Digital Commons Network^™

Extensive Thiol Profiling For Assessment Of Intracellular Redox Status In Cultured Cells By Hplc-Ms/Ms, Jiandong Wu, Anna Chernatynskaya, Annalise Pfaff, Huari Kou, Nan Cen, Nuran Ercal, Honglan Shi

Computer Science Faculty Research & Creative Works

Oxidative stress may contribute to the pathology of many diseases, and endogenous thiols, especially glutathione (GSH) and its metabolites, play essential roles in the maintenance of normal redox status. Understanding how these metabolites change in response to oxidative insult can provide key insights into potential methods of prevention and treatment. Most existing methodologies focus only on the GSH/GSH disulfide (GSSG) redox couple, but GSH regulation is highly complex and depends on several pathways with multiple redox-active sulfur-containing species. In order to more fully characterize thiol redox status in response to oxidative insult, a high-performance liquid chromatography with tandem mass spectrometry …

Optimizing Exterior Lighting Illuminance And Spectrum For Human, Environmental, And Economic Factors., S. M. Simmons, Stuart Werner Baur, William L. Gillis, Devin Michael Burns, Heath Pickerill

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

With the recent widespread adoption of LED lighting in outdoor areas, numerous concerns have been raised about the potential for harmful effects on humans, animals, plants, and the night sky. These stem from the high blue light content of some LED bulbs and an incentive to increase lighting levels caused by higher efficiency and lower costs. While new lighting installations are often described as environmentally friendly due to their energy efficiency, factors such as light pollution are often neglected or not given enough weight. This research focuses on optimizing the design of exterior lighting for human, environmental, and economic factors …

The Center Cannot Hold: Zoom As A Potemkin Village, Hadar Aviram

FIU Law Review

The time has come to click the “join” button once more. It is the end of the semester, and our colleague Abe, chair of our ad-hoc task force for online teaching, has convened an online teaching excellence panel. The purveyors of said excellence are four faculty members whose evaluations showed that they were, as his email said, “online teaching rockstars.” Unfathomably, I am one of the four, and the last scheduled to present. One by one, little rectangles pop against the black backdrop of the screen, like the bubbles my three-year-old son and I blow in the backyard out of …

Stereotypes, Sexism, And Superhuman Faculty, Teneille R. Brown

FIU Law Review

This symposium article explores how law professors with caretaking responsibilities struggled so greatly during the first year of the COVID-19 pandemic. Because legal academia prioritizes masculine ideals of competence over warmth, faculty were expected to suppress their emotions and mental health needs in order to maintain the appearance of competence. While students were allowed to be seen as vulnerable individuals needing accommodations, we did not extend this same compassion to our faculty colleagues. To explain why the treatment was so disparate, I incorporated existing research on the stereotype content model (SCM) and psychological theories of dehumanization. These theories help to …

Cheshire County 4-H Presents!, Dugray

UNH Cooperative Extension

No abstract provided.

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/β cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …

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 …

Essential, Not Expendable: Protecting The Economic Citizenship Of Agricultural Workers, Hunter Knapp

University of Colorado Law Review

No abstract provided.

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Metabolic Mechanisms Connecting Alzheimer's And Parkinson's Diseases: Potential Avenues For Novel Therapeutic Approaches, Jerry R Colca, Brian N Finck

2020-Current year OA Pubs

Alzheimer's (AD) and Parkinson's Diseases (PD) are common neurodegenerative disorders growing in incidence and prevalence and for which there are no disease-modifying treatments. While there are considerable complexities in the presentations of these diseases, the histological pictures of these pathologies, as well as several rare genetic predispositions for each, point to the involvement of maladaptive protein processing and inflammation. Importantly, the common presentations of AD and PD are connected to aging and to dysmetabolism, including common co-diagnosis of metabolic syndrome or diabetes. Examination of anti-diabetic therapies in preclinical models and in some observational clinical studies have suggested effectiveness of the …

Associations Of Polymorphisms In The Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis, Tessa Schillemans, Sharon Cresci, Et Al

2020-Current year OA Pubs

No abstract provided.

Cilia Action In Islets: Lessons From Mouse Models, Jung Hoon Cho, Jing W Hughes

2020-Current year OA Pubs

Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause …