Digital Commons Network^™

Advances In Understanding Interferon-Mediated Immune Responses To Enteric Viruses In Intestinal Organoids, Lila S Nolan, Megan T Baldridge

2020-Current year OA Pubs

Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses

The Structural Basis Of Long-Term Potentiation In Hippocampal Synapses, Revealed By Electron Microscopy Imaging Of Lanthanum-Induced Synaptic Vesicle Recycling, John E Heuser

2020-Current year OA Pubs

Hippocampal neurons in dissociated cell cultures were exposed to the trivalent cation lanthanum for short periods (15-30 min) and prepared for electron microscopy (EM), to evaluate the stimulatory effects of this cation on synaptic ultrastructure. Not only were characteristic ultrastructural changes of exaggerated synaptic vesicle turnover seen within the presynapses of these cultures-including synaptic vesicle depletion and proliferation of vesicle-recycling structures-but the overall architecture of a large proportion of the synapses in the cultures was dramatically altered, due to large postsynaptic "bulges" or herniations into the presynapses. Moreover, in most cases, these postsynaptic herniations or protrusions produced by lanthanum were …

Bsl2-Compliant Lethal Mouse Model Of Sars-Cov-2 And Variants Of Concern To Evaluate Therapeutics Targeting The Spike Protein, Mohanraj Manangeeswaran, Derek D C Ireland, Seth G Thacker, Ha-Na Lee, Logan Kelley-Baker, Aaron P Lewkowicz, Paul W Rothlauf, Marjorie Cornejo Pontelli, Louis-Marie Bloyet, Michael A Eckhaus, Mirian I Mendoza, Sean Whelan, Daniela Verthelyi

2020-Current year OA Pubs

Since first reported in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly acquiring mutations, particularly in the spike protein, that can modulate pathogenicity, transmission and antibody evasion leading to successive waves of COVID19 infections despite an unprecedented mass vaccination necessitating continuous adaptation of therapeutics. Small animal models can facilitate understanding host-pathogen interactions, target selection for therapeutic drugs, and vaccine development, but availability and cost of studies in BSL3 facilities hinder progress. To generate a BSL2-compatible

Predicting Coronary Stenosis Progression Using Plaque Fatigue From Ivus-Based Thin-Slice Models: A Machine Learning Random Forest Approach, Xiaoya Guo, Akiko Maehara, Mingming Yang, Liang Wang, Jie Zheng, Habib Samady, Gary S Mintz, Don P Giddens, Dalin Tang

2020-Current year OA Pubs

No abstract provided.

Influenza: Toward Understanding The Immune Response In The Young, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

Annually influenza causes a global epidemic resulting in 290,000 to 650,000 deaths and extracts a massive toll on healthcare and the economy. Infants and children are more susceptible to infection and have more severe symptoms than adults likely mitigated by differences in their innate and adaptive immune responses. While it is unclear the exact mechanisms with which the young combat influenza, it is increasingly understood that their immune responses differ from adults. Specifically, underproduction of IFN-γ and IL-12 by the innate immune system likely hampers viral clearance while upregulation of IL-6 may create excessive damaging inflammation. The infant's adaptive immune …

Cardiac Immune Cell Infiltration Associates With Abnormal Lipid Metabolism, Vincenza Cifarelli, Ondrej Kuda, Kui Yang, Xinping Liu, Richard W Gross, Terri A Pietka, Gyu Seong Heo, Deborah Sultan, Hannah Luehmann, Josie Lesser, Morgan Ross, Ira J Goldberg, Robert J Gropler, Yongjian Liu, Nada A Abumrad

2020-Current year OA Pubs

CD36 mediates the uptake of long-chain fatty acids (FAs), a major energy substrate for the myocardium. Under excessive FA supply, CD36 can cause cardiac lipid accumulation and inflammation while its deletion reduces heart FA uptake and lipid content and increases glucose utilization. As a result, CD36 was proposed as a therapeutic target for obesity-associated heart disease. However, more recent reports have shown that CD36 deficiency suppresses myocardial flexibility in fuel preference between glucose and FAs, impairing tissue energy balance, while CD36 absence in tissue macrophages reduces efferocytosis and myocardial repair after injury. In line with the latter homeostatic functions, we …

Analysis Of Neuronal Injury Transcriptional Response Identifies Ctcf And Yy1 As Co-Operating Factors Regulating Axon Regeneration, Oshri Avraham, Jimmy Le, Kathleen Leahy, Tiandao Li, Guoyan Zhao, Valeria Cavalli

2020-Current year OA Pubs

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons

Mesenchymal Gene Expression Subtyping Analysis For Early-Stage Human Papillomavirus-Negative Head And Neck Squamous Cell Carcinoma Reveals Prognostic And Predictive Applications, Gregory M Mayhew, Joshua M Uronis, David Neil Hayes, Jose P Zevallos

2020-Current year OA Pubs

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(-), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(-) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, …

Four Decades Of Mapping And Quantifying Neuroreceptors At Work In Vivo By Positron Emission Tomography, Albert Gjedde, Dean F Wong

2020-Current year OA Pubs

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods …

The Role Of Endogenous Opioid Neuropeptides In Neurostimulation-Driven Analgesia, Susan T Lubejko, Robert D Graham, Giulia Livrizzi, Robert Schaefer, Matthew R Banghart, Meaghan C Creed

2020-Current year OA Pubs

Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms …

Weakly Activated Core Neuroinflammation Pathways Were Identified As A Central Signaling Mechanism Contributing To The Chronic Neurodegeneration In Alzheimer's Disease, Fuhai Li, Abdallah M Eteleeb, William Buchser, Christopher Sohn, Guoqiao Wang, Chengjie Xiong, Philip R Payne, Eric Mcdade, Celeste M Karch, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVES: Neuroinflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.

MATERIALS AND METHODS: From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets …

Abnormal Synergies And Associated Reactions Post-Hemiparetic Stroke Reflect Muscle Activation Patterns Of Brainstem Motor Pathways, Laura M Mcpherson, Julius P A Dewald

2020-Current year OA Pubs

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when …

Magnetic Resonance Imaging Of The Supra-Cervical Fetal Membrane Detects An Increased Risk Of Prelabor Rupture Of Membranes, Wenxu Qi, Peinan Zhao, Wei Wang, Zichao Wen, Zhexian Sun, Wenjie Wu, Pamela Karen Woodard, Qing Wang, Robert C Mckinstry, Yong Wang

2020-Current year OA Pubs

OBJECTIVE: In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.

METHODS: This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, …

Actin Capping Protein Regulates Postsynaptic Spine Development Through Cpi-Motif Interactions, Kenneth R Myers, Yanjie Fan, Patrick Mcconnell, John A Cooper, James Q Zheng

2020-Current year OA Pubs

Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to …

Totally Percutaneous Endovascular Repair For Ruptured Abdominal Aortic Aneurysms, Shirli Tay, Mohamed S Zaghloul, Mehreen Shafqat, Chao Yang, Kshitij A Desai, Gayan De Silva, Luis A Sanchez, Mohamed A Zayed

2020-Current year OA Pubs

PURPOSE: The PEVAR Trial demonstrated that compared to open femoral exposure, elective percutaneous endovascular AAA repair (ePEVAR) is associated with decreased perioperative morbidity and access site complications. We hypothesized that PEVAR for ruptured AAA (rPEVAR) may also improve perioperative morbidity compared to open femoral exposure (rEVAR). There are currently no reports that evaluate the utility and outcomes of rPEVAR.

MATERIALS AND METHODS: From 2015 to 2021, all patients who underwent an endovascular repair of a ruptured AAA at a single institution were included in the study and grouped into rPEVAR and rEVAR. Demographics, procedural details (successful preclose technique, conversion to …

Expansion Of A Novel Population Of Nk Cells With Low Ribosome Expression In Juvenile Dermatomyositis, Kinsey A Hilliard, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Hani S Zaher, Anthony R French

2020-Current year OA Pubs

Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring …

Correlating Electroconvulsive Therapy Response To Electroencephalographic Markers: Study Protocol, Subha Subramanian, Alyssa K Labonte, Thomas Nguyen, Anhthi H Luong, Orlandrea Hyche, S Kendall Smith, R Edward Hogan, Nuri B Farber, Ben Julian A Palanca, Mohammadmehdi Kafashan, Cet-Rem Study Group

2020-Current year OA Pubs

INTRODUCTION: Electroconvulsive therapy (ECT) is an effective intervention for patients with major depressive disorder (MDD). Despite longstanding use, the underlying mechanisms of ECT are unknown, and there are no objective prognostic biomarkers that are routinely used for ECT response. Two electroencephalographic (EEG) markers, sleep slow waves and sleep spindles, could address these needs. Both sleep microstructure EEG markers are associated with synaptic plasticity, implicated in memory consolidation, and have reduced expression in depressed individuals. We hypothesize that ECT alleviates depression through enhanced expression of sleep slow waves and sleep spindles, thereby facilitating synaptic reconfiguration in pathologic neural circuits.

METHODS: Correlating …

Personalized Practice Dosages May Improve Motor Learning In Older Adults Compared To "Standard Of Care" Practice Dosages: A Randomized Controlled Trial, Geneviève N Olivier, Leland E Dibble, Serene S Paul, Keith R Lohse, Christopher S Walter, Ryan J Marker, Heather A Hayes, K Bo Foreman, Kevin Duff, Sydney Y Schaefer

2020-Current year OA Pubs

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [

Control Of Aging By The Renin-Angiotensin System: A Review Of C. Elegans, Drosophila, And Mammals, Brian M Egan, Andrea Scharf, Franziska Pohl, Kerry Kornfeld

2020-Current year OA Pubs

The free-living, non-parasitic nematode

Reciprocal Regulation Of Mitofusin 2-Mediated Mitophagy And Mitochondrial Fusion By Different Pink1 Phosphorylation Events, Jiajia Li, Xiawei Dang, Antonietta Franco, Gerald W Dorn

2020-Current year OA Pubs

Mitochondrial repair is essential to metabolic homeostasis. Outer mitochondrial membrane mitofusin (MFN) proteins orchestrate mitochondrial fusion that opposes mitochondrial degeneration caused by senescence. Depending upon physiological context, MFN2 can either mediate mitochondrial fusion or recruit cytosolic Parkin to initiate mitophagic elimination. Because it is not clear how these events are counter-regulated we engineered and expressed MFN2 mutants that mimic phosphorylated or non-phosphorylatable MFN2 at its PINK1 phosphorylation sites: T111, S378, and S442. By interrogating mitochondrial fusion, polarization status, and Parkin binding/mitophagy as a function of inferred MFN2 phosphorylation, we discovered that individual MFN2 phosphorylation events act as a biological "bar-code", …

Advances In Our Clinical Understanding Of Autonomic Regulation Therapy Using Vagal Nerve Stimulation In Patients Living With Heart Failure, Marvin A Konstam, Douglas L Mann, John James E Udelson, Jeffrey L Ardell, Gaetano M De Ferrari, Martin R Cowie, Helmut U Klein, Douglas D Gregory, Joseph M Massaro, Imad Libbus, Lorenzo A Dicarlo, Javed Butler, John D Parker, John R Teerlink

2020-Current year OA Pubs

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to …

Cdc20 Regulates Sensitivity To Chemotherapy And Radiation In Glioblastoma Stem Cells, Diane D. Mao, Ryan T. Cleary, Amit Gujar, Tatenda Mahlokozera, Albert H. Kim

2020-Current year OA Pubs

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment …

Preeclampsia Is Associated With Reduced Isg15 Levels Impairing Extravillous Trophoblast Invasion, Asli Ozmen, Anthony O Odibo, Et Al

2020-Current year OA Pubs

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (

Molecular Heterogeneity In Pediatric Malignant Rhabdoid Tumors In Patients With Multi-Organ Involvement, Katherine E Miller, Margaret Shatara, Et Al

2020-Current year OA Pubs

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with

Efficient T Cell Migration And Activation Require L-Plastin, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T …

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

Antidiscrimination Law Through A Sociolegal Lens, Anna Offit

Faculty Journal Articles and Book Chapters

This Symposium invites reflection on whether the Anthropology of Law has “any space left for the content of rules” at a time when the concerns of legal anthropologists have largely shifted to processes, materials, and practices that are “adjacent to law.”1 Taking the jury system as an illustrative case, this Essay advocates for the relevance and value of the anthropological study of rules, their content, and their effects. Looking in particular at antidiscrimination rules derived from Batson v. Kentucky,2 decided in 1986, it argues that a sociolegal, ethnographic approach to how lawyers perpetuate discrimination in jury selection offers insight into …

Systematic Review With Meta-Analysis: Safety And Effectiveness Of Combining Biologics And Small Molecules In Inflammatory Bowel Disease, Quazim A Alayo, Osama Altayar, Matthew A Ciorba, Deborah Thomas, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND: Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients.

METHODS: We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.gov until November 3, 2020, including studies with 2 or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each …

Analyte-Sensing Particles And Impact Of Plastics On Environmentally Abundant Bacteria, Tania Thalyta Silva De Oliveira

Open Access Dissertations

Nano and microscale materials exhibit exciting chemical, physical and biological properties that dictate how they function. Furthermore, their surface chemistry influences how they respond to a specific application and interact with their surroundings. In this dissertation, a technique used to synthesize tunable hybrid gold nanoparticles for environmental sensing applications by Raman is presented, as well as the fate of nano and microplastics when in the presence of an abundant bacteria in the aquatic environment.Gold nanoparticles are widely used in many applications due to their various properties, such as facile synthesis, biocompatibility, surface conjugation with various ligand types, and tunability. The …

Chemically Tuned Sers Sensors And Signal Processing For Marine Sensing, Robert Chevalier

Open Access Dissertations

The aim of this dissertation was to explore and develop tools for marine sensing by surface-enhanced Raman spectroscopy (SERS). The first chapter focuses on the development of a real-time signal processing program to deal with background removal in different spectroscopic techniques such as UV/Vis, SERS and XPS. Background removal by a dual-tree complex wavelet transform with an iterative algorithm (DTCWT-IA) was compared to different background removal methods such as: linear, spline, Tougaard, Shirley, and unspecified proprietary methods from the instrument software companies. Unlike the more conventional methods, DTCWT-IA more resembled the presumed background shape and was generalizable across different spectroscopic …