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

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

Differences In Subjective Well-Being Between Individuals With Distinct Joint Personality (Temperament-Character) Networks In A Bulgarian Sample, Danilo Garcia, Maryam Kazemitabar, Kristina Stoyanova, Drozdstoy Stoyanov, C Robert Cloninger

2020-Current year OA Pubs

Background: Personality is the major predictor of people's subjective well-being (

Method: The sample consisted of 443 individuals from Bulgaria (68.70% females) with a mean age of 34 years (

Results: We found two Temperament Profiles and two Character Profiles that clustered into two distinctive Joint Personality Networks. All individuals in Joint Personality Network 1 had a Reliable (nhRP) Temperament Profile in combination with an Organized (SCt) Character Profile (

Conclusions: Although a stable temperament and a healthy character were separately important for well-being, it was clear that it was the interaction between such temperament and character configuration that yielded …

Child Dietary Patterns In Homo Sapiens Evolution: A Systematic Review, Lora L Iannotti, Emmanuel A Gyimah, Miranda Reid, Melissa Chapnick, Mary Kate Cartmill, Chessa K Lutter, Charles Hilton, Theresa E Gildner, Elizabeth A Quinn

2020-Current year OA Pubs

Dietary patterns spanning millennia could inform contemporary public health nutrition. Children are largely absent from evidence describing diets throughout human evolution, despite prevalent malnutrition today signaling a potential genome-environment divergence. This systematic review aimed to identify dietary patterns of children ages 6 months to 10 years consumed before the widespread adoption of agriculture. Metrics of mention frequency (counts of food types reported) and food groups (globally standardized categories) were applied to: compare diets across subsistence modes [gatherer-hunter-fisher (GHF), early agriculture (EA) groups]; examine diet quality and diversity; and characterize differences by life course phase and environmental context defined using Köppen-Geiger …

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

Examining Virtual Driving Test Performance And Its Relationship To Individuals With Hiv-Associated Neurocognitive Disorders, David Grethlein, Vanessa Pirrone, Kathryn N Devlin, Will Dampier, Zsofia Szep, Flaura K Winston, Santiago Ontañón, Elizabeth A Walshe, Kim Malone, Shinika Tillman, Beau M Ances, Venk Kandadai, Dennis L Kolson, Brian Wigdahl

2020-Current year OA Pubs

SIGNIFICANCE: Existing screening tools for HIV-associated neurocognitive disorders (HAND) are often clinically impractical for detecting milder forms of impairment. The formal diagnosis of HAND requires an assessment of both cognition and impairment in activities of daily living (ADL). To address the critical need for identifying patients who may have disability associated with HAND, we implemented a low-cost screening tool, the Virtual Driving Test (VDT) platform, in a vulnerable cohort of people with HIV (PWH). The VDT presents an opportunity to cost-effectively screen for milder forms of impairment while providing practical guidance for a cognitively demanding ADL.

OBJECTIVES: We aimed to: …

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 …

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 …

"Second-Class" Rhetoric, Ideology, And Doctrinal Change, Eric M. Ruben, Joseph Blocher

Faculty Journal Articles and Book Chapters

A common refrain in current constitutional discourse is that lawmakers and judges are systematically disfavoring certain rights. This allegation has been made about the rights to free speech and free exercise of religion, but it is most prominent in debates about the right to keep and bear arms. Such “second-class” treatment, the argument goes, signals that the Supreme Court must intervene aggressively to police the disrespected rights. Past empirical work casts doubt on the descriptive claim that judges and policymakers are disrespecting the Second Amendment, but that simply highlights how little we know about how the second-class argument functions as …

Extraterritoriality And Conflict Of Laws, Anthony J. Colangelo

Faculty Journal Articles and Book Chapters

This Article views the modern federal presumption against the extraterritoriality of U.S. law through the lens of conflict of laws. It argues that the presumption makes many of the same mistakes that conflict methodologies have already made, and sometimes the mistakes are worse. It then proposes a way to harmonize federal extraterritoriality and state choice of law to identify a superior approach to both.

Power, Primacy, And The Corporate Law Pivot, Grant M. Hayden, Matthew T. Bodie

Faculty Journal Articles and Book Chapters

As a Vice Chancellor, Chancellor, Chief Justice, and now a private citizen, Leo Strine has consistently recognized the shape of power relations within corporate law. With his wry wit and sharp prose, he has cut to the quick on issues such as director independence, shareholder rights, and the separation of ownership from ownership. Underlying these decisions are both the recognition of the underlying power dynamics at play and the pursuit of fairness under the law. As the Chief Justice has gone from lawmaker to commentator, his perspective has shifted on the role of corporate law in shaping society. Like him, …

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 …

Impacts Of Hypertension And Thrombosis In A Rat Model Of Cerebral Amyloid Angiopathy (Rtg-Di), Aleksandra Stanisavljevic

Open Access Dissertations

Hypertension (HTN) and thrombotic events cause vascular compromise and are both related to pathology of cerebral amyloid angiopathy (CAA). Both HTN and CAA are cerebral small vessel diseases that cause many of the same pathologies, particularly thrombosis, intracerebral hemorrhage, and stroke. The purpose of this dissertation is to elucidate how introducing the common vascular comorbidity HTN (with two differing rat models) or the pharmacological targeting of thrombin by dabigatran etexilate, impacts pathology in the transgenic rTg-DI rat model of CAA to elucidate mechanisms of the disease with and without a comorbidity.

Cross breeding of rTg-DI with Spontaneously Hypertensive Stroke Prone …

Chemical Biology Of Dna Adduct Repair, Bypass And Mutagenesis, Rui Qi

Open Access Dissertations

DNA is necessarily to be stable and intact since it is the repository of genetic information in each living cell. However, DNA is not inert, and it is vulnerable to the endogenous and environmental assault including reactive oxygen species (ROS), ultraviolet (UV) light, and various carcinogens. Exposure to these DNA damaging agents is associated with various adducts ranging from small methyl or etheno adducts to bulky adducts such as acetylaminofluorene. These resulting damages, if not repaired, will lead to replication block or mutation which can eventually cause cancer or other genetic diseases. The research covered by this dissertation falls into …

Bruton's Tyrosine Kinase Supports Gut Mucosal Immunity And Commensal Microbiome Recognition In Autoimmune Arthritis, Rachel H Bonami, Christina E Thurman, Sonam Verma, Camille S Westlake, Lindsay E Nyhoff, Bridgette B Barron, Andrea Reboldi, Peggy L Kendall

2020-Current year OA Pubs

Bruton's tyrosine kinase (

Epithelial Abnormalities In The Small Intestine Of Zambian Children With Stunting, Chola Mulenga, Sanja Sviben, Kanta Chandwe, Beatrice Amadi, Violet Kayamba, James A J Fitzpatrick, Victor Mudenda, Paul Kelly

2020-Current year OA Pubs

BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen

METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.

RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes …

Loss Of Function Of Wfs1 Causes Er Stress-Mediated Inflammation In Pancreatic Β-Cells, Shuntaro Morikawa, Lindsey Blacher, Chinyere Onwumere, Fumihiko Urano

2020-Current year OA Pubs

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration. Pathogenic variants in the

Distinguishing Tumor Admixed In A Radiation Necrosis (Rn) Background: 1h And 2h Mr With A Novel Mouse Brain-Tumor/Rn Model, Xia Ge, Kyu-Ho Song, John A Engelbach, Liya Yuan, Feng Gao, Sonika Dahiya, Keith M Rich, Joseph J H Ackerman, Joel R Garbow

2020-Current year OA Pubs

PURPOSE: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (

MATERIALS AND METHODS: A pipeline of common quantitative

RESULTS: Differences in quantitative

CONCLUSIONS: These findings, employing a pipeline of quantitative

Avoid Or Embrace? Practice Effects In Alzheimer's Disease Prevention Trials, Andrew J Aschenbrenner, Jason Hassenstab, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects"). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials …

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Leptomeningeal Disease And Tumor Dissemination In A Murine Diffuse Intrinsic Pontine Glioma Model: Implications For The Study Of The Tumor-Cerebrospinal Fluid-Ependymal Microenvironment, Shelei Pan, Dezhuang Ye, Yimei Yue, Lihua Yang, Christopher P Pacia, Dakota Defreitas, Prabagaran Esakky, Sonika Dahiya, David D Limbrick, Joshua B Rubin, Hong Chen, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor-CSF-ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG.

METHODS: A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic …

Metal Coordinating Inhibitors Of Rift Valley Fever Virus Replication, Elizabeth Geerling, Mohamed Elagawany, Bahaa Elgendy, Et Al

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1-103 and 50% effective concentrations of 1.2-56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective …

Expression Variation Of Ogg1 And Hprt Gene And Dna Damage In Arsenic Exposed Industrial Workers, Zertashia Akram, Ishrat Mahjabeen, Muhammad Umair, Muhammad Fahim, Mahmood Akhter Kayani, Lulu Fatima, Malik Waqar Ahmad, Sarwat Jahan, Tayyaba Afsar, Ali Almajwal, Nawaf W. Alruwaili, Iftikhar Ali Khawar, Suhail Razak

2020-Current year OA Pubs

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Low Risk For Developing Diabetes Among The Offspring Of Individuals With Exceptional Longevity And Their Spouses, Iva Miljkovic, Ryan Cvejkus, Ping An, Bharat Thyagarajan, Kaare Christensen, Mary Wojczynski, Nicole Schupf, Joseph M Zmuda

2020-Current year OA Pubs

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean …

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that

Parks As Persons: Legal Innovation Or Colonial Appropriation?, Alexandra Flynn

All Faculty Publications

This Article, considers personhood, a mechanism that has been used in other jurisdictions — including cities — to legally reconfigure land ownership.Te Urewara, once a national park in New Zealand, the Atrato River in Colombia, and the Magpie and Fraser Rivers in Canada became legal “persons” after decades of advocacy by Indigenous Peoples. These natural resources now have rights, a new material and representational making of property that centres a governance role for Indigenous Peoples. This Article asks what personhood could mean for Stanley Park and for Canadian urban parks more broadly. In particular, it explores whether personhood is a …

Concentration Of Fecal Coliforms In Marine Waters Using Satellite Images In The Vicinity Of Pucusana. Bay, Peru., Y A. Palma-Gongora, F V. Zuta-Medina, Luis Angel Gomez-Cunya

Civil Engineering Faculty Publications

Water quality monitoring in coastal areas is challenging due to cost and time constraints. Identifying and selecting sampling sites accurately and effectively is crucial for efficient monitoring. The need for efficient monitoring of marine waters has led to exploring the use of remote sensing as one helpful alternative. Remote sensing is practical in several applications based on pattern recognition and information processing of large terrestrial and aquatic surface areas. Collected information is processed with various image processing techniques to identify objects such as microorganisms. Fecal coliforms are microorganisms that are indicators of sanitary quality and are present in human and …