Medicine and Health Sciences Commons^™

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Steamed Broccoli Sprouts Alleviate Dss-Induced Inflammation And Retain Gut Microbial Biogeography In Mice, Johanna M. Holman, Louisa Colucci, Dorien Baudewyns, Joe Balkan, Timothy Hunt, Benjamin Hunt, Marissa Kinney, Lola Holcomb, Allesandra Stratigakis, Grace Chen, Peter L. Moses, Gary M. Mawe, Tao Zhang, Yanyan Li, Suzanne L. Ishaq

Pharmacy Faculty Scholarship

Inflammatory bowel diseases (IBDs) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective and affordable for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin (GLR), and can be metabolized by certain mammalian gut bacteria into antiinflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin-metabolizing bacteria affects antiinflammatory benefits. We fed specific pathogen-free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet and gave a three-cycle regimen of 2.5% dextran sodium …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Sctiger: A Deep-Learning Method For Inferring Gene Regulatory Networks From Single-Cell Gene Expression Data, Madison Dautle

Theses and Dissertations

Inferring gene regulatory networks (GRNs) from single-cell RNA-sequencing (scRNA-seq) data is an important computational question to reveal fundamental regulatory mechanisms. Although many computational methods have been designed to predict GRNs, none work on condition specific GRNs by directly using paired datasets of case versus control experiments, common in diverse biological research projects. We present a novel deep-learning based method, scTIGER, for GRN detection by using the co-dynamics of gene expression. scTIGER also employs cell type-based pseudotiming, an attention-based convolutional neural network method, and permutation-based significance testing to infer GRNs from gene modules. We first applied scTIGER to scRNA-seq datasets of …

A Novel Fuzzy Relative-Position-Coding Transformer For Breast Cancer Diagnosis Using Ultrasonography, Yanhui Guo, Ruquan Jiang, Xin Gu, Heng-Da Cheng, Harish Garg

Computer Science Faculty and Staff Publications

Breast cancer is a leading cause of death in women worldwide, and early detection is crucial for successful treatment. Computer-aided diagnosis (CAD) systems have been developed to assist doctors in identifying breast cancer on ultrasound images. In this paper, we propose a novel fuzzy relative-position-coding (FRPC) Transformer to classify breast ultrasound (BUS) images for breast cancer diagnosis. The proposed FRPC Transformer utilizes the self-attention mechanism of Transformer networks combined with fuzzy relative-position-coding to capture global and local features of the BUS images. The performance of the proposed method is evaluated on one benchmark dataset and compared with those obtained by …

Predictors Of Pharmacy Students' Attitudes About The Therapeutic Use Of Psilocybin, Nm Mahmudul Alam Bhuiya, Robin J. Jacobs, Karina Wang, Yiqun Sun, Brenda Nava, Luke Sampiere, Akhila Yerubandi, Joshua Caballero

HPD Articles

Background Psilocybin has been studied for its potential therapeutic benefits, particularly for the treatment of psychiatric disorders such as anxiety, depression, and obsessive-compulsive disorder. While more research is needed as psilocybin-assisted therapy becomes more prevalent, future pharmacists will probably be involved at some level. At present, pharmacists receive minimal training on psilocybin, and little is known about their attitudes toward its use for medical purposes. Findings from recent clinical studies have attempted to establish the safety and medical efficacy of psilocybin, leading to an increased interest in therapeutic psilocybin use in the United States. This study aimed to assess if …

Inferior Vena Cava Thrombus Associated With Renal Cell Carcinoma With An Atypical Radiological Presentation: A Case Report, Kareem Elgendi, Mohamadhusni Zarli, Sohaib Ahmed, Nicole Szell

HPD Articles

Renal cell carcinoma (RCC) is characterized by the development of kidney masses, which can lead to various long-term complications. Among the extrarenal manifestations associated with RCC, the formation of a thrombus within the inferior vena cava (IVC) is particularly prevalent due to the substantial tumor burden imposed by the kidneys. In this report, we present an exceptional case involving an 80-year-old male patient who presented with an intravascular thrombus within the inferior vena cava (IVC), which originated from RCC. The diagnosis of RCC was conclusively established through core needle biopsy and subsequent tumor marker staining. Remarkably, despite the confirmation of …

Epidural Hematoma Risks Associated With Ceasing Vs. Maintaining Anticoagulant And/Or Antiplatelet Medications For Cervical And Thoracic Interlaminar Epidural Steroid Injections, Michael Furman, Jesse Bernstein, Lelia Gilhool, Christopher Bednarek, Holden Caplan, Ajay Kurup, Byron Schneider

SKMC Student Presentations and Publications

Background: There is a lack of substantiated evidence to support or refute the risks of ceasing vs maintaining anticoagulant and/or antiplatelet medications (ACAP) prior to cervical and thoracic interlaminar epidural steroid injections. The ACAP medication is frequently stopped pre-procedure due to concerns for potential bleeding complications, particularly epidural hematomas (EH). This article provides evidence regarding EH incidence in this population. Methods: Data for this study was collected retrospectively on all patients from September 19, 2009–Jun 16, 2017 who were scheduled for an Interlaminar Cervical and/or Thoracic Epidural Steroid Injections (IL-CTESI) and were on an ACAP medication at the time a …

Lean Six Sigma Body Of Knowledge For Healthcare Industry Administrators: Implementation Of Lessons Learned In Applied Engineering, Mohammed Ali

Technology Faculty Publications and Presentations

The purpose of this paper is to propose a Lean Six Sigma (LSS) course curriculum for healthcare administration and management majors. It identifies the relevant opportunities and challenges for the application of LSS within the healthcare industry. The paper also discusses the cultural changes necessary to provide an appropriate climate for its long-term success. This work contains a comprehensive description of the body of knowledge in LSS, which were successful in applied engineering. Additionally, the paper describes how LSS may be applied in the hospital setting to improve processes in patient-care services. Upon successful completion of the course, the healthcare …

Implementation Of Endotracheal Tube Cuff Manometry In The Operating Room: A Quality Improvement Project, Emily Davenport, Jennifer Stephan, Paul Winson

Doctor of Nursing Practice (DNP) Student Projects

Background and Review of Literature: Endotracheal tube cuff pressure should be maintained between 20 to 30 cmH2O to prevent adverse airway outcomes. Standardized practice is not endorsed by any major anesthesia organization nor by Washington University School of Medicine’s Department of Anesthesia. The common practice of manual palpation is unreliable. Use of a manometer is effective to measure and achieve appropriate cuff pressure.

Purpose: Implement a quality improvement project to increase the proportion of anesthesia providers using syringe manometers.

Methods: The facility’s EHR was used to obtain data reports on AG Cuffill syringe manometer use and documentation at specific time …

Noise Reduction In The Obstetric Operating Room, Maddy Schroeder, Meghan Woodham

Doctor of Nursing Practice (DNP) Student Projects

Noise is a significant problem in the operating room with numerous negative impacts physically, mentally, and emotionally for both healthcare workers and patients. In particular, the obstetric operating room is the noisiest operating room in the hospital. The majority of patients in the obstetric operating room do not receive sedation medications and remain fully awake throughout the procedure; thus, they are fully aware of the noise levels surrounding them during their procedures. Elevated noise levels impair communication between providers and decrease satisfaction scores among patients and providers. Noise reduction strategies, including educating staff about the importance of noise reduction, have …

Evaluation Of Provider Adherence To An Intraoperative Glucose Monitoring Guideline At A Midwestern Academic Hospital, Lauren Schoolfield, Taylor Crittenden

Doctor of Nursing Practice (DNP) Student Projects

Background and Review of Literature: Patients with diabetes (PWD) are at higher risk of requiring surgery and developing complications in the perioperative period making euglycemia an important component of intraoperative care. There is an association between dysglycemias and adverse perioperative outcomes. Implementation science evidence indicates that education with audit feedback strategies towards barrier identification to clinical practice guideline (CPG) uptake will improve implementation success.

Purpose: The purpose of this quality improvement project was to evaluate and improve adherence to intraoperative glucose monitoring outlined by the current intraoperative glucose management guideline at a midwestern academic hospital through barrier identification with tailored …

The Effectiveness Of Disinfection Protocols In Osteopathic Family Medicine Offices, Riley Phyu, Harrison A Patrizio, Thomas Boyle, Todd Schachter

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Healthcare-associated infections (HAIs) pose a substantial public health threat. Despite significant strides to curb HAIs in hospital environments, outpatient settings have not received the same degree of attention. Given their emphasis on holistic, patient-centered care, osteopathic family medicine offices are pivotal in both disease prevention and comprehensive patient treatment. The importance of simple yet effective disinfection protocols, such as thorough cleaning between patient appointments, cannot be overstated in these settings because they are integral to minimizing disease transmission.

OBJECTIVES: This study aims to assess the effectiveness of the current disinfection protocols in osteopathic family medicine offices.

METHODS: A cross-sectional …

Folate Conjugated Nanomedicines For Selective Inhibition Of Mtor Signaling In Polycystic Kidneys At Clinically Relevant Doses, Rajasekharreddy Pala, Ayan K. Barui, Ashraf M. Mohieldin, Jing Zhou, Surya M. Nauli

Pharmacy Faculty Articles and Research

Although rapamycin is a very effective drug for rodents with polycystic kidney disease (PKD), it is not encouraging in the clinical trials due to the suboptimal dosages compelled by the off-target side effects. We here report the generation, characterization, specificity, functionality, pharmacokinetic, pharmacodynamic and toxicology profiles of novel polycystic kidney-specific-targeting nanoparticles (NPs). We formulated folate-conjugated PLGA-PEG NPs, which can be loaded with multiple drugs, including rapamycin (an mTOR inhibitor) and antioxidant 4-hydroxy-TEMPO (a nephroprotective agent). The NPs increased the efficacy, potency and tolerability of rapamycin resulting in an increased survival rate and improved kidney function by decreasing side effects and …

"I Believe More In The Ability Of The Small Person To Make Big Changes": Innovation And Social Entrepreneurship To Promote Public Health In Israel., Keren Dopelt, Nila Mordehay, Shir Goren, Aviya Cohen, Paul Barach

College of Population Health Faculty Papers

Social entrepreneurship has grown worldwide in recent decades as it attempts to create and implement innovative solutions to social and environmental issues through business strategies. The aim of this study was to explore what motivates public health social entrepreneurs to act, the challenges and barriers they face, achievements, and competencies required for success. As such, we interviewed 15 social entrepreneurs in Israel. Budget issues, regulatory barriers, and struggles against powerful companies were the frequent barriers to success. The interviewees indicated several achievements at the health policy level by positioning and becoming an authority in the field, positively influencing other people's …

Pathogen-Driven Crispr Screens Identify Trex1as A Regulator Of Dna Self-Sensing During Influenza Virus Infection, Cason R King, Yiping Liu, Katherine A Amato, Grace A Schaack, Clayton Mickelson, Autumn E Sanders, Tony Hu, Srishti Gupta, Ryan A Langlois, Judith A Smith, Andrew Mehle

Faculty, Staff and Student Publications

Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the …

Identification Of Sentinel Lymph Nodes In Esophageal Cancer Patients Using Contrast-Enhanced Eus With Peritumoral Injections, Ji-Bin Liu, Priscilla Machado, John R. Eisenbrey, Sriharsha Gummadi, Flemming Forsberg, Corinne E. Wessner, Anand Raman Kumar, Austin Chiang, Anthony Infantolino, Alexander Schlachterman, Thomas Kowalski, Robert Coben, David Loren

Department of Medicine Faculty Papers

OBJECTIVES: The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer.

METHODS: Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration …

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).

Location And Extent Of Cavernous Transformation Of The Portal Vein Dictates Different Visceral Side Revascularization In Meso-Rex Bypass, Rui Tang, Guangdong Wu, Qiang Yu, Xuan Tong, Xiangfei Meng, Yucheng Hou, Xin Huang, Abudusalamu Aini, Lihan Yu, Weidong Duan, Qian Lu, Jun Yan

Faculty, Staff and Student Publications

BACKGROUND: As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a new classification of PVCT to guide MRB operations.

METHODS: Demographic data, the extent of extrahepatic PVCT, surgical methods for visceral side revascularization, intraoperative blood loss, operating time, changes in visceral venous pressure before and after MRB, postoperative complications and the condition of bypass vessels after MRB were extracted retrospectively from the medical records of 19 patients.

RESULTS: The median age of the patients (13 males and 6 females) was 32.5 years, while …

The Mex-Cog Cognitive Assessment Battery: Discriminant Analysis Of The Cognitive Performance Profile In Older Adults, Silvia Mejia-Arango, Sara Aguilar-Navarro, Alberto José Mimenza-Alvarado

School of Medicine Publications

Objective. To analyze the cognitive profile of a clinical sample using the Mex-Cog cognitive battery and establish which cognitive measures and domains contribute most to group separation.

Materials and methods. A group of 145 older adults previously diagnosed with dementia (n= 47), mild cognitive impairment MCI (n= 47), or as cognitively normal (n= 51) were assessed with the Mex-Cog cognitive battery. Six linear discriminant analyses (LDA) were estimated to compare dementia vs. cognitively normal, MCI vs. cognitively normal, and MCI vs. dementia, using ten individual measures and six cognitive domains. We used a leave-one-out cross-validation procedure to evaluate the predictive …

Radio-Pathomic Approaches In Pediatric Neurooncology: Opportunities And Challenges, Ariana M. Familiar, Aria Mahtabfar, Anahita Fathi Kazerooni, Mahsa Kiani, Arastoo Vossough, Angela Viaene, Philip B. Storm, Adam C. Resnick, Ali Nabavizadeh

Department of Neurosurgery Faculty Papers

With medical software platforms moving to cloud environments with scalable storage and computing, the translation of predictive artificial intelligence (AI) models to aid in clinical decision-making and facilitate personalized medicine for cancer patients is becoming a reality. Medical imaging, namely radiologic and histologic images, has immense analytical potential in neuro-oncology, and models utilizing integrated radiomic and pathomic data may yield a synergistic effect and provide a new modality for precision medicine. At the same time, the ability to harness multi-modal data is met with challenges in aggregating data across medical departments and institutions, as well as significant complexity in modeling …

Precision Modulation Of Dysbiotic Adult Microbiomes With A Human-Milk-Derived Synbiotic Reshapes Gut Microbial Composition And Metabolites, Julie E Button, Casey M Cosetta, Abigail L Reens, Sarah L Brooker, Aislinn D Rowan-Nash, Richard C Lavin, Russell Saur, Shuning Zheng, Chloe A Autran, Martin L Lee, Adam K Sun, Amin M Alousi, Christine B Peterson, Andrew Y Koh, David J Rechtman, Robert R Jenq, Gregory J Mckenzie

Faculty, Staff and Student Publications

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol …

A Real-Time Contouring Feedback Tool For Consensus-Based Contour Training, Christopher L Nelson, Callistus Nguyen, Raymond Fang, Laurence E Court, Carlos E Cardenas, Dong Joo Rhee, Tucker J Netherton, Raymond P Mumme, Skylar Gay, Casey Gay, Barbara Marquez, Mohammad D El Basha, Yao Zhao, Mary Gronberg, Soleil Hernandez, Kelly A Nealon, Mary K Martel, Jinzhong Yang

Faculty, Staff and Student Publications

PURPOSE: Variability in contouring structures of interest for radiotherapy continues to be challenging. Although training can reduce such variability, having radiation oncologists provide feedback can be impractical. We developed a contour training tool to provide real-time feedback to trainees, thereby reducing variability in contouring.

METHODS: We developed a novel metric termed localized signed square distance (LSSD) to provide feedback to the trainee on how their contour compares with a reference contour, which is generated real-time by combining trainee contour and multiple expert radiation oncologist contours. Nine trainees performed contour training by using six randomly assigned training cases that included one …

Using Co-Creation Focus Groups To Customise A Remote Multidomain Programme Designed To Increase Dementia Literacy, Walter Wittich, Edeltraut Kröger, Gabrielle Aubin, Asma Fadhlaoui, Nicole D Anderson, Nouha Ben Gaied, Inbal Itzhak, Sylvie Belleville

Faculty, Staff and Student Publications

Objectives

To adapt the content and functionalities of Brain Health PRO, a web-based multidomain program designed to increase dementia literacy, to the context and needs of users, providers and community organisations across Québec, Canada.

Design

Five consecutive qualitative co-creation focus group sessions 30–90 min in duration each, exploring potential barriers and facilitators to usability, accessibility, comprehensibility, participant recruitment and retention.

Setting

Virtual meetings.

Participants

A 15-member team based in Québec and Ontario, Canada, consisting of 9 researchers (including a graduate student and the project coordinator), representing occupational therapy, sensory rehabilitation, neuropsychology, psychology, health science and research methods, 3 informal caregivers …

Dosimetry Of A Novel 111indium-Labeled Anti-P-Cadherin Monoclonal Antibody (Ff-21101) In Non-Human Primates, Gregory Ravizzini, William Erwin, Louis De Palatis, Lucia Martiniova, Vivek Subbiah, Vincenzo Paolillo, Jennifer Mitchell, Asa P Mccoy, Jose Gonzalez, Osama Mawlawi

Faculty, Staff and Student Publications

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were …

Exploring Acute Pancreatitis Clinical Pathways Using A Novel Process Mining Method, Xue Yang, Wei Huang, Weiling Zhao, Xiaobo Zhou, Na Shi, Qing Xia

Faculty, Staff and Student Publications

Mining process models of medical behavior from electronic medical records is an effective way to optimize clinical pathways. However, clinical medical behavior is an extremely complex field with high nonlinearity and variability, and thus we need to adopt a more effective method. In this study, we developed a fuzzy process mining method for complex clinical pathways. Firstly, we designed a multi-level expert classification system with fuzzy values to preserve finer details. Secondly, we categorized medical events into long-term and temporary events for more specific data processing. Subsequently, we utilized electronic medical record (EMR) data of acute pancreatitis spanning 9 years, …

Bond Strength Of Reline Materials To 3d-Printed Provisional Crown Resins, Jorge Palavicini, Sherrod L. Quin, Wael Zakkour, Karim Zakkour, Safa Manafi Varkiani, Xiaoming Xu, Nathaniel C. Lawson, Amir Hossein Nejat

School of Dentistry Faculty Publications

(1) Purpose: The aim of the present study was to compare the bond strength between two 3D-printed resins designed for long-term provisional crowns and three different reline materials. (2) Materials and Methods: Rectangular specimens were prepared from two 3D-printed resins (Envision Tech and NextDent C&B) and a conventional self-cure PMMA. Transparent tubes filled with three different reline materials including composite resin, Bis-acryl, and PMMA were bonded to the 3D-printed specimens (n = 11 per group, total of 6 study groups). Tubes filled with PMMA were bonded to the prepared PMMA specimens which served as the control group (n = 11, …

Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson

School of Medicine Faculty Publications

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …

Gut Barrier Defects, Intestinal Immune Hyperactivation And Enhanced Lipid Catabolism Drive Lethality In Ngly1-Deficient Drosophila, Ashutosh Pandey, Antonio Galeone, Seung Yeop Han, Benjamin A Story, Gaia Consonni, William F Mueller, Lars M Steinmetz, Thomas Vaccari, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not …

Global Impact Of Somatic Structural Variation On The Cancer Proteome, Fengju Chen, Yiqun Zhang, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics data with whole genome sequencing data across 1307 human tumors spanning various tissues to determine the extent somatic structural variant (SV) breakpoint patterns impact protein expression of nearby genes. We find that about 25% of the hundreds of genes with SV-associated cis-regulatory alterations at the mRNA level are similarly associated at the protein level. SVs associated with enhancer hijacking, retrotransposon translocation, altered DNA methylation, or fusion transcripts are implicated in protein over-expression. SVs combined with altered protein levels …