Medicine and Health Sciences Commons^™

Organ Of Corti Macrophages: A Distinct Group Of Cochlear Macrophages With Potential Roles In Supporting Cell Degeneration And Survival, Mengxiao Ye, Celia Zhang, Dalian Ding, Guang-Di Chen, Henry J Adler, Rania Sharaf, Bo Hua Hu

Faculty, Staff and Student Publications

Macrophages are the primary immune cells in the cochlea, essential for maintaining cochlear homeostasis and orchestrating inflammatory responses to pathological events. Although these cells have been found in various parts of the cochlea, their presence in the organ of Corti, a critical structure for acoustic sensing, remains poorly understood. The present study was designed to examine macrophage responses to ototoxic drug-induced cochlear damage and age-related cochlear degeneration, with a particular focus on the pathological conditions that trigger macrophage recruitment into the organ of Corti. We used a model of ototoxicity induced by cyclodextrin, a cyclic oligosaccharide known for its ability …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Methods: We performed a retrospective chart review of 476 patients treated with ICIs for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to the results of BAL cell percentage, confirmed the diagnosis of ICIP or other …

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …

General Kernel Machine Methods For Multi-Omics Integration And Genome-Wide Association Testing With Related Individuals, Amarise Little, Ni Zhao, Anna Mikhaylova, Angela Zhang, Wodan Ling, Florian Thibord, Andrew D. Johnson, Laura M. Raffield, Joanne E. Curran, John Blangero

School of Medicine Publications

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.g. genotypes and gene expression levels) on a phenotype, particularly while accommodating routine issues, such as having related subjects' data in analyses. In this paper, we extend an existing composite kernel machine regression model to integrate two multi-omics data types, while accommodating for general correlation structures amongst outcomes. Due …

Characterization Of The Biofilm-Forming Ability And Certain Virulence Characters Ofaeromonas Spp. Isolates From Rainbow Trout, Türker Çelebi̇, Ertan Emek Onuk, Esra Demi̇rbaş, Gökçen Di̇nç

Turkish Journal of Veterinary & Animal Sciences

Aeromonas spp., commonly found in the aquatic environment, cause infections in both fish and humans. Their pathogenicitydepends on various virulence factors and ability to form biofilm. The current study aimed to determine the biofilm-forming capabilitiesand certain virulence characteristics of 25 Aeromonas spp. isolates obtained from rainbow trout in Türkiye. The biofilm-forming abilitiesof isolates were investigated comparatively using Congo red agar (CRA), the tube method (TM), and tissue culture plates (TCPs).Potential virulence factors, including hemolytic activity, gelatinase production, serine protease activity, DNase activity, and motility,were evaluated using phenotypic tests. Additionally, the distribution of four known virulence genes, namely aerA, exu, fla, …

Effects Of A Diet Supplemented With A Blend Of Protected Organic Acids And Essential Oilson Growth Performance And Cecal Microbiota Composition In Broilers, Mehmet Akan, Kadi̇r Serdar Di̇ker, Serdar Özlü, Murat Çelebi̇, Seyyi̇de Sariçam İnce, Barişhan Doğan, Okan Eli̇bol

Turkish Journal of Veterinary & Animal Sciences

Organic acids (OAs) and essential oils (EOs) have several positive effects on the gut microbiota of broilers. In this study, weaimed to determine the efficacy of a blend of protected OAs and EOs [P(OA+EO)] on the growth performance and cecal microbiota ofbroiler chickens. A total of 160 Ross 308 broiler chickens, including 80 male and 80 female birds, all 1 day old, were randomly distributedbetween the control group (basal diet) and the treatment group [basal diet + 300 g/t P(OA+EO)] according to an 8-pen arrangementwith 4 replicates of 20 birds. Body weight (BW), body weight gain (BWG), feed consumption (FC), …

Validation Of Nutrition Focus Physical Assessment Via Telehealth, Ann Flickinger Ms, Rd, Ldn, Melissa Faura Rd, Ldn, Shae Duka Mph

Clinical Nutrition Service

No abstract provided.

Beyond Strong: A Phenomenology Of Women Executives And The Connection Between Leadership And Fitness, Nozomi Bullock

Antioch University Dissertations & Theses

Senior-level executive leaders’ work in a dynamic, competitive, 24/7 business environment can be physically rigorous, mentally demanding, and emotionally isolating. The same holds true for women pursuing senior-level leadership roles in corporate America. Women who achieve and succeed in such roles remain the minority: Outsiders in elite spaces who are held to higher standards and overly scrutinized. Among senior-level executive women leaders, those committed to a fitness and training regimen including weightlifting constitute an even smaller minority. Senior-level executive roles require stamina, resilience, and courage—qualities that make up the foundation of the mindset of fitness and strength training (Foyster et …

The Role Of Floodplain Complexity In Wood Turtle Habitat Use, Laura S. Deming

Antioch University Dissertations & Theses

Wood turtles occupy cold, low-gradient riverine habitat throughout the northeastern United State and southeastern Canada. Stream alterations, such as dams, channel straightening, and floodplain development have diminished the natural hydrologic and sedimentation regimes that result in complex channel and floodplain geomorphology. Studies throughout the species’ range have quantified many aspects of their habitat, but none have quantified components of geomorphology of wood turtle sites. The goal of this study was to explore the role of stream channel and floodplain geomorphology in wood turtle habitat use, with specific objectives to (1) quantify components of stream channel and floodplain geomorphic complexity, (2) …

Heterogeneous Clustering Of Multiomics Data For Breast Cancer Subgroup Classification And Detection, Joseph Pateras, Musaddiq Lodi, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

The rapid growth of diverse -omics datasets has made multiomics data integration crucial in cancer research. This study adapts the expectation–maximization routine for the joint latent variable modeling of multiomics patient profiles. By combining this approach with traditional biological feature selection methods, this study optimizes latent distribution, enabling efficient patient clustering from well-studied cancer types with reduced computational expense. The proposed optimization subroutines enhance survival analysis and improve runtime performance. This article presents a framework for distinguishing cancer subtypes and identifying potential biomarkers for breast cancer. Key insights into individual subtype expression and function were obtained through differentially expressed gene …

Deepssetracer 2.0: Improved Deep Learning Model Performance For Protein Secondary Structure Segmentation From Cryo-Em Maps, Bryan Hawickhorst, Thu Nguyen, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

DeepSSETracer is a method for segmenting protein secondary structure from medium-resolution (5-10Å) cryogenic electron microscopy (cryo-EM) density maps. We conducted experiments and ablation studies to examine the effects of normalization methods, max-pooling, activation functions, and loss calculation region on DeepSSETracer. By combining multiple technical improvements, the performance of the new version, DeepSSETracer 2.0, was significantly enhanced compared to DeepSSETracer 1.1. On a set of 77 test cases, the weighted average per-voxel F1 score increased from 62.1% to 70.3% for helix detection, and from 47.8% to 62.5% for β-sheet detection. While each of the five modifications in the network enhanced the …

Benchmarking And Improving Foundation Model Dietary Estimates From Meal Images, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Accurate quantifying dietary contents, such as calories, proteins, carbohydrates, and fats, from an image of a meal plate is vital for managing diabetes. Recently, Large Multimodal Models (LMMs) have excelled in complex vision-language tasks due to their use of very large, highly diverse data. This study benchmarked the use of seven LMMs that include full and lightweight models of GPT, Gemini, and Llama for nutrition estimation based on Google's Nutrition5k dataset and our own phone-collected DonateAndLearn dataset. We analyzed the performance of LMMs and the RGB-D fusion model, in which the RGB-D model was specifically trained using Nutrition5k data. On …

Positive Allosteric Modulation Of Glun1/Glun3 Nmda Receptors, Mia Ruth Johns

Graduate Student Theses, Dissertations, & Professional Papers

N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors that mediate excitatory neurotransmission in the central nervous system (CNS) where they play critical roles in normal and pathological brain functions and neurodevelopment. While the glutamate/glycineactivated GluN2-containing NMDA receptors (GluN1/GluN2) have been extensively studied, the physiological roles and pharmacology of glycine-activated GluN3-containing receptors (GluN1/GluN3) remain less understood. Although GluN1/GluN3 receptors exhibit unique functional properties and play distinct roles in neuronal development and synapse maturation, studies of their precise roles in neurophysiology and circuit function are impeded by limited availability of GluN3-selective pharmacological tools. This study describes UCM-A86, a novel GluN3-selective positive allosteric …

Effects Of Ionophore And Yeast Addition To The Diet On Starch Digestion And Rumen Andblood Parameters In Sheep With Subacute Rumen Acidosis, Şevket Evci̇, Mehmet Aki̇f Karsli, Mehmet Demi̇rci̇, Gökhan Şen

Turkish Journal of Veterinary & Animal Sciences

This study aimed to investigate the prevention of acidosis in ruminants, which causes yield and financial losses, and toevaluate the effects of feed additives on starch digestion. Four male Bafra yearling lambs with cannulated rumens were used in a 60-daystudy. Each lamb underwent 10 days of adaptation to a ration and 5 days of sampling for four different rations including a control ration(CR), monensin ration (MR), Saccharomyces cerevisiae ration (SR), and a ration with the combination of monensin and Saccharomycescerevisiae (MSR). The experiment followed a 4 × 4 Latin-square design. Dry matter intake and digestion rates were recorded as 2404 …

Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee

Journal Articles: Cellular & Integrative Physiology

Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-Prkdc^scidIl2rgt^m1Wjl/SzJ humanized mice (Hu-mice) infected with HIV-1_ADA and treated for 13 weeks with dolutegravir …

Fiber Photometry Analysis Of Spontaneous Dopamine Signals: The Z-Scored Data Are Not The Data, Conner W. Wallace, Clare Y. Slinkard, Rachael Shaughnessy, Katherine M. Holleran, Samuel W. Centanni, Christopher C. Lapish, Sara R. Jones

Department of Medicine Faculty Publications

Fluorescent sensors have revolutionized the measurement of molecules in the brain, and the dLight dopamine sensor has been used extensively to examine reward- and cue-evoked dopamine release, but only recently has the field turned its attention to spontaneous release events. Analysis of spontaneous events typically requires evaluation of hundreds of events over minutes to hours, and the most common method of analysis, z-scoring, was not designed for this purpose. Here, we compare the accuracy and reliability of three different analysis methods to identify pharmacologically induced changes in dopamine release and uptake in freely moving C57BL/6J mice. The D1-like receptor antagonist …

Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin

Department of Medicine Faculty Publications

Background: Cardiac sequelae in Hodgkin Lymphoma (HL) can manifest as involvement of the heart and pericardium. Direct cardiac involvement is rare, and myocardial infiltration is distinctly unusual.¹ When it does occur, it is often a late manifestation of lymphoma, with a median onset of 20 months after initial diagnosis, and it is usually associated with advanced-stage disease.²

Case: A 34-year-old male was diagnosed with classic HL by lymph node biopsy. During his hospitalization, the patient remained in sinus tachycardia with heart rate up to 150 with no dysrhythmias. Transthoracic echocardiogram (TTE) revealed a reduced ejection fraction (EF) of 36% concerning …

Oral Microbiome And Inflammatory Bowel Disease: New Understanding And Call To Action, Michael Saadeh, Sydney Donohue, Shaina Ailawadi, Gordon Hong, David A. Johnson

Department of Medicine Faculty Publications

The oral microbiome is the second largest microbial community in the human body after the gut microbiome. It includes an array of fungi, bacteria, amoebae, flagellates, archaea, and viruses, all of which are potential pathogens. This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs. Although conventional thought is this is primarily in terms of oral health issues, such as dental caries and gingival disease. The systemic effects of the oral microbiome however, are relevant to both gastrointestinal (GI) disease and non-GI disease. These systemic risks occur for several reasons, including upregulation …

Key Brain Region Identification In Obesity Prediction With Structural Mri And Probabilistic Uncertainty Aware Model, Walia Farzana, Megan A. Witherow, Ahmed Temtam, Liangsuo Ma, Melanie Bean, F. Gerry Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

Mody Calculator And Clinical Features Routinely Used To Distinguish Mody From Type 2 Diabetes In Adults Perform Poorly For Youth Clinically Diagnosed With Type 2 Diabetes, Raymond J Kreienkamp, Beverley M Shields, Toni I Pollin, Amy S Shah, Angela D Liese, Anna Bellatorre, Catherine Pihoker, Mustafa Tosur, Jose C Florez, Shylaja Srinivasan, Andrew T Hattersley, Miriam S Udler, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Modeling Functional Connectivity With Learning And Memory In A Mouse Model Of Alzheimer’S Disease, Lindsay Fadel, Elizabeth Hipskind, Steen E Pedersen, Jonathan Romero, Caitlyn Ortiz, Eric Shin, Md Abul Hassan Samee, Robia G Pautler

Faculty, Staff and Students Publications

Introduction: Functional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.

Methods: We assessed the APP/PS1 mouse model of AD and wild-type controls …

Identifying Notch-Regulated Genes Using A Specific Notch Signaling Inhibitor, Hammed Gafar

EWU Masters Thesis Collection

Bone remodeling is a dynamic process that requires a balance between bone resorption by osteoclasts and bone formation by osteoblasts to maintain skeletal integrity. Disruptions to this equilibrium can lead to pathological conditions such as osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated by several signaling pathways, notably the notch signaling pathway. Gamma-secretase, an enzyme crucial for initiating notch signaling, can be inhibited by DAPT. However, DAPT also targets non-Notch substrates, complicating the identification of genes specifically regulated by Notch. To address this limitation, this study employed IMR-1A, a selective Notch pathway inhibitor that disrupts the assembly of …

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …

Eeg Spectral Analysis Of Nighttime Sleep And Daytime Mslts And Neurocognitive Evaluations In Subjects With Co-Morbid Insomnia And Osa, Yuan Shi, Yuru Nie, Fengyi Hao, Xujun Feng, Ye Zhang, Larry D. Sanford, Rong Ren, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

Background

Chronic insomnia and obstructive sleep apnea commonly co-occur. Few studies have explored the neurophysiological and neurocognitive characteristics of COMISA, which could help guide improving treatment diagnostic tools and determining novel therapeutic targets. This study aims to explore the neurophysiological and neurocognitive characteristics of COMISA using electroencephalographic (EEG) spectral analysis and subjective and objective neurocognitive measurements.

Methods

Participants were from our community recruited OSA-insomnia-COMISA cohort with 206 included for our current analysis including 74 chronic insomniacs (CIs), 55 OSA patients and 77 COMISA patients. Standard polysomnography (PSG) and multiple sleep latency tests (MSLTs) were recorded and used to obtain relative …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White

Department of Biomedical and Translational Sciences Faculty Publications

Myosins produce force and movement in cells through interactions with F-actin¹. Generation of movement is thought to arise through actin-catalysed conversion of myosin from an ATP-generated primed (pre-powerstroke) state to a post-powerstroke state, accompanied by myosin lever swing²,³. However, the initial, primed actomyosin state has never been observed, and the mechanism by which actin catalyses myosin ATPase activity is unclear. Here, to address these issues, we performed time-resolved cryogenic electron microscopy (cryo-EM)⁴ of a myosin-5 mutant having slow hydrolysis product release⁵,⁶. Primed actomyosin was predominantly captured 10 ms after …