Digital Commons Network^™

Apoptosis Detection In Retinal Ganglion Cells Using Quantitative Changes In Multichannel Fluorescence Colocalization, Xudong Qiu, Seth T Gammon, James R Johnson, Federica Pisaneschi, Steven W Millward, Edward M Barnett, David Piwnica-Worms

2020-Current year OA Pubs

KcapTR488 is a dual-fluorophore peptide sensor for the real-time reporting of programmed cell death by fluorescence imaging. KcapTR488 contains a nuclear localization sequence (NLS) conjugated with Texas Red, a caspase-cleavable sequence (DEVD), and a C-terminus conjugated to Alexa Fluor 488 (AF488). The synthesis and preliminary evaluation in cellulo of KcapTR488 for monitoring cell death by fluorescence imaging has been previously reported, but its utility in vivo has yet to be tested or validated. Herein, in vitro solution experiments verified the intramolecular fluorescence resonance energy transfer (FRET) between the two fluorophores and enabled a quantitative analysis of enzyme rates and selectivity. …

Capg Is Required For Ebola Virus Infection By Controlling Virus Egress From Infected Cells, Hiroyuki Mori, James P Connell, Callie J Donahue, Ruthmabel Boytz, Yen Thi Kim Nguyen, Daisy W Leung, Douglas J Lacount, Robert A Davey

2020-Current year OA Pubs

The replication of Ebola virus (EBOV) is dependent upon actin functionality, especially at cell entry through macropinocytosis and at release of virus from cells. Previously, major actin-regulatory factors involved in actin nucleation, such as Rac1 and Arp2/3, were shown important in both steps. However, downstream of nucleation, many other cell factors are needed to control actin dynamics. How these regulate EBOV infection remains largely unclear. Here, we identified the actin-regulating protein, CAPG, as important for EBOV replication. Notably, knockdown of CAPG specifically inhibited viral infectivity and yield of infectious particles. Cell-based mechanistic analysis revealed a requirement of CAPG for virus …

Organization Of The Gravity-Sensing System In Zebrafish, Zhikai Liu, David G C Hildebrand, Joshua L Morgan, Yizhen Jia, Nicholas Slimmon, Martha W Bagnall

2020-Current year OA Pubs

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion …

Statistical Validation Of Risk Alleles In Genetic Addiction Risk Severity (Gars) Test: Early Identification Of Risk For Alcohol Use Disorder (Aud) In 74,566 Case-Control Subjects, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in

Neurogenetic And Epigenetic Aspects Of Cannabinoids, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold

2020-Current year OA Pubs

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately …

Impacts Of A Workplace-Based Weight-Control Intervention On Objective And Perceived Physical Activity Among A Subgroup Of Workers, Rachel Tabak, Ryan Colvin, Jaime R Strickland, Ann Marie Dale, Maura Kepper, Tara Ruggeri, Bradley Evanoff

2020-Current year OA Pubs

Physical activity (PA) has many benefits; however, groups facing barriers to health-promoting behaviors are less likely to be physically active. This may be addressed through workplace interventions. The current study employs objective (accelerometry) and perceived (International Physical Activity Questionnaire [IPAQ]) measures of PA among a subset of participants from the "Working for You" study, which tests a multi-level (work group and individual) workplace intervention targeted at workers with low-incomes. Linear mixed and hierarchical logistic regression models are used to determine the intervention's impact on moderate- to vigorous-PA (MVPA) and achieving the PA Guideline for Americans (≥150 minutes MVPA/week), respectively from …

Modelling Neurological Diseases In Large Animals: Criteria For Model Selection And Clinical Assessment, Samantha L Eaton, Jonathan D Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.

Heavy Metals In Breast Implant Capsules And Breast Tissue: Findings From The Systemic Symptoms In Women-Biospecimen Analysis Study: Part 2, Roger Wixtrom, Caroline Glicksman, Marshall Kadin, Marisa Lawrence, Melinda Haws, Sarah Ferenz, James Sung, Patricia Mcguire

2020-Current year OA Pubs

BACKGROUND: Breast Implant Illness (BII), as described in recent medical literature and by social media, describes a range of symptoms in patients with breast implants for which there are no physical findings or laboratory results that explain their symptoms.

OBJECTIVES: Part 2 of this study aims to determine whether heavy metals are present in the capsules around saline and silicone implants and if there are statistical differences in the type or level of these metals between women with or without symptoms. Demographic data was collected to investigate potential alternate sources of metals: inhaled, absorbed, or ingested.

METHODS: A prospective, blinded …

C10pred: A First Machine Learning Based Tool To Predict C10 Family Cysteine Peptidases Using Sequence-Derived Features, Adeel Malik, Nitin Mahajan, Tanveer Ali Dar, Chang-Bae Kim

2020-Current year OA Pubs

No abstract provided.

Layer-Specific Developmentally Precise Axon Targeting Of Transient Suppressed-By-Contrast Retinal Ganglion Cells (Tsbc Rgcs), Nai-Wen Tien, Carmela Vitale, Tudor C Badea, Daniel Kerschensteiner

2020-Current year OA Pubs

The mouse retina encodes diverse visual features in the spike trains of >40 retinal ganglion cell (RGC) types. Each RGC type innervates a specific subset of the >50 retinorecipient brain areas. Our catalog of RGC types and feature representations is nearing completion. Yet, we know little about where specific RGC types send their information. Furthermore, the developmental strategies by which RGC axons choose their targets and pattern their terminal arbors remain obscure. Here, we identify a genetic intersection (

Perioperative Mental Health Intervention Bundle For Older Surgical Patients: Protocol For An Intervention Development And Feasibility Study, Joanna Abraham, Katherine J Holzer, Emily M Lenard, Kenneth E Freedland, Bethany R Tellor Pennington, Rachel C Wolfe, Theresa A Cordner, Ana A Baumann, Mary Politi, Michael Simon Avidan, Eric Lenze

2020-Current year OA Pubs

INTRODUCTION: The perioperative period is high risk for older adults. Depression and anxiety are common perioperative problems, frequently coexisting with cognitive impairment. Older patients with these conditions are more likely than younger patients to experience postoperative delirium, long hospital stays, poor quality of life and rehospitalisation. These experiences can, in turn, exacerbate anxiety and depressive symptoms. Despite these risks, little is known about how to treat perioperative anxiety and depression among older adults.

METHODS AND ANALYSIS: We designed a feasibility study of a perioperative mental health intervention bundle to improve perioperative mental health, specifically depression and anxiety. The overarching goals …

Mutational Analyses Of The Cysteine-Rich Domain Of Yvh1, A Protein Required For Translational Competency In Yeast, Hannah Zang, Robert Shackelford, Alice Bewley, Alexander E Beeser

2020-Current year OA Pubs

Ribosome assembly is a complex biological process facilitated by >200

Association Between Antidepressant Use And Ed Or Hospital Visits In Outpatients With Sars-Cov-2, Bradley A Fritz, Nicolas Hoertel, Eric J Lenze, Farid Jalali, Angela M Reiersen

2020-Current year OA Pubs

Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive SARS-CoV-2 test performed in a non-hospital setting. Logistic regression analyses tested associations between home use of antidepressant medications and a composite outcome of ED visitation or hospital admission within 30 days. Secondary …

High-Resolution Imaging Of Protein Secretion At The Single-Cell Level Using Plasmon-Enhanced Fluorodot Assay, Anushree Seth, Ekansh Mittal, Jingyi Luan, Samhitha Kolla, Monty B Mazer, Hemant Joshi, Rohit Gupta, Priya Rathi, Zheyu Wang, Jeremiah J Morrissey, Joel D Ernst, Cynthia Portal-Celhay, Sharon Celeste Morley, Jennifer A Philips, Srikanth Singamaneni

2020-Current year OA Pubs

Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of proteins secreted by single cells, to study cell-to-cell heterogeneity in secretion, or to detect proteins of low abundance or incipient secretion. Here, we introduce the "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging of protein secretion. We find that plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise compared with conventional fluorescence labels. We demonstrate high-resolution imaging of different secreted cytokines in the single-plexed and spectrally multiplexed FluoroDOT assay that revealed cellular heterogeneity in secretion of multiple proteins …

Cochlear Ribbon Synapse Maturation Requires Nlgn1 And Nlgn3, Miguel A Ramirez, Yuzuru Ninoyu, Cayla Miller, Leonardo R Andrade, Seby Edassery, Ewa Bomba-Warczak, Briana Ortega, Uri Manor, Mark A Rutherford, Rick A Friedman, Jeffrey N Savas

2020-Current year OA Pubs

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We report

A User-Friendly Tool For Cloud-Based Whole Slide Image Segmentation With Examples From Renal Histopathology, Brendon Lutnick, Sanjay Jain, Et Al

2020-Current year OA Pubs

Background: Image-based machine learning tools hold great promise for clinical applications in pathology research. However, the ideal end-users of these computational tools (e.g., pathologists and biological scientists) often lack the programming experience required for the setup and use of these tools which often rely on the use of command line interfaces.

Methods: We have developed

Results: By segmenting glomeruli, interstitial fibrosis and tubular atrophy, and vascular structures from renal and non-renal WSIs, we demonstrate the scalability, best practices for transfer learning, and effects of dataset variability. Finally, we demonstrate an application for animal model research, analyzing glomerular features in three …

Human Total, Basal And Activity Energy Expenditures Are Independent Of Ambient Environmental Temperature, Xueying Zhang, Susan B Racette, Et Al.

2020-Current year OA Pubs

Lower ambient temperature (T

Natural Locus Coeruleus Dynamics During Feeding, Natale R Sciolino, Alexxai V Kravitz, Et Al

2020-Current year OA Pubs

Recent data demonstrate that noradrenergic neurons of the locus coeruleus (LC-NE) are required for fear-induced suppression of feeding, but the role of endogenous LC-NE activity in natural, homeostatic feeding remains unclear. Here, we found that LC-NE activity was suppressed during food consumption, and the magnitude of this neural response was attenuated as mice consumed more pellets throughout the session, suggesting that LC responses to food are modulated by satiety state. Visual-evoked LC-NE activity was also attenuated in sated mice, suggesting that satiety state modulates LC-NE encoding of multiple behavioral states. We also found that food intake could be attenuated by …

Examining The Complementarity Between The Eric Compilation Of Implementation Strategies And The Behaviour Change Technique Taxonomy: A Qualitative Analysis, Sheena Mchugh, Justin Presseau, Courtney T Luecking, Byron J Powell

2020-Current year OA Pubs

BACKGROUND: Efforts to generate evidence for implementation strategies are frustrated by insufficient description. The Expert Recommendations for Implementing Change (ERIC) compilation names and defines implementation strategies; however, further work is needed to describe the actions involved. One potentially complementary taxonomy is the behaviour change techniques (BCT) taxonomy. We aimed to examine the extent and nature of the overlap between these taxonomies.

METHODS: Definitions and descriptions of 73 strategies in the ERIC compilation were analysed. First, each description was deductively coded using the BCT taxonomy. Second, a typology was developed to categorise the extent of overlap between ERIC strategies and BCTs. …

Human Induced Pluripotent Stem Cell Engineering Establishes A Humanized Mouse Platform For Pediatric Low-Grade Glioma Modeling, Corina Anastasaki, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne M Scheaffer, Amanda De Andrade Costa, Anna F Wilson, Chloe M Kernan, Ameera H Zafar, Xia Ge, Joel R Garbow, Fausto J Rodriguez, David H Gutmann

2020-Current year OA Pubs

A major obstacle to identifying improved treatments for pediatric low-grade brain tumors (gliomas) is the inability to reproducibly generate human xenografts. To surmount this barrier, we leveraged human induced pluripotent stem cell (hiPSC) engineering to generate low-grade gliomas (LGGs) harboring the two most common pediatric pilocytic astrocytoma-associated molecular alterations, NF1 loss and KIAA1549:BRAF fusion. Herein, we identified that hiPSC-derived neuroglial progenitor populations (neural progenitors, glial restricted progenitors and oligodendrocyte progenitors), but not terminally differentiated astrocytes, give rise to tumors retaining LGG histologic features for at least 6 months in vivo. Additionally, we demonstrated that hiPSC-LGG xenograft formation requires the absence …

Engineering Rotating Apical-Out Airway Organoid For Assessing Respiratory Cilia Motility, Piyumi Wijesekara, Prakarsh Yadav, Lydia A. Perkins, Donna B. Stolz, Jonathan M. Franks, Simon C. Watkins, Emily Reinoso Jacome, Steven L. Brody, Amjad Horani, Jian Xu, Amir Barati Farimani, Xi Ren

2020-Current year OA Pubs

Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Owing to cilia's nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) from a defined number of cells. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and correlated it with the direct measurement of cilia motility. We further established the feasibility of using AOAO …

The Feel Of Inclusivity, Kristen M Patti, Gary J Patti

2020-Current year OA Pubs

Collaboration between diverse groups with different perspectives promotes scientific discovery. To enhance these partnerships and facilitate communication, innovative advances in universal design are essential.

Integrating De Novo And Inherited Variants In 42,607 Autism Cases Identifies Mutations In New Moderate-Risk Genes, Xueya Zhou, Tychele N. Turner, Et Al

2020-Current year OA Pubs

No abstract provided.

Localization Of Epigenetic Markers In Leishmania Chromatin, Jacquelyn R Mcdonald, Bryan C Jensen, Aakash Sur, Iris L K Wong, Stephen M Beverley, Peter J Myler

2020-Current year OA Pubs

Eukaryotes use histone variants and post-translation modifications (PTMs), as well as DNA base modifications, to regulate DNA replication/repair, chromosome condensation, and gene expression. Despite the unusual organization of their protein-coding genes into large polycistronic transcription units (PTUs), trypanosomatid parasites also employ a "histone code" to control these processes, but the details of this epigenetic code are poorly understood. Here, we present the results of experiments designed to elucidate the distribution of histone variants and PTMs over the chromatin landscape of

Automated Diagnosing Primary Open-Angle Glaucoma From Fundus Image By Simulating Human's Grading With Deep Learning, Mingquan Lin, Bojian Hou, Lei Liu, Mae Gordon, Michael Kass, Fei Wang, Sarah H Van Tassel, Yifan Peng

2020-Current year OA Pubs

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Although deep learning methods have been proposed to diagnose POAG, it remains challenging to develop a robust and explainable algorithm to automatically facilitate the downstream diagnostic tasks. In this study, we present an automated classification algorithm, GlaucomaNet, to identify POAG using variable fundus photographs from different populations and settings. GlaucomaNet consists of two convolutional neural networks to simulate the human grading process: learning the discriminative features and fusing the features for grading. We evaluated GlaucomaNet on two datasets: Ocular Hypertension Treatment Study (OHTS) participants and the Large-scale Attention-based …

Employment Loss And Food Insecurity - Race And Sex Disparities In The Context Of Covid-19, Jacquelyn V Coats, Sarah Humble, Kimberly J Johnson, Havisha Pedamallu, Bettina F Drake, Elvin Geng, Charles W Goss, Kia L Davis

2020-Current year OA Pubs

INTRODUCTION: Applying an intersectional framework, we examined sex and racial inequality in COVID-19-related employment loss (ie, job furlough, layoff, and reduced pay) and food insecurity (ie, quality and quantity of food eaten, food worry, and receipt of free meals or groceries) among residents in Saint Louis County, Missouri.

METHODS: We used cross-sectional data from adults aged 18 or older (N = 2,146), surveyed by using landlines or cellular phones between August 12, 2020, and October 27, 2020. We calculated survey-weighted prevalence of employment loss and food insecurity for each group (Black female, Black male, White female, White male). Odds ratios …

Sars-Cov-2 Productively Infects Primary Human Immune System Cells In Vitro And In Covid-19 Patients, Marjorie C Pontelli, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive …

Pediatric Open Long-Bone Fracture And Subsequent Deep Infection Risk: The Importance Of Early Hospital Care, Andrew W Kuhn, Stockton C Troyer, Jeffrey E Martus

2020-Current year OA Pubs

The purpose of the current study was to identify risk factors for deep infection after an open long-bone fracture in pediatric patients. Systematic billing queries were utilized to identify pediatric patients who presented to a level I trauma center from 1998 to 2019 with open long-bone fractures. There were 303 open long-bone fractures, and 24 (7.9%) of these became infected. Fractures of the tibia/fibula (

Defining Hierarchical Protein Interaction Networks From Spectral Analysis Of Bacterial Proteomes, Mark A Zaydman, Alexander S Little, Fidel Haro, Valeryia Aksianiuk, William J Buchser, Aaron Diantonio, Jeffrey I Gordon, Jeffrey Milbrandt, Arjun S Raman

2020-Current year OA Pubs

Cellular behaviors emerge from layers of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be defined from the statistical pattern of proteome variation measured across thousands of diverse bacteria and that these networks reflect the emergence of complex bacterial phenotypes. Our results are validated through gene-set enrichment analysis and comparison to existing experimentally derived databases. We demonstrate the biological utility of our approach by creating a model of motility in

A Central Alarm System That Gates Multi-Sensory Innate Threat Cues To The Amygdala, Sukjae J Kang, Shijia Liu, Mao Ye, Dong-Il Kim, Gerald M Pao, Bryan A Copits, Benjamin Z Roberts, Kuo-Fen Lee, Michael R Bruchas, Sung Han

2020-Current year OA Pubs

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various …