Digital Commons Network^™

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

The Past, Present, And Future Of A Human T-Cell Leukemia Virus Type 1 Vaccine, Joshua J Tu, Victoria Maksimova, Lee Ratner, Amanda R Panfil

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5-10 million persons are infected with HTLV-1 worldwide - a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and …

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Immune Deconvolution And Temporal Mapping Identifies Stromal Targets And Developmental Intervals For Abrogating Murine Low-Grade Optic Glioma Formation, Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Elizabeth Cordell, Astoria Chao, Suzanne Schaeffer, Andrea Goldstein, Sonika Dahiya, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Brain tumor formation and progression are dictated by cooperative interactions between neoplastic and non-neoplastic cells. This stromal dependence is nicely illustrated by tumors arising in the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, where children develop low-grade optic pathway gliomas (OPGs). Using several authenticated

METHODS: A combination of bulk and single-cell RNA mouse optic nerve sequencing, immunohistochemistry, T cell assays, and pharmacologic and antibody-mediated inhibition methods were used in these experiments.

RESULTS: We show that T cells and microglia are the main non-neoplastic immune cell populations in both murine and human LGGs. Moreover, we demonstrate that CD8

CONCLUSIONS: Collectively, …

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

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 …

Tourette Syndrome Research Highlights From 2021, Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Marinette Debes, Natalia Szejko, Keisuke Ueda, Kevin J. Black

2020-Current year OA Pubs

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers.

The Incidence Of Candidate Binding Sites For Β-Arrestin In Drosophila Neuropeptide Gpcrs, Paul H. Taghert

2020-Current year OA Pubs

To support studies of neuropeptide neuromodulation, I have studied beta-arrestin binding sites (BBS's) by evaluating the incidence of BBS sequences among the C terminal tails (CTs) of each of the 49 Drosophila melanogaster neuropeptide GPCRs. BBS were identified by matches with a prediction derived from structural analysis of rhodopsin:arrestin and vasopressin receptor: arrestin complexes [1]. To increase the rigor of the identification, I determined the conservation of BBS sequences between two long-diverged species D. melanogaster and D. virilis. There is great diversity in the profile of BBS's in this group of GPCRs. I present evidence for conserved BBS's in a …

Psychiatric Diagnoses And Medications In Wolfram Syndrome, Angela M Reiersen, Jacob S Noel, Tasha Doty, Richa A Sinkre, Anagha Narayanan, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the

OBJECTIVE: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

METHOD: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

RESULTS: Study participants with Wolfram …

Increased Virus Dissemination Leads To Enhanced Lung Injury But Not Inflammation During Influenza-Associated Secondary Bacterial Infection, Amanda P Smith, Lindey C Lane, Ivan Ramirez Zuniga, David M Moquin, Peter Vogel, Amber M Smith

2020-Current year OA Pubs

Secondary bacterial infections increase influenza-related morbidity and mortality, particularly if acquired after 5-7 d from the viral onset. Synergistic host responses and direct pathogen-pathogen interactions are thought to lead to a state of hyperinflammation, but the kinetics of the lung pathology have not yet been detailed, and identifying the contribution of different mechanisms to disease is difficult because these may change over time. To address this gap, we examined host-pathogen and lung pathology dynamics following a secondary bacterial infection initiated at different time points after influenza within a murine model. We then used a mathematical approach to quantify the increased …

Investigating How Speech And Animation Realism Influence The Perceived Personality Of Virtual Characters And Agents, Sean A. Thomas, Ylva Ferstl, Rachel Mcdonnell, Cathy Ennis

Articles

The portrayed personality of virtual characters and agents is understood to influence how we perceive and engage with digital applications. Understanding how the features of speech and animation drive portrayed personality allows us to intentionally design characters to be more personalized and engaging. In this study, we use performance capture data of unscripted conversations from a variety of actors to explore the perceptual outcomes associated with the modalities of speech and motion. Specifically, we contrast full performance-driven characters to those portrayed by generated gestures and synthesized speech, analysing how the features of each influence portrayed personality according to the Big …

The Rise Of The 'Immigrant-As-Injury' Theory Of State Standing, Jennifer Lee Koh

American University Law Review

Despite the Biden Administration’s efforts to hold itself out as a humane alternative to the excesses of immigration enforcement during the Trump presidency, federal courts have prevented a number of immigration policy changes from going forward during the first half of the Biden era. States serve as the primary plaintiffs in these lawsuits, which have impacted cornerstone immigration policies such as the termination of exclusionary border policies, the restoration of Deferred Action for Childhood Arrivals (DACA), and the application of enforcement priorities. During the 2022-23 term, the Supreme Court will hear certain states’ challenge to immigration enforcement priorities in United …

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

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: …

Cognitive And Brain Reserve Predict Decline In Adverse Driving Behaviors Among Cognitively Normal Older Adults, Samantha A Murphy, Ling Chen, Jason M Doherty, Prerana Acharyya, Noah Riley, Ann M Johnson, Alexis Walker, Hailee Domash, Maren Jorgensen, Sayeh Bayat, David B Carr, Beau M Ances, Ganesh M Babulal

2020-Current year OA Pubs

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain's adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer's …

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 …

Development Of A Food Composition Database For Assessing Nitrate And Nitrite Intake From Animal-Based Foods, Liezhou Zhong, Alex H. Liu, Lauren C. Blekkenhorst, Nicola P. Bondonno, Marc Sim, Richard J. Woodman, Kevin D. Croft, Joshua R. Lewis, Jonathan M. Hodgson, Catherine P. Bondonno

Research outputs 2022 to 2026

Scope:

Nitrate and nitrite are approved food additives in some animal-based food products. However, nitrate and nitrite in foods are strictly regulated due to health concerns over methaemoglobinaemia and the potential formation of carcinogenic nitrosamines. In contrast, plants (like leafy vegetables) naturally accumulate nitrate ions; a growing body of research reveals beneficial metabolic effects of nitrate via its endogenous conversion to nitric oxide. To refine the association of dietary nitrate and nitrite intake with health outcomes, reliable measures of nitrate and nitrite intake from dietary food records are required. While a vegetable nitrate content database has been developed, there is …

Evaluation Of Virtual Screening Strategies For The Identification Of Γ-Secretase Inhibitors And Modulators, Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino

Research outputs 2022 to 2026

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized …

Solving The Procedural Puzzles Of The Texas Heartbeat Act And Its Imitators: The Limits And Opportunities Of Offensive Litigation, Howard M. Wasserman, Charles W. Rhodes

American University Law Review

The Texas Heartbeat Act, enacted in 2021 as Senate Bill 8 (S.B. 8), prohibits abortions following detection of a fetal heartbeat, a constitutionally invalid ban under current Supreme Court precedent. But the method of enforcement in the Texas law is unique—it prohibits enforcement by government officials in favor of private civil actions brought by “any person,” regardless of injury. Texas sought to burden reproductive-health providers and rights advocates with costly litigation and potentially crippling liability.

In a series of articles, we explore how S.B. 8's reliance on exclusive private enforcement at the expense of public enforcement creates procedural and jurisdictional …

The Racial Justice Imperative To Reimagine Immigrant Children's Rights: Special Immigrant Juveniles As A Case Study, Dalia Castillo-Granados, Rachel Leya Davidson, Laila L. Hlass, Rebecca Scholtz

American University Law Review

The immigration legal system has codified and perpetuated racial violence in many ways, yet the experiences of young people of color in this system have yet to be deeply examined. This Article surfaces the distinct and varied racialized harms that children experience in the immigration system through the example of Special Immigrant Juveniles. Special Immigrant Juvenile Status (SIJS) is the only immigration status created for and limited to children. A child—defined in immigration law as someone who is under twenty-one years of age and unmarried—is eligible to seek SIJS with U.S. Citizenship and Immigration Services (USCIS) if a state court …

Defining "Habitat" Post-Weyerhaeuser: Critical Habitat Regulations Under The Endangered Species Act Must Promote Species Recovery, Nate Mccabe

American University Law Review

As one of the strongest federal environmental statutes, the Endangered Species Act (ESA) is a powerful tool for environmental litigators to uphold the important conservation objectives articulated by Congress in 1973. In recent years, the role of “critical habitat” within the ESA has come into question. The Supreme Court decided in Weyerhaeuser that “critical habitat” must also qualify as “habitat,” but it failed to articulate any guidelines for determining what “habitat” actually is. This decision incited a regulatory tug-of-war over the proper definition of “habitat” within the ESA. This Comment explores the approaches to defining “habitat” employed by the Trump …

Spider-Man: Work From Home And Retain No Copyright Under The Instance And Expense Test, Shahnoor Kamal Khan

American University Law Review

From Spider-Man to Ms. Marvel, superheroes are beloved by many, but owned by the few. Marvel Entertainment retains the copyright to iconic characters such as these, despite the fact that Marvel’s employees did not create them. These characters were created by freelance artists Jack Kirby, Steve Ditko, and Lawrence Lieber, among others. Yet, the Second Circuit ruled in Marvel Characters v. Kirby that these freelance artists have no claim of copyright over their own masterful works. The Second Circuit relied on the instance and expense test for copyright, as opposed to the Supreme Court’s leading copyright decision, Community for Creative …

It's About The Patients: Practical Antibiotic Stewardship In Outpatient Settings In The United States, Alpesh N Amin, E Patchen Dellinger, Glenn Harnett, Bryan D Kraft, Kerry L Laplante, Frank Lovecchio, James A Mckinnell, Glenn Tillotson, Salisia Valentine

2020-Current year OA Pubs

Antibiotic-resistant pathogens cause over 35,000 preventable deaths in the United States every year, and multiple strategies could decrease morbidity and mortality. As antibiotic stewardship requirements are being deployed for the outpatient setting, community providers are facing systematic challenges in implementing stewardship programs. Given that the vast majority of antibiotics are prescribed in the outpatient setting, there are endless opportunities to make a smart and informed choice when prescribing and to move the needle on antibiotic stewardship. Antibiotic stewardship in the community, or "smart prescribing" as we suggest, should factor in antibiotic efficacy, safety, local resistance rates, and overall cost, in …

Regulation Of Rod Photoreceptor Function By Farnesylated G-Protein Γ-Subunits, Alexander V. Kolesnikov, Elena Lobysheva, Jaya P. Gnana-Prakasam, Vladimir J. Kefalov, Oleg G. Kisselev

2020-Current year OA Pubs

Heterotrimeric G-protein transducin, Gt, is a key signal transducer and amplifier in retinal rod and cone photoreceptor cells. Despite similar subunit composition, close amino acid identity, and identical posttranslational farnesylation of their Gγ subunits, rods and cones rely on unique Gγ1 (Gngt1) and Gγc (Gngt2) isoforms, respectively. The only other farnesylated G-protein γ-subunit, Gγ11 (Gng11), is expressed in multiple tissues but not retina. To determine whether Gγ1 regulates uniquely rod phototransduction, we generated transgenic rods expressing Gγ1, Gγc, or Gγ11 in Gγ1-deficient mice and analyzed their properties. Immunohistochemistry and Western blotting demonstrated the robust expression of each transgenic Gγ in …

Hinterlands To Cities: The Archaeology Of Northwest Mexico And Its Vecinos, Matthew C. Pailes, Michael T. Searcy

Faculty Publications

Tis approachable book is a comprehensive synthesis of Northwest Mexico from the US border to the Mesoamerican frontier. Filling a vital gap in the regional literature, it serves as an essential reference not only for those interested in the specific history of this area of Mexico but western North America writ large. A period-by-period review of approximately14,000 years reveals the dynamic connections that knitted together societies inhabiting the Sea of Cortez coast, the Sonoran and Chihuahuan deserts, and the Sierra Madre Occidental. Networks of interaction spanned these diverse ecological, topographical, and cultural terrains in the millennia following the demise of …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

A T-Cell Engaging Bispecific Antibody With A Tumor-Selective Bivalent Folate Receptor Alpha Binding Arm For The Treatment Of Ovarian Cancer, Brian C Avanzino, Kirthana Prabhakar, Pranjali Dalvi, Sharon Hartstein, Hannes Kehm, Aarti Balasubramani, Andrew A Boudreau, Ben Buelow, Karen Chang, Laura M Davison, Suhasini Iyer, Vidyut Kalwit, Kristin Lewis Wilson, Harbani K Malik-Chaudhry, Will Pierson, Geovanni Pineda, Udaya S Rangaswamy, Sowmya Saiganesh, Ute Schellenberger, Harshad S Ugamraj, Rodolfovan D Yabut, Roland Buelow, Jocelyn Chapman, Nathan D Trinklein, Katherine E Harris

Faculty, Staff and Student Publications

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density …