Digital Commons Network^™

Tlr5 Agonists Enhance Anti-Tumor Immunity And Overcome Resistance To Immune Checkpoint Therapy, Caleb Gonzalez, Sarah Williamson, Seth T Gammon, Sarah Glazer, Joon Haeng Rhee, David Piwnica-Worms

Faculty, Staff and Student Publications

Primary and adaptive resistance to immune checkpoint therapies (ICT) represent a considerable obstacle to achieving enhanced overall survival. Innate immune activators have been actively pursued for their antitumor potential. Herein we report that a syngeneic 4T1 mammary carcinoma murine model for established highly-refractory triple negative breast cancer showed enhanced survival when treated intra-tumorally with either the TLR5 agonist flagellin or CBLB502, a flagellin derivative, in combination with antibodies targeting CTLA-4 and PD-1. Long-term survivor mice showed immunologic memory upon tumor re-challenge and a distinctive immune activating cytokine profile that engaged both innate and adaptive immunity. Low serum levels of G-CSF …

Systematic Design Of Adenosine Analogs As Inhibitors Of A Clostridioides Difficile- Specific Dna Adenine Methyltransferase Required For Normal Sporulation And Persistence, Jujun Zhou, John R Horton, Martina Menna, Francesco Fiorentino, Ren Ren, Dan Yu, Taraneh Hajian, Masoud Vedadi, Giulia Mazzoccanti, Alessia Ciogli, Elmar Weinhold, Michael Hüben, Robert M Blumenthal, Xing Zhang, Antonello Mai, Dante Rotili, Xiaodong Cheng

Faculty, Staff and Student Publications

Antivirulence agents targeting endospore-transmitted Clostridioides difficile infections are urgently needed. C. difficile-specific DNA adenine methyltransferase (CamA) is required for efficient sporulation and affects persistence in the colon. The active site of CamA is conserved and closely resembles those of hundreds of related S-adenosyl-l-methionine (SAM)-dependent methyltransferases, which makes the design of selective inhibitors more challenging. We explored the solvent-exposed edge of the SAM adenosine moiety and systematically designed 42 analogs of adenosine carrying substituents at the C6-amino group (N6) of adenosine. We compare the inhibitory properties and binding affinity of these diverse compounds and present the crystal structures of …

Antihuman T Lymphocyte Porcine Immunoglobulin Combined With Cyclosporine As First-Line Immunosuppressive Therapy For Severe Aplastic Anemia In China: A Large Single-Center, 10-Year Retrospective Study, Wenrui Yang, Xu Liu, Xin Zhao, Li Zhang, Guangxin Peng, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009.

OBJECTIVES: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019.

DESIGN: This is a single-center retrospective study of medical records.

METHODS: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to …

Trogocytosis Of Neurons And Glial Cells By Microglia In A Healthy Adult Macaque Retina, Megan Goyal, Andrea S Bordt, Jay Neitz, David W Marshak

Faculty, Staff and Student Publications

Microglial cells are the primary resident immune cells in the retina. In healthy adults, they are ramified; that is, they have extensive processes that move continually. In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. In the mouse hippocampus, microglia engulf small pieces of axons and presynaptic terminals via a process called trogocytosis. Here we report that microglia in the adult macaque retina also engulf pieces of neurons and glial cells, but not at sites of synapses. We analyzed microglia in a volume of …

Treatment Of Recurrent Carpal Tunnel Syndrome With Fat Grafting As An Adjunct, Raysa Cabrejo, Alison Podsednik, Joseph Rosen

School of Medicine Publications

Aim: The purpose of this study is to compare the surgical outcomes of treating recurrent carpal tunnel with recurrent carpal tunnel release only compared to recurrent carpal tunnel release with fat grafting as an adjunct.

Methods: Retrospective case-control study was performed of the recurrent carpal tunnels treated, excluding explicit nerve injury such as transections, neuromas in continuity, etc. Patients with recurrent carpal tunnel received re-release of carpal tunnel only or fat grafting as an adjunct. The outcomes of both groups were compared utilizing chi-square analysis.

Results: A total number of 81 patients were found to meet the …

A Clustering Of Heterozygous Missense Variants In The Crucial Chromatin Modifier Wdr5 Defines A New Neurodevelopmental Disorder, Lot Snijders Blok, Jolijn Verseput, Dmitrijs Rots, Hanka Venselaar, A Micheil Innes, Connie Stumpel, Katrin Õunap, Karit Reinson, Eleanor G Seaby, Shane Mckee, Barbara Burton, Katherine Kim, Johanna M Van Hagen, Quinten Waisfisz, Pascal Joset, Katharina Steindl, Anita Rauch, Dong Li, Elaine H Zackai, Sarah E Sheppard, Beth Keena, Hakon Hakonarson, Andreas Roos, Nicolai Kohlschmidt, Anna Cereda, Maria Iascone, Erika Rebessi, Kristin D Kernohan, Philippe M Campeau, Francisca Millan, Jesse A Taylor, Hanns Lochmüller, Martin R Higgs, Amalia Goula, Birgitta Bernhard, Danita J Velasco, Andrew A Schmanski, Zornitza Stark, Lyndon Gallacher, Lynn Pais, Paul C Marcogliese, Shinya Yamamoto, Nicholas Raun, Taryn E Jakub, Jamie M Kramer, Joery Den Hoed, Simon E Fisher, Han G Brunner, Tjitske Kleefstra

Faculty, Staff and Students Publications

WDR5 is a broadly studied, highly conserved key protein involved in a wide array of biological functions. Among these functions, WDR5 is a part of several protein complexes that affect gene regulation via post-translational modification of histones. We collected data from 11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11), intellectual disability (n = 9), epilepsy (n = 7), and autism spectrum disorder (n = 4). Additional phenotypic features …

Descartes Meets Samkhya, Edgar J. Vasquez

McNair Scholars Research Journal

One of the great shortcomings of Cartesian Mind-Body Dualism has been what is known as the Mind-Body Problem. Specifically, how does the mind (an immaterial substance) affect the body (a material substance) and vice versa. The credit for the identification of this problem is often given to Princess Elisabeth of Bohemia. One of the first Indian philosophical traditions, Samkhya, provides a strict Dualism as Descartes does but does not encounter the Mind-Body Problem. Samkhya avoids the problem of mind-body interaction by drawing the dividing line differently than Descartes does. Instead of dividing the world into mental and physical, Samkhya divides …

Probing The Role Of The Ventral Hippocampus To Nucleus Accumbens Pathway In Individual Differences In Appetitive Learning, Jacklyn C. Staffeld

McNair Scholars Research Journal

A critical issue in substance abuse research is why some individuals can actively use addictive drugs and quit with relative ease, while others may only try a small dose before becoming life-long dependent (Fitzpatrick et al., 2016). The use of designer receptors exclusively activated by designer drugs (DREADDs) may shed light on individual differences in learning behaviors and why some individuals seem to be more prone to addiction and relapse than others. Using stereotaxic surgery on rats, an in vivo dual-vector approach was used to bilaterally inject Cre recombinase into the nucleus accumbens (NAc) and an excitatory Cre-dependent, G protein-coupled …

Habitat Fragmentation Reduces Survival And Drives Source–Sink Dynamics For A Large Carnivore, Anna C. Nisi, John F. Benson, Richard King, Christopher C. Wilmers

School of Natural Resources: Faculty Publications

Rigorous understanding of how environmental conditions impact population dynamics is essential for species conservation, especially in mixed-use landscapes where source–sink dynamics may be at play. Conservation of large carnivore populations in fragmented, human-dominated landscapes is critical for their long-term persistence. However, living in human-dominated landscapes comes with myriad costs, including direct anthropogenic mortality and sublethal energetic costs. How these costs impact individual fitness and population dynamics are not fully understood, partly due to the difficulty in collecting long-term demographic data for these species. Here, we analyzed an 11-year dataset on puma (Puma concolor) space use, mortality, and reproduction …

Brief Of Legal Scholars As Amici Curiae In Support Of Petitioners, Pamela Foohey

Amicus Briefs

Amici curiae are professors at law schools throughout the United States. Amici’s expertise encompasses student-financial-assistance programs under Title IV of the Higher Education Act of 1965, consumer finance, administrative and constitutional law, modes of statutory interpretation, and the development of the major questions doctrine. Amici have a strong interest in assisting this Court in resolving questions of law that go to the core of their professional expertise and scholarship, namely, the scope of the Department of Education’s authority to provide relief to borrowers and the development of this Court’s statutory interpretation methodology, particularly in the context of its precedent …

Investigating The Absence Of A Dietary Response At The Neuromuscular Junction In Larval Drosophila Melanogaster, Suzanna Louise Marbach

Honors Program Theses and Research Projects

Research in Drosophila melanogaster (D. melanogaster) has been growing in order to identify the fundamental processes of human disorders of the central nervous system such as Alzheimer’s disease, diabetes, and other neurological disorders at a molecular level. Altered insulin signaling itself has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathies, and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on nervous system function is still incomplete. The focus behind investigating the insulin signaling pathway is derived from our observations in the adult D. melanogaster neuromuscular junction (NMJ) to changes in …

Metamorphis, Luca Lee Sobarzo Faust

Theses and Dissertations

Web3D interactive experience that explores time, communication, and transformation, from a personal storytelling perspective. Hosted on a web platform, the experience displays three environments: Metamorphis, Cuir AI, and Hain. These spaces propose a fragmented narrative that seeks to interrogate both the characters and the viewer’s perception on the linearity of time

Sound Enhances Sea Turtle Conservation, Erin Garrett

University of Mississippi News

OXFORD, Miss. – Two researchers at the University of Mississippi's National Center for Physical Acoustics are battling sea turtle endangerment with an unlikely weapon.

Sgc-Camkk2-1: A Chemical Probe For Camkk2, Carrow Wells, Yi Liang, Thomas L Pulliam, Chenchu Lin, Dominik Awad, Benjamin Eduful, Sean O'Byrne, Mohammad Anwar Hossain, Carolina Moura Costa Catta-Preta, Priscila Zonzini Ramos, Opher Gileadi, Carina Gileadi, Rafael M Couñago, Brittany Stork, Christopher G Langendorf, Kevin Nay, Jonathan S Oakhill, Debarati Mukherjee, Luigi Racioppi, Anthony R Means, Brian York, Donald P Mcdonnell, John W Scott, Daniel E Frigo, David H Drewry

Faculty, Staff and Student Publications

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

Michael Pappas, Oral History Interview, 2023, Matt Jones

Oral Histories

Mike Pappas, brother of fellow Arm Tony Pappas, was an active member of the Arm of Honor Fraternity from 1970-1974, living in the Arm house fo the entirety of his stint at EMU. Growing up in Ypsilanti Township and Ann Arbor, Pappas describes the Seven Seas Restaurant, which his parents owned and lived above, and his formative years at St. John's Catholic School in Ypsilanti. Pappas describes the Ypsilanti he knew as a child and the differences between the local religious schools. Pappas describes hitchhikinig culture of the 1960s, and talks about how improtant the history fo the Arm of …

Office Of Research, Economic Engagement And Outreach Update, January 11, 2023, Office Of Research, Economic Engagement And Outreach

Office of Research, Economic Engagement and Outreach

No abstract provided.

Risk Factors For Strabismus Surgery After Pediatric Cataract Surgery In The United States, Bryce Hwang, Isdin Oke, Scott R. Lambert

Wills Eye Hospital Papers

Purpose: To determine the cumulative incidence of strabismus surgery after pediatric cataract surgery and identify the associated risk factors.

Design: US population-based insurance claims retrospective cohort study.

Participants: Patients ≤ 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics Data Mart (2003e2021) and IBM MarketScan (2007e2016). Methods: Individuals with at least 6 months of prior enrollment were included, and those with a history of strabismus surgery were excluded. The primary outcome was strabismus surgery within 5 years of cataract surgery. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), intraocular lens (IOL) placement, nystagmus …

Driverdrowsyandyawnsystemalertusingdeepcascadeconvolutionneuralnetworkdccnn, Zainab Ali Abbood, Janan Farag Yonan

Iraqi Journal for Computer Science and Mathematics

Driver drowsiness and fatigue are widely recognized as prevailing factors contributing to motor vehicle collisions. Annually, there is a significant increase in the number of deaths and fatalities due to a multitude of factors. The implementation of a driver warning system is imperative in order to mitigate traffic accidents, ultimately resulting in the preservation of human lives and public infrastructure. In this article, DDDS utilizing eye measure and head measure ensued developed as well as implemented. The DDDS was designed utilizing a high-resolution camera and employs Deep Cascaded Convolutional Neural Networks (DCCNN) to accurately identify instances of driver drowsiness. The …

Microbiomes In Acne Vulgaris And Their Susceptibility To Antibiotics In Indonesia: A Systematic Review And Meta-Analysis, Lili Legiawati, Paulus Anthony Halim, Magna Fitriani, Hardya Gustada Hikmahrachim, Henry W. Lim

Dermatology Articles

Hot and humid countries such as Indonesia have a higher prevalence of acne vulgaris (AV). The activity of skin microbes, not only Cutibacterium acnes, contribute to the formation of AV. Topical and oral antibiotics are routinely prescribed to treat AV. As antimicrobial resistance rates increase globally, there are concerns about decreased efficacy. This study intends to systematically evaluate the microbiomes isolated from AV lesions and their antibiotics susceptibility in Indonesia. The data were retrieved through PubMed, EMBASE, Google Scholar, and ScienceDirect searches for articles published until July 2022 using three multiword searches. Sixteen studies published between 2001 and 2022 were …

Class 1 And 2 Integrons In Escherichia Coli Strains Isolated From Diarrhea And Bacteremia In Children Less Than 2 Years Of Age From Peru, Maribel Riveros, Maria J Pons, David Durand, Theresa J Ochoa, Joaquim Ruiz

Faculty, Staff and Student Publications

Class 1 and Class 2 integrons are mobilizable elements able to carry a variety of antibiotic resistance determinants. In the present study, Class 1 and 2 integrons present in 355 pathogenic Escherichia coli (285 diarrheagenic, of these 129 were enteropathogenic, 90 enteroaggregative, 66 enterotoxigenic, and 70 bacteremic) isolated from healthy and ill children under age 5 from periurban areas of Lima, Peru, were characterized. The presence of integrase 1 and 2 was established by polymerase chain reaction (PCR), and variable regions were grouped by PCR-restriction fragment length polymorphism and subsequent sequencing. Antimicrobial resistance was established by disk diffusion. Ninety-seven isolates …

Characterization Of Antiviral Immunity, Host Virus Interactions, And Toxicity Of Agrochemical Residues In The Western Honey Bee, Christopher Fellows

LSU Doctoral Dissertations

Honey bee colonies have perished at an alarming rate for over 15 years. Among the multitude of threats to bee health, virus infections and agrochemical exposure appear to be major drivers of colony loss. As virus infection is among the most damaging influences on bee health, we first investigated a putative target for antiviral immunity, termed K_ATP channels. We previously demonstrated that pharmacologically activating K_ATP channels induces the production of reactive oxygen species and increases survival during infection with Israeli Acute Paralysis Virus. Here, we demonstrate that K_ATP modulation and ROS induction reduce virus replication and enhance …

Antibody-Drug Conjugates In Lung Cancer: Dawn Of A New Era?, Niamh Coleman, Timothy A Yap, John V Heymach, Funda Meric-Bernstam, Xiuning Le

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) are one of fastest growing classes of oncology drugs in modern drug development. By harnessing the powers of both cytotoxic chemotherapy and targeted therapy, ADCs are unique in offering the potential to deliver highly potent cytotoxic agents to cancer cells which express a pre-defined cell surface target. In lung cancer, the treatment paradigm has shifted dramatically in recent years, and now ADCs are now joining the list as potential options for lung cancer patients. Since 2020, the first ADC for NSCLC patients has been FDA-approved (trastuzumab deruxtecan) and two ADCs have been granted FDA Breakthrough Therapy Designation, …

Food Web Structure And Microenvironment Affect Chagas Disease Vector Infection And Abundance In A Rural Landscape, Azael Saldaña, Christina P. Varian, Jennifer K. Peterson, Jose E. Calzada, Multiple Additional Authors

University Honors College Faculty Publication and Presentations

Vector-borne pathogen transmission is shaped by multiple abiotic and biotic factors. Understanding the relative importance of these factors on vector abundance and infection is important for developing vector-borne disease control strategies. The crown of the Attalea butyracea palm provides a natural arboreal mesocosm suitable for studying how food web relations and microclimate affect Chagas disease vectors of the genus Rhodnius, which feed on vertebrate blood and interact with many vertebrate and invertebrate species, vegetation, and detritus within the palm crown. We performed a cross-sectional, observational study of A. butyracea crowns using a community ecology network approach to evaluate abiotic …

Enhanced Neutralization Resistance Of Sars-Cov-2 Omicron Subvariants Bq1, Bq11, Ba46, Bf7, And Ba2752, Panke Qu, John P Evans, Julia N Faraone, Yi-Min Zheng, Claire Carlin, Mirela Anghelina, Patrick Stevens, Soledad Fernandez, Daniel Jones, Gerard Lozanski, Ashish Panchal, Linda J Saif, Eugene M Oltz, Kai Xu, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

The continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Here, we examine the neutralization resistance of these subvariants against sera from 3-dose vaccinated healthcare workers, hospitalized BA.1-wave patients, and BA.4/5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially in the BQ.1 and BQ.1.1 subvariants driven by N460K and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. All Omicron subvariants maintained their weakened infectivity in Calu-3 cells, with the F486S mutation driving further diminished titer for the BA.2.75.2 subvariant. …

Does Covid-19 Pandemic Crisis Affect Csr Costs? Case Of Indonesia, Elisabeth Ria Viana Praningtyas, Rini Subekti, Putu Ayu Anggya Agustina

Journal of Accounting Auditing and Business

The outbreak of COVID-19 that has been happening all around the world since early 2020 was a tough challenge for business entities. What was let down to keep the business alive was none other than sustainability performance, which is funded by CSR cost. This study examines the potential moderation effect of the COVID-19 pandemic crisis on the relationship between the company size and the current ratio of CSR costs, especially for developing countries. The data was collected from public companies listed on Indonesia Stock Exchange from 2019-2020. This study shows that regarding the size of the company, the commitment to …

Full Issue

Insights: The Newsletter of the Neal A. Maxwell Institute for Religious Scholarship

No abstract provided.

Investigating New World Volcanism At The Time Of Christ’S Death

Insights: The Newsletter of the Neal A. Maxwell Institute for Religious Scholarship

A recent article in the Journal of Book of Mormon Studies reported that ice cores taken from Greenland and Antarctica yield evidence broadly consistent with the 3 Nephi 8 account of cataclysmic New World events—presumably including a violent volcanic eruption—at the time of Christ’s death (Benjamin R. Jordan, “Volcanic Destruction in the Book of Mormon: Possible Evidence from Ice Cores,” JBMS 12/1 [2003]: 78–87). What other methods might yield corroborating evidence of
such an eruption? Two possibilities are the analysis of tree rings and sea and lake sediments.

Sustainable Consumption And The Fair Trade Idea Versus The Consumption Behavior Of Young Singles In Poland, Tomasz Zalega

European Management Studies

Purpose: The article is a research paper. The aim of this study is to provide some insight into the consumption behavior of young Polish singles that conform to the idea of sustainable consumption and the fair trade movement. Design/methodology: The methodological part synthetically discusses the conceptualization of research and selection of the research sample. The empirical part, based on the research conducted by the author, examines young Polish singles’ pro-environmental behaviors that can be defined as sustainable consumption and are aligned with the fair trade idea. The analysis is based on a survey questionnaire administered from 1 October to 30 …

Leveraging Genetic Diversity In Mice To Inform Individual Differences In Brain Microstructure And Memory., Thomas J Murdy, Amy R Dunn, Surjeet Singh, Maria Telpoukhovskaia, Shanrong Zhang, Jacqueline K White, Itamar Kahn, Marcelo Febo, Catherine Kaczorowski

Faculty Research 2023

In human Alzheimer's disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically …

Zoom Affordances And Identity: A Case Study, Angela Cirucci

College of Communication & Creative Arts Departmental Research

While how to engage students in online settings is a popular topic of study, largely left out are the ways in which virtual learning environments (VLEs) have implications for identity performance (and subsequently learning quality). This case study pairs a walkthrough analysis of Zoom with an open-ended survey (n = 250, M = 21.5) to investigate how VLE affordances impact student identifications. Findings indicate that students prefer Zoom because it is “user-friendly,” forgoing wordy options and instead presenting a more “appified” user interface. Students were concerned about their classmates and professors seeing their physical backgrounds, particularly those who reported family …