Avinash Mudireddy, Abrar Majeedi, Wissam Shalish, Douglas E Lake, Zachary A Vesoulis

2020-Current year OA Pubs

BACKGROUND: Predicting mortality risk in neonatal intensive care units (NICUs) is challenging due to complex, variable clinical and physiological data. Machine learning (ML) offers potential for more accurate risk stratification.

OBJECTIVE: To compare the performance of various ML models in predicting NICU mortality using a team-based modeling competition.

METHODS: We conducted a modeling competition with five neonatologist-led teams applying ML techniques-logistic regression, CatBoost, neural networks, random forest, and XGBoost-to a shared dataset from over 6,000 NICU admissions. The dataset included static demographic and clinical variables, alongside daily samples of heart rate and oxygen saturation. Each team developed models to predict …

Muscle Biopsy Findings In Valosin-Containing Protein Multisystem Proteinopathy, Marianela Schiava, Manouela V. Valtcheva, Conrad Weihl, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Valosin Containing Protein-associated multisystem proteinopathy (VCP-MSP) is a progressive, autosomal dominant disorder caused by pathogenic variants in the VCP gene, resulting in a heterogeneous clinical presentation. Muscle biopsy findings are characteristic but not pathognomonic. This study aimed to comprehensively analyse VCP-related myopathology and explore correlations with clinical phenotypes, genetic variants, and disease progression.

METHODS: Muscle biopsy images and data were collected retrospectively from adults (≥18 years) with pathogenic or likely pathogenic VCP variants enrolled in the VCP Multicentre International Study. Biopsy data were standardized using the "Common Data Elements for Muscle Biopsy Reporting." Variations in biopsy findings …

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Autophagy Regulates Müller Glial Cell Inflammatory Activation, Teresa A Doggett, Zhenqing Zhou, Sohini Rebba, Jacqueline Unsinger, Philip A Ruzycki, Thomas A Ferguson

2020-Current year OA Pubs

PURPOSE: We tested whether Müller cells utilize autophagy to support immune privilege in the eye.

METHODS: The essential autophagy gene Atg5 was deleted in retinal Müller cells. Inflammation was induced by intravitreal injection of lipopolysaccharide (LPS) that was monitored by hematoxylin and eosin (H&E) staining, immunofluorescent confocal microscopy, and flow cytometry. Single-cell RNA sequencing was performed on retinal Müller cells isolated from control and Atg5-deficient mice. Markers of Müller cell gliosis were assessed, and cytokine production in the eye was measured. Small interfering RNA knockdown techniques were used to examine LPS-induced inflammatory pathways in culture.

RESULTS: We observed increased and …

Germline Genetic Variation Impacts Clonal Hematopoiesis Landscape And Progression To Malignancy, Jie Liu, Duc Tran, Brian J Wiley, Irenaeus C C Chan, Indraniel Das, Li Ding, Yin Cao, Matthew J Walter, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

With age, clonal expansions occur pervasively across normal tissues yet only in rare instances lead to cancer, despite being driven by well-established cancer drivers. Characterization of the factors that influence clonal progression is needed to inform interventional approaches. Germline genetic variation influences cancer risk and shapes tumor mutational profile, but its influence on the mutational landscape of normal tissues is not well known. Here we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 new CH-predisposition genes, most of which predispose to CH driven by specific mutational events. CH-predisposition genes contribute to …

Autism And Intellectual Disability Due To A Novel Gain-Of-Function Mutation In Ube3a, Anna M Gunelson, Kwang-Soo Kim, Connolly G Steigerwald, Devorah Segal, Nicolas J Abreu, Jason J Yi

2020-Current year OA Pubs

The loss of maternal UBE3A causes Angelman syndrome whereas its duplication is associated with a heterogeneous neurodevelopmental disorder. Here, we describe two affected brothers who possess a novel UBE3A

A Measurement Science Framework To Optimize Cds For Opioid Use Disorder Treatment In The Ed, Mark S. Iscoe, Carolina Diniz Hooper, Deborah R. Levy, John Lutz, Hyung Paek, Christian Rose, Thomas Kannampallil, Daniella Meeker, James D. Dziura, Edward R. Melnick

2020-Current year OA Pubs

In the emergency department-initiated buprenorphine for opioid use disorder (EMBED) trial, a clinical decision support (CDS) tool had no effect on rates of buprenorphine initiation in emergency department (ED) patients with opioid use disorder. The Agency for Healthcare Research and Quality (AHRQ) recently released a CDS Performance Measure Inventory to guide data-driven CDS development and evaluation. Through partner co-design, we tailored AHRQ inventory measures to evaluate EMBED CDS performance and drive improvements.Relevant AHRQ inventory measures were selected and adapted using a partner co-design approach grounded in consensus methodology, with three iterative, multidisciplinary partner working group sessions involving stakeholders from various …

Impact Of Transcatheter Aortic Valve Replacement Use Ratio On Outcomes In Patients With Aortic Valve Disease, Theodore Marghitu, Sophia H Roberts, June He, Nicholas Kouchoukos, Puja Kachroo, Harold Roberts, Ralph Damiano, Alan Zajarias, Marc Sintek, John Lasala, Alexander A Brescia, Tsuyoshi Kaneko

2020-Current year OA Pubs

OBJECTIVE: Use of the Heart Team has been the standard of care for the treatment of aortic valve disease; however, its efficacy has not been evaluated. We sought to analyze its impact using the transcatheter aortic valve replacement (TAVR) use ratio (number of TAVR/total aortic valve replacement [AVR] volume) on TAVR, surgical aortic valve replacement (SAVR), and overall AVR outcomes.

METHODS: We analyzed all TAVRs and SAVRs sampled by the National Readmissions Database between 2016 and 2020. Hospitals were stratified into quartiles on the basis of their TAVR/AVR ratio. Centers with a ratio below the first quartile were considered "low …

Inter-Organ Communication Is A Critical Machinery To Regulate Metabolism And Aging, Kyohei Tokizane, Shin-Ichiro Imai

2020-Current year OA Pubs

Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologies, implicating these processes as a potential target for therapeutic intervention to promote healthy aging. In this review, we delve into IOC mediated by hormonal signaling, circulating factors, organelle signaling, and neuronal networks and examine their roles in regulating metabolism and aging. Given the role of the hypothalamus as a high-order control center for aging and longevity, we particularly emphasize the importance of its communication with peripheral organs and pave the way …

Massively Parallel Immunopeptidome By Dna Sequencing Provides Insights Into Cancer Antigen Presentation, Quanming Shi, Cheryl F Lichti, Et Al.

2020-Current year OA Pubs

Human leukocyte antigens (HLAs) are encoded by the most polymorphic genes in the human genome. HLA class I alleles control antigen presentation for T cell recognition, which is pivotal for autoimmunity, infectious diseases and cancer. Current knowledge of HLA-bound peptides is limited, skewed and falls short of population-wide HLA binding profiles for high-value targets. Here we present ESCAPE-seq (enhanced single-chain antigen presentation sequencing), a massively parallel platform for comprehensive screening of class I HLA-peptide combinations for antigen presentation via deep DNA sequencing. ESCAPE-seq demonstrates programmability, high throughput, sensitivity and nominated viral and cancer epitopes. We simultaneously assessed over 75,000 peptide-HLA …

Screening Programmes And Breast Cancer Mortality: An Observational Study Of 194 Countries, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

OBJECTIVE: To investigate the associations between national breast cancer screening programmes and breast cancer mortality globally.

METHODS: We collected data on breast cancer screening programmes and breast cancer mortality from the World Health Organization's Global Health Observatory, the Global Burden of Diseases 2021 study and the Eurostat database. We assessed differences in breast cancer mortality between countries with regular and irregular screening programmes, adjusting for sociodemographic index. We calculated annual changes in breast cancer mortality from 2015 to 2021 and assessed differences in mortality changes between countries with regular and irregular screening programmes.

FINDINGS: Between 2015 and 2021, 94 of …

Formation Control Between Leader And Migratory Follower Tissues Allows Coordinated Growth, Toru Kawanishi, Takamichi Sushida, Tony Y-C Tsai, Hiroyuki Takeda, Sean G Megason

2020-Current year OA Pubs

Coordinated growth of multiple tissues is fundamental to shaping our body, but the underlying mechanisms remain underexplored. In zebrafish embryos, midline tissues composed of the notochord, floorplate, and hypochord elongate synchronously with their lengths aligned. We show that floorplate and hypochord cells collectively migrate posteriorly along the nascent notochord extracellular matrix as it extends posteriorly, maintaining the tripartite configuration. Fibroblast growth factor-mediated migration in a spatially graded manner causes cell stretching, which triggers Yap-dependent proliferation and controls floorplate and hypochord growth. Supported by mathematical modeling, we further suggest that their growth is fine-tuned by mechanical tethering to the notochord via …

Real-World Outcomes And Management Considerations Following Surgical Aortic Valve Replacement With The Trifecta Valve, Dan Gutfinger, Ibrahim Sultan, Gorav Ailawadi, Danny Ramzy, Tsuyoshi Kaneko, Yang Yu, Geetanjali Meka, Julie B Prillinger, Joseph E Bavaria

2020-Current year OA Pubs

BACKGROUND: Bioprosthetic surgical aortic valve replacement (SAVR) using the Trifecta valve was frequently chosen because of its large opening area and low transvalvular gradient. However, long-term follow-up revealed the potential for early structural valve deterioration. To further assess the long-term clinical outcomes and management considerations for patients implanted with the Trifecta valve, a real-world study using Medicare fee-for-service claims data was conducted with a focus on Trifecta valve reintervention.

METHODS: De-identified patients undergoing SAVR with the Trifecta™ valve (Abbott) in the U.S. between 1/1/2011-12/31/2021 were selected by ICD-9/10 procedure codes and then linked to a manufacturer device tracking database. All-cause …

Implementation Outcomes Of A Patient Decision-Aid In A Diverse Population With Systemic Lupus Erythematosus In 15 Us Rheumatology Clinics, Jasvinder A Singh, Seth Eisen, Alfred Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus.

METHODS: We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical …

Shared And Disease-Specific Pathways In Frontotemporal Dementia And Alzheimer's And Parkinson's Diseases, Muhammad Ali, Yike Chen, Ying Xu, Katherine Gong, Menghan Liu, Jigyasha Timsina, Daniel Western, Chengran Yang, Gyujin Heo, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementia (FTD), exhibit distinct yet overlapping pathological mechanisms. Leveraging large-scale plasma proteomics data from the Global Neurodegeneration Proteomics Consortium, we analyzed 10,527 plasma samples (1,936 AD, 525 PD, 163 FTD, 1,638 dementia and 6,265 controls) to identify disease-specific and shared proteins across NDs. We identified 5,187 proteins significantly associated with AD, 3,748 with PD and 2,380 with FTD that revealed both common and divergent proteomic signatures, which were confirmed by multiple analytical approaches and orthogonal validation. PD and FTD showed the highest overlap (r

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Muhammad Ali, Carlos Cruchaga, Chengran Yang, Et Al.

2020-Current year OA Pubs

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Integrative Genomic Reconstruction Reveals Heterogeneity In Carbohydrate Utilization Across Human Gut Bifidobacteria, Aleksandr A Arzamasov, Dmitry A Rodionov, Matthew C Hibberd, Janaki L Guruge, James E Kent, Marat D Kazanov, Semen A Leyn, Marinela L Elane, Kristija Sejane, Annalee Furst, Lars Bode, Michael J Barratt, Jeffrey I Gordon, Andrei L Osterman

2020-Current year OA Pubs

Bifidobacteria are beneficial saccharolytic microbes that are widely used as probiotics or in synbiotic formulations, yet individual responses to supplementation can vary with strain type, microbiota composition, diet and lifestyle, underscoring the need for strain-level insights into glycan metabolism. Here we reconstructed 68 pathways for the utilization of mono-, di-, oligo- and polysaccharides by analysing the distribution of 589 curated metabolic gene functions (catabolic enzymes, transporters and transcriptional regulators) across 3,083 non-redundant Bifidobacterium genomes of human origin. Thirty-eight predicted phenotypes were validated in vitro for 30 geographically diverse strains, supporting genomics-based predictions. Our analysis uncovered extensive inter- and intraspecies functional …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R. Cox, Rabie Habib, Michael J. Bolt, Jessica B. Felix, Claudia E. Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M. Hartig

2020-Current year OA Pubs

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Impact Of Hereditary Angioedema Attacks On Health-Related Quality Of Life And Work Productivity, Maeve O'Connor, Paula J Busse, Timothy J Craig, Cristine Radojicic, H James Wedner, Sherry Danese, Julie Ulloa, Vibha Desai, Tomas Andriotti, Paul K Audhya, Sandra Christiansen

2020-Current year OA Pubs

BACKGROUND: Hereditary angioedema (HAE) negatively impacts health-related quality of life (HRQoL). Few studies have characterized impairments to HRQoL, work productivity, and well-being during and following HAE attacks.

METHODS: Patients with ≥1 HAE attack in the previous 3 months were recruited by the United States (US) HAE Association (HAEA) to complete an online survey. Respondents were categorized into those who did (Treated Cohort) and did not (Untreated Cohort) manage their last attack with on-demand treatment (OD). Adapted versions of the EuroQol-Five Dimensions-Five Levels (EQ-5D-5L), EuroQol Visual Analogue Scale (EQ VAS), and Work Productivity and Activity Impairment-General Health assessments were used.

RESULTS: …

Advanced Quantification Pipeline Reveals New Spatial And Temporal Tumor Characteristics In Preclinical Multiple Myeloma, Zhixin Sun, Jacqueline M Godbe, Alexander Zheleznyak, Brad Manion, Junhao Hu, Julie L Prior, Kathleen Duncan, Ulugbek S Kamilov, Monica Shokeen

2020-Current year OA Pubs

BACKGROUND: Radiological imaging plays an indispensable role in both preclinical and clinical studies of multiple myeloma (MM). However, manual quantification in longitudinal small animal PET/CT is limited by annotator bias, signal artifacts from urinary/fecal excretion, and voxel misalignment due to non-rigid registration. To address these challenges and improve characterization of tumor biology, we developed a semi-automated PET/CT quantification pipeline targeting defined regions of interest (ROIs) within the bone marrow-rich mouse skeleton, achieving sub-organ spatial resolution, including in anatomically complex sites such as the pelvis. We applied this MM-specific preclinical pipeline to analyze tumor distribution in a longitudinal molecular PET study …

Musical Distractions: Music-Based Rhythmic Auditory Stimulation Fails To Improve Gait In Huntington's Disease, Sidney T Baudendistel, Lauren E Tueth, Allison M Haussler, Gammon M Earhart

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Huntington's disease (HD) is a neurodegenerative disorder involving the basal ganglia and is characterized by psychiatric, cognitive, and movement dysfunction, including gait and balance impairment. Given the limited efficacy of pharmacological treatments for HD motor symptoms, nonpharmacological approaches like rhythmic auditory stimulation are being explored. This study aims to describe walking performance in people with HD during rhythmic auditory stimulation using external musical cues and internal singing cues.

METHODS: Individuals in the manifest stage of HD performed walking in four conditions: (1) comfortable pace, (2) cognitive dual task, (3) musical cue (music was played aloud), and (4) singing cue …

Efficacy And Safety Of Dapagliflozin In Patients Hospitalized With Covid-19 With And Without Type 2 Diabetes: A Prespecified Analysis Of The Dare-19 Randomized Trial, Mohammad Abdel Jawad, Ali Javaheri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although several previous studies tested SGLT2 inhibitors in the setting of an acute, non-cardiovascular illness, detailed information on their efficacy and safety among participants with and without type 2 diabetes (T2D) from double-blind randomized trials is lacking. In this secondary prespecified analysis of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial, we sought to evaluate the safety and efficacy of initiating dapagliflozin during acute illness with COVID-19 in patients with and without T2D.

METHODS: The DARE-19 trial randomized 1250 patients hospitalized with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. T2D was present in 636/1250 …

Effects Of The Gut Microbiota On Placental Angiogenesis And Intrauterine Growth In Gnotobiotic Mice, Reyan Coskun, Zenan L Chang, Athziri Marcial Rodríguez, Haoxin Liu, Jiye Cheng, Yael Alippe, Michael S Diamond, Jeffrey I Gordon

2020-Current year OA Pubs

Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.5 (near term). Pregnancy- and microbiota-associated changes in gene expression occur along the gut, including those related to angiogenesis, while bacterial composition and fermentation activity remain stable. Placental weights at E11.5 and fetal weights at E17.5 are significantly reduced in GF animals. Compared to CONV-R dams, the GF maternal decidua exhibits similar vascular histomorphometric features at E11.5 and E17.5, and numbers …

Cd206+Il-4rα+ Macrophages Are Drivers Of Adverse Cardiac Remodeling In Ischemic Cardiomyopathy, Qiongxin Wang, Mohamed Ameen Ismahil, Yujie Zhu, Gregg Rokosh, Tariq Hamid, Guihua Zhou, Steven M. Pogwizd, Sumanth D. Prabhu

2020-Current year OA Pubs

BACKGROUND: The role of cardiac CD (cluster of differentiation) 206

METHODS: Adult C57BL/6 mice underwent nonreperfused myocardial infarction to induce HF. Macrophages in murine and human hearts were profiled using flow cytometry and immunostaining. In vivo myeloid-specific IL-4Rα deletion and intramyocardial macrophage adoptive transfer defined the functional effects of macrophages polarized by IL-4 (M[IL-4]). Antisense oligonucleotides were used for in vivo IL-4Rα gene silencing in mice.

RESULTS: CD206

CONCLUSIONS: Cardiac CD206

The 18s Rrna Methyltransferase Dimt-1 Regulates Lifespan In The Germline Later In Life, M Hafiz Rothi, Gautam Chandra Sarkar, Joseph Al Haddad, Wayne Mitchell, Kejun Ying, Nancy Pohl, Roberto G Sotomayor-Mena, Julia Natale, Scarlett Dellacona, Vadim N Gladyshev, Eric Lieberman Greer

2020-Current year OA Pubs

Specialized ribosomes help determine which proteins are synthesized, however, the influence of age on ribosome heterogeneity and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified 18S rRNA N6'-dimethyl adenosine (m

The Biophysical Basis For Karyopherin-Dependent Ebola Virus Vp24 Nuclear Transport, Junjie Zhao, Bojie Zhang, Olivia Vogel, Benjamin W Walker, Leonard W Ma, Nicole D Wagner, Christopher F Basler, Daisy W Leung, Michael L Gross, Gaya K Amarasinghe

2020-Current year OA Pubs

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription. However, the molecular interactions of eVP24-KPNA5 binding that lead to the nuclear localization of eVP24 remain poorly characterized. Here, we show that trafficking of eVP24 …