Medical Sciences Commons^™

Role Of The Etv5/P38 Signaling Axis In Aggressive Thyroid Cancer Cells, Jerry H Houl, Rozita Bagheri-Yarmand, Muthusamy Kunnimalaiyaan, Paola Miranda Mendez, Joseph L Kidd, Ali Dadbin, Andrea Ruiz-Jurado, Parag A Parekh, Ying C Henderson, Nikhil S Chari, Aatish Thennavan, Reid T Powell, Clifford C Stephan, Xiao Zhao, Anastasios Maniakas, Roza Nurieva, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mark Zafereo, Jennifer R Wang, Stephen Y Lai, Marie-Claude Hofmann

Faculty, Staff and Student Publications

Patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) face a much poorer prognosis than those with differentiated thyroid cancers. Around 25% of PDTCs and 35% of ATCs carry the BRAFV600E mutation, which constitutively activates the MAPK pathway, a key driver of cell growth. Although combining BRAF and MEK inhibitors can shrink tumors, resistance often develops. The exact cause of this resistance remains unclear. We previously found that in PDTC and ATC cells, the BRAFV600E mutation is strongly linked to the expression of ETV5, a transcription factor downstream of the MAPK pathway. In the current study, we …

Selective Deletion Of Slc2a1 From The Rpe Reveals That Rods But Not Cones Depend On Glucose Transport Across The Outer Blood-Retinal Barrier, Lauren L. Daniele, John Y.S. Han, Minzhong Yu, Ravi A. Sangani, Craig D. Beight, Cyrus Rostami, Philip D. Kiser, Neal S. Peachy, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. …

Glutamatergic Projection Neurons In The Basal Forebrain Underlie Learned Olfactory Associational Valence Assignments, Pey-Shyuan Chin, Zhuokun Ding, Mikhail Kochukov, Snigdha Srivastava, Elizabeth H Moss, Qingchun Tong, Benjamin R Arenkiel

Faculty, Staff and Student Publications

Sensory perception is shaped by experience, giving stimuli behavioral significance. Basal forebrain (BF) cholinergic neurons in mice, which are crucial for arousal and motivation, also regulate sensory processing. Within BF nuclei, glutamatergic (vGlut2BF) neurons receive cholinergic input and modulate behaviors, but their roles in encoding sensory significance remain unclear. Using in vivo calcium imaging, we found that vGlut2BF neurons initially poorly encoded odor identity. However, their response to conditioned odors increased following associative learning, and their population activity more distinctly encoded paired stimuli, reflecting emergent value representation. Furthermore, pairing stimulation or inhibition of vGlut2BF neurons with specific odors altered odor …

Rare Heterozygous De Novo Variants In Rapgef2 Are Associated With A Neurodevelopmental Disorder, Ali H Bereshneh, Kirkland A Wilson, Xueyang Pan, Shabab B Hannan, Megan A Cooper, Jullianne Diaz, Eyby Leon, Tiana M Moses, Mahshid S Azamian, Daryl A Scott, Ping Yee Billie Au, Juan Pablo Appendino, Ingrid E Scheffer, Antony Kaspi, Melanie Bahlo, Michael S Hildebrand, Angela T Morgan, Ekanem Ekure, Joshua M Shulman, Friedhelm Hildebrandt, Jennifer E Posey, Paul Kruszka, Eric Vilain, Shinya Yamamoto, Oguz Kanca, Seth Berger, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

Methods: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We …

Rnai-Based Screen For Pigmentation In Drosophila Melanogaster Reveals Regulators Of Brain Dopamine And Sleep, Samantha L Deal, Danqing Bei, Shelley B Gibson, Harim Delgado-Seo, Yoko Fujita, Kyla Wilwayco, Elaine S Seto, Amita Sehgal, Shinya Yamamoto

Faculty, Staff and Students Publications

The dopaminergic system has a large role in behavior and neurological disease, and understanding dopamine level regulation in vivo is critical. To identify dopamine regulators, we utilized Drosophila melanogaster cuticle pigmentation, where dopamine is a precursor to melanin. We measured dopamine from known pigmentation mutants (e.g., tan, ebony, black) and performed an RNAi-based screen to identify additional regulators. We found 153 hits, enriched for developmental signaling pathways and mitochondria-associated proteins. From 35 prioritized candidates, 11 affected head dopamine levels. Effects on brain dopamine were mild, even knocking down the rate-limiting synthesis enzyme Tyrosine hydroxylase (TH), suggesting …

Knowledge, Attitude, And Practice Of Pharmacovigilance And Adverse Drug Reactions Reporting Among Healthcare Providers In The Middle East: A Systematic Review, Amina H. Saleem, Harith Kh. Al-Qazaz, Omer Q. Allela, Ramadan M. Elkalmi

BioMed Visions Journal

The main purpose of pharmacovigilance (PV) is to ensure medication safety through detecting, assessing, and preventing adverse drug reactions (ADRs). Healthcare providers (HCPs) are the main contributors in PV systems all over the world. However, their knowledge, attitudes, and practices (KAP) of PV and ADRs reporting vary among different medical professions and different countries.

Aim: To assess the knowledge, attitudes, and practices among the HCPs in the Middle East, toward PV and ADRs reporting.

Methods: A systematic review was performed. EBSCO, PubMed, and Semantic Scholar, FreeFullPDF and Google Scholar were searched for articles published from January 2014 to December 2024. …

Developing Pharmacy Education: Review Of Virtual Reality Technology In Improving Clinical Training And Learning Skill Development, Samer Imad Mohammed, Mohammed Khudhair Hasan, Mohammad Yawuz Jamal

BioMed Visions Journal

Incorporating modern technology into education is becoming imperative. Numerous pharmacy institutions are incorporating virtual reality (VR) technology training into their curricula to enhance educational experience. This review examines the current state, historical evolution, and application of VR programs in pharmacy education and training. The review also provides details about the main challenges and limitations associated with the use of this technology. The VR technology, including virtual laboratories and simulations, significantly improves clinical training and educational outcomes. The utilization of VR in clinical teaching encounters numerous barriers, including ethical concerns and technological constraints, as well as other restrictions in its execution …

The Impact Of Vdr Gene And Biochemical Indicators In Osteoporosis, Sabah Subhi Ismael Barani, Mohammed Abdullah Ajeel, Safwan Jasim Sultan

BioMed Visions Journal

Osteoporosis is a disorder caused by bone remodeling imbalance in which bone resorption outpaces bone production, resulting in weaker bone structure. Factors such as heredity and insufficient calcium and vitamin D consumption.

This study included an examination of 80 female patients of different ages (40–58 years) in Mosul. The participants were divided into two groups: 20 individuals served as the control group, while the rest 60 were osteoporotic women based on clinical cases and taking X ray DEXA. The blood samples are divided into two parts serum for biochemical tests and blood for genetic diversity in genes associated to Vitamin …

Postoperative Duodenal Stricture In A Neonate With Duodenal Atresia – Innovative Approach And Lessons Learned, Raniah I. Alnaser, Dr Mussalam L Alobaidy, Dr Fawaz A. Alassaf, Dr Mohammed N. Abed

BioMed Visions Journal

Background and aim: Duodenal atresia (DoA) is a congenital condition that is characterized by complete or incomplete duodenal obstruction. This condition needs urgent surgical intervention that carries risks of postoperative complications especially in low-birth-weight babies and with associated comorbidities. The success rate of the surgical procedure was reported to be higher than 90%. This case study details a neonate’s clinical course reporting the challenge in the management of delayed stricture and malnutrition after the primary surgery.

Case presentation and results: A female neonate was born at 38 weeks of gestation with 2.6 kg weight. During the immediate postnatal period, she …

Knowledge And Diagnostic Skills Of Dental Residents Towards Endodontically Involved Teeth In Specialized Dental Center In Mosul City / Iraq, Huda Kh. Abdulkader, Dina Waadallah Azeez

BioMed Visions Journal

Objectives: to assess the knowledge regarding the diagnosis of endodontically affected teeth and the decision-making abilities regarding specific clinical situations among the dental residents in dental specialist center/ left bank/ Mosul / Iraq.

Materials & method: A self–administered questionnaire consisting of 20–questions was distributed to the dental residents at the Dental Specialist Center on the Left Bank in Mosul city, Iraq, in order to assess their diagnostic skills and decision-making abilities in relation to endodontically involved teeth. Additionally, the impacts of taking an endodontic course were investigated. SPSS version 21 was used for data analysis.

Results: Forty-one dental residents participated …

Helicobacter Pylori Infection’S Impact On Thyroid Dysfunction And Serum Interleukin-6 Levels, Mohamed M. Sehree, Ashraf R. Salem Al-Safar

BioMed Visions Journal

Helicobacter pylori is a Gram-negative bacterium associated with peptic ulcer disease and gastric cancer. The study aimed to evaluate its prognosis and its relationship to sex, age, thyroid function, IL-6, and blood groups. 120 blood samples were collected from patients with gastrointestinal disorders at Al-Salam Hospital in Mosul between May and October 2024. The samples underwent clinical examination, including anti-H. pylori antibodies (chromatography and IgA ELISA to confirm active infection), thyroid hormones (Minvidus), interleukin-6 (ELISA), and blood typing using serological techniques.

The study results revealed that the rapid test revealed 40 positive cases out of 120, while the ELISA (IgA) …

Sirtuins And Cartilage Preservation: From Cellular Function To Therapeutic Innovation, Muthanna K. Zaki, Khalil A. Hadid, Mohammed N. Abed, Fawaz A. Alassaf

BioMed Visions Journal

The bones are cushioned by a thin layer of hyaline cartilage that permits physical activity to be performed without experiencing any discomfort. However, these tissues are susceptible to several diseases involving osteoarthritis and rheumatoid arthritis resulting in cartilage degradation. Sirtuins (SRTs) and SRT-activating molecules have been shown in previous studies to affect cartilage and chondrocytes positively. This review aims to explore the potential protective effects of SRTs on cartilage and chondrocytes. It also highlighting various SRT-activating substances and their potential therapeutic applications in managing cartilage-related diseases. Google Scholar, Cochrane Library, and PubMed were used to search about related studies. The …

Bdcd: A Comprehensive Brain Disease Cell-Cell Communication Database, Xinyi Liu, Citu Citu, Gang Qu, Wendao Liu, Nitesh Enduru, Andi Liu, Chia-Hao Tung, Zhongming Zhao

Faculty, Staff and Student Publications

Dysregulated cell–cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, …

Epilepsy Disease Classification: A Community Effort To Enhance The Mondo Disease Ontology, Nicole Vasilevsky, Sarah Gehrke, Kathleen Mullen, Subit Barua, Ian Braun, Tobias Brünger, Curtis Coughlin, Alina Ivaniuk, Daniel Korn, Dennis Lal, Stephanie Marsh, Elaine O'Loughlin, Daniel Olson, Yousif Shwetar, Christalena Sofocleous, Vanessa Vogel-Farley, Heidi Grabenstatter, Melissa Haendel, Christopher Mungall, Sabrina Toro

Faculty, Staff and Student Publications

Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies-often severe and genetically complex-pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research.

Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical …

Unilateral Cervical Spine Facet Fractures: Radiographic Predictors Of Instability, Erisha Tashakori, Reese Svetgoff, Jacob Siahaan, Norman Zheng, Nicholas Beckmann, James Showery, Ran Lador, Mark L Prasarn

Faculty, Staff and Student Publications

Study design: Retrospective cohort study.

Objective: The purpose of our study is to identify CT characteristics of unilateral cervical spine facet fractures that are predictive of instability on MRI.

Summary of background data: Management of isolated subaxial cervical spine facet fractures is typically based on the neurological status of the patient and perceived stability of the injury. It has been shown that the degree of ligamentous instability can help predict instability and need for surgery, and MRIs are increasingly being used to evaluate these injuries, but not always. While there are studies that evaluate radiographic characteristics of facet fractures on …

Serendipity In Psychiatric Discoveries: Historical Lessons And Future Imperatives For Clinical Observation, Stanley Lyndon, Vineeth P John

Faculty, Staff and Student Publications

Aims and method: Serendipity has driven many of psychiatry's most important treatments, yet contemporary systems may undermine clinicians' ability to notice and develop unexpected therapeutic effects. This selective narrative review synthesises landmark discovery stories, conceptual accounts of serendipity and contemporary case examples to clarify how chance observations become robust advances.

Results: Across historical and modern examples, serendipitous discoveries consistently reflected the interaction of unexpected events with prepared observers working in supportive institutional and research systems. We identify current barriers created by standardised care, funding and trial structures, and professional fragmentation, and outline a multi-level framework for cultivating serendipity through phenomenological …

The Impact Of Indigenous American-Like Ancestry On The Risk Of Acute Lymphoblastic Leukemia In Hispanic/Latino Children, Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J De Smith, Charleston W K Chiang

Faculty, Staff and Students Publications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Bridging Hypoxia And Vision Loss: The Emerging Role Of Connexins In Local And Systemic Eye Diseases, Xianping Zhang, Yalong Cheng, Jean X Jiang, Yuting Li

Faculty, Staff and Student Publications

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue's compensatory capacity, it triggers pathological retinal neovascularization, blood-retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes …

Epigenome-Wide Association Study Meta-Analysis Of Bmi In African Americans, Kendra Ferrier, Mariaelisa Graff, Iain R Konigsberg, Maggie Stanislawski, Heather M Highland, Laura M Raffield, April P Carson, Eric Boerwinkle, Jill M Norris, Chris R Gignoux, Audrey E Hendricks, Sridharan Raghavan, Kari E North, Kristin L Young, Anne E Justice, Matthew A Allison, Mathew J Budoff, Silva Kasela, François Aguet, Joshua J Joseph, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Ethan M Lange, Leslie A Lange

Faculty, Staff and Student Publications

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and …

Dna Methyltransferase Inhibitors In Hematological Malignancies And Solid Tumors, Valentin Wenger, Guillermo Garcia-Manero, Robert Zeiser, Michael Lübbert

Faculty, Staff and Student Publications

Epigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy (IC), by virtue of their favorable safety profile. Despite these clinical achievements, however, single-agent DNMTi treatment …

C Elegans As A Tractable Infection Model For The Emerging Fungal Pathogen Candida Auris, Melissa Martinez, Melissa R Cruz, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida auris is an emerging multidrug-resistant fungal pathogen. The genetic factors contributing to the virulence, drug resistance, and stress-tolerant nature of C. auris are mostly unknown. Additional animal models of virulence are needed, especially those amenable to high-throughput analysis. The nematode Caenorhabditis elegans has been validated as an effective tool for studying multiple fungal and bacterial pathogens. We describe here a C. elegans infection model in which exposure to C. auris is lethal to worms with kinetics similar to killing by Candida albicans; in contrast to C. albicans, C. auris does not form hyphae, indicating distinct virulence mechanisms. …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

Egfr Inhibitor-Resistant Lung Cancers Exhibit Collateral Sensitivity To A Covalent, Cysteine-Independent Keap1 Oligomerizing Molecular Bridge, Christopher F Bassil, Kerry Dillon, Gray R Anderson, Benjamin Mayro, Kayleigh N Askin, Peter S Winter, Stefan Harry, Samuel Gruber, Tierney M Hall, Jacob P Hoj, Christian Cerda-Smith, Haley M Hutchinson, Shane T Killarney, Ava Heffernan, Caroline Teddy, Katherine R Singleton, Li Qin, Kévin Jubien-Girard, Cécile Favreau, Guillaume Robert, Barr Tivon, Ella Livnah, Nir London, Rachid Benhida, Patrick Auberger, Ann Marie Pendergast, Liron Bar-Peled, David M Lonard, Anthony R Martin, Alexandre Puissant, Kris C Wood

Faculty, Staff and Students Publications

Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a PAINS-like small molecule, MCB-613. Systematic proteomic, functional genomic, and biochemical studies revealed that MCB-613 binds KEAP1 in a covalent, cysteine-independent fashion, acting as a divalent molecular bridge that relies upon lysine residues in the KEAP1 dimerization domain to join monomers of KEAP1 together. Oligomerization of KEAP1 by MCB-613 sets into motion a fatal cascade of KEAP1 …

Ophiobolin A Impacts Mitochondrial Redox Biology In An Epithelial-Mesenchymal Transition (Emt)-Specific Manner, Haleigh N Parker, Yongfeng Tao, Jenna Tobin, Kayla L Haberman, Samantha Davis, Emily York, Alysia Martinez, Nobuyuki Matsumoto, Jaquelin Aroujo, Jun Hyoung Park, Bernd Zechmann, Benny Abraham Kaipparettu, Angela Boari, Christie M Sayes, Antonio Evidente, Alexander Kornienko, Benjamin Cravatt, Daniel Romo, Joseph H Taube

Faculty, Staff and Students Publications

Breast cancer progression is facilitated by the epithelial to mesenchymal transition (EMT), generating cancer cells with enhanced metastatic capacity and resistance to chemotherapeutics. The fungus-derived sesterterpenoid natural produce compound, ophiobolin A (OpA), possesses nanomolar cytotoxic activity and a high therapeutic index, although its molecular targets and mechanism of action are not well characterized. Herein, we utilized a model of mammary epithelial cells and breast cancer cell lines with and without EMT features to characterize the mechanism of selectivity towards EMT(+) cells by OpA. Proteins interacting with OpA in EMT(+) cells, including mitochondrial glutathione transporter SLC25A40, were identified through via mass …

Progress And Challenges In Profiling Protein-Rna And Protein-Associated Rna-Rna Interactions, Zhuoyi Song, Eric L Van Nostrand

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-RNA interactions that include both well-studied examples of small regulatory RNAs (e.g. microRNAs, snRNAs, snoRNAs, piRNAs) guiding ribonucleoprotein complexes to their targets as well as structured RNA elements defining the interaction landscape for an RBP. To elucidate the full scope of RBP-RNA interactions, CLIP ( crosslinking and immunoprecipitation)-based methods have emerged as powerful tools. Even with the wide application …

Resolution Of A Human Chromosomal Mystery: Evolutionary Complexity Revealed, Jeffrey Rogers

Faculty, Staff and Students Publications

The human complement of chromosomes differs from our closest primate relatives by virtue of a unique chromosome fusion event. In this issue of Cell Genomics, Yang et al. provide the first detailed analysis of the site of chromosome fusion and reconstruct the complex evolutionary relationships among the genomic elements within the human fusion site and their related sequences in our great ape relatives.

Autograft Enlargement After The Ross Procedure In Pediatric Patients: Somatic Growth Or Pathologic Dilatation?, Ioannis Zoupas, Alexander C Mills, Scott D Olson, Damien J Lapar

Faculty, Staff and Student Publications

Purpose of ReviewPulmonary autograft autotransplantation represents a popular surgical approach for pediatric patients requiring aortic valve replacement due to the potential for autograft enlargement to accommodate somatic growth. Nevertheless, autograft dilatation and the subsequent need for reintervention are quite common. Published data suggest that autograft enlargement may result from pathological passive remodeling rather than active somatic growth and vice versa. The present review serves to comprehensively evaluate available evidence related to the fate of the pulmonary autograft after the Ross procedure as it relates to the etiology, risk factors and patterns of autograft failure.ResultsStudies present conflicting results supporting both pathological …

Understanding The Compatibility Of Fluoride-Based Radiopharmaceutical Reaction Solutions And Pdms, Mark Mc Veigh, Charles Frech, Mai Lin, Robert Ta, H Charles Manning, Leon M Bellan

Faculty, Staff and Student Publications

Microfluidic devices offer unique and exciting benefits when applied to radiopharmaceutical manufacturing, and these platforms are now starting to be integrated into commercial products. The field has strayed away from the use of polydimethylsiloxane (PDMS), the most common microfluidic device material, due to its suspected incompatibility with 18F, the most commonly used radionuclide. However, existing literature provides conflicting conclusions as to the existence and extent of this incompatibility. In this study, we use several analytical instruments to uncover the underlying interaction between fluoride and PDMS. SEM imaging and profilometry confirm the reactive relationship between the two materials and suggest that …

Diet-Responsive Genetic Determinants Of Intestinal Colonization In The Yeast Candida Albicans, Musfirat Shubaita, Mazen Oneissi, Elena Lindemann-Pérez, Cecilia Fadhel Alvarez, Anne-Marie Krachler, Diana M Proctor, J Christian Pérez

Faculty, Staff and Student Publications

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. …