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Abrogation Of Esophageal Carcinoma Development In Mir-31 Knockout Rats., Louise Y Fong, Cristian Taccioli, Alexey Palamarchuk, Guidantonio Malagoli Tagliazucchi, Ruiyan Jing, Karl J Smalley, Sili Fan, Joseph Altemus, Oliver Fiehn, Kay Huebner, John L Farber, Carlo M Croce 2020 Thomas Jefferson University

Abrogation Of Esophageal Carcinoma Development In Mir-31 Knockout Rats., Louise Y Fong, Cristian Taccioli, Alexey Palamarchuk, Guidantonio Malagoli Tagliazucchi, Ruiyan Jing, Karl J Smalley, Sili Fan, Joseph Altemus, Oliver Fiehn, Kay Huebner, John L Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% (P = 0.038) and miR-31 gene knockout abrogated development of ESCC (P = 1 × 10-6). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear factor κB (NF-κB), as ...


A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos 2020 National Center for Scientific Research Demokritos

A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos

Open Access Articles

Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination ...


Comparison Of Pre- And Post-Operative Shoulder Muscle Emg Profiles In Reverse Total Shoulder Arthroplasty Patients, Emily Lau, Sreten Franovic, Noah Kuhlmann, Eric C. Makhni MD, Stephanie Muh MD 2020 Henry Ford Health System

Comparison Of Pre- And Post-Operative Shoulder Muscle Emg Profiles In Reverse Total Shoulder Arthroplasty Patients, Emily Lau, Sreten Franovic, Noah Kuhlmann, Eric C. Makhni Md, Stephanie Muh Md

Medical Student Research Symposium

Background: Deltoid muscle function is central in reverse total shoulder arthroplasty (RTSA) function; however, there is limited information available regarding changes in deltoid activity before and after surgery. Few tests exist to evaluate specific muscle metrics pre and post operatively. Surface Electromyographic (EMG) is non-invasive and allows for observation of motions with multifaceted analysis of movement with minimal patient demand. Understanding the changes in shoulder muscle activation, namely in the deltoid, in patients pre and post-RTSA can further advance understanding of the procedure and rehabilitation efforts.

Methods: Nine individuals were recruited for this study: all patients underwent RTSA by a ...


Application Of Laser Technology In The Non-Surgical Management Of Periprosthetic Joint Infection (Pji); Novel Insights From Peri-Implantitis, Kareem Giovanni Elhage, Mohamed Awad, Ahmad Hasan, Brendan Farley, Khaled Saleh 2020 Wayne State University

Application Of Laser Technology In The Non-Surgical Management Of Periprosthetic Joint Infection (Pji); Novel Insights From Peri-Implantitis, Kareem Giovanni Elhage, Mohamed Awad, Ahmad Hasan, Brendan Farley, Khaled Saleh

Medical Student Research Symposium

Introduction: The management of periprosthetic joint infection (PJI) is challenging, and its socio-economic impact is significant. Moreover, the incidence of MRSA and other resistant organisms are on the rise. Recently, laser technology has been incorporated into treatment protocols of dental peri-implantitis. This review explores the possibility of using laser technology to manage peri-implantitis.

Methods: This article will provide a detailed, comprehensive, and perspective review of the existing evidence of laser technology in management of dental peri-implantitis.

Results: Dental literature investigated the efficacy of several types of lasers. It was shown that diode lasers improved periodontal probing depth (PPD) and bleeding ...


Premature Termination Codon Readthrough Upregulates Progranulin Expression And Improves Lysosomal Function In Preclinical Models Of Grn Deficiency, Jonathan Frew, Fen-Biao Gao, Haakon B. Nygaard 2020 University of British Columbia

Premature Termination Codon Readthrough Upregulates Progranulin Expression And Improves Lysosomal Function In Preclinical Models Of Grn Deficiency, Jonathan Frew, Fen-Biao Gao, Haakon B. Nygaard

Open Access Articles

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the progranulin gene (GRN) is an important cause of FTLD (FTLD-GRN), and nearly a quarter of these genetic cases are due to a nonsense mutation. Premature termination codons (PTC) can be therapeutically targeted by compounds allowing readthrough, and aminoglycoside antibiotics are known to be potent PTC readthrough drugs. Restoring endogenous PGRN through PTC readthrough has not previously been explored as a therapeutic intervention in FTLD.

METHODS: We studied whether the aminoglycoside G418 ...


Flexibility And Constraint In Preimplantation Gene Regulation In Mouse, Colin C. Conine, Marina Krykbaeva, Lina Song, Robert C. Brewster, Nir Friedman, Oliver J. Rando 2020 University of Massachusetts Medical School

Flexibility And Constraint In Preimplantation Gene Regulation In Mouse, Colin C. Conine, Marina Krykbaeva, Lina Song, Robert C. Brewster, Nir Friedman, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

Although many features of embryonic development exhibit remarkable stability in the face of environmental perturbations, it is also clear that some aspects of early embryogenesis can be modulated by non-genetic influences during and after fertilization. Among potential perturbations experienced during reproduction, understanding the consequences of differing ex vivo fertilization methods at a molecular level is imperative for comprehending both the basic biology of early development and the potential consequences of assisted reproduction. Here, we set out to explore stable and flexible aspects of preimplantation gene expression using single-embryo RNA-sequencing of mouse embryos fertilized by natural mating, in vitro fertilization, or ...


Jc Virus Infected Choroid Plexus Epithelial Cells Produce Extracellular Vesicles That Infect Glial Cells Independently Of The Virus Attachment Receptor, Bethany A. O'Hara, Jenna Morris-Love, Gretchen V. Gee, Sheila A. Haley, Walter J. Atwood 2020 Brown University

Jc Virus Infected Choroid Plexus Epithelial Cells Produce Extracellular Vesicles That Infect Glial Cells Independently Of The Virus Attachment Receptor, Bethany A. O'Hara, Jenna Morris-Love, Gretchen V. Gee, Sheila A. Haley, Walter J. Atwood

Open Access Articles

The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV is common and the virus establishes a long-term persistent infection in the urogenital system of 50-70% of the human population worldwide. A major gap in the field is that we do not know how the virus traffics from the periphery to the brain to cause disease. Our recent discovery that human choroid plexus epithelial cells are fully susceptible to virus infection together with reports of JCPyV infection of choroid plexus in vivo has led us to hypothesize that ...


Does Dna Methylation Matter In Fshd, Valentina Salsi, Frederique Magdinier, Rossella Ginevra Tupler 2020 University of Modena and Reggio Emilia

Does Dna Methylation Matter In Fshd, Valentina Salsi, Frederique Magdinier, Rossella Ginevra Tupler

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest that in the case of FSHD1, D4Z4 ...


Cell Cycle-Associated Expression Patterns Predict Gene Function In Mycobacteria, Aditya Bandekar, Sishir Subedi, Thomas Ioerger, Christopher M. Sassetti 2020 University of Massachusetts Medical School

Cell Cycle-Associated Expression Patterns Predict Gene Function In Mycobacteria, Aditya Bandekar, Sishir Subedi, Thomas Ioerger, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

While the major events in prokaryotic cell cycle progression are likely to be coordinated with transcriptional and metabolic changes, these processes remain poorly characterized. Unlike many rapidly-growing bacteria, DNA replication and cell division are temporally-resolved in mycobacteria, making these slow-growing organisms a potentially useful system to investigate the prokaryotic cell cycle. To determine if cell-cycle dependent gene regulation occurs in mycobacteria, we characterized the temporal changes in the transcriptome of synchronously replicating populations of Mycobacterium tuberculosis (Mtb). By enriching for genes that display a sinusoidal expression pattern, we discover 485 genes that oscillate with a period consistent with the cell ...


Dipeptide Repeat Proteins Inhibit Homology-Directed Dna Double Strand Break Repair In C9orf72 Als/Ftd, Nadja S. Andrade, Abbas Abdallah, Christian Mueller, Zane Zeier 2020 University of Miami

Dipeptide Repeat Proteins Inhibit Homology-Directed Dna Double Strand Break Repair In C9orf72 Als/Ftd, Nadja S. Andrade, Abbas Abdallah, Christian Mueller, Zane Zeier

Open Access Articles

BACKGROUND: The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. The C9ORF72 expansion encodes five dipeptide repeat proteins (DPRs) that are produced through a non-canonical translation mechanism. Among the DPRs, proline-arginine (PR), glycine-arginine (GR), and glycine-alanine (GA) are the most neurotoxic and increase the frequency of DNA double strand breaks (DSBs). While the accumulation of these genotoxic lesions is increasingly recognized as a feature of disease, the mechanism(s) of DPR-mediated DNA damage are ill-defined and the effect of DPRs on the efficiency ...


Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy MacLatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange 2020 University of Westminster

Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy Maclatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange

Open Access Articles

Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 ...


Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet 2020 California State University, San Bernardino

Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet

Q2S Enhancing Pedagogy

The syllabus has newly developed learning objectives that will prepare students entering the field of clinical exercise physiology. This course will cover the etiology and pathophysiology of many chronic diseases that plague the population. Assessments of chronic diseases include but are not limited to understanding symptomology will also be covered. Due to the limitations in time the most prevalent chronic disease will be covered and students will have to present on a disease that was not presented in class. The practical application portion of this course will take place during a lab section. Here students will have the opportunity to ...


Stride-A Fluorescence Method For Direct, Specific In Situ Detection Of Individual Single- Or Double-Strand Dna Breaks In Fixed Cells, Magdalena M. Kordon, Miroslaw Zarebski, Kamil Solarczyk, Hanhui Ma, Thoru Pederson, Jurek W. Dobrucki 2020 Jagiellonian University

Stride-A Fluorescence Method For Direct, Specific In Situ Detection Of Individual Single- Or Double-Strand Dna Breaks In Fixed Cells, Magdalena M. Kordon, Miroslaw Zarebski, Kamil Solarczyk, Hanhui Ma, Thoru Pederson, Jurek W. Dobrucki

Open Access Articles

We here describe a technique termed STRIDE (SensiTive Recognition of Individual DNA Ends), which enables highly sensitive, specific, direct in situ detection of single- or double-strand DNA breaks (sSTRIDE or dSTRIDE), in nuclei of single cells, using fluorescence microscopy. The sensitivity of STRIDE was tested using a specially developed CRISPR/Cas9 DNA damage induction system, capable of inducing small clusters or individual single- or double-strand breaks. STRIDE exhibits significantly higher sensitivity and specificity of detection of DNA breaks than the commonly used terminal deoxynucleotidyl transferase dUTP nick-end labeling assay or methods based on monitoring of recruitment of repair proteins or ...


Optimal Multi-Stage Arrhythmia Classification Approach, Jianwei Zhang, Huimin Chu, Daniele Struppa, Jianming Zhang, Sir Magdi Yacoub, Hesham el-Askary, Anthony Chang, Louis Ehwerhemuepha, Islam Abudayyeh, Alexander Barrett, Guohua Fu, Hai Yao, Dongbo Li, Hangyuan Guo, Cyril Rakovski 2020 Chapman University

Optimal Multi-Stage Arrhythmia Classification Approach, Jianwei Zhang, Huimin Chu, Daniele Struppa, Jianming Zhang, Sir Magdi Yacoub, Hesham El-Askary, Anthony Chang, Louis Ehwerhemuepha, Islam Abudayyeh, Alexander Barrett, Guohua Fu, Hai Yao, Dongbo Li, Hangyuan Guo, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Arrhythmia constitutes a problem with the rate or rhythm of the heartbeat, and an early diagnosis is essential for the timely inception of successful treatment. We have jointly optimized the entire multi-stage arrhythmia classification scheme based on 12-lead surface ECGs that attains the accuracy performance level of professional cardiologists. The new approach is comprised of a three-step noise reduction stage, a novel feature extraction method and an optimal classification model with finely tuned hyperparameters. We carried out an exhaustive study comparing thousands of competing classification algorithms that were trained on our proprietary, large and expertly labeled dataset consisting of 12-lead ...


Validity Of The Body Scan Scanner® And Structure Sensor To Measure Limb Volume In Healthy Adults, Mary Insana Fisher, Michaela Claire Viola, Noah James Brueckner, Madison Elizabeth Wolfe, Rachel Lynn Kremer 2020 University of Dayton

Validity Of The Body Scan Scanner® And Structure Sensor To Measure Limb Volume In Healthy Adults, Mary Insana Fisher, Michaela Claire Viola, Noah James Brueckner, Madison Elizabeth Wolfe, Rachel Lynn Kremer

Physical Therapy Faculty Publications

Purpose/Hypothesis: Secondary lymphedema is a chronic condition that can develop in approximately 30 percent of women treated for breast cancer. It is important to measure limb volume changes for early detection of lymphedema, when it is possible to reverse the swelling (stage 1). Common clinical measures carry concerns of infection control (water displacement), are time consuming (truncated cone calculation using circumferential measures), or expensive (perometry). Use of a portable 3D scanner addresses these concerns, but the validity is unknown. The purpose of this phase I study is to investigate the validity of the Body Scan Scanner to measure limb ...


Cytosine Methylation Dynamics During Post-Testicular Sperm Maturation In Mammals, Carolina Galan, Ryan W. Serra, Fengyun Sun, Vera Rinaldi, Colin C. Conine, Oliver J. Rando 2020 University of Massachusetts Medical School

Cytosine Methylation Dynamics During Post-Testicular Sperm Maturation In Mammals, Carolina Galan, Ryan W. Serra, Fengyun Sun, Vera Rinaldi, Colin C. Conine, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

Beyond the haploid genome, mammalian sperm contribute a payload of epigenetic information which can modulate offspring phenotypes. Recent studies have shown that the small RNA payload of sperm undergoes extensive remodeling during post-testicular maturation in the epididymis. Intriguingly, epididymal maturation has also been linked to changes in the sperm methylome, suggesting that the epididymis might play a broader role in remodeling the sperm epigenome. Here, we build on prior studies of the maturing sperm methylation landscape, further characterizing the genome-wide methylation landscape in seven germ cell populations collected from throughout the male reproductive tract. Overall, we find very few changes ...


Ncapg Dynamically Coordinates The Myogenesis Of Fetal Bovine Tissue By Adjusting Chromatin Accessibility, Xin Hu, Yishen Xing, Xing Fu, Qiyuan Yang, Ling Ren, Yahui Wang, Qian Li, Junya Li, Lupei Zhang 2020 University of Liège

Ncapg Dynamically Coordinates The Myogenesis Of Fetal Bovine Tissue By Adjusting Chromatin Accessibility, Xin Hu, Yishen Xing, Xing Fu, Qiyuan Yang, Ling Ren, Yahui Wang, Qian Li, Junya Li, Lupei Zhang

Open Access Articles

NCAPG is a subunit of condensin I that plays a crucial role in chromatin condensation during mitosis. NCAPG has been demonstrated to be associated with farm animal growth traits. However, its role in regulating myoblast differentiation is still unclear. We used myoblasts derived from fetal bovine tissue as an in vitro model and found that NCAPG was expressed during myogenic differentiation in the cytoplasm and nucleus. Silencing NCAPG prolonged the mitosis and impaired the differentiation due to increased myoblast apoptosis. After 1.5 days of differentiation, silencing NCAPG enhanced muscle-specific gene expression. An assay for transposase-accessible chromatin- high throughput sequencing ...


A 12-Lead Electrocardiogram Database For Arrhythmia Research Covering More Than 10,000 Patients, Jianwei Zhang, Jianming Zhang, Sidy Daniako, Hai Yao, Hangyuan Guo, Cyril Rakovski 2020 Chapman University

A 12-Lead Electrocardiogram Database For Arrhythmia Research Covering More Than 10,000 Patients, Jianwei Zhang, Jianming Zhang, Sidy Daniako, Hai Yao, Hangyuan Guo, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

This newly inaugurated research database for 12-lead electrocardiogram signals was created under the auspices of Chapman University and Shaoxing People’s Hospital (Shaoxing Hospital Zhejiang University School of Medicine) and aims to enable the scientific community in conducting new studies on arrhythmia and other cardiovascular conditions. Certain types of arrhythmias, such as atrial fibrillation, have a pronounced negative impact on public health, quality of life, and medical expenditures. As a non-invasive test, long term ECG monitoring is a major and vital diagnostic tool for detecting these conditions. This practice, however, generates large amounts of data, the analysis of which requires ...


Regulation Of Adipose Tissue Inflammation By Interleukin 6, Myoung Souk Han, Alexis White, Rachel J. Perry, Joao-Paulo Camporez, Juan Hidalgo, Gerald I. Shulman, Roger J. Davis 2020 University of Massachusetts Medical School

Regulation Of Adipose Tissue Inflammation By Interleukin 6, Myoung Souk Han, Alexis White, Rachel J. Perry, Joao-Paulo Camporez, Juan Hidalgo, Gerald I. Shulman, Roger J. Davis

Open Access Articles

Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These ...


Steps-T Program Improves Endovascular Treatment Outcomes Of Acute Ischemic Stroke; A 6-Year Study, Ameer E. Hassan, Rani R. Rabah, Laurie Preston, Wondwossen G. Tekle 2020 The University of Texas Rio Grande Valley

Steps-T Program Improves Endovascular Treatment Outcomes Of Acute Ischemic Stroke; A 6-Year Study, Ameer E. Hassan, Rani R. Rabah, Laurie Preston, Wondwossen G. Tekle

School of Medicine Publications and Presentations

Background: Early endovascular recanalization of occluded vessels in acute ischemic stroke (AIS) is a major contributor to good clinical outcome. We report the analysis of all AIS patients throughout a 6-year experience following the deployment of a quality initiative aiming at improving care, speed and maintaining quality for AIS treatment.

Methods: Using a prospectively collected endovascular database at a comprehensive stroke center between 2012 and 2017, workflow/outcomes were recorded. There were no exclusion criteria. During the first year, a quality program employing “digital-object” technology, staff education, and workflow improvement was implemented to reduce time-to-treatment. Using electronic recording, workflow times ...


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