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Synthesis And Antitumor Activity Of Brominated-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Hassan Mandil, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chuahan Oct 2023

Synthesis And Antitumor Activity Of Brominated-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Hassan Mandil, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chuahan

School of Medicine Publications

Aberrant regulation of β-catenin signaling is strongly linked with cancer proliferation, invasion, migration, and metastasis, thus, small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that ormeloxifene (ORM), a triphenylethylene molecule that docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (−7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anticancer activity in cervical cancer models. Br-ORM treatment effectively inhibited tumorigenic features (cell proliferation …


An Exploration Of Defensive Mediatization Strategies And Motherhood Media Decision-Making, Emily B. Young Oct 2023

An Exploration Of Defensive Mediatization Strategies And Motherhood Media Decision-Making, Emily B. Young

Doctoral Dissertations and Projects

This quantitative study focused on media-related decision-making in motherhood, with mediatization theory serving as a framework for the research. The study began with an overview of recent changes to motherhood and family media use. The purpose of this study was to explore the problem of how mothers make decisions about their children’s media use. After providing a basic overview of the changes to motherhood and family media use, as well as establishing the purpose and problem for the study, the literature on relevant topics for this study was discussed. Primarily, the literature review focused on mediatization theory. Next, the survey …


Studying Borderline Personality Disorder And Childhood Trauma: Exploring Clinicians’ Lived Experiences And Attitudes Toward Treating Bpd Individuals, Tracy F. Coggins Oct 2023

Studying Borderline Personality Disorder And Childhood Trauma: Exploring Clinicians’ Lived Experiences And Attitudes Toward Treating Bpd Individuals, Tracy F. Coggins

Doctoral Dissertations and Projects

A recurring theme in research on borderline personality disorder (BPD) and childhood trauma was the stigma associated with a BPD diagnosis often resulting in barriers to recovery processes and challenges to treatment for this population. The purpose of this transcendental phenomenological study focused on the lived experience of licensed clinicians who work with BPD clients, with the aim to find common themes experienced by clinicians regarding clinicians’ BPD clients, what successes and challenges experienced by clinicians led to their attitudes and perspectives toward treating BPD clients, and what perspectives clinicians have regarding what resources (education, training, etc.) are available in …


Quantitative Gender And Ethnicity Differences In Emergency Medicine Residency Applications, Steven Jay Warrington Oct 2023

Quantitative Gender And Ethnicity Differences In Emergency Medicine Residency Applications, Steven Jay Warrington

Doctoral Dissertations and Projects

The purpose of this quantitative causal-comparative study is to examine if gender affects a medical student’s electronic Standardized Letters of Evaluation, or the characteristics of language used, in their application materials to an emergency medicine residency program through the Electronic Residency Application Service. This study is important as research is needed to determine if there is a difference in ratings or language used in emergency residency applications based on a medical student’s gender. The participants include 173 applicants from the 2022-2023 cycle that submitted material to a single emergency medicine residency program through the Electronic Residency Application Service. Instruments used …


A Phenomenological Study On Perceived Academic And Social Factors That Attribute To The Collegiate Success Or Failure Of Low-Income, First-Generation Black Males, Tre' Antonio Finklea Oct 2023

A Phenomenological Study On Perceived Academic And Social Factors That Attribute To The Collegiate Success Or Failure Of Low-Income, First-Generation Black Males, Tre' Antonio Finklea

Doctoral Dissertations and Projects

The purpose of this phenomenological study was to analyze and discover the factors that contributed to the success or failure of first-generation Black male collegiates at four-year institutions and effectively provide an in-depth understanding of these issues. The theory guiding this study was Tinto’s theory of integration, which focuses on the norms of academic and social integration. Related to this theory was a series of studies that presented the idea that students’ involvement in the social environment and educational setups were critical to their success and retention in college. Participants completed a questionnaire to determine their eligibility for the study. …


A Comparison Of Adult Black And White Male Killers' Behaviors, Their Motives For Murder, And What They Do With Their Victims' Bodies, Tracy Sargent Oct 2023

A Comparison Of Adult Black And White Male Killers' Behaviors, Their Motives For Murder, And What They Do With Their Victims' Bodies, Tracy Sargent

Doctoral Dissertations and Projects

Studies involving murder are often focused on one offender group or a specific victim type. Due to focused research on this topic, there is a need to explore homicidal research between two offender groups in order to compare deviant behaviors of persons who commit murder. The comparison of adult black male offenders and adult white male offenders, their motivations for murder, and what offenders do with their victims’ bodies is explored in the study. A total of 300 solved homicide cases, which consists primarily of adult male and female victims, and several child murders was collected. Such murder motivations of …


A Phenomenological Study Exploring The Lack Of Baptist Church Participation In Seminole County, Florida, Ismael Melendez Oct 2023

A Phenomenological Study Exploring The Lack Of Baptist Church Participation In Seminole County, Florida, Ismael Melendez

Doctoral Dissertations and Projects

This phenomenological study explores the reasons for a lack of participation in in-person Baptist churches and the rise of participation in online Baptist churches in Seminole County, Florida. The theory guiding this study was Martin Heidegger’s hermeneutical framework which focuses on the commonality of experiences. Heidegger believed that to arrive at the essence of a phenomenon a researcher must go through the revisionary process of what Heidegger termed the Hermeneutic Circle. The principal research question in this study explored existing relationship(s) between in-person and online Baptist church leaders and how such relationship(s) contributed to a lack of church participation. The …


Negative Predictive Value Of Circulating Tumor Tissue Modified Viral (Ttmv)-Hpv Dna For Hpv-Driven Oropharyngeal Cancer Surveillance, Noah Kalman, Sreenija Yarlagadda Oct 2023

Negative Predictive Value Of Circulating Tumor Tissue Modified Viral (Ttmv)-Hpv Dna For Hpv-Driven Oropharyngeal Cancer Surveillance, Noah Kalman, Sreenija Yarlagadda

All Publications

Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.

Experimental design: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up …


Negative Predictive Value Of Circulating Tumor Tissue Modified Viral (Ttmv)-Hpv Dna For Hpv-Driven Oropharyngeal Cancer Surveillance, Noah Kalman, Sreenija Yarlagadda Oct 2023

Negative Predictive Value Of Circulating Tumor Tissue Modified Viral (Ttmv)-Hpv Dna For Hpv-Driven Oropharyngeal Cancer Surveillance, Noah Kalman, Sreenija Yarlagadda

All Publications

Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.

Experimental design: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up …


Deep Learning For Plant Bioinformatics: An Explainable Gradient-Based Approach For Disease Detection, Muhammad Shoaib, Babar Shah, Nasir Sayed, Farman Ali, Rafi Ullah, Irfan Hussain Oct 2023

Deep Learning For Plant Bioinformatics: An Explainable Gradient-Based Approach For Disease Detection, Muhammad Shoaib, Babar Shah, Nasir Sayed, Farman Ali, Rafi Ullah, Irfan Hussain

All Works

Emerging in the realm of bioinformatics, plant bioinformatics integrates computational and statistical methods to study plant genomes, transcriptomes, and proteomes. With the introduction of high-throughput sequencing technologies and other omics data, the demand for automated methods to analyze and interpret these data has increased. We propose a novel explainable gradient-based approach EG-CNN model for both omics data and hyperspectral images to predict the type of attack on plants in this study. We gathered gene expression, metabolite, and hyperspectral image data from plants afflicted with four prevalent diseases: powdery mildew, rust, leaf spot, and blight. Our proposed EG-CNN model employs a …


The Overlap Of Skin And Blood T-Cell Clones In Early-Stage Mycosis Fungoides, Daniel Joffe, Safiyyah Bhatti, Lauren Banner, Romsin Zaya, Laura Gleason, Anjali Mishra, Ilan Kirsch, Pierluigi Porcu, Neda Nikbakht Oct 2023

The Overlap Of Skin And Blood T-Cell Clones In Early-Stage Mycosis Fungoides, Daniel Joffe, Safiyyah Bhatti, Lauren Banner, Romsin Zaya, Laura Gleason, Anjali Mishra, Ilan Kirsch, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.


A Retrospective, Observational Study Of 12 Cases Of Expanded-Access Customized Phage Therapy: Production, Characteristics, And Clinical Outcomes, Sabrina I Green, Justin R Clark, Haroldo H Santos, Kyle E Weesner, Keiko C Salazar, Saima Aslam, J William Campbell, Sarah B Doernberg, Emily Blodget, Michele I Morris, Gina A Suh, Karam Obeid, Fernanda P Silveira, Andrey A Filippov, Katrine L Whiteson, Barbara W Trautner, Austen L Terwilliger, Anthony Maresso Oct 2023

A Retrospective, Observational Study Of 12 Cases Of Expanded-Access Customized Phage Therapy: Production, Characteristics, And Clinical Outcomes, Sabrina I Green, Justin R Clark, Haroldo H Santos, Kyle E Weesner, Keiko C Salazar, Saima Aslam, J William Campbell, Sarah B Doernberg, Emily Blodget, Michele I Morris, Gina A Suh, Karam Obeid, Fernanda P Silveira, Andrey A Filippov, Katrine L Whiteson, Barbara W Trautner, Austen L Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related …


Pptc7 Maintains Mitochondrial Protein Content By Suppressing Receptor-Mediated Mitophagy, Natalie M Niemi, Lianjie Wei, Andrew J Smith, Merima Forny, David J Pagliarini, Et Al. Oct 2023

Pptc7 Maintains Mitochondrial Protein Content By Suppressing Receptor-Mediated Mitophagy, Natalie M Niemi, Lianjie Wei, Andrew J Smith, Merima Forny, David J Pagliarini, Et Al.

2020-Current year OA Pubs

PPTC7 is a resident mitochondrial phosphatase essential for maintaining proper mitochondrial content and function. Newborn mice lacking Pptc7 exhibit aberrant mitochondrial protein phosphorylation, suffer from a range of metabolic defects, and fail to survive beyond one day after birth. Using an inducible knockout model, we reveal that loss of Pptc7 in adult mice causes marked reduction in mitochondrial mass and metabolic capacity with elevated hepatic triglyceride accumulation. Pptc7 knockout animals exhibit increased expression of the mitophagy receptors BNIP3 and NIX, and Pptc7


A Venn Diagram Of Secondary-Postsecondary Teaching And Learning: The Transformative Power Of Concurrent Enrollment Partnerships, Christine Denecker Oct 2023

A Venn Diagram Of Secondary-Postsecondary Teaching And Learning: The Transformative Power Of Concurrent Enrollment Partnerships, Christine Denecker

Concurrent Enrollment Review

For decades, researchers have explored the reasons why students show up for college unprepared. In an effort to explain this phenomenon, scholars have gravitated toward a “gap” metaphor to explain the liminal space between what high school students are capable of and what colleges expect of them. The pandemic has exacerbated this situation leaving many students further behind in the academic and personal growth needed to succeed in college. Conventional wisdom says that college is “harder” than high school and students simply must adapt. And while college may, indeed, be “harder,” another perspective is that college isdifferent from high school: …


The Difficult Search For Life After Death, Corinne Stonebraker Oct 2023

The Difficult Search For Life After Death, Corinne Stonebraker

Quill & Scope

No abstract provided.


Vulnerability Of Elevation-Restricted Endemic Birds Of The Cordillera De Talamanca (Costa Rica And Panama) To Climate Change, Zhen Lui, Luis Sandoval, Lauren B. Sherman, Andrew M. Wilson Oct 2023

Vulnerability Of Elevation-Restricted Endemic Birds Of The Cordillera De Talamanca (Costa Rica And Panama) To Climate Change, Zhen Lui, Luis Sandoval, Lauren B. Sherman, Andrew M. Wilson

Environmental Studies Faculty Publications

Animals endemic to tropical mountains are known to be especially vulnerable to climate change. The Cordillera de Talamanca (Costa Rica and Panama) is a geographically isolated mountain chain and global biodiversity hotspot, home to more than 50 endemic bird species. We used eBird community science observations to predict the distributions of a suite of 48 of these endemic birds in 2006–2015, and in 2070, under four climate change scenarios. Species distributions were predicted using program Maxent, incorporating elevation, satellite derived habitat data, and WorldClim climate variables. Model fit, as assessed by Area under the Receiver Operator Curve (AUC), was very …


Fecal Microbe Transplants: B. Vulgatus Genes That Correlate With Early Colonization, Jeff Hansen Oct 2023

Fecal Microbe Transplants: B. Vulgatus Genes That Correlate With Early Colonization, Jeff Hansen

Browse All News

No abstract provided.


Burrowing Owl Skull, Nicolas M. Caracuel, Hannah Lesko, David Kerstetter Oct 2023

Burrowing Owl Skull, Nicolas M. Caracuel, Hannah Lesko, David Kerstetter

All Scans: Kerstetter Fisheries and Avian Ecology 3D Scan Series

No abstract provided.


Spectator 2023-10-12, Editors Of The Spectator Oct 2023

Spectator 2023-10-12, Editors Of The Spectator

The Spectator

No abstract provided.


The Grizzly, October 12, 2023, Marie Sykes, Michael Nieves-Hoblin, Nico Yanzaguano, Andrew J. Perez, Adam Denn, Dominic Minicozzi Oct 2023

The Grizzly, October 12, 2023, Marie Sykes, Michael Nieves-Hoblin, Nico Yanzaguano, Andrew J. Perez, Adam Denn, Dominic Minicozzi

Ursinus College Grizzly Newspaper, 1978 to Present

Meet the New Professors on Campus • Center for Career and Post-Graduate Events • Professor Feature: Dr. Andy Davis • Let's Do the (Rocky Horror: A Breakaway Student Production) Again • The Captivating Collegeville Diner • Crossword Puzzle • Ursinus Field is Keeping the Program's Legacy Alive • Sports Shout-outs!


Towards A Scientific Community Consensus On Designating Vulnerable Marine Ecosystems From Imagery, Amy R. Baco, Rebecca Ross, Franziska Althaus, Diva Amon, Amelia E.H. Bridges, Saskia Brix, Pål Buhl-Mortensen, Ana Colaco, Marina Carreiro-Silva, Malcolm R. Clark, Preez C Du, Mari Lise Franken, Matthew Gianni, Genoveva Gonzalez-Mirelis, Thomas Hourigan, Kerry Howell, Lisa A. Levin, Dhugal J. Lindsay, Tina N. Molodtsova, Nicole Morgan, Telmo Morato, Beatriz E. Mejia-Mercado, D O’Sullivan, Tabitha Pearman, David Price, Katleen Robert, Laura Robson, Ashley A. Rowden, J Taylor, M Taylor, Lissette Victorero, Les Watling, Alan Williams, Joana R. Xavier, Chris Yesson Oct 2023

Towards A Scientific Community Consensus On Designating Vulnerable Marine Ecosystems From Imagery, Amy R. Baco, Rebecca Ross, Franziska Althaus, Diva Amon, Amelia E.H. Bridges, Saskia Brix, Pål Buhl-Mortensen, Ana Colaco, Marina Carreiro-Silva, Malcolm R. Clark, Preez C Du, Mari Lise Franken, Matthew Gianni, Genoveva Gonzalez-Mirelis, Thomas Hourigan, Kerry Howell, Lisa A. Levin, Dhugal J. Lindsay, Tina N. Molodtsova, Nicole Morgan, Telmo Morato, Beatriz E. Mejia-Mercado, D O’Sullivan, Tabitha Pearman, David Price, Katleen Robert, Laura Robson, Ashley A. Rowden, J Taylor, M Taylor, Lissette Victorero, Les Watling, Alan Williams, Joana R. Xavier, Chris Yesson

School of Biological and Marine Sciences

Management of deep-sea fisheries in areas beyond national jurisdiction by Regional Fisheries Management Organizations/Arrangements (RFMO/As) requires identification of areas with Vulnerable Marine Ecosystems (VMEs). Currently, fisheries data, including trawl and longline bycatch data, are used by many RFMO/As to inform the identification of VMEs. However, the collection of such data creates impacts and there is a need to collect non-invasive data for VME identification and monitoring purposes. Imagery data from scientific surveys satisfies this requirement, but there currently is no established framework for identifying VMEs from images. Thus, the goal of this study was to bring together a large international …


Multivariate Adaptive Shrinkage Improves Cross-Population Transcriptome Prediction And Association Studies In Underrepresented Populations, Daniel Araujo, Chris Nguyen, Xiaowei Hu, Anna V. Mikhaylova, Christopher R. Gignoux, Kristin Ardlie, Kent D. Taylor, Peter Durda, Yongmei Liu, George Papanicolaou, Michael H. Cho, Stephen S. Rich, Jerome I. Rotter, Nhlbi Topmed Consortium, Hae Kyung Im, Ani Manichaikul, Heather Wheeler Oct 2023

Multivariate Adaptive Shrinkage Improves Cross-Population Transcriptome Prediction And Association Studies In Underrepresented Populations, Daniel Araujo, Chris Nguyen, Xiaowei Hu, Anna V. Mikhaylova, Christopher R. Gignoux, Kristin Ardlie, Kent D. Taylor, Peter Durda, Yongmei Liu, George Papanicolaou, Michael H. Cho, Stephen S. Rich, Jerome I. Rotter, Nhlbi Topmed Consortium, Hae Kyung Im, Ani Manichaikul, Heather Wheeler

Biology: Faculty Publications and Other Works

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy …


Cover, Title Page, Table Of Contents, Introduction, Messay Kebede Oct 2023

Cover, Title Page, Table Of Contents, Introduction, Messay Kebede

Ethiopian Modernization: Opportunities and Derailments

This book examines and theoretically articulates the various facets and crucial phases of Ethiopia’s encounter with the modern world and the challenges its efforts to modernize faced during the course of three consecutive yet highly divergent political regimes. These phases roughly correspond to Haile Selassie’s and post-Haile Selassie’s Ethiopia, with the post-period spreading over two milestones, namely, the revolutionary shift of the Provisional Military Administrative Council (the Derg) and the no less critical reshaping of the Ethiopian political system by an ethnonationalist agenda subsequent to the Tigray People's Liberation Front’s (TPLF) seizure of state power. Despite their drastic differences, a …


Establishing An Informed Consent Model For Gender Confirmation Surgery In Minors, Michael Coco Oct 2023

Establishing An Informed Consent Model For Gender Confirmation Surgery In Minors, Michael Coco

Seton Hall Journal of Legislation and Public Policy

No abstract provided.


On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato Oct 2023

On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Recent advances in the understanding of the molecular mechanisms underlying cancer progression have led to the development of novel therapeutic targeting strategies. Aberrant glycosylation patterns and their implication in cancer have gained increasing attention as potential targets due to the critical role of glycosylation in regulating tumor-specific pathways that contribute to cancer cell survival, proliferation, and progression. A special type of glycosylation that has been gaining momentum in cancer research is the modification of nuclear, cytoplasmic, and mitochondrial proteins, termed O-GlcNAcylation. This protein modification is catalyzed by an enzyme called O-GlcNAc transferase (OGT), which uses the final product of the …


Cancer Origin Tracing And Timing In Two High-Risk Prostate Cancers Using Multisample Whole Genome Analysis: Prospects For Personalized Medicine, Anssi Nurminen, Serafiina Jaatinen, Sinja Taavitsainen, Gunilla Högnäs, Tom Lesluyes, Naser Ansari-Pour, Teemu Tolonen, Kerstin Haase, Antti Koskenalho, Matti Kankainen, Juho Jasu, Hanna Rauhala, Jenni Kesäniemi, Tiia Nikupaavola, Paula Kujala, Irina Rinta-Kiikka, Jarno Riikonen, Antti Kaipia, Teemu Murtola, Teuvo L Tammela, Tapio Visakorpi, Matti Nykter, David C Wedge, Peter Van Loo, G Steven Bova Oct 2023

Cancer Origin Tracing And Timing In Two High-Risk Prostate Cancers Using Multisample Whole Genome Analysis: Prospects For Personalized Medicine, Anssi Nurminen, Serafiina Jaatinen, Sinja Taavitsainen, Gunilla Högnäs, Tom Lesluyes, Naser Ansari-Pour, Teemu Tolonen, Kerstin Haase, Antti Koskenalho, Matti Kankainen, Juho Jasu, Hanna Rauhala, Jenni Kesäniemi, Tiia Nikupaavola, Paula Kujala, Irina Rinta-Kiikka, Jarno Riikonen, Antti Kaipia, Teemu Murtola, Teuvo L Tammela, Tapio Visakorpi, Matti Nykter, David C Wedge, Peter Van Loo, G Steven Bova

Faculty, Staff and Student Publications

BACKGROUND: Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question.

METHODS: We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of …


Immune-Depleted Tumor Microenvironment Is Associated With Poor Outcomes And Btk Inhibitor Resistance In Mantle Cell Lymphoma, Preetesh Jain, Krystle Nomie, Nikita Kotlov, Vitaiy Segodin, Holly Hill, Chi Young Ok, Ahmed Fetooh, Rashmi Kanagal-Shamanna, Francisco Vega, Alexander Bagaev, Nathan Fowler, Christopher R Flowers, Michael Wang Oct 2023

Immune-Depleted Tumor Microenvironment Is Associated With Poor Outcomes And Btk Inhibitor Resistance In Mantle Cell Lymphoma, Preetesh Jain, Krystle Nomie, Nikita Kotlov, Vitaiy Segodin, Holly Hill, Chi Young Ok, Ahmed Fetooh, Rashmi Kanagal-Shamanna, Francisco Vega, Alexander Bagaev, Nathan Fowler, Christopher R Flowers, Michael Wang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is a generally aggressive B cell non-Hodgkin lymphoma (B-NHL). Outcomes of patients have improved in the era of Bruton’s tyrosine kinase inhibitors (BTKi). However, MCL patients can develop resistance to BTKi over time and can progress [1]. Ibrutinib resistance in MCL is correlated with an overexpression of OXPHOS, MYC and PI3K/AKT/m-TOR pathways. Somatic mutations in TP53, KMT2D, NSD2, SMARCA4, CCND1, TRAF2, NFKBIE genes are reported with ibrutinib resistance [2]. A few reports have also demonstrated that a decrease in T cell numbers [3, 4] or a downregulation of effector/cytotoxic …


Activation Of Chaperone-Mediated Autophagy Inhibits The Aryl Hydrocarbon Receptor Function By Degrading This Receptor In Human Lung Epithelial Carcinoma A549 Cells, Rui Xiong, Dan Shao, Sandra Do, William K. Chan Oct 2023

Activation Of Chaperone-Mediated Autophagy Inhibits The Aryl Hydrocarbon Receptor Function By Degrading This Receptor In Human Lung Epithelial Carcinoma A549 Cells, Rui Xiong, Dan Shao, Sandra Do, William K. Chan

Pacific Faculty Work

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a substrate protein of a Cullin 4B E3 ligase complex responsible for diverse cellular processes. In the lung, this receptor is responsible for the bioactivation of benzo[a]pyrene during tumorigenesis. Realizing that the AHR function is affected by its expression level, we are interested in the degradation mechanism of AHR in the lung. Here, we have investigated the mechanism responsible for AHR degradation using human lung epithelial A549 cells. We have observed that the AHR protein levels increase in the presence of chloroquine (CQ), an autophagy inhibitor, in a dose-dependent …


Bola3 And Nfu1 Link Mitoribosome Iron–Sulfur Cluster Assembly To Multiple Mitochondrial Dysfunctions Syndrome, Hui Zhong, Alexandre Janer, Oleh Khalimonchuk, Hana Antonicka, Eric A. Shoubridge, Antoni Barrientos Oct 2023

Bola3 And Nfu1 Link Mitoribosome Iron–Sulfur Cluster Assembly To Multiple Mitochondrial Dysfunctions Syndrome, Hui Zhong, Alexandre Janer, Oleh Khalimonchuk, Hana Antonicka, Eric A. Shoubridge, Antoni Barrientos

Department of Biochemistry: Faculty Publications

The human mitochondrial ribosome contains three [2Fe–2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the e xpression of Fe–S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [2Fe–2S] clusters from the GLRX5-BOLA3 node. Additionally, the assembly of the small subunit depends on the mitoribosome biogenesis factor METTL17, recently reported containing a [4Fe–4S] cluster, which we …


Milk-Borne Small Extracellular Vesicles: Kinetics And Mechanisms Of Transport, Distribution, And Elimination, Alice Ngu, Javaria Munir, Janos Zempleni Oct 2023

Milk-Borne Small Extracellular Vesicles: Kinetics And Mechanisms Of Transport, Distribution, And Elimination, Alice Ngu, Javaria Munir, Janos Zempleni

Department of Nutrition and Health Sciences: Faculty Publications

Small extracellular vesicles (sEVs) in milk have the qualities desired for delivering therapeutics to diseased tissues. The production of bovine milk sEVs is scalable (1021 annually per cow), and they resist degradation in the gastrointestinal tract. Most cells studied to date internalize milk sEVs by a saturable process that follows Michaelis-Menten kinetics. The bioavailability of oral milk sEVs is approximately 50%. In addition to crossing the intestinal mucosa, milk sEVs also cross barriers such as the placenta and blood-brain barrier, thereby enabling the delivery of therapeutics to hard-to-reach tissues. In time course studies, levels of milk sEVs peaked in …