Digital Commons Network^™

Functionality Of The Putative Surface Glycoproteins Of The Wuhan Spiny Eel Influenza Virus, Guha Asthagiri Arunkumar, Disha Bhavsar, Tiehai Li, Shirin Strohmeier, Veronika Chromikova, Fatima Amanat, Mehman Bunyatov, Patrick C Wilson, Ali H Ellebedy, Geert-Jan Boons, Viviana Simon, Robert P De Vries, Florian Krammer

Open Access Publications

A panel of influenza virus-like sequences were recently documented in fish and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterize the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV. Functionally, we show that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, …

Discovering Disease-Disease Associations Using Electronic Health Records In The Guideline Advantage (Tga) Dataset, Aixia Guo, Yosef M Khan, James R Langabeer 2nd, Randi E Foraker

Open Access Publications

Certain diseases have strong comorbidity and co-occurrence with others. Understanding disease-disease associations can potentially increase awareness among healthcare providers of co-occurring conditions and facilitate earlier diagnosis, prevention and treatment of patients. In this study, we utilized the valuable and large The Guideline Advantage (TGA) longitudinal electronic health record dataset from 70 outpatient clinics across the United States to investigate potential disease-disease associations. Specifically, the most prevalent 50 disease diagnoses were manually identified from 165,732 unique patients. To investigate the co-occurrence or dependency associations among the 50 diseases, the categorical disease terms were first mapped into numerical vectors based on disease …

Cumulative Dna Damage By Repeated Low-Dose Cisplatin Injection Promotes The Transition Of Acute To Chronic Kidney Injury In Mice, Noriyuki Yamashita, Kunihiro Nakai, Tomohiro Nakata, Itaru Nakamura, Yuhei Kirita, Satoaki Matoba, Benjamin D Humphreys, Keiichi Tamagaki, Tetsuro Kusaba

Open Access Publications

Cisplatin is a commonly used anticancer drug, but nephrotoxicity is a dose-limiting adverse effect. Recent experimental and clinical observations have demonstrated that multiple injections of cisplatin induce the transition to chronic kidney disease; however, the underlying mechanisms remain unclear. We found that multiple injections of higher doses of cisplatin in a shorter interval affected the severity of kidney injury, causing kidney fibrosis to develop at a later time point. An additional injection of cisplatin during the recovery period after a prior injury, when proximal tubule epithelia are actively proliferating, induced substantial tubular injury by inducing more severe DNA damage than …

Excellent Response To Very-Low-Dose Radiation (4 Gy) For Indolent B-Cell Lymphomas: Is 4 Gy Suitable For Curable Patients?, Brandon S. Imber, Joanna C. Yang, Et Al

Open Access Publications

No abstract provided.

6-Thioguanine Blocks Sars-Cov-2 Replication By Inhibition Of Plpro, Caleb D Swaim, Varun Dwivedi, Yi-Chieh Perng, Xu Zhao, Larissa A Canadeo, Houda H Harastani, Tamarand L Darling, Adrianus C M Boon, Deborah J Lenschow, Viraj Kulkarni, Jon M Huibregtse

Open Access Publications

The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 μM. 6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro …

Comparison Of 2-Year Outcomes With Car T Cells (Zuma-1) Vs Salvage Chemotherapy In Refractory Large B-Cell Lymphoma, Sattva S. Neelapu, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Surgical Strategy For The Management Of Cervical Deformity Is Based On Type Of Cervical Deformity, Han Jo Kim, Munish Gupta, Et Al

Open Access Publications

OBJECTIVES: Cervical deformity morphotypes based on type and location of deformity have previously been described. This study aimed to examine the surgical strategies implemented to treat these deformity types and identify if differences in treatment strategies impact surgical outcomes. Our hypothesis was that surgical strategies will differ based on different morphologies of cervical deformity.

METHODS: Adult patients enrolled in a prospective cervical deformity database were classified into four deformity types (Flatneck (FN), Focal kyphosis (FK), Cervicothoracic kyphosis (CTK) and Coronal (C)), as previously described. We analyzed group differences in demographics, preoperative symptoms, health-related quality of life scores (HRQOLs), and surgical …

Brief Electrical Stimulation Accelerates Axon Regeneration And Promotes Recovery Following Nerve Transection And Repair In Mice, Junichi Sayanagi, Jesús A Acevedo-Cintrón, Deng Pan, Lauren Schellhardt, Daniel A Hunter, Alison K Snyder-Warwick, Susan E Mackinnon, Matthew D Wood

Open Access Publications

BACKGROUND: Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes.

METHODS: C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the …

Syndrome Of Reversible Cardiogenic Shock And Left Ventricular Ballooning In Obstructive Hypertrophic Cardiomyopathy, Mark V Sherrid, Daniel G Swistel, Iacopo Olivotto, Maurizio Pieroni, Omar Wever-Pinzon, Katherine Riedy, Richard G Bach, Mustafa Husaini, Sharon Cresci, Alex Reyentovich, Daniele Massera, Martin S Maron, Barry J Maron, Bette Kim

Open Access Publications

Background Cardiogenic shock from most causes has unfavorable prognosis. Hypertrophic cardiomyopathy (HCM) can uncommonly present with apical ballooning and shock in association with sudden development of severe and unrelenting left ventricular (LV) outflow obstruction. Typical HCM phenotypic features of mild septal thickening, outflow gradients, and distinctive mitral abnormalities differentiate these patients from others with Takotsubo syndrome, who have normal mitral valves and no outflow obstruction. Methods and Results We analyzed 8 patients from our 4 HCM centers with obstructive HCM and abrupt presentation of cardiogenic shock with LV ballooning, and 6 cases reported in literature. Of 14 patients, 10 (71%) …

Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia In Subarachnoid Hemorrhage In Response To Hypoxic Postconditioning, Deepti Diwan, Ananth K Vellimana, Diane J Aum, Julian Clarke, James W Nelson, Molly Lawrence, Byung Hee Han, Jeffrey M Gidday, Gregory J Zipfel

Open Access Publications

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O

Neurotoxins Subvert The Allosteric Activation Mechanism Of Sarm1 To Induce Neuronal Loss, Tong Wu, Jian Zhu, Amy Strickland, Kwang Woo Ko, Yo Sasaki, Caitlin B Dingwall, Yurie Yamada, Matthew D Figley, Xianrong Mao, Alicia Neiner, A Joseph Bloom, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

SARM1 is an inducible TIR-domain NAD

Nrf2 Promotes Urothelial Cell Response To Bacterial Infection By Regulating Reactive Oxygen Species And Rab27b Expression, Chetanchandra S Joshi, Amy Mora, Paul A Felder, Indira U Mysorekar

Open Access Publications

Uropathogenic Escherichia coli (UPEC) cause urinary tract infections (UTIs) by invading urothelial cells. In response, the host mounts an inflammatory response to expel bacteria. Here, we show that the NF-E2-related factor 2 (NRF2) pathway is activated in response to UPEC-triggered reactive oxygen species (ROS) production. We demonstrate the molecular sequence of events wherein NRF2 activation in urothelial cells reduces ROS production, inflammation, and cell death, promotes UPEC expulsion, and reduces the bacterial load. In contrast, loss of NRF2 leads to increased ROS production, bacterial burden, and inflammation, both in vitro and in vivo. NRF2 promotes UPEC expulsion by regulating transcription …

The Content And Quality Of Publicly Available Information About Congenital Diaphragmatic Hernia: Descriptive Study, Frank Coyle Soltys, Kimi Spilo, Mary C Politi

Open Access Publications

BACKGROUND: Congenital diaphragmatic hernia (CDH) diagnosis in an infant is distressing for parents. Parents often feel unable to absorb the complexities of CDH during prenatal consultations and use the internet to supplement their knowledge and decision making.

OBJECTIVE: We aimed to examine the content and quality of publicly available, internet-based CDH information.

METHODS: We conducted internet searches across 2 popular search engines (Google and Bing). Websites were included if they contained CDH information and were publicly available. We developed a coding instrument to evaluate websites. Two coders (FS and KS) were trained, achieved interrater reliability, and rated remaining websites independently. …

Relationship Between Quality Of Life Indicators And Cardiac Status Indicators In Chemotherapy Patients, Blaž Matija Geršak, Andreja Kukec, Henning Steen, Moritz Montenbruck, Maja Šoštarič, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Pia Wülfing, Susan Dent, Daniel Lenihan

Open Access Publications

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients.

METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. …

Elevated Mics Of Susceptible Antipseudomonal Cephalosporins In Non-Carbapenemase-Producing, Carbapenem-Resistant Pseudomonas Aeruginosa: Implications For Dose Optimization, Christian M Gill, Carey-Ann D Burnham, Et Al

Open Access Publications

The present study evaluated the

Alternative Pre-Mrna Splicing Of The Mu Opioid Receptor Gene, Oprm1: Insight Into Complex Mu Opioid Actions, Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan

Open Access Publications

Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene,

Aducanumab For Alzheimer Disease: The Amyloid Hypothesis Moves From Bench To Bedside, Erik S. Musiek, Teresa Gomez-Isla, David M Holtzman

Open Access Publications

No abstract provided.

Cullin4 E3 Ubiquitin Ligases Regulate Male Gonocyte Migration, Proliferation And Blood-Testis Barrier Homeostasis, Yan Yin, Liming Zhu, Qiufang Li, Pengbo Zhou, Liang Ma

Open Access Publications

Ubiquitination, an essential posttranslational modification, plays fundamental roles during mammalian spermatogenesis. We previously reported the requirement of two Cullin 4 ubiquitin ligase family genes, Cullin 4a (

Formylglycine-Generating Enzyme-Like Proteins Constitute A Novel Family Of Widespread Type Vi Secretion System Immunity Proteins, Juvenal Lopez, Nguyen-Hung Le, Ki Hwan Moon, Dor Salomon, Eran Bosis, Mario F Feldman

Open Access Publications

Competition is a critical aspect of bacterial life, as it enables niche establishment and facilitates the acquisition of essential nutrients. Warfare between Gram-negative bacteria is largely mediated by the type VI secretion system (T6SS), a dynamic nanoweapon that delivers toxic effector proteins from an attacking cell to adjacent bacteria in a contact-dependent manner. Effector-encoding bacteria prevent self-intoxication and kin cell killing by the expression of immunity proteins, which neutralize effector toxicity by specifically binding their cognate effector and either occluding its active site or preventing the structural rearrangements necessary for effector activation. In this study, we investigate Tsi3, a previously …

Plasmid-Encoded H-Ns Controls Extracellular Matrix Composition In A Modern Acinetobacter Baumannii Urinary Isolate, Saida Benomar, Gisela Di Venanzio, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCPs). LCPs encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here, we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes …

Nuclear-Localized Human Respiratory Syncytial Virus Ns1 Protein Modulates Host Gene Transcription, Jingjing Pei, Nina R Beri, Angela J Zou, Philipp Hubel, Hannah K Dorando, Valter Bergant, Rebecca D Andrews, Jiehong Pan, Jared M Andrews, Kathleen C F Sheehan, Andreas Pichlmair, Gaya K Amarasinghe, Steven L Brody, Jacqueline E Payton, Daisy W Leung

Open Access Publications

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on …

Braf Mutations May Identify A Clinically Distinct Subset Of Glioblastoma, Samantha N Mcnulty, Katherine E Schwetye, Cole Ferguson, Chad E Storer, George Ansstas, Albert H Kim, David H Gutmann, Joshua B Rubin, Richard D Head, Sonika Dahiya

Open Access Publications

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Prior studies examining the mutational landscape of GBM revealed recurrent alterations in genes that regulate the same growth control pathways. To this regard, ~ 40% of GBM harbor EGFR alterations, whereas BRAF variants are rare. Existing data suggests that gain-of-function mutations in these genes are mutually exclusive. This study was designed to explore the clinical, pathological, and molecular differences between EGFR- and BRAF-mutated GBM. We reviewed retrospective clinical data from 89 GBM patients referred for molecular testing between November 2012 and December 2015. Differences in tumor mutational profile, …

Rn7sk Small Nuclear Rna Controls Bidirectional Transcription Of Highly Expressed Gene Pairs In Skin, Roberto Bandiera, Rebecca E Wagner, Thiago Britto-Borges, Christoph Dieterich, Sabine Dietmann, Susanne Bornelöv, Michaela Frye

Open Access Publications

Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis …

Inhibition Of The Nlrp3 Inflammasome Improves Lifespan In Animal Murine Model Of Hutchinson-Gilford Progeria, Alvaro González-Dominguez, Raúl Montañez, Beatriz Castejón-Vega, Jéssica Nuñez-Vasco, Débora Lendines-Cordero, Chun Wang, Gabriel Mbalaviele, José M Navarro-Pando, Elísabet Alcocer-Gómez, Mario D Cordero

Open Access Publications

Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste24

Comparative Cellular Analysis Of Motor Cortex In Human, Marmoset And Mouse, Trygve E. Bakken, Xinxin Wang, Et Al

Open Access Publications

No abstract provided.

Coronary Artery Calcification And Plaque Characteristics In People Living With Hiv: A Systematic Review And Meta-Analysis, Cullen Soares, Amjad Samara, Matthew F Yuyun, Justin B Echouffo-Tcheugui, Ahmad Masri, Ahmad Samara, Alan R Morrison, Nina Lin, Wen-Chih Wu, Sebhat Erqou

Open Access Publications

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta-analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study-specific estimates were pooled using meta-analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV-positive participants were younger (mean age 49 versus 57 …

Disparities In Treatment Decisions For Abnormal Uterine Bleeding, Lulu Yu, Bhavana Janga, Rebecca Mcalister, Donna B Jeffe, Tammy Sonn

Open Access Publications

No abstract provided.

Role Of Enhancers In Development And Diseases, Shailendra S Maurya

Open Access Publications

Enhancers are cis-regulatory elements containing short DNA sequences that serve as binding sites for pioneer/regulatory transcription factors, thus orchestrating the regulation of genes critical for lineage determination. The activity of enhancer elements is believed to be determined by transcription factor binding, thus determining the cell state identity during development. Precise spatio-temporal control of the transcriptome during lineage specification requires the coordinated binding of lineage-specific transcription factors to enhancers. Thus, enhancers are the primary determinants of cell identity. Numerous studies have explored the role and mechanism of enhancers during development and disease, and various basic questions related to the functions and …

A Transcriptomic And Epigenomic Cell Atlas Of The Mouse Primary Motor Cortex, Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Xinxin Wang, Et Al

Open Access Publications

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain

Structure Of Venezuelan Equine Encephalitis Virus In Complex With The Ldlrad3 Receptor, Katherine Basore, Hongming Ma, Natasha M Kafai, Samantha Mackin, Arthur S Kim, Christopher A Nelson, Michael S Diamond, Daved H Fremont

Open Access Publications

LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)