Digital Commons Network^™

Selective Reduction Of Astrocyte Apoe3 And Apoe4 Strongly Reduces Aβ Accumulation And Plaque-Related Pathology In A Mouse Model Of Amyloidosis, Thomas E Mahan, Chao Wang, Xin Bao, Ankit Choudhury, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

BACKGROUND: One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, …

Single Circulating-Tumor-Cell-Targeted Sequencing To Identify Somatic Variants In Liquid Biopsies In Non-Small-Cell Lung Cancer Patients, Mouadh Barbirou, Amanda Miller, Yariswamy Manjunath, Arturo B Ramirez, Nolan G Ericson, Kevin F Staveley-O'Carroll, Jonathan B Mitchem, Wesley C Warren, Aadel A Chaudhuri, Yi Huang, Guangfu Li, Peter J Tonellato, Jussuf T Kaifi

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) accounts for most cancer-related deaths worldwide. Liquid biopsy by a blood draw to detect circulating tumor cells (CTCs) is a tool for molecular profiling of cancer using single-cell and next-generation sequencing (NGS) technologies. The aim of the study was to identify somatic variants in single CTCs isolated from NSCLC patients by targeted NGS. Thirty-one subjects (20 NSCLC patients, 11 smokers without cancer) were enrolled for blood draws (7.5 mL). CTCs were identified by immunofluorescence, individually retrieved, and DNA-extracted. Targeted NGS was performed to detect somatic variants (single-nucleotide variants (SNVs) and insertions/deletions (Indels)) across 65 oncogenes and …

Fractality Of Tics As A Quantitative Assessment Tool For Tourette Syndrome, Payton Beeler, Nicholas O Jensen, Soyoung Kim, Amy Robichaux-Viehoever, Bradley L Schlaggar, Deanna J Greene, Kevin J. Black, Rajan K Chakrabarty

2020-Current year OA Pubs

Tics manifest as brief, purposeless and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Previous work has hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbour-to-neighbour correlation at all levels of timescale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent-called the fractal dimension

Rpop: Robust Pet-Only Processing Of Community Acquired Heterogeneous Amyloid-Pet Data, Leonardo Iaccarino, Renaud La Joie, Robert Koeppe, Barry A Siegel, Bruce E Hillner, Constantine Gatsonis, Rachel A Whitmer, Maria C Carrillo, Charles Apgar, Monica R Camacho, Rachel Nosheny, Gil D Rabinovici, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (

Importance Of The Intersection Of Age And Sex To Understand Variation In Incidence And Survival For Primary Malignant Gliomas, Gi-Ming Wang, Gino Cioffi, Nirav Patil, Kristin A Waite, Robert Lanese, Quinn T Ostrom, Carol Kruchko, Michael E Berens, James R Connor, Justin D Lathia, Joshua B Rubin, Jill S Barnholtz-Sloan

2020-Current year OA Pubs

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States.

METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC's NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models …

A Prospective Multicenter Evaluation Of Initial Treatment Choice In Metastatic Renal Cell Carcinoma Prior To The Immunotherapy Era: The Marcc Registry Experience, Brian A. Costello, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC).

METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations.

RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest …

Validation Of Actigraphy For Sleep Measurement In Children With Cerebral Palsy, Bing Xue, Amy Licis, Jill Boyd, Catherine R Hoyt, Yo-El S Ju

2020-Current year OA Pubs

OBJECTIVES: Sleep issues are common in children with cerebral palsy (CP), although there are challenges in obtaining objective data about their sleep patterns. Actigraphs measure movement to quantify sleep but their accuracy in children with CP is unknown. Our goals were to validate actigraphy for sleep assessment in children with CP and to study their sleep patterns in a cross-sectional cohort study.

METHODS: We recruited children with (N = 13) and without (N = 13) CP aged 2-17 years (mean age 9 y 11mo [SD 4 y 10mo] range 4-17 y; 17 males, 9 females; 54% spastic quadriplegic, 23% spastic …

Host Cell-Intrinsic Innate Immune Recognition Of Sars-Cov-2, Emily A Madden, Michael S Diamond

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged at the end of 2019 and caused the pandemic of coronavirus disease 2019 (COVID-19). Basic and clinical investigations indicate that severe forms of COVID-19 are due in part to dysregulated immune responses to virus infection. The innate immune system is the first line of host defense against most virus infections, with pathogen recognition receptors detecting SARS-CoV-2 RNA and protein components and initiating pro-inflammatory and antiviral responses. Notwithstanding this response, SARS-CoV-2 proteins evade, inhibit, and skew innate immune signaling early in infection. In this review, we highlight the components of cell-based recognition of SARS-CoV-2 …

No Difference In Radiologic Outcomes For Natalizumab Patients Treated With Extended Interval Dosing Compared With Standard Interval Dosing: Real-World Evidence From Ms Paths, Lana Zhovtis Ryerson, Robert T. Naismith, Lauren B. Krupp, Leigh E. Charvet, Shirley Liao, Elizabeth Fisher, Carl De Moor, James R. Williams, Nolan Campbell

2020-Current year OA Pubs

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients …

Protein Phosphatase 2a Restrains Dlk Signaling To Promote Proper Drosophila Synaptic Development And Mammalian Cortical Neuron Survival, Margaret Hayne, Aaron Diantonio

2020-Current year OA Pubs

Protein phosphatase 2A (PP2A) is a major cellular phosphatase with many protein substrates. As expected for a signaling molecule with many targets, inhibition of PP2A disrupts fundamental aspects of cellular physiology including cell division and survival. In post-mitotic neurons, the microtubule associated protein Tau is a particularly well-studied PP2A substrate as hyperphosphorylation of Tau is a hallmark of Alzheimer's disease. Although many cellular targets are likely altered by loss of PP2A, here we find that activation of a single pathway can explain important aspects of the PP2A loss-of-function phenotype in neurons. We demonstrate that PP2A inhibits activation of the neuronal …

Utility Of Covid-19 Antigen Testing In The Emergency Department, W Frank Peacock, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis.

METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of …

A Unique Sarcopenic Progression In The Mouse Rotator Cuff, Gretchen A Meyer, Karen C Shen

2020-Current year OA Pubs

BACKGROUND: In response to chronic injury, the muscles of the rotator cuff (RC) experience a unique degeneration characterized by extensive fatty infiltration and loss of contractile function. Human studies suggest this degeneration is also a feature of RC sarcopenia and may precede RC injury. In this study, we investigated whether RC muscles exhibit a similar unique sarcopenia in the mouse.

METHODS: Male and female mice were subdivided into four age groups: 3, 9, 18, and 24 months. The supraspinatus (SS) and infraspinatus muscles of the RC and the tibialis anterior (TA) muscle of the hindlimb were assessed. Muscle mass, contractile …

Clinical Image: Calcinosis Cutis Universalis In A Patient With Polymyositis/Scleroderma Overlap Syndrome, Katie Carbonell, Nicole Droz

2020-Current year OA Pubs

No abstract provided.

Mental Health In The Uk Biobank: A Roadmap To Self-Report Measures And Neuroimaging Correlates, Rosie K Dutt, Kayla Hannon, Ty O Easley, Joseph C Griffis, Wei Zhang, Janine D Bijsterbosch

2020-Current year OA Pubs

The UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in …

Echocardiographic And Clinical Predictors Of Cardiac Amyloidosis: Limitations Of Apical Sparing, Douglas Kyrouac, Walter Schiffer, Brandon Lennep, Nicole Fergestrom, Kathleen W Zhang, John Gorcsan Iii, Daniel J Lenihan, Joshua D Mitchell

2020-Current year OA Pubs

AIMS: The accuracy of an apical-sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice.

METHODS AND RESULTS: As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We …

Significant Variations In Surgical Construct And Return To Sport Protocols With Syndesmotic Injuries: An Isakos Global Perspective, Kenneth J. Hunt, Jonathan Bartolomei, Shanthan C. Challa, Jeremy J. Mccormick, Pieter D'Hooghe, Michael Tuffiash, Annunziato Amendola, Isakos Leg, Ankle Foot Committee

2020-Current year OA Pubs

No abstract provided.

Brain Stimulation Treatments In Epilepsy: Basic Mechanisms And Clinical Advances, Thomas J. Foutz, Michael Wong

2020-Current year OA Pubs

Drug-resistant epilepsy, characterized by ongoing seizures despite appropriate trials of anti-seizure medications, affects approximately one-third of people with epilepsy. Brain stimulation has recently become available as an alternative treatment option to reduce symptomatic seizures in short and long-term follow-up studies. Several questions remain on how to optimally develop patient-specific treatments and manage therapy over the long term. This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy and highlight recent advances that may both improve outcomes and present new challenges. Finally, a rational approach to …

Gene Expression Predicts Dormant Metastatic Breast Cancer Cell Phenotype, Qihao Ren, Weng Hua Khoo, Alexander P Corr, Tri Giang Phan, Peter I Croucher, Sheila A Stewart

2020-Current year OA Pubs

BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study.

METHODS: To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell …

Development Of A Standard Of Care For Patients With Valosin-Containing Protein Associated Multisystem Proteinopathy, Manisha Korb, Nupur Ghoshal, Conrad Weihl, Et Al.

2020-Current year OA Pubs

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, …

Analysis Of Non-Relapsed And Relapsed Adult Type Granulosa Cell Tumors Suggests Stable Transcriptomes During Tumor Progression, Noora Andersson, Ulla-Maija Haltia, Anniina Färkkilä, Swee Chong Wong, Katja Eloranta, David B Wilson, Leila Unkila-Kallio, Marjut Pihlajoki, Antti Kyrönlahti, Markku Heikinheimo

2020-Current year OA Pubs

Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3' mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic Forkhead Box L2 (

Acute Minocycline Administration Reduces Brain Injury And Improves Long-Term Functional Outcomes After Delayed Hypoxemia Following Traumatic Brain Injury, Marta Celorrio, Kirill Shumilov, Camryn Payne, Sangeetha Vadivelu, Stuart H Friess

2020-Current year OA Pubs

Clinical trials of therapeutics for traumatic brain injury (TBI) demonstrating preclinical efficacy for TBI have failed to replicate these results in humans, in part due to the absence of clinically feasible therapeutic windows for administration. Minocycline, an inhibitor of microglial activation, has been shown to be neuroprotective when administered early after experimental TBI but detrimental when administered chronically to human TBI survivors. Rather than focusing on the rescue of primary injury with early administration of therapeutics which may not be clinically feasible, we hypothesized that minocycline administered at a clinically feasible time point (24 h after injury) would be neuroprotective …

Steroid-Sensitive Nephrotic Syndrome Candidate Gene Clvs1 Regulates Podocyte Oxidative Stress And Endocytosis, Brandon M. Lane, Andrew F. Malone, Et Al.

2020-Current year OA Pubs

We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking …

Safety Profile Of Rapamycin Perfluorocarbon Nanoparticles For Preventing Cisplatin-Induced Kidney Injury, Qingyu Zhou, Justin Doherty, Antonina Akk, Luke E Springer, Ping Fan, Ivan Spasojevic, Ganesh V Halade, Huanghe Yang, Christine T N Pham, Samuel A Wickline, Hua Pan

2020-Current year OA Pubs

Cancer treatment-induced toxicities may restrict maximal effective dosing for treatment and cancer survivors' quality of life. It is critical to develop novel strategies that mitigate treatment-induced toxicity without affecting the efficacy of anti-cancer therapies. Rapamycin is a macrolide with anti-cancer properties, but its clinical application has been hindered, partly by unfavorable bioavailability, pharmacokinetics, and side effects. As a result, significant efforts have been undertaken to develop a variety of nano-delivery systems for the effective and safe administration of rapamycin. While the efficacy of nanostructures carrying rapamycin has been studied intensively, the pharmacokinetics, biodistribution, and safety remain to be investigated. In …

Grandi Byen-Supporting Child Growth And Development Through Integrated, Responsive Parenting, Nutrition And Hygiene: Study Protocol For A Randomized Controlled Trial, Patricia L Kohl, Emmanuel A Gyimah, Jenna Diaz, F Matthew Kuhlmann, Sherlie Jean-Louis Dulience, Fithi Embaye, Derek S Brown, Shenyang Guo, Joan L Luby, Jennifer L Nicholas, Jay Turner, Melissa Chapnick, Joseline Marhone Pierre, Jacques Boncy, Rony St Fleur, Maureen M Black, Lora L Iannotti

2020-Current year OA Pubs

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development.

METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional …

Transition To Invasive Breast Cancer Is Associated With Progressive Changes In The Structure And Composition Of Tumor Stroma, Tyler Risom, Deborah J Veis, Katherine Deschryver, Graham A Colditz, Michael Angelo, Et Al.

2020-Current year OA Pubs

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune …

Substantial Overlap Between Symptomatic And Asymptomatic Genitourinary Microbiota States, Boahemaa Adu-Oppong, Robert Thänert, Meghan A Wallace, Carey-Ann D Burnham, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: The lack of a definition of urinary microbiome health convolutes diagnosis of urinary tract infections (UTIs), especially when non-traditional uropathogens or paucity of bacteria are recovered from symptomatic patients in routine standard-of-care urine tests. Here, we used shotgun metagenomic sequencing to characterize the microbial composition of asymptomatic volunteers in a set of 30 longitudinally collected urine specimens. Using permutation tests, we established a range of asymptomatic microbiota states, and use these to contextualize the microbiota of 122 urine specimens collected from patients with suspected UTIs diagnostically categorized by standard-of-care urinalysis within that range. Finally, we used a standard-of-care culture …

Murine Roseolovirus Does Not Accelerate Amyloid-Β Pathology And Human Roseoloviruses Are Not Over-Represented In Alzheimer Disease Brains, Tarin M Bigley, Monica Xiong, Muhammad Ali, Yun Chen, Chao Wang, Javier Remolina Serrano, Abdallah Eteleeb, Oscar Harari, Liping Yang, Swapneel J Patel, Carlos Cruchaga, Wayne M Yokoyama, David M Holtzman

2020-Current year OA Pubs

BACKGROUND: The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen …

Automated Sleep State Classification Of Wide-Field Calcium Imaging Data Via Multiplex Visibility Graphs And Deep Learning, Xiaohui Zhang, Eric C. Landsness, Wei Chen, Hanyang Miao, Michelle Tang, Lindsey M. Brier, Joseph P. Culver, Jin-Moo Lee, Mark A. Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) allows for monitoring of cortex-wide neural dynamics in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming and often suffers from low inter- and intra-rater reliability and invasiveness. Therefore, an automated sleep state classification method that operates on WFCI data alone is needed.

NEW METHOD: A hybrid, two-step method is proposed. In the first step, spatial-temporal WFCI data is mapped to multiplex visibility graphs (MVGs). Subsequently, a two-dimensional …

"It's Good To Feel Like You're Doing Something": A Qualitative Study Examining State Health Department Employees' Views On Why Ineffective Programs Continue To Be Implemented In The Usa, Stephanie Mazzucca, Louise Farah Saliba, Romario Smith, Emily Rodriguez Weno, Peg Allen, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Mis-implementation, the inappropriate continuation of programs or policies that are not evidence-based or the inappropriate termination of evidence-based programs and policies, can lead to the inefficient use of scarce resources in public health agencies and decrease the ability of these agencies to deliver effective programs and improve population health. Little is known about why mis-implementation occurs, which is needed to understand how to address it. This study sought to understand the state health department practitioners' perspectives about what makes programs ineffective and the reasons why ineffective programs continue.

METHODS: Eight state health departments (SHDs) were selected to participate in …

Nipah Virus V Protein Binding Alters Mda5 Helicase Folding Dynamics, Nicole D Wagner, Hejun Liu, Henry W Rohrs, Gaya K Amarasinghe, Michael L Gross, Daisy W Leung

2020-Current year OA Pubs

Nipah virus (NiV) is an emerging and deadly zoonotic paramyxovirus that is responsible for periodic epidemics of acute respiratory illness and encephalitis in humans. Previous studies have shown that the NiV V protein antagonizes host antiviral immunity, but the molecular mechanism is incompletely understood. To address this gap, we biochemically characterized NiV V binding to the host pattern recognition receptor MDA5. We find that the C-terminal domain of NiV V (V