Digital Commons Network^™

Dna-Fish Metaphase Spreads To Distinguish Extrachromosomal Dna From Homogeneously Staining Regions In Human Cancer Cell Lines, Lauren Marie Masters, Katelin Maria Hagstrom, Graham Scott Erwin

Faculty, Staff and Students Publications

Whole-genome sequencing identifies focal DNA amplifications with base-pair resolution but cannot determine whether amplified sequences reside on extrachromosomal DNA (ecDNA, also known as double minutes) or within chromosomally integrated homogeneously staining regions (HSRs). DNA fluorescence in situ hybridization (DNA-FISH) metaphase spreads remain the gold standard for distinguishing these amplification states at single-cell resolution. Here, we present a detailed protocol for DNA-FISH metaphase spreads using human cancer cell lines, encompassing cell culture, metaphase arrest, hypotonic treatment, fixation, chromosome spreading, fluorescent probe hybridization, and fluorescence imaging. The protocol incorporates intermediate quality-control steps to verify successful chromosome dispersion and optimize metaphase spread quality, …

Al Kuwait Hospital Dubai, Emirates Health Services 1st Research Week 2025: Research Abstracts Of Clinical And Scientific Advances, Suad Hannawi, Linda Saf Eldin, Alaa Abuquta, Yusra Abdulrahman, Maryam Yaslam, Sabaa Saleh Al-Hemyari, Maimouneh Qazi, Noor Majed Al Mheiri, Ahmed Alamadi, Alia Aljasmi, Sondos Al Salmi, Maria Al-Salmi, Moza Aljamri, Ahmed Ibrahim Abdulrahman, Sharifa Alamadi, Haifa Hannawi

Saudi Medical Journal

No abstract provided.

The Outcome Of Thrombectomy Can Be Improved By Shortening The Door-To-Needle And The Onset-To-Door Time, Sounira Mehri, Josef Finsterer

Saudi Medical Journal

No abstract provided.

Awareness Of The Mediterranean Diet And Its Perceived Effect On Cardiovascular Health In The Western Region, Saudi Arabia, Abdullah M. Alharbi, Mohammed S. Alsaedi, Mutaz S. Alharbi, Faisal F. Almutairi, Adeeb M. Aloufi, Azzam M. Alharbi, Rakan D. Alsaedi, Hatim F. Alhejaili, Motasem M. Alyamani

Saudi Medical Journal

Objective: To increase awareness of mediterranean diet (MD) and its perceived effects on cardiovascular health, enhance knowledge and inform public health efforts aimed at improving the population's health outcomes of. The MD comprises heart-healthy eating patterns high in vegetables, legumes, nuts and seeds, and fruits. Methods: This cross-sectional study involved adult participants who were living in the Western region of the Kingdom of Saudi Arabia. The data were collected online through social media platforms, then cleaned, coded, and analyzed using Statistical Package for the Social Sciences, version 21 to generate key insights. Results: A total of 390 participants were included …

Early Initiation And Dual Patterns Of Cigarette And E-Cigarette Use Among Adults In The Eastern Province, Saudi Arabia: A Cross-Sectional Study, Haidar A. Alridha, Nora A. Alafif

Saudi Medical Journal

Objectives: To explore the early initiation of cigarette and e-cigarette use and the dual patterns of usage among adults in the Eastern Province of Saudi Arabia. Methods: A cross-sectional survey was conducted from December 2024 to February 2025 among adults living in the Eastern Province. An online self-administered questionnaire collected data on sociodemographic characteristics, smoking behaviors, age of initiation, dual-use patterns, and quit attempts. Convenience sampling was applied, and a total of 551 participants were included. Descriptive statistics summarized distributions of smoking behavior and initiation age. Pearson's Chi-square tests were used to examine associations between smoking status, age of initiation, …

Artificial Intelligence In Pharmaceutical Care: Transforming Drug Discovery, Development, And Patient-Care Delivery, Abdulrahman G. Alharbi, Abdulrahman A. Aljabri

Saudi Medical Journal

The integration of artificial intelligence (AI) into pharmaceutical care represents a paradigm shift in healthcare delivery, offering unprecedented opportunities to revolutionize medication management, accelerate drug development, and enhance patient outcomes. This comprehensive review synthesized evidence from global literature (2021–2025) examining AI applications across drug discovery and development, clinical trials optimization, medication therapy management, and pharmacy operations. The AI demonstrated prediction accuracies of 86–98% in drug discovery, 80% improvement in clinical trial recruitment efficiency, and 32.7% increase in medication adherence over standard care. The global AI drug discovery market, valued at \$1.5 billion (2023), is projected to reach \$11.8 billion by …

Healthcare-Associated Infection Causes And Mitigation Strategies: A Systematic Review, Mohammad Irfan, Nahed Alquwez

Saudi Medical Journal

Objective: To describe the landscape of healthcare-associated infections (HAI) and, in particular, to pay attention to the types of infection that are usually seen, the most common infectious agents involved and the effective prevention strategies. Methods: A detailed search was performed using Google and PubMed, and studies that exclusively addressed healthcare associated infections or their mitigation. Studies published since 2000 were included. Data from individual articles were extracted and categorized by study focus, type of infection, causes and contributing factors, and documented mitigation strategies. Editorials, reviews, case studies, meta-analyses, and systematic reviews were excluded. Results: The analysis showed that infections …

Extracellular Vesicle-Mediated Transfer Of Gsdme-Nt Pores As A Mechanism Of Inflammation Propagation, Bifeng Xiao

Master's Theses

Inflammasomes are multiprotein complexes that initiate inflammatory signaling through activation of caspase-1, cytokine maturation, and cleavage of Gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that contribute to cytokine release and pyroptotic cell death. Recent evidence suggests that extracellular vesicles (EVs) may facilitate the intercellular transfer of inflammatory mediators. This study investigated whether GSDMD N-terminal fragment (GSDMD-NT) associates with EV-enriched fractions and contributes to inflammation propagation. Doxycycline-inducible HeLa cells expressing FLAG-tagged GSDMD-NT were used to generate EV-enriched fractions. Western blot analysis detected GSDMD-NT-associated material within EV fractions, while EV marker analysis supported successful enrichment of EV-associated material. Exposure of recipient …

Congenital Heart Disease In Infants Of Diabetic Mothers (Pediatrics Hospital Based Study), Esraa Ali Mathboob Mahdi, Basil M. Hanudi

Iraqi Postgraduate Medical Journal

Background: Infants born to diabetic mothers are at elevated risk for neonatal complications, including metabolic, hematologic, respiratory, cardiac, and neurological disorders. Notably, insulin-dependent diabetes increases the likelihood of congenital heart diseases (CHDs). Aim: This study aimed to determine the incidence and associated factors of cardiac complications among neonates born to diabetic mothers and to identify the prevalent patterns of congenital heart defects in this population. Methods: An analytical cross-sectional study was conducted over a 10-month period (July 1, 2020 to April 30, 2021) at the Neonatal Care Unit of Child’s Central Teaching Hospital. The study included 100 neonates admitted within …

The Role Of The Hs1582 Enhancer In The Regulation Of Spry1 In Human Neural Crest Cells, Maia Williams, Vershanna E Morris

Summer Research Program Abstracts

No abstract provided.

Assessing Hpv And Hpv Vaccine Awareness And Perception Amongst Undergraduate Students, Maura Hawkins

Honors Theses

Human Papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. Vaccination rates remain low among college-aged students despite an effective vaccine being available. This study investigates HPV and HPV vaccination-related knowledge, beliefs, and perceptions among undergraduate students to inform targeted intervention strategies. Participants included undergraduate students (n = 19) who attended one of three focus groups conducted in April 2025 at the University of South Alabama. Structured interview guides explored HPV knowledge, perceived risk and severity, attitudes towards vaccination, autonomy in health decision-making, trust in health information sources, and preferred educational strategies. Discussions were …

Social Phobia, Coping Strategies, And Socio-Demographic Associations Among Late Adolescents: A Cross-Sectional Study, Ezhilan B U, Jesymol Joy, Smitha Chandrashekarappa Dr.

Digital Journal of Clinical Medicine

Background: Adolescence is a transitional period from childhood to adulthood, often marked by psychological challenges such as social anxiety, also known as social phobia. It is characterized by excessive fear of social interactions and can lead to impaired functioning or depression. Globally, its prevalence ranges from 6-10% in developed countries and 10-44% in developing countries. Coping strategies play a crucial role in managing social phobia, varying by individual characteristics. This study aimed to determine the prevalence of social phobia, identify coping strategies, and evaluate their association with socio-demographic factors among late adolescents.

Methodology: A cross-sectional study was conducted …

The Effects Of Abstinence Status And Sleep Quality On Resting State Alpha Power In Cocaine Use Disorder, Heather E Webber, Danielle A Kessler, Joy M Schmitz, Scott D Lane, Robert Suchting

Faculty, Staff and Student Publications

Rationale

Substance use disorders are associated with notable sleep disturbances. Electroencephalogram (EEG) alpha power occurs during wakeful rest, is associated with sleepiness, and indicates neural deactivation.

Objectives

The goal of the current study was to assess the effects of abstinence on the relationship between alpha power and subjective sleep quality in participants with cocaine use disorder (CUD).

Methods

Participants with CUD (n = 32) who were recently or non-abstinent completed a resting-state EEG paradigm (90 s eyes open/closed). Absolute alpha power was calculated using the fast Fourier transform and by averaging within the power spectra of the alpha band (8–13 …

The Poly-Arginine Peptide R18d Inhibits Amyloid-Beta (Aβ) Aggregation And Aβ-Induced Cytotoxicity, Reduces Intracellular Tau Aggregation, And Exhibits Oral Bioavailability, Vaishali Bagda, Zainab H. Farooz, Neville W. Knuckey, Samantha M. South, Stuart K. Gribble, Maitri Tomar, Prashant Bharadwaj, Ajish Ariyath, Kevin Taddei, Ralph N. Martins, Bruno P. Meloni

Research outputs 2022 to 2026

Background/Objectives: Effective disease-modifying therapies targeting pathogenic proteins associated with Alzheimer’s disease (AD) remain limited. This study investigated the therapeutic potential of the neuroprotective, cationic arginine-rich peptide R18D to mitigate the pathogenic effects of amyloid-beta (Aβ) and tau associated with AD.

Methods: R18D was examined for its ability to inhibit Aβ aggregation in a cell-free assay, attenuate Aβ-induced cytotoxicity in MC65 cells, and suppress intracellular tau aggregation in two neural cell models. Intracellular tau aggregation was quantified using a homogeneous time-resolved fluorescence assay. Additionally, a pilot pharmacokinetic study of R18D was conducted in mice following oral gavage administration.

Results: In the …

Neuroprotective Effects Of Sorghum Polyphenol In Alzheimer’S Disease: In Vitro And In Silico Analyses, Rasheed A. Abdulraheem, Ralph N. Martins, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Vijay Jayasena, Stuart K. Johnson, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Background/Objective: Accumulation of amyloid-beta (Aβ) senile plaques in the human brain is a major hallmark of Alzheimer’s disease (AD), which manifests as progressive decline in memory and cognitive functions and currently lacks effective disease-modifying therapies. Emerging evidence demonstrates that polyphenol-rich plant foods are potential complementary therapies for AD. Methods: In this study, we investigated crude polyphenol extracts (CPEs) and purified polyphenol extracts (PPEs) from three sorghum genotypes for their ability to inhibit Aβ42-induced toxicity in MC-65 cells. Thioflavin T fluorescence, cell viability, mitochondrial function, oxidative stress assays, and Western blotting, along with RNA sequencing and computational analyses, were used to …

Blinded, Bias-Controlled Multi-Rater Evaluation Of Human-Versus-Ai Brain Metastasis Segmentation Using A Hybrid Foundation-Model Framework, Yiding Han, Enze Zhu, Mhd Hasan Ai Mekdash, Omar Awad, Piyush Pathak, Shixiao Liang, Daniel Allan Hamstra, Xizhe Zhang, Zaid Ali Siddiqui, Baozhou Sun

Faculty, Staff and Students Publications

Background: Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance.

Purpose: To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment.

Methods: TUM-SAM integrates nnU-Net-based lesion detection with a …

Mental Health Stigma In Latin American Youth With Obsessive-Compulsive Disorder, Ryan J Mccarty, Matias Jensen, Elissa Paz Jensen Santa Cruz, Melisa N Sagarnaga, Pamela Claisse Quiroz, Tomás Miño, Paola Giusti-Rodriguez, Mayra C Martinez Mallen, Maria B Moyano, Dayan Berrones, Jacey L Anderberg, Renee M Frederick, Hannah C Moore, Josselyn S Muñoz, Vanessa Zavala Cruz, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Working Group (Gttoc), Ogechi C Onyeka, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is an impairing mental health condition that affects individuals across the lifespan. Some literature has evaluated mental health stigma in adults with OCD but limited attention has been given to youth, as well as those of Latino ancestry. The present study reported the extent of stigma experiences among Latin American youth with OCD, as well as examined sociodemographic, clinical and psychological correlates. 235 youth with clinician confirmed diagnoses of OCD from 10 North and South American countries completed questionnaires assessing stigma experiences, symptomatology, and functioning. Sociodemographic and clinical variables were also collected. The average OCD stigma response …

Nuclear-Specific Reductive Carboxylation Of Alpha-Ketoglutarate Fuels Histone Acetylation To Induce Chromatin Accessibility And Gene Activation, Abhisha Sawant Dessai, Nadya A Elhalawany, Tao Dai, Justine J Jacobi, Christian Prechtl, Alphonse N Dimeck, Sierra R Morton, Mark D Long, Prashant K Singh, Nagireddy Putluri, Mariana Lopes, Song Liu, Dominic J Smiraglia, Katerina V Gurova, Peder J Lund, Leah A Gates, Sung Yun Jung, Subhamoy Dasgupta

Faculty, Staff and Students Publications

Mitochondria remain at the core of cell metabolism, whereas the nucleus integrates cellular and environmental signals to activate genes. However, the mechanisms that directly link cellular metabolism to gene regulation are not well understood. Here we show, a metabolic pathway in the nucleus controls acetylation of histones by nuclear localization of mitochondrial enzymes aconitase (ACO2) and isocitrate dehydrogenase (IDH2). Metabolic tracing studies show that IDH2 and ACO2 catalyze reductive carboxylation of α-ketoglutarate to rapidly synthesize citrate to increase nuclear acetyl-CoA pool. Genetic and proteomic analyses reveal nuclear IDH2 and ACO2 form a complex with KAT2A/GCN5 for acetylation of histones to …

Altered Glr-1 Expression After Etoh Withdrawal Is Linked To Associative Behavior Deficits In C. Elegans, Katie Brandel-Ankrapp, Rachel N Arey

Faculty, Staff and Students Publications

Chronic ethanol (EtOH) exposure and withdrawal are linked to worsened memory and cognitive outcomes. One target of EtOH is the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Both EtOH exposure and withdrawal influences AMPAR expression, function, and broad glutamate signaling. Previous work suggests that EtOH regulation of AMPARs drives behaviors related to dependence and memory phenotypes. However, due to the complexity of the mammalian brain, it is difficult to unravel the precise mechanism by which EtOH regulates AMPARs in mammals to modify specific memory behaviors. In Caenorhabditis elegans, GLR-1, an AMPAR ortholog, has tightly defined expression in relatively few neurons, conserved …

Endophytic Actinobacteria: Deciphering Therapeutic And Industrial Potential, And Prospects Of Genome Mining In Novel Products Discovery, Yusra Waheed, Rabia Shahdin, Imran Sajid

Journal of Bioresource Management

Endophytic actinobacteria are a diverse group of Gram-positive bacteria with high G+C content, which inhabit plants’ internal tissues, and represent a significant yet underexplored reservoir of bioactive secondary metabolites. In host plants, a remarkable repertoire of metabolites, including broad-spectrum antibiotics, anticancer, antiviral, antifungal, antioxidant, and immunomodulatory compounds, is synthesized by these microbial allies, carrying significant medicinal and agricultural potential. These endophytes, in contrast to their soil relatives, have developed unique biosynthetic gene clusters (BGCs) strongly influenced by plant-associated factors, leading to the production of structurally novel metabolites. In recent years, the advances in genome mining, metagenomics, and metabolomics have accelerated …

Antiseizure Drug Adherence In Pediatric Patients With Epilepsy And The Associated Factors In Saudi Arabia, Ola A Shawky, Shaima A Althoubaiti, Reham M Alkahtani, Amirah S Alharthi

Neurosciences

Objectives: To assess the prevalence of adherence to antiseizure medications and related factors in Saudi Arabia. Pediatric epilepsy presents significant challenges to the well-being and quality of life of children. Adherence to antiseizure medication is associated with better outcomes.

Methods: This study was carried out using a cross-sectional methodology to determine the prevalence of antiseizure medication adherence among children with epilepsy aged ≤ 17 years in Saudi Arabia. Data were collected between July and September 2024 via an online self-administered questionnaire, using convenience sampling through social platforms (Telegram and WhatsApp). Medication adherence was assessed using the MMAS-8 and categorized as …

Wearable Sensor Technology And Biomechanical Gait Analysis In Post-Stroke Rehabilitation: A Review With Implications For The Saudi Healthcare System, Abdullah H. Alzahrani

Neurosciences

Stroke remains a major cause of disability worldwide, with gait impairment affecting up to 80% of survivors and contributing to long-term dependence, fall risk, and reduced quality of life. In Saudi Arabia, stroke incidence is rising, with a significant burden on younger populations and disparities in access to post-stroke rehabilitation services. Conventional gait analysis tools rely on expensive, specialized laboratory equipment, which limits their availability in low-resource and rural settings. Recent advances in wearable sensor technologies, including inertial measurement units, pressure insoles, and electromyography systems, offer portable, scalable, and cost-efficient options for assessing gait in real-world environments. These systems can …

Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis Imperfecta (OI) is a rare disorder causing bone fragility, pain, and functional impairment that causes substantial psychosocial burden. This study examined how self-perceived burden (SPB), or distress from feelings of dependence on caregivers, relates to depression, anxiety, and suicidality in adults with OI. A total of 208 adults (M age = 42.9, predominately White and female) with OI were recruited to complete a cross-sectional survey assessing SPB, psychological symptoms, health, and sociodemographics. Results indicated that SPB was significantly higher among younger individuals, those not living with a partner, those living with adult family members, lower-income groups, and individuals …

Point-Of-Care Hrhpv Mrna Detection With Reverse Transcription Recombinase Polymerase Amplification On A Portable Fluorimeter From Provider-Collected Cervical Samples In Maputo, Mozambique, Emilie Newsham Novak, Cannon J Hansen, Zoha Wazir, Ariel Ma, Jennifer Carns, Hira Atif, Jane R Montealegre, Michael E Scheurer, Cesaltina Lorenzoni, Daniel G Rosen, Mila P Salcedo, Kathleen M Schmeler, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

Background: Cervical cancer is the most common cancer in women in Mozambique, where limited screening infrastructure contributes to high disease burden. While testing for high-risk human papillomavirus (hrHPV) DNA can identify women at risk for cervical cancer, its limited specificity may lead to overtreatment in screen-and-treat programs, straining resources. We performed a pilot study to evaluate preliminary feasibility of a novel, accessible test to detect hrHPV mRNA, a more specific biomarker for cervical cancer risk, from 22 women who previously screened positive for visual inspection with acetic acid at Maputo Central Hospital in Mozambique.

Methods: Cervicovaginal samples were analyzed for …

Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla

The Brown Foundation: Institute of Molecular Medicine

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced …

Intouch Week Of June 22, 2026, New York Medical College

InTouch

• Sixth Annual NYMC Golf Tournament Drives Support for Future Health Care Leaders
• Center for Disaster Medicine Receives NYS Funding
• Dean’s Faculty Awards Recognize Excellence in Teaching, Mentoring, and Service
• Football Associated with Nearly One in Five Brain Injuries in Youth Sports
• Touro College of Dental Medicine Hosts Its Ninth Annual Golf, Tennis and Mahjong Event
• Alumni Spotlight: Sumaita Mahmood, M.D./M.P.H. ’26, Receives National Public Health Award

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas

Faculty, Staff and Students Publications

Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …

Conformational Cycling Of The Wntless Transporter Drives Trafficking And Secretion Of Wnt Morphogens, Yunhui Ge, Taciani De Almeida Magalhaes, Hongjiang Wu, Dick J H Van Den Boomen, Thu Uyen Nguyen, Tongyi Dou, Gaya P Yadav, Sukyeong Lee, Zhao Wang, Andrew Lemoff, Xuemei Luo, Sumitha S Menon, Min Zhang, Jin Wang, Zhicheng Jin, Jiansen Jiang, Adrian Salic, Pengxiang Huang

Faculty, Staff and Students Publications

Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts from the endoplasmic reticulum to the plasma membrane, then transfers them to extracellular carriers, forming active and soluble morphogen-carrier complexes. To dissect the mechanisms involved, we solve cryo-EM structures of Wnt-bound WLS and unliganded WLS, and perform structure-guided functional experiments. Wnts engage WLS via three conserved hairpins, which are all required for Wnt trafficking to the cell surface and carrier-mediated secretion. Wnt release from cells is driven by dramatic conformational changes in the WLS transmembrane domain, reminiscent …

The Role Of 14-3-3 Proteins In The Pro-Inflammatory Response Of Microglia And The Neuronal Stress Response To Trichloroethylene Exposure, William Stone

ETDs from 2020-2029

ABSTRACT This dissertation examines how 14-3-3 proteins, with a focus on the 14-3-3θ iso-form, regulate signaling pathways relevant to neurodegeneration. While tradition-ally described as molecular hubs that organize protein–protein interactions, our work reveals how 14-3-3 function is shaped by environmental insults, namely bac-terial and neurotoxicant exposures, and how its disruption contributes to disease-associated processes. Two complementary approaches were used, focusing on microglial inflammatory signaling and neuronal responses to an environmental neurotoxicant, to define a broader role for 14-3-3 proteins in disease associated pathways in the brain. Chapter I identifies 14-3-3 proteins as modulators of microglial activation. Disrup-tion of 14-3-3 interactions …