Digital Commons Network^™

Viscoelastic And Morphologic Changes In The Lumbar Intervertebral Discs Of The 5xfad Mouse Model Of Alzheimer's Disease, C E Gonzalez, C A Schurman, K A Wilson, B Schilling, L M Ellerby, S Y Tang

2020-Current year OA Pubs

BACKGROUND: Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.

AIMS: The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.

MATERIALS AND METHODS: Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we …

Early Results Of Sotatercept Treatment In Patients With Severe Pulmonary Hypertension And A Potts Shunt, Manish A Aggarwal, Kelly Merrill, Delphine Yung, R Mark Grady

2020-Current year OA Pubs

Twelve patients with severe pulmonary hypertension (PH) who had a pulmonary artery-to-descending aorta (Potts) shunt were treated with the novel PH drug sotatercept for an average of 12 months. Overall, the group showed significant improvement in a number of clinical parameters with no serious complications. Thus, a trial of sotatercept could be considered prior to an invasive intervention in patients with severe PH. Similarly, it may also be useful in patients with Eisenmenger-like physiology.

Quantitative Assessment Of Cardiac Phosphocreatine Metabolism Under Physiological And Pharmacological Stress Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Qi Huang, Caleb Berberet, Ryan Wahidi, Todd Pavek, Cihat Eldeniz, Liya Dai, Rong Guo, Yang Yang, Scott Bugenhagen, Linda R Peterson, Thomas H Schindler, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Phosphocreatine (PCr) exhibits a distinct chemical exchange saturation transfer (CEST) resonance at ∼2.5 ppm with slower exchange kinetics and lower pH sensitivity than creatine. This pilot study evaluated the feasibility of quantifying myocardial PCr-dominated concentration ([PCr]

METHODS: Phantoms with varied concentrations of PCr and Cr were scanned to characterize PCr CEST signals under physiological conditions. Experiments were conducted at both room temperature and 37 °C with full Z-spectra acquisition. For the study in vivo, CEST imaging was performed in normal canines (n = 13), at rest and after regadenoson vasodilation, and during dobutamine stress (n = 5). In addition, …

Synergistic Effects Of Diabetic Neuropathy And Kidney Function Decline On Second Metatarsal Skeletal Health And Foot Function: A Pilot Study, Victor A Cheuy, Saghi Sadoughi, Hasung Moon, Jalen Ellis, Rodney Gross, David R Sinacore, Mary K Hastings, Richard B Souza, Galateia J Kazakia

2020-Current year OA Pubs

A discouraging increase in diabetes-related nontraumatic lower-extremity amputations (NLEA) has occurred over the last decade. Individuals with diabetic neuropathy (DMPN) and CKD are at the highest risk for NLEA. Despite the critical implications, little is known about the factors that initiate the cascade of events leading to NLEA, limiting early and effective interventions. We aimed to develop and implement a technique for quantifying metatarsal bone density and microstructure using HR-pQCT. Twelve participants were enrolled:

Toward Better Response Assessment Of Cutaneous Chronic Graft-Versus-Host Disease: A Report From The National Institutes Of Health Consensus Project Task Force, Alina Markova, Iskra Pusic, Et Al.

2020-Current year OA Pubs

The National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) Consensus Project established response criteria that enabled clinical trials and facilitated regulatory approval of multiple therapies. Nonetheless, organ-specific assessments have limitations, particularly for severe sclerotic skin involvement. Cutaneous manifestations occur in approximately half of patients with chronic GVHD but are difficult to evaluate due to heterogeneous clinical features. To address these challenges, the NIH Consensus Skin Task Force convened from 2024 to 2025 to refine skin response measures for use in clinical trials. This report (1) summarizes current diagnosis and scoring of skin chronic GVHD, (2) reviews existing response assessments, …

Expanding The Omop Common Data Model To Support Extracorporeal Life Support Research, Clemens Rieder, Ahmed Said, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Despite the increased availability of electronic health records, open-source standardized data collection to facilitate high-resolution data during extracorporeal life support (ECLS) is lacking. This project aimed to assess the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) for interoperability to store data sufficiently generated in the context of ECLS and to develop a custom data model expansion in case the OMOP CDM proved insufficient.

DESIGN AND SETTING: The OMOP CDM was analyzed qualitatively by expert consensus for its capability to capture data relative to ECLS as well as the presence of fitting ECLS-related concepts. Database entries necessary to …

Neural Plasticity Across Hormonal States In Females: From Modulator To Dynamic Regulator, Takahiro Sasaki, Christine Nwaigwe, Sayaka Inoue

2020-Current year OA Pubs

Ovarian sex steroid hormones play a critical role in regulating fertility. In addition, these hormones influence behavior and mood across the lifespan in females. Converging evidence from rodent studies and human neuroimaging shows that ovarian hormones dynamically regulate neuronal excitability, synaptic efficacy, and structural remodeling across menstrual/estrous cycles, puberty, and reproductive aging. Estrogen and progesterone reorganize network dynamics and gate plasticity eligibility rather than uniformly scaling synaptic strength, with additional contributions from glia, the extracellular matrix, and neurosteroid signaling. Here we synthesize recent cross-scale advances that link structural and functional changes to cellular and circuit mechanisms, and relate these dynamics …

Use Of Wearable Sensors To Measure Improvements In Real World Upper Extremity Activity After Brachial Plexus Reconstruction, Arakua N Welbeck, Catherine E Lang, David M Brogan, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Current functional assessments after brachial plexus (BP) reconstruction, including surgeon-graded active range of motion and strength scores, and patient-reported outcomes (PROs), have limitations. This study evaluated the feasibility of wearable sensors to quantify recovery and functional outcomes following BP reconstruction. We hypothesized that sensor-derived measures of daily upper-extremity use would correlate with PROs and that real-world upper-extremity use would improve.

METHODS: Traumatic BP injury patients wore bilateral wrist accelerometers for 7-day periods at 3- to 6-month intervals. Data were grouped relative to timing of reconstruction. Duration and magnitude of upper-extremity activity were expressed as ratios of injured to uninjured …

Fibroblast Growth Factor Receptor Inhibition For Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumors: A Phase 2 Trial, Priscilla Merriam, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

While most gastrointestinal stromal tumors are driven by oncogenic mutations in KIT or PDGFRA, 10-15% exhibit functional loss of the succinate dehydrogenase (SDH) complex and genome-wide DNA hypermethylation. Excess methylation in SDH-deficient gastrointestinal stromal tumors disrupts genomic insulators, inducing aberrant expression of oncogenic ligands FGF3, FGF4, and activating an autocrine signaling loop mediated through FGFR1. We conducted a phase 2 trial of pan-fibroblast growth factor receptor inhibitor rogaratinib in patients with sarcoma and report here on the cohort of patients with advanced SDH-deficient GIST. The primary objective was to estimate objective response rate. Secondary objectives were to estimate progression-free survival …

Non-Invasive Profiling Of The Tumour Microenvironment With Spatial Ecotypes, Wubing Zhang, Abul Usmani, Noah Earland, Chloe M Sachs, Peter K Harris, David Y Chen, Et Al.

2020-Current year OA Pubs

Multicellular programs in the tumour microenvironment (TME) drive cancer pathogenesis and response to therapy but remain challenging to identify and profile clinically

Focal White Matter Lesions Drive Grey Matter Inflammation And Synapse Loss, Omar De Faria Jr, Sabine Dietmann, Et Al.

2020-Current year OA Pubs

Focal white matter lesions occur in most neurodegenerative disorders

Frame-Wise Multi-Echo Distortion Correction For Superior Functional Mri, Andrew N Van, David F Montez, Timothy O Laumann, Philip N Cho, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Roselyne J Chauvin, Samuel R Krimmel, Athanasia Metoki, Aishwarya Rajesh, Jarod L Roland, Anxu Wang, Aristeidis Sotiras, Joshua S Shimony, Benjamin P Kay, Scott A Marek, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities, which currently must be corrected using separately acquired field map data. However, changes in the head position of a participant across fMRI frames cause changes in the B0 field, preventing accurate correction of geometric distortions. Movement during field map acquisitions corrupts field maps, preventing distortion correction altogether. In this study, we use multi-echo (ME) fMRI data to dynamically sample and correct for magnetic field image distortions caused by head motion. Our distortion correction pipeline, MEDIC (Multi-Echo DIstortion Correction), leverages magnetic field inhomogeneity information found in the difference between …

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

2020-Current year OA Pubs

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), …

Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov

2020-Current year OA Pubs

Aging strongly impacts CD8

Regulation Of Pfh1 Helicase Activity By Nucleic Acid Interactions And Mitochondrial Ssb, María Ortiz-Rodríguez, Saurabh P Singh, Francisco J Cao-García, Roberto Galletto, Borja Ibarra

2020-Current year OA Pubs

Pif1-family helicases are essential for proper nuclear and mitochondrial genome maintenance, yet the regulation of their activities remains incompletely understood. Here, we use single-molecule manipulation and visualization techniques to dissect the real-time mechanochemical behavior of Pfh1, the sole Pif1-family helicase in

Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Advanced systemic mastocytosis (AdvSM), a clonal hematologic neoplasm driven predominantly by D816V-mutant KIT, is often characterized by organ damage. Associated hematologic neoplasms (AHNs; usually myeloid) are often present, leading to poor survival. We report on the oral, highly selective, potent KIT D816V inhibitor avapritinib (200 mg once daily, starting dose) with >4 years follow-up from the fully enrolled PATHFINDER study. End points included overall response rate (ORR; primary), duration of response (DOR), progression-free survival (PFS), overall survival (OS), changes in objective biomarkers of disease, and safety (all secondary). Of 107 patients with AdvSM (including 71 [66%] with SM-AHN; overall population …

Isg15 Negatively Regulates Ripk3-Mediated Cell Death And Viral Pathogenesis, Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt, Douglas R Green, Yi-Nan Gong, Deborah J Lenschow

2020-Current year OA Pubs

Necroptosis, a form of programmed, inflammatory necrosis, plays an important role in viral-host defense and inflammation. The receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway mediates necroptosis. Yet, the mechanisms that control necroptosis to limit immunopathology are poorly understood. Here, we report that interferon-stimulated gene 15 (ISG15) negatively regulates RIPK3-mediated cell death, including necroptosis, and limits immunopathology during chikungunya virus (CHIKV) infection. ISG15-deficient mice infected with CHIKV display increased levels of necroptosis, resulting in elevated proinflammatory cytokine and chemokine production, leading to increased lethality. This dysregulated host response is fully prevented when MLKL or RIPK3 is ablated …

Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia

2020-Current year OA Pubs

Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for cancer and other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast cancer cells, highlighting the …

Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al.

2020-Current year OA Pubs

Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, …

Real-World Evidence For Pembrolizumab Gemcitabine Vinorelbine And Liposomal Doxorubicin In Classical Hodgkin Lymphoma, Grace Baek, Nancy L Bartlett, Marcus Watkins, Et Al.

2020-Current year OA Pubs

No abstract provided.

Benchmarking Genome Choice In Functional Genomics Analyses, Juan F Macias-Velasco, Xiaoyu Zhuo, Chad Tomlinson, Eddie A Belter, Milinn Kremitzki, Derek Albracht, Tina Lindsay, Xiaoyun Xing, Nina Tekkey, Wenjin Zhang, John E Garza, Zheng Xu, Zilan Xin, Qichen Fu, Heather A Lawson, Nathan O Stitziel, Robert S Fulton, Daofeng Li, Human Pangenome Reference Consortium, Ting Wang

2020-Current year OA Pubs

The human genome reference established a shared coordinate system for genome function, but it is incomplete and not fully representative of human diversity. Here, we benchmark how genome representation and corresponding analytical frameworks for each representation shape functional genomics using chromatin accessibility sequencing (ATAC-seq), RNA sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) data from lymphoblastoid cell lines derived from five individuals with fully phased genome assemblies. We compare results across hg38, CHM13, the draft human pangenome, and each individual's maternal and paternal assemblies. Because current pipelines and quality control conventions are tuned to hg38, several of these comparisons …

Generalizability Of An Ai-Based Mammogram Risk Score (Mrs) For Breast Cancer Among Diverse Populations Of Women, Shu Jiang, Debbie L Bennett, Peter Kraft, Graham A Colditz

2020-Current year OA Pubs

Conventional prediction models incorporating genetic and clinical factors including breast density underperform in non-European populations. We investigated an artificial intelligence-derived mammogram risk score (MRS), a summary of texture features that captures intrinsic breast-tissue characteristics-the substrate for cancer development. This study leveraged data from two North American screening cohorts totaling >226,000 women, including non-Hispanic white, non-Hispanic Black, East Asian, South Asian, and Indigenous women. MRS distributions showed nonsignificant shifts (and similar SDs) between cohorts and across race and ethnic subgroups. MRS increased with age and was significantly associated with breast cancer risk, with hazard ratios per SD ranging from 2.24 [95% …

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E Irmen, Nicholas J Constantino, Chanung Wang, Michael F Kanan, Marco Colonna, Shannon L Macauley, Jocelyn Y Cheng, Ken Hatanaka, Margaret Moline, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer's disease (AD). The orexin/hypocretin system regulates sleep-wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

METHODS: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …

Co-Occurring Clonal Hematopoiesis Exhibits Strong Selection And High Leukemia Risk, Kara M Barnao, Irenaeus C C Chan, Duc Tran, Yin Cao, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have …

Target Ii Data Portal: A Multi-Omics Resource For Environmental Toxicant Studies In Mice, Prashant K Kuntala, Benpeng Miao, Deepak Purushotham, Bo Zhang, Daofeng Li, Ting Wang

2020-Current year OA Pubs

The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) program is a multiphase program that aims to understand how environmental factors contribute to disease susceptibility using toxicant-exposed mouse models. Here, we present the TaRGET II Data Portal ( https://data.targetepigenomics.org/ ), a comprehensive repository of multi-omics datasets generated from mice exposed to a range of environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di(2-ethylhexyl) phthalate (DEHP), tetrachlorodibenzo-p-dioxin (TCDD), and ambient air pollution (PM2.5). Epigenomic profiling assays capturing alterations in chromatin accessibility, DNA methylation, gene expression, and histone modifications were produced across multiple research …

Associations Between Residential Segregation, Ambient Air Pollution, And Hippocampal Features In Recent Trauma Survivors, Sophia S Liang, Stacey L House, Et Al.

2020-Current year OA Pubs

Residential segregation is associated with differential exposure to air pollution. Hippocampus structure and function are highly susceptible to pollutants and associated with posttraumatic stress disorder (PTSD) development. Therefore, we investigated associations between residential segregation, air pollutants, hippocampal neurobiology, and PTSD in recent trauma survivors. Participants (N = 278; 34% non-Hispanic white, 46% Non-Hispanic Black, 16% Hispanic) completed multimodal neuroimaging two weeks after trauma. Yearly averages of air pollutants (PM

Decoding Spatial Transcriptomics Across Multicellular And Subcellular Resolutions, Chongyue Zhao, Hanqiu Zhao, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

Current whole-genome spatial transcriptomics (ST) platforms, which range from multicellular (e.g., Visium) to subcellular resolution (e.g., Visium HD, Stereo-seq), face significant challenges in accurately decomposing or aggregating spots into single cells-the fundamental units of biological activity. To date, most existing computational methods operate at the spot level, and no method has effectively reconstructed transcriptomes at single-cell resolution. In this study, we present STARS (Spatial Transcriptomics across Resolutions for Single Cells). Leveraging Vision Transformer model and contrastive learning, STARS combines high-resolution histology images with spot-level transcriptomics data to reconstruct single-cell-level gene expression from multicellular and subcellular platforms. We demonstrate the advantage …

Subclinical Neuropsychiatric Trait Variation In Parents Of Children With Autism Spectrum Disorder: A Cohort Study, Lindsay J Mullin, Carolyn Lasch, Natasha Marrus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.

METHODS: Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were …

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …

Quantification Of Sarm1 Nadase Activity In Human Peripheral Blood Mononuclear Cells, Lila F Dabill, Ivana R Shen, Jennifer M Brazill, Alicia Neiner, Yo Sasaki, Erica L Scheller

2020-Current year OA Pubs

SARM1 (sterile α and TIR motif-containing protein-1) is an NADase enzyme that serves as the central executioner of Wallerian axon degeneration. Given this, SARM1 is of high interest as a candidate therapeutic target, and SARM1 inhibitors are currently in clinical trials for treatment of neurodegeneration. Beyond neuroscience, emerging studies reveal that SARM1 may also drive aspects of bone fragility, liver pathology, adipose expansion, and insulin resistance in metabolic disease. However, we lack methods to quantify SARM1 activation in humans to better define patients at high risk of SARM1-mediated tissue damage. Unlike neurons, peripheral blood mononuclear cells (PBMCs) represent an easily …