Digital Commons Network^™

Human Neuronal Firing Varies With The Frequency Of Local Field Potential Oscillations, Zahra Jourahmad, Raissa K Mathura, Layth S Mattar, Melissa C Franch, Danika L Paulo, Mohammed Hasen, Nicole R Provenza, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli, Andrew J Watrous

Faculty, Staff and Students Publications

Neural oscillations play a critical role in shaping neuronal firing patterns. While phase-locked neuronal firing ("phase tuning") has been extensively studied in animal models and human invasive recordings, much less is known about whether neurons show preferential firing at specific oscillatory frequencies, termed frequency tuning. Here, we employ human intracranial recordings across several brain regions including hippocampus, entorhinal cortex, anterior and posterior cingulate cortex, and orbitofrontal cortex to test the hypothesis that neurons exhibit frequency-specific firing. We analyzed 357 single units recorded simultaneously with local field potentials in 19 neurosurgical patients during awake resting. We estimated the instantaneous frequency of …

Comprehensive Proteogenomic Characterization Reveals Clinically Relevant Molecular Subtypes Associated With Medulloblastoma Progression, Seong-Min Park, Kyung-Hee Kim, Jong Hyuk Yoon, Fulvio D'Angelo, Seung Ah Choi, Chan Il Kim, Harim Koo, Seungmin Park, Hyondeog Kim, Sreeja Sundara Raj, Sung Soo Kim, Ae Kyung Park, Eun Jung Koh, Seong-Ik Kim, Yu-Mi Shim, Lee Kwang-Hoon, Eric Eunshik Kim, Ji Hoon Phi, Yeon Suk Jo, Do Hyun Nam, Daehee Hwang, Do Young Hyeon, Sunghyun Huh, Hyung Joon Kwon, Seokjun Ha, Sanha Park, Hyeji Shin, Jeong Taik Kwon, Heon Yoo, Ho-Shin Gwak, Michael D Taylor, Bong Jin Park, Jason K Sa, Youngwook Kim, Antonio Iavarone, Sung-Hye Park, Seung-Ki Kim, Jong Bae Park

Faculty, Staff and Students Publications

Current treatment strategies for medulloblastoma remain ineffective owing to extensive tumor heterogeneity. We generated five platforms of omics data including liquid chromatography and mass spectrometry-based proteome and performed integrated multi-omic characterization to improve the conventional molecular classification of medulloblastoma. We identified seven refined distinct subtypes. The sonic hedgehog (SHH) group was reclassified into two subgroups, SHHα and SHHβ, whereas group 4 was divided into three subgroups, G4α, G4β, and G4γ. SHH and group 4 subtypes exhibit two distinct neuronal differentiation trajectories: granular neuron and unipolar brush cell differentiation (SHHβ and G4γ, respectively), both of which associated with more favorable clinical …

Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy And Phenotypic Expansions, Sarah Araji, Xiaonan Zhao, Jill A Rosenfeld, Seema R Lalani, Daryl A Scott

Faculty, Staff and Students Publications

Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine …

Retrospective Analysis Of A Washu-Based Knowledge-Based Planning (Kbp) Model For Breast And Chest Wall Planning In Guatemala: Compliance With American Society For Radiation Oncology (Astro) 2026 Guidelines, Milton E Ixquiac Cabrera, Erick O Montenegro, Matthew Schmidt, Baozhou Sun, James A Kavanaugh, Taoran Li, Angel Velarde, Vicky De Falla, Francisco Reynoso

Faculty, Staff and Students Publications

Background/purpose

Breast cancer is among the most prevalent malignancies treated at the Liga Nacional Contra el Cáncer (LNCC) in Guatemala, representing a significant proportion of annual radiotherapy cases. Access to high-quality, standardized treatment planning in resource-constrained settings remains a critical challenge. This study evaluates the dosimetric performance of knowledge-based planning (KBP) models adapted from Washington University (WashU) in St. Louis for breast and chest wall radiotherapy at LNCC, validated against a retrospective 2025 clinical cohort, and benchmarked against the ASTRO 2026 Practical Radiation Oncology guidelines.

Materials and methods

A retrospective analysis of 84 treatment plans (40 left, 44 right) for …

Menopause May Partially Explain Age-Related Increased Risk Of Masld Fibrosis: A Causal Mediation Analysis, Itunu O Sokale, Yan Liu, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

No abstract provided.

Structural Determinants Of Ligand Response Specificity In The Mast Cell Activating Gpcr, Mrgprx2, Abiodun Adefola R Adeosun, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The mast cell-specific G-protein-coupled receptor (GPCR) MRGPRX2 (Mas-Related G Protein-coupled Receptor X2) has roles in itch and pain, and it mediates clinically relevant allergy-like responses to a diverse assortment of drugs. The varied responses of individuals to MRGPRX2 agonists, leading to drug hypersensitivity reactions in some cases, suggests the presence of consequential variants in the population. However, genetic associations with drug responses are poorly understood. We used heterologously-expressed MRGPRX2 to investigate the effect of 18 naturally occurring non-synonymous single nucleotide polymorphisms on activation by representative compounds from several classes, including neuropeptides, opioid agonists, antibiotics, neuromuscular blocking agents, and polycationic aromatic …

Choline Counteracts Pregnancy Undernutrition-Associated Colitis In Sheep By Restoring Microbiota Driven Bile Acid Metabolism, Weibin Wu, Peng Jiao, Yamei Gu, Huizhen Lu, Caiyun Fan, Zheng Sun, Lizhuang Hao, Shengyong Mao, Jianbo Cheng, Yanfeng Xue

Faculty, Staff and Students Publications

High-fertility sheep experience undernutrition during late gestation, which induces body metabolic disruption and intestinal inflammation. Crucially, the gut microbiota-bile acid axis is a promising intestinal inflammation target, but how choline modulates this axis in livestock enteritis is unknown. This study investigated choline's protective mechanisms against undernutrition-induced intestinal inflammation in sheep, focusing on gut microbiota and bile acid regulation. Choline consistently alleviates colitis severity, restores epithelial barrier integrity, and suppresses intestinal inflammation. These protective effects are accompanied by pronounced remodeling of the colonic microbial ecosystem, characterized by the enrichment of Clostridiales bacterium to elevate bile salt hydrolase activity and regulate bile …

Toxitarget: A Multi-Omics Database For Toxicant-Responsive Molecular Targets, Ravindra Kumar, Tianyi Fu, Prashant Kumar Kuntala, Benpeng Miao, Shuhua Fu, Daofeng Li, Frederick L Tyson, Marisa S Bartolomei, Cheryl L Walker, Ting Wang, Bo A Zhang

Faculty, Staff and Students Publications

Environmental toxicant exposures can induce widespread alterations in both the transcriptome and epigenome of mammals, and directly contribute to the increased risk of various diseases, including cardiovascular disorders, cancer, and neurological disorders. To evaluate how early-life toxicants produce long-term impacts on the transcriptome and epigenome in mice, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 3607 multi-omics datasets from longitudinal studies in mice. The molecular changes in responding to distinct environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), …

Unbiased Niche Labeling Maps Immune-Excluded Niche In Bone Metastasis, Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Icam1high Neutrophils Sculpt Tumor Evolution And Metastasis Through Symbiotic Adhesion And Reverse Migration, Ling Wu, Zhan Xu, Jun Wang, Fengshuo Liu, Yunfeng Ding, Yang Gao, Siyue Wang, Jun Liu, Hilda L Chan, Weiguo Wu, Yi-Hsuan Wu, Liqun Yu, Xiaoxin Hao, Xuan Li, David G Edwards, Cher Sha, Tobie D Lee, Nan Guan, Sergio Aguirre, Luis Becerra-Dominguez, Dane Hoffman, Xiang Chen, Charlotte Helena Rivas, Xiaoyuan G Yan, Igor L Bado, Weijie Zhang, Qian Zhu, Arun Sreekumar, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Neutrophils are a prominent component of the tumor microenvironment that can have both pro- and anti-tumor functions. By analyzing neutrophils across different human cancers, we revealed an ICAM1high subset enriched in the tumor microenvironment, which were also observed in murine triple negative breast cancer (TNBC) models. ICAM1high neutrophils exhibited an enhanced capacity for cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion conferred mutual advantages to both cell types. In contrast, cancer cells with mesenchymal-like phenotypes were vulnerable to neutrophil-mediated cytotoxicity due to decreased cell adhesion and elastase resistance. These opposite effects drove tumor evolution toward a …

Brain Age Prediction In Generalized Anxiety Disorder Using A Convolutional Neural Network, Corey Richier, André Zugman, Anita Harrewijn, Elise M Cardinale, Parmis Khosravi, Moji Aghajani, Willem B Bruin, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Marta Cano, Savannah Gosnell, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, Karina S Blair, James R Blair, Mohammed R Milad, Katie L Burkhouse, K Luan Phan, Heidi K Schroeder, Jeffrey R Strawn, Katja Beesdo-Baum, Neda Jahanshad, Sophia I Thomopoulos, Jared A Nielsen, Jordan W Smoller, Jair C Soares, Benson Mwangi, Mon-Ju Wu, Giovana B Zunta-Soares, Michal Assaf, Gretchen J Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rebecca B Price, Gisele G Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza Jovanovic, Brenda Benson, Gabrielle F Freitag, Ellen Leibenluft, Grace V Ringlein, Kathryn Werwath, Hannah Zwiebel, Hans J Grabe, Sandra Van Der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L Balderston, Monique Ernst, Lilianne R Mujica-Parodi, Helena Van Nieuwenhuizen, Hugo D Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Gregory A Fonzo, Martin P Paulus, Murray B Stein, Raquel E Gur, Ruben C Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Jennifer Harper, Michael T Perino, Chad M Sylvester, Qiongru Yu, Patrick Mcclure, Francisco Pereira, Ulrike Lueken, Dick J Veltman, Paul M Thompson, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Dan J Stein, Nic J A Van Der Wee, Anderson M Winkler, Daniel S Pine, Chelsea K Sawyers

Faculty, Staff and Student Publications

Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

A Reappraisal On The Use Of Mechanical Circulatory Support In Acute Coronary Syndrome And High-Risk Percutaneous Coronary Intervention—Lessons From Stemi-Dtu And Chip-Bcis3, Marwan F. Jumean, Mir Babar Basir, Biswajit Kar

Journal of Shock and Hemodynamics

None.

Phkg2 Confers Resistance Of Escc To Cisplatin And Enhances Cxcl8-Dependent Immunosuppression To Exacerbate Tumorigenesis, Jiayan Wu, Chengrui Zhong, Haosheng Zheng, Fei Qin, Xianyu Qin, Yuzhen Zheng, Junguo Chen, Gengfeng Wang, Bozhu Jian, Zui Liu, Xingping Yang, Chao Cheng, Guolin Li, Hongying Liao

Faculty, Staff and Students Publications

Cisplatin (DDP)-based chemotherapy serves as a foundational cornerstone in the clinical management of esophageal squamous cell carcinoma (ESCC). However, intrinsic or acquired resistance to DDP persists as a significant clinical challenge, severely undermining therapeutic efficacy and contributing to unfavorable patient prognoses. Through functional screening with a CRISPR/Cas9 knockout library, transcriptomic profiling of cisplatin-resistant cell lines and clinical specimens, and in vitro/in vivo validation assays, we identified PHKG2 as a key mediator of cisplatin resistance in ESCC. Mechanistically, PHKG2-mediated cisplatin resistance is driven by the phosphorylation of IGF2BP3 at residues T225 and T306. This post-translational modification enhances IGF2BP3 phase separation, thereby …

Movement-Stabilized Three-Dimensional Optical Recordings Of Membrane Potential Changes And Calcium Dynamics In Hippocampal Ca1 Dendrites, Kevin C Gonzalez, Satoshi Terada, Asako Noguchi, George N Zakka, Cliodhna O'Toole, Giuliana Bilbao, Luke Reynolds, Anna Jász, Borbála Kertész, Zoltán Szadai, Alissa Shen, François St-Pierre, Franck Polleux, Attila Losonczy, Balázs Rózsa

Faculty, Staff and Students Publications

Local dendritic computations are thought to critically influence neuronal signaling and plasticity yet remain largely unexplored in vivo due to challenges in stably imaging small structures at ultrafast timescales. We developed a 3D real-time motion correction platform for movement-stabilized, ultrafast two-photon voltage imaging. By co-labeling CA1 pyramidal neurons with voltage and calcium indicators, we simultaneously measured somato-dendritic and electro-calcium coupling at multiple dendritic sites. We characterized isolated dendritic spikes and distance-dependent backpropagation of naturally occurring and photostimulation-evoked bursts and single spikes. We found that bursts backpropagated more reliably than single spikes, validated that somato-dendritic coupling decreases with distance from soma, …

Deep-Learning Endomicroscope With Large Field-Of-View And Depth-Of-Field For Real-Time In Vivo Imaging Of Epithelial Cancer Hallmarks, Huayu Hou, Jimin Wu, Jinyun Liu, Vivek Boominathan, Argaja Shende, Karthik Goli, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Preetha Ramalingam, Mila P Salcedo, Kathleen M Schmeler, Tomasz S Tkaczyk, Jacob T Robinson, Ashok Veeraraghavan, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface …

Latest In Resuscitation Research: Highlights From The 2025 American Heart Association's Resuscitation Science Symposium, Caleb T Suh, Clark G Owyang, Lindsay Shepard, Betty Yang, Ryan W Morgan, Daniel M Rolston, Catherine R Counts, Tommaso Scquizzato, James Horowitz, Tatyana Shvilkina, Katherine Berg, Sam Parnia, Sanam Alilou, Catherine Swarts, Ryan A Coute, Lama A Ammar, William C Herring, Thomas Lederer, Joaquin Araos, Benjamin S Abella, Cameron Dezfulian, Sarah M Perman, Felipe Teran

Faculty, Staff and Students Publications

No abstract provided.

Developing A Durable, Memory-Driven, Cspz-Targeting Lyme Disease Vaccine By Rationale Adjuvant Selection\, Miranda Mccarty, Sergio A Hernández, Jill Malfetano, Ana Carolina Leão, Maria Jose Villar, Xiuli Yang, Yi-Lin Chen, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Maria Elena Bottazzi, Utpal Pal, Klemen Strle, Wen-Hsiang Chen, Yi-Pin Lin

Faculty, Staff and Students Publications

Rational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacterium Borrelia burgdorferi (Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no approved human vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S, with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy after Bb infection. We identified Alum-CpG and Alum-αGal …

Tumor Implantation Site Of Syngeneic Oral Cancer Models Differentially Induces Site-Dependent Local And Systemic Immunosuppression, Andrea H Molina, Gemalene M Sunga, Shawn Nguyen, Neeraja Dharmaraj, Ratna Veeramachaneni, Roberto Rangel, Jeffrey N Myers, Jeffrey D Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Background/objectives: Preclinical studies of head and neck squamous cell carcinoma (HNSCC) commonly use subcutaneous heterotopic (flank) tumor models for simplicity; however, orthotopic models may better reflect the native tumor environment. Direct comparisons of the tumor immune microenvironments (TIME) and tumor-draining lymph nodes (tdLNs) between these models remain limited. Better understanding of site-specific immune differences could improve model selection and interpretation of translational HNSCC studies.

Methods: ROC1 tumors were established in murine heterotopic and orthotopic sites, followed by assessment of tumor growth kinetics, survival, and the tumor microenvironment. Immune composition of tumors, blood, tdLNs, and spleen was evaluated at three tumor …

Exploring Spike-Dependent And Ace2-Independent Sars-Cov-2 Interactions With Salivary Epithelial Cells In The Absence Of Ace2, Caitlynn M L Barrows, Thaise C Geremias, Simon Young, Mary C Farach-Carson

Faculty, Staff and Student Publications

Salivary gland infection by SARS-CoV-2 requires viral entry via routes and mechanisms that remain unresolved. This study examined the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in salivary tissues and basal cell-derived human salivary progenitor cells (hS/PCs), an unstudied potential entry point for SARS-CoV-2. Multiple detection modalities, including immunocytochemistry, Western blotting, flow cytometry and RT-PCR, demonstrated a consistent lack of ACE2 protein and transcript in both tissue specimens and primary salivary epithelial cells. Antigen retrieval at pH 9 was determined to be optimal for immunodetection protocols, yet ACE2 remained undetectable. Small intestine tissue served as a positive control, confirming …

Cardiac Hdac3 Disruption Contributes To Hdac Inhibitor-Induced Qt Prolongation, Jiao Lu, Christopher Ward, Sichong Qian, Lilei Zhang, Jiang Chang, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, …

Wnt-Dependent Ontogeny Of Acellular Cementum-Forming Cementoblasts On The Tooth Root Surface, Taishi Komori, Mizuki Nagata, Natnicha Praneetpong, Hanwen Fan, Yuxiao Zhou, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

Cementum is a specialized mineralized tissue that covers the tooth root surface and anchors the tooth to the surrounding periodontal ligament. The cervical acellular cementum (AC) is indispensable for periodontal attachment and represents a key target for periodontal regenerative therapies. However, the developmental origin and molecular identity of AC-forming cementoblasts remain poorly understood. Here, through an integrated spatial and single-cell transcriptomic analysis, we identify AC-forming cementoblasts as a distinct population of noncanonical mineralizing cells enriched for cell-matrix organization and Wnt signaling signatures, distinguishing them from cellular cementum-forming cementoblasts localized in the apical portion. Lineage tracing using a Wnt inhibitory factor …

Selective And Differential Roles Of Pvhcrh Neurotransmitters In Diet-Induced Obesity In Mice, Zhiying Jiang, Yuhan Cao, Michelle He, Cunjin Su, Runzhou Yang, Maojie Yang, Jing Cai, Hongli Li, Yuanzhong Xu, Shi-Bin Li, Hiroshi Yamaguchi, Luis De Lecea, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Stress and diet are known to synergistically promote risks of obesity but the underlying neural basis remains elusive. Corticotropin-releasing hormone neurons in the paraventricular hypothalamus (PVHCRH) are stress responsive and release both CRH and glutamate. Here we generated a mouse model with gain or loss of release in CRH or glutamate from PVHCRH neurons. While these models showed no changes in body weight when fed chow, they exhibited contrasting effects when fed high-fat high-caloric diets (HFD). Whereas disrupting glutamate release from PVHCRH neurons led to diet-induced obesity (DIO), that of CRH caused no impact. Conversely, augmented CRH release led to …

Robust Magnetoelectric Backscatter Communication System For Bioelectronic Implants, Fatima Alrashdan, Joshua E Woods, Ellie C Chen, Wendy Tan, Zhanghao Yu, Wei Wang, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Kaiyuan Yang, Mehdi Razavi, Jacob T Robinson

Faculty, Staff and Students Publications

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

Animal Models Of Delirium: A Narrative Review, Tatiana Barichello, Carla Sasso Simon, Diogo Dominguini, Cristiane Ritter, Tsuyoshi Nishiguchi, Gen Shinozaki, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Delirium is an acute cognitive failure characterized by an acute onset and psychomotor disturbances. It is associated with poor outcomes in hospitalized patients, resulting in prolonged hospital stays, elevated rates of mortality, and cognitive dysfunctions after hospital discharge. The pathophysiology of delirium remains poorly understood, making the development of animal models a promising avenue for researchers to elucidate the mechanisms underlying human delirium. These models not only aid in understanding the pathophysiology and etiology of the disease but also enhance the efficacy of nonpharmacological interventions and identify pharmacological therapies. This review aims to present the most relevant and translational animal …

Identifying Novel Gene Dysregulation Associated With Opioid Overdose Death: A Meta-Analysis Of Differential Gene Expression In Human Prefrontal Cortex, Javan K Carter, Bryan C Quach, Caryn Willis, Melyssa S Minto, Dana B Hancock, Janitza Montalvo-Ortiz, Olivia Corradin, Ryan W Logan, Consuelo Walss-Bass, Brion S Maher, Eric Otto Johnson

Faculty, Staff and Student Publications

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate <  0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …