Digital Commons Network^™

Pgc1Α/Β Expression Predicts Therapeutic Response To Oxidative Phosphorylation Inhibition In Ovarian Cancer, Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R Marszalek, Christopher P Vellano, Roberta Pastorelli, Mariarosa Bani, Alessandra Decio, Raffaella Giavazzi

Faculty, Staff and Student Publications

Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling …

Camk2/Camkii Activates Mlkl In Short-Term Starvation To Facilitate Autophagic Flux, Qionghui Zhan, Jaepyo Jeon, Ying Li, Yu Huang, Jian Xiong, Qiaochu Wang, Tian-Le Xu, Yong Li, Fu-Hai Ji, Guangwei Du, Michael X Zhu

Faculty, Staff and Student Publications

MLKL (mixed lineage kinase domain like pseudokinase) is a well-known core component of necrosome that executes necroptotic cell death upon phosphorylation by RIPK3 (receptor interacting serine/threonine kinase 3). Recent studies also implicate a role of MLKL in endosomal trafficking, which is not always dependent on RIPK3. Using mouse Neuro-2a and L929 as well as human HEK293 and HT29 cells, we show here that MLKL is phosphorylated in response to serum and amino acid deprivation from the culture medium, in a manner that depends on CAMK2/CaMKII (calcium/calmodulin dependent protein kinase II) but not RIPK3. The starvation-induced increase in MLKL phosphorylation was …

The Paradox Of Immunosuppressants And Covid-19, Guang-Shing Cheng, Scott E Evans

Faculty, Staff and Student Publications

Lessons learned from a large registry analysis show worse COVID-19 outcomes for patients previously exposed to glucocorticoids https://bit.ly/306rNrk

Alterations Of The Mdm2 C-Terminus Differentially Impact Its Function In Vivo, Vinod Pant, Neeraj K Aryal, Shunbin Xiong, Gilda P Chau, Natalie W Fowlkes, Guillermina Lozano

Faculty, Staff and Student Publications

Murine double minute 2 (Mdm2) is the principal E3-ubiquitin ligase for p53 and contains a C2H2C4 type RING domain wherein the last cysteine residue is followed by an evolutionarily conserved 13 amino acid C-terminal tail. Previous studies have indicated that integrity of the C-terminal tail is critical for Mdm2 function. Recently, a mutation extending the MDM2 length by five amino acids was identified and associated with enhanced p53 response in fibroblasts and premature aging in a human patient. To investigate the importance of the conserved Mdm2 C-terminal length on p53 regulatory function in vivo, we engineered three novel mouse alleles …

Β-Adrenergic Signaling In Skin Cancer, Jennifer Batalla-Covello, Shahrukh Ali, Tongxin Xie, Moran Amit

Faculty, Staff and Student Publications

Activation of the sympathetic nervous system releases catecholamines that can interact with β-adrenergic receptors on tumor cells. Preclinical models have shown that the signaling processes initiated by activation of β-adrenergic receptors increase tumorigenesis, stimulate cell proliferation, and inhibit apoptosis. Indeed, preclinical studies have also shown that β-adrenergic blockade can decrease tumor burden. Researchers have been studying the effects of β-adrenergic receptor blockers on tumor cells and how they may slow the progression of melanoma, basal cell carcinoma, and squamous cell carcinoma. Moreover, clinical data have shown improved prognosis in patients with skin cancer who take β-blockers. This review discusses the …

Inhibition Of Bcl2a1 By Stat5 Inactivation Overcomes Resistance To Targeted Therapies Of Flt3-Itd/D835 Mutant Aml, Kotoko Yamatani, Tomohiko Ai, Kaori Saito, Koya Suzuki, Atsushi Hori, Sonoko Kinjo, Kazuho Ikeo, Vivian Ruvolo, Weiguo Zhang, Po Yee Mak, Bogumil Kaczkowski, Hironori Harada, Kazuhiro Katayama, Yoshikazu Sugimoto, Jered Myslinski, Takashi Hato, Takashi Miida, Marina Konopleva, Yoshihide Hayashizaki, Bing Z Carter, Yoko Tabe, Michael Andreeff

Faculty, Staff and Student Publications

Tyrosine kinase inhibitors (TKIs) are established drugs in the therapy of FLT3-ITD mutated acute myeloid leukemia (AML). However, acquired mutations, such as D835 in the tyrosine kinase domain (FLT3-ITD/D835), can induce resistance to TKIs. A cap analysis gene expression (CAGE) technology revealed that the gene expression of BCL2A1 transcription start sites was increased in primary AML cells bearing FLT3-ITD/D835 compared to FLT3-ITD. Overexpression of BCL2A1 attenuated the sensitivity to quizartinib, a type II TKI, and venetoclax, a selective BCL2 inhibitor, in AML cell lines. However, a type I TKI, gilteritinib, inhibited the expression of BCL2A1 through inactivation of STAT5 and …

The Nephrocheck Bedside System For Detecting Stage 3 Acute Kidney Injury After Open Thoracoabdominal Aortic Repair, Mark Hwang, Michael H Weisman

Faculty, Staff and Student Publications

No abstract provided.

Interspecific And Ontogenic Differences In The Molar Occlusal Surfaces Of Manatees (Sirenia: Trichechidae), Lyle Goulbourne

Honors Theses

While much is known regarding limitless horizontal replacement of manatee teeth, the morphology and topography of the teeth have not been formally described, nor have interspecific differences and ontogenic changes in relative tooth size been described in detail. To physically describe the teeth, photographs of the molars from West Indian manatees (Trichechus manatus) and Amazonian manatees (T. inunguis) were taken and the features of the teeth were identified. To compare tooth size differences, the area of the posterior-most molar in occlusion was measured from both the upper and lower molars of the manatee skulls from West Indian and Amazonian manatees. …

Effects Of Socioeconomic Status On Consumer Behavior And Attitudes Towards A Brand’S Image, Abbey Haymond

Honors Program: Senior Projects (Public)

This research seeks to understand more about the effects of socioeconomic background on consumer behavior and its impact on the perception of brand images. Data from people of different SES were compared to understand how they view advertisements intended for different audiences and their corresponding effects. It was conducted by sending out a confidential, voluntary survey to a convenience sample targeting 100 consumers. Consumers were asked to rate statements, on a scale of one to five, for each of the research questions to assess specific aspects of their consumer attitudes and behaviors. The high SES group has a higher average …

Hiv-Associated Nephropathy Presenting As The First Manifestation Of Hiv-2 Infection, Kamil Sardarli, Rania Daboul, Sumesh Khanal, Sami Zarouk

Conference Presentation Abstracts

HIV-2 is distinguished from HIV-1 with low virulence, longer asymptomatic period, slower decline in CD4 count, low viral load, and low mortality from AIDS. While the kidney pathology associated with HIV-1 is well established, due to its low prevalence, kidney pathology in HIV-2 is not well documented. We report a case of HIV associated nephropathy (HIVAN) as the first presentation in a patient with HIV-2. A 65 year old man from Ghana presented within a few days of arrival to the United States with nausea, loss of appetite, shortness of breath, and bilateral lower extremity edema. He has a past …

Inhibiting Type I Arginine Methyltransferase Activity Promotes T Cell-Mediated Antitumor Immune Responses, Andrew Fedoriw, Leilei Shi, Shane O'Brien, Kimberly N Smitheman, Yunfei Wang, Jiakai Hou, Christian Sherk, Satyajit Rajapurkar, Jenny Laraio, Leila J Williams, Chunyu Xu, Guangchun Han, Qin Feng, Mark T Bedford, Linghua Wang, Olena Barbash, Ryan G Kruger, Patrick Hwu, Helai P Mohammad, Weiyi Peng

Faculty, Staff and Student Publications

Protein arginine methyltransferases (PRMT) are a widely expressed class of enzymes responsible for catalyzing arginine methylation on numerous protein substrates. Among them, type I PRMTs are responsible for generating asymmetric dimethylarginine. By controlling multiple basic cellular processes, such as DNA damage responses, transcriptional regulation, and mRNA splicing, type I PRMTs contribute to cancer initiation and progression. A type I PRMT inhibitor, GSK3368715, has been developed and has entered clinical trials for solid and hematologic malignancies. Although type I PRMTs have been reported to play roles in modulating immune cell function, the immunologic role of tumor-intrinsic pathways controlled by type I …

Pan-Methylarginine Antibody Generation Using Peg Linked Gar Motifs As Antigens, Yalong Wang, Maria D Person, Mark T Bedford

Faculty, Staff and Student Publications

Arginine methylation is a prevalent posttranslational modification which is deposited by a family of protein arginine methyltransferases (PRMTs), and is found in three different forms in mammalian cells: monomethylarginine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Pan-methylarginine antibodies are critical for identifying proteins that are methylated on arginine residues, and are also used for evaluating signaling pathways that modulate this methyltransferase activity. Although good pan-MMA, -ADMA and -SDMA antibodies have been developed over the years, there is still room for improvement. Here we use a novel antigen approach, which involves the separation of short methylated motifs with inert polyethylene …

Comparative Molecular Genomic Analyses Of A Spontaneous Rhesus Macaque Model Of Mismatch Repair-Deficient Colorectal Cancer, Nejla Ozirmak Lermi, Stanton B Gray, Charles M Bowen, Laura Reyes-Uribe, Beth K Dray, Nan Deng, R Alan Harris, Muthuswamy Raveendran, Fernando Benavides, Carolyn L Hodo, Melissa W Taggart, Karen Colbert Maresso, Krishna M Sinha, Jeffrey Rogers, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

Effect Of Perfluorocarbon Composition On Activation Of Phase-Changing Ultrasound Contrast Agents, Trevor M Mitcham, Dmitry Nevozhay, Yunyun Chen, Linh D Nguyen, Gianmarco F Pinton, Stephen Y Lai, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US.

PURPOSE: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical …

Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

Faculty, Staff and Student Publications

PURPOSE: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV-induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus-induced immunotherapy.

EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of patients with recurrent glioblastoma (GBM) treated with oHSV was used to evaluate the effect of NOTCH signaling on virus-induced immunotherapy.

RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly …

Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu

Faculty, Staff and Student Publications

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.

Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.

Setting: From 2010 to 2018, 8-15 counties/districts of West China were included.

Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.

Results: …

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

Citation Analysis Of The Most Influential Ependymoma Research Articles Illustrates Improved Knowledge Of The Molecular Biology Of Ependymoma, Nolan J Brown, Bayard Wilson, Brian V Lien, Alexander Himstead, Ali R Tafreshi, Shane Shahrestani, Jack Birkenbeuel, Katelynn Tran, David Horton, Anushka Paladugu, Lydia R Kirillova, Chen Yi Yang, Seth C Ransom, Ronald Sahyouni, Isaac Yang

Faculty, Staff and Student Publications

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, …

Role Of Government In Protecting The Institution Of Marriage, Laila El Baradei

Faculty Journal Articles

No abstract provided.

Diversity, Equity, Inclusion: Crucial For Organizational Learning And Health Equity, Bret Lyman, Joy Parchment, Kaitlyn C. George

Faculty Publications

Achieving health equity requires a diversity of perspectives, values, and insights, yet the composition of the United States’ nursing workforce does not reflect the communities where they practice. Nurse leaders can advance health equity and exemplary clinical outcomes by creating diverse, equitable, and inclusive health care teams. Such teams are well-equipped for organizational learning, a crucial process for advancing health equity. Nurse leaders advance health equity by fostering diversity, equity, inclusion, and thus organizational learning in the workplace.

Shadow Nursing Home Ownership: How A Failure In Government Oversight Of For-Profit Nursing Homes In New York Has Allowed Profits To Balloon And Standards Of Care To Plummet, Marissa Espinoza

Cardozo Journal of Equal Rights & Social Justice

Complex corporate nursing home structures have become commonplace in for-profit nursing home ownership. These structures, designed to shield owners from regulation and liability, allow owners to evade public scrutiny by obscuring the identify of true owners and allow the true owners to direct revenue to other companies they own or benefit from, such as staffing agencies, payroll businesses, and management companies. This has led to a deterioration in the standard of care for nursing home residents, society's most vulnerable population, while providing a boon in profits for the true owners. Money that should be spent on care is instead diverted …

The Roberts Court's Transformative Religious Freedom Cases: The Doctrine And The Politics Of Grievance, Stephen M. Feldman

Cardozo Journal of Equal Rights & Social Justice

The article argues that the Roberts Court has adopted a conservative approach in religious freedom cases, shifting toward a jurisprudence that favors Christianity and undermines the separation of church and state. This approach, rooted in tradition and a de facto Christian America, has led to significant changes in both Establishment Clause and Free Exercise Clause doctrines. The Court's decisions increasingly protect Christian practices and institutions while marginalizing non-Christian religions, reflecting a broader ideological shift toward judicial engagement and away from principles of federalism and judicial restraint.

Hostile Shores: Racial Exclusion Laws And The West Coast, Brendan Williams

Cardozo Journal of Equal Rights & Social Justice

The article examines the historical and ongoing racial exclusion laws on the West Coast, focusing on California, Oregon, and Washington. It argues that despite their progressive reputation, these states have a legacy of discriminatory laws targeting Chinese, Black, and Japanese populations, which has led to enduring racial inequities that persist today.

Effects Of Gamification On Knowledge Acquisition: Aviation Weather Online Training, Jacqueline Mcsorley

Doctoral Dissertations and Master's Theses

Due to the high popularity of gaming, researchers have begun to implement aspects of these games into real life (known as gamification). Motivation and engagement may be influenced by certain game mechanics and user types, which then could also impact learning. A gap still exists as to whether leaderboards and narratives impact motivation or engagement when implemented in a non-game context (i.e., an online training program). Studies indicate that aviation weather training for general aviation pilots is underdeveloped, particularly for NEXRAD. In considering the competitive/ goal-oriented nature of pilots, gamification elements such as Achievements and Stories could best motivate pilots-in-training …

The Cost Of Playing The Game: Modeling In-Game Purchase Intention And Investigating Purchase Behavior Of Mobile Gamers, William J. Shelstad

Doctoral Dissertations and Master's Theses

Free-to-play games typically have a monetization model that relies on players to purchase in-game items or virtual goods to generate revenue (Nguyen, 2015). There have been several empirical efforts to investigate purchase intention of virtual goods in video games with some focusing on quantitative models of purchase intention. Most of these studies tend to be with virtual worlds and lack the use of validated instruments to measure constructs (Hamari & Keronen, 2017). This research sought to gain a greater understanding of purchase intention of in-game content or virtual goods in mobile games through two studies.

Study 1 modeled purchase intention …

The Impact Of Individual And Team-Level Variables On Burnout In Healthcare Providers, Logan M. Gisick

Doctoral Dissertations and Master's Theses

Burnout among medical providers is a growing issue with effects that start at the provider level and span outward to affect the entire hospital system. The consensus of the literature is that there are multiple categories of factors which lead to the development of burnout including personal characteristics, social characteristics, and job/work characteristics. Because of the highly collaborative and interpersonal nature of healthcare work, the interactions among team members have the potential to significantly influence provider burnout and recent studies are beginning to examine this interaction more carefully. However, there is little research that examines the relationship between multiple personal …

Annotated Legal Bibliography

Cardozo Journal of Equal Rights & Social Justice

No abstract provided.

Field Research In The Era Of The Islamic State And Trump, William Yaworsky, Dawid K. Wladyka, Katarzyna Sepielak

Anthropology Faculty Publications

We survey anthropologists who work in Arab League countries to ascertain their perceptions of fieldwork security conditions. Based on the responses of forty-seven specialists reporting on conditions in 127 field sites, we find the security environment in the Arab League to be diverse. Scholars working in nations such as Morocco, Oman, and Qatar report overwhelmingly favorable research conditions, while their colleagues working in Lebanon and Syria report a largely dismal situation. The paper also queries respondents on their perceptions of the impact that Trump administration policies and rhetoric have on their ongoing field research. Here, we find Arab League specialists …

Pharmacological Extension Of Lifespan Via Mitochondrial Uncoupling In Drosophila Melanogaster, Analisa Taylor

Honors Capstones

No abstract provided.

Biden, Trump, Durbin, And Taxes: The 2020 Election In Illinois, John Jackson, John Foster

The Simon Review (Occasional Papers of the Paul Simon Public Policy Institute)

This paper provides a summary of the 2020 presidential race, both nationally and in Illinois. It also analyzes the U.S. Senate race in Illinois and the referendum on the graduated income tax proposal, which was Governor JB Pritzker’s highest policy priority for that year. The results are placed in the larger context of the deep polarization of America and Illinois. The analysis uses the results of the 1996 presidential election (Clinton vs. Dole) and senatorial election (Durbin vs. Salvi) and the 1998 gubernatorial election (Ryan vs. Poshard) as a baseline to demonstrate the profound geographical realignment of the two parties …