tbuckley/cabot-search huggingface dataset:
Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy
Authors: Hanisah Sharif, Swati Acharya, Gopal Krishna R. Dhondalay, Gilda Varricchi, Shoshanna Krasner-Macleod, Wannada Laisuan, Amy Switzer, Madison Lenormand, Elena Kashe, Rebecca V. Parkin, Yi Yi, Merve Koc, Oleksandra Fedina, Gemma Vilà-Nadal, Gianni Marone, Aarif Eifan, Guy W. Scadding, David J. Fear, Kari C. Nadeau, Stephen R. Durham, Mohamed H. Shamji
Journal: Journal of Allergy and Clinical Immunology (2020)

Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.We sought to evaluate the role of circulating CXCR5+PD-1+ T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape.Phenotype and function of cTFH cells were initially evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC, n = 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n = 12), GPA (n = 14), SCIT- (n = 10), and SLIT- (n = 8) treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups.cTFH cells were shown to be distinct from TH2- and TH2A-cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B-cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH-cell proliferation in the GPA group but not in the NAC group (P < .05). cTFH cells were higher in the GPA group compared with the NAC group and were lower in the SCIT and SLIT groups (P < .01). Time-dependent induction of IL-4, IL-21, and IL-6 was observed in nasal mucosa following intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT groups (all, P < .01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups.For the first time, we showed dysregulation of cTFH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cTFH and TFR cells.
C/EBPα/miR‐7 Controls CD4+ T‐Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice
Authors: Juanjuan Zhao, Fengyun Chu, Hualin Xu, Mengmeng Guo, Shan Shan, Wen Zheng, Yijing Tao, Ya Zhou, Yan Hu, Chao Chen, Tao Ren, Lin Xu
Journal: Hepatology (2020)

Background and Aims Increasing evidence in recent years has suggested that microRNA‐7 (miR‐7) is an important gene implicated in the development of various diseases including HCC. However, the role of miR‐7 in autoimmune hepatitis (AIH) is unknown. Approach and Results Herein, we showed that miR‐7 deficiency led to exacerbated pathology in Concanavalin‐A‐induced murine acute autoimmune liver injury (ALI) model, accompanied by hyperactivation state of CD4 + T cells. Depletion of CD4 + T cells reduced the effect of miR‐7 deficiency on the pathology of ALI. Interestingly, miR‐7 deficiency elevated CD4 + T‐cell activation, proliferation, and cytokine production in vitro . Adoptive cell transfer experiments showed that miR‐7 def CD4 + T cells could exacerbate the pathology of ALI. Further analysis showed that miR‐7 expression was up‐regulated in activated CD4 + T cells. Importantly, the transcription of pre‐miR‐7b, a major resource of mature miR‐7 in CD4 + T cells, was dominantly dependent on transcription factor CCAAT enhancer binding protein alpha (C/EBPα), which binds to the core promoter region of the miR‐7b gene. Global gene analysis showed that mitogen‐activated protein kinase 4 (MAPK4) is a target of miR‐7 in CD4 + T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4 + T cells with or without miR‐7 deficiency. Our studies document the important role of miR‐7 in the setting of AIH induced by Concanavalin‐A. Specifically, we provide evidence that the C/EBPα/miR‐7 axis negatively controls CD4 + T‐cell activation and function through MAPK4, thereby orchestrating experimental AIH in mice. Conclusions This study expands on the important role of miR‐7 in liver‐related diseases and reveals the value of the C/EBPα/miR‐7 axis in CD4 + T‐cell biological function for the pathogenesis of immune‐mediated liver diseases.
Three-Year Follow-up from a Phase 2 Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia
Authors: Kerry A. Rogers, Ying Huang, Amy S. Ruppert, Lynne V. Abruzzo, Seema A Bhat, Corinne Hoffman, Kami J. Maddocks, Gerard Lozanski, Adam S. Kittai, Mollie E. Moran, Mark Reid, Jennifer A. Woyach, John C. Byrd
Journal: Blood (2020)
Adoptive Therapy with Allogeneic Cord Blood T Regulatory Cells Show Safety and Early Clinical Signal in Primary Myelofibrosis
Authors: Tapan M. Kadia, Naveen Pemmaraju, Musa Yilmaz, Li Li, Mi-Ae Lyu, Meixian Huang, Ke Zeng, Simrit Parmar, Courtney D. DiNardo, Naval Daver, Ghayas C. Issa, Elias Jabbour, Gautam Borthakur, Srdan Verstovsek
Journal: Blood (2020)
Evaluating Outcomes of Adult Patients with Acute Lymphoblastic Leukemia Treated on the GMALL Protocol
Authors: Danielle Fredman, Yulia Volchek, Gabriel Heering, Keren Shichrur, Ronit Yerushalmi, Noga Shem-Tov, Elena Ribakovsky, Avichai Shimoni, Abraham Avigdor, Arnon Nagler, Jonathan Canaani
Journal: Blood (2020)
Next-Generation Sequencing Identifies a Previously Uncharacterized Gene ANKRD36 As a Common Biomarker for Blast Crisis Chronic Myeloid Leukemia: Molecular and Protein Bio-Modeling Studies
Authors: Zafar Iqbal, Muhammad Absar, Abid Jamil, Tanveer Akhtar, Salman Basit, Sibtain Afzal, Khushnooda Ramzan, Kulsoom Qureshi, Muhammad Farooq Sabar, Muhammad Arshad, Aamer Aleem, Ullah Anhar, Zeenat Mirza, Sajjad Karim, Naila Batool Khalid, Mahmood Rasool, Muhammad Asif, Mujib Ullah, Ahmad M Khalid, Amer Mahmood, Nawaf Alanazi
Journal: Blood (2020)
Ocular and Systemic Risk Markers for Development of Macular Edema and Proliferative Retinopathy in Type 2 Diabetes: A 5-Year Longitudinal Study
Authors: António C.-V. Martinho, Inês P. Marques, Ana L. Messias, Torcato Santos, Maria H. Madeira, David C. Sousa, Conceição Lobo, José Cunha-Vaz
Journal: Diabetes Care (2020)

Diabetic retinopathy (DR) is a common complication of diabetes and may lead to blindness through vision-threatening complications, such as diabetic macular edema and proliferative DR (PDR). Several studies have established that certain systemic factors have associations with incidence and progression of DR, namely, glycemic control, arterial hypertension, high cholesterol and hyperlipidemia obesity, inflammatory markers, sleep-disordered breathing, and exercise (1,2). In addition to systemic factors, there are ocular factors that should be considered, since they may identify the eyes at risk (2).

We here report a 5-year prospective longitudinal observational cohort study that investigates the risk of both systemic and ocular factors that may play a role in the development of diabetic macular edema and PDR, the vision-threatening complications of DR.

This observational cohort study included eyes/patients with mild nonproliferative PDR, Early Treatment Diabetic Retinopathy Study (ETDRS) classification grades 20 and 35 (3), who were followed for a period of 5 years or until the time of development of center-involved macular edema (CIME), clinically significant macular edema (CSME), or PDR. A total of 212 patients were included: men and women with diagnosed adult-onset type 2 diabetes, aged 42–82 years, with a maximum baseline HbA1c value of 10% (86 mmol/mol). Exclusion criteria included any laser treatment or intravitreal injections or any other comorbidity that could affect the retina. …
Abnormal Metaphase Cytogenetics Adds to Currently Known Risk-Factors for Venous Thromboembolism in Multiple Myeloma: Derivation of the <i>PRISM</i> score
Authors: Rajshekhar Chakraborty, Lisa Rybicki, Jason Valent, Alex V. Mejia Garcia, Beth M. Faiman, Jack Khouri, Nathaniel Rosko, Christy J. Samaras, Matt Kalaycio, Faiz Anwer, Alok A Khorana
Journal: Blood (2020)
Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis
Authors: Zhiwen Liu, Danyi Yang, Jingli Gao, Xiaohong Xiang, Xiaoru Hu, Siyao Li, Wenwen Wu, Juan Cai, Chengyuan Tang, Dongshan Zhang, Zheng Dong
Journal: Theranostics (2020)

Rationale: Sepsis is the cause of nearly half of acute kidney injury (AKI) and, unfortunately, AKI in sepsis is associated with unacceptably high rates of mortality. Early detection of AKI would guide the timely intervention and care of sepsis patients. Currently, NephroCheck, based on urinary [TIMP2]*[IGFBP7], is the only FDA approved test for early detection of AKI, which has a relatively low sensitivity for sepsis patients. Methods:In vitro, BUMPT (Boston University mouse proximal tubular cell line) cells were treated with lipopolysaccharides (LPS). In vivo, sepsis was induced in mice by LPS injection or cecal ligation and puncture (CLP). To validate the biomarker potential of miR-452, serum and urinary samples were collected from 47 sepsis patients with AKI, 50 patients without AKI, and 10 healthy subjects. Results: miR-452 was induced in renal tubular cells in septic AKI, and the induction was shown to be mediated by NF-κB. Notably, serum and urinary miR-452 increased early in septic mice following LPS or CLP treatment, prior to detectable renal dysfunction or tissue damage. Sepsis patients with AKI had significantly higher levels of serum and urinary miR-452 than the patients without AKI. Spearman's test demonstrated a remarkable positive correlation between urinary miR-452 and serum creatinine in sepsis patients (r=0.8269). The area under the receiver operating characteristic curve (AUC) was 0.8985 for urinary miR-452. Logistic regression analysis showed a striking 72.48-fold increase of AKI risk for every 1-fold increase of urinary miR-452 in sepsis patients. The sensitivity of urinary miR-452 for AKI detection in sepsis patients reached 87.23%, which was notably higher than the 61.54% achieved by urinary [TIMP2]*[IGFBP7], while the specificity of urinary miR-452 (78.00%) was slightly lower than that of [TIMP2]*[IGFBP7] (87.18%). Conclusions: miR-452 is induced via NF-κB in renal tubular cells in septic AKI. The increase of miR-452, especially that in urine, may be an effective biomarker for early detection of AKI in sepsis patients.
Abstract 399: Tip60 Depletion in Adult Cardiomyocytes Promotes Proliferation and Preserves Cardiac Function After Myocardial Infarction
Authors: Xinrui Wang, Tina C Wan, Amelia Lauth, Michaela Patterson, John W Lough, John A Auchampach
Journal: Circulation Research (2020)

Cardiac disease and injury are accompanied by significant cardiomyocyte (CM) loss. CMs are essentially non-regenerable, preventing re-muscularization and resulting in permanent dysfunction during the healing process. The identification of factors from multiple layers of inhibitors that induce and maintain CM’s pronounced state of proliferative senescence provides potential therapeutic targets. Tip60 ( T at- i nteractive p rotein, 60 kD), a pan-acetylase tumor suppressor encoded by the Kat5 gene, activates multiple anti-proliferative pathways in other cell types. Tip60 is known to acetylate Atm and p53, which respectively activate the DNA damage response and apoptosis. And, Tip60 regulates intracellular levels of p21 and Tert polymerase in a fashion designed to maintain proliferative senescence. Although these functions promote CM proliferative senescence and Tip60 is strongly expressed in the myocardium, whether Tip60 regulates these activities in CMs remains unknown. This study tests the hypothesis that Tip60 inhibits CM cell-cycle activation, promotes apoptosis in the myocardium, and prevents regeneration after cardiac injury. In adult mice containing LoxP -flanked Kat5 alleles and a tamoxifen-inducible Cre-recombinase transgene driven by Myh6 (Kat5 flox/flox;Myh6-merCremer ) , Tip60 depletion three days after myocardial infarction (MI) preserved cardiac function as assessed by echocardiography at 10, 21, and 28 days post-MI. Histologic evaluation revealed that depletion of Tip60 in CMs significantly diminished scarring and increased CM cell-cycle activation, as indicated by increased numbers of Ki67-, BrdU- and pH3-positive CMs at 28 days post-MI. This was accompanied by the presence of CMs in the infarct border zone expressing smooth muscle α-actin, indicative of CM de-differentiation, and by reduced apoptosis in the remote zone as assessed by TUNEL and cleaved caspase-3 staining, suggesting reduced cardiac remodeling. These findings suggest that genetic depletion of Tip60 protects CMs from ischemia-induced cell death while promoting CM proliferation, implicating Tip60 as a novel candidate for cardiac therapeutics.
Mutations Based on Next-Generation Sequencing May be Complementally to Prognostic Risk in Myelodysplastic Syndromes
Authors: Jing Wang, Jinsong Jia, Xiaohong Liu, Lizhong Gong, Shengye Lu, Yu Wang, Lanping Xu, Xiaohui Zhang, Chenhua Yan, Yueyun Lai, Xiaosu Zhao, Yazhen Qin, Guorui Ruan, Yingjun Chang, Hongxia Shi, Kaiyan Liu, Xiaojun Huang, Hao Jiang
Journal: Blood (2020)
Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis
Authors: George Goshua, Yiwen Liu, Matthew L. Meizlish, Rebecca Fine, Kejal Amin, Eric Chang, Yuxin Liu, Dayna McManus, Adina Petrosan, Cassius Ilya Ochoa Chaar, Hyung J. Chun, Nicholas A. Defilippo, Donna S. Neuberg, Kent A. Owusu, Alfred Ian Lee
Journal: Blood (2020)
A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib As Frontline Therapy for Patients with MYC-Aberrant Lymphoid Malignancies: The Daciphor Regimen
Authors: Carlos Galvez, Reem Karmali, Mehdi Hamadani, Leo I. Gordon, Jane N. Winter, Shuo Ma, Valerie Nelson, Brett Alan Palmer, Timothy S. Fenske, Nirav N. Shah, Deepa Jagadeesh, Andreas Klein, Irene Helenowski, Borko Jovanovic, Adam M Petrich, Andrew M. Evens, Barbara Pro
Journal: Blood (2020)
Abstract PO-059: The genomic landscape of the <i>in situ</i> to invasive ductal breast carcinoma transition shaped by the immune system
Authors: Anne Trinh, Carlos R. Gil Del Alcazar, Sachet A. Shukla, Koei Chin, Young Hwan Chen, Guillaume Thibault, Jennifer Eng, Bojana Jovanovic, C. Marcelo Aldaz, So Yeon Park, Joon Jong, Catherine Wu, Joe Gray, Kornelia Polyak
Journal: Cancer Research (2020)

Abstract Background: The transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is an evolutionary bottleneck where progression occurs only in 30% of patients. Whilst the genetic drivers of this transition remain poorly understood, we have previously shown that immune escape is a key event. In this study, we profile the evolutionary trajectory of matched pure DCIS and IDC in the context of the immune microenvironment. Methods: We have evaluated changes in copy number profiles, mutational profiles, expression and neoantigen load in 6 cases of matched pure DCIS and IDC using exome and RNA sequencing. We have integrated this information with topologic assessment of H&amp;E images and cyclic immunofluorescence. Results: We provide evidence for an evolutionary bottleneck during DCIS to IDC in matched patient samples, showing that copy number aberrations are early events, but low overlap in mutational profiles. Variation in immune composition and spatial orientation can arise as early as in DCIS and are subtype specific. Tumor-specific copy number changes including loss of MHC-I presentation machinery or changes at cytokine rich loci specifically in ER− tumors could contribute to a more immunosuppressive environment in IDC. Oncogenic hotspot mutations can present as neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition. We suggest these mutations have a secondary immune-modulatory function or may be present in normal tissue, escaping immune surveillance as early as in DCIS. Conclusions: We show both genomic and microenvironmental differences in matched pure DCIS and recurrent IDC, highlighting that progression is shaped by both tumor and immune system at this evolutionary bottleneck. Citation Format: Anne Trinh, Carlos R. Gil Del Alcazar, Sachet A. Shukla, Koei Chin, Young Hwan Chen, Guillaume Thibault, Jennifer Eng, Bojana Jovanovic, C. Marcelo Aldaz, So Yeon Park, Joon Jong, Catherine Wu, Joe Gray, Kornelia Polyak. The genomic landscape of the in situ to invasive ductal breast carcinoma transition shaped by the immune system [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-059.
Inhibit Clinical Trials Platform to Prevent and Eradicate Inhibitors: Feasibility Survey of Current Prophylaxis and Immune Tolerance Practices
Authors: Margaret V. Ragni, Frederico Xavier, Craig D. Seaman, Suchitra Acharya, Catherine E. McGuinn, Eric J. Werner, Courtney Elizabeth Lawrence, Allison P. Wheeler, Ulrike Reiss, Irmel Ayala, Erin Cockrell, Cristina Tarango, Amy Dunn, Roshni Kulkarni, Sanjay P Ahuja, Meera B. Chitlur, Steven W. Pipe, Lynn M Malec, Vilmarie Rodriguez, Shelley Crary, Deborah Brown, Rosa Diaz, Maria Velez, Cindy A. Leissinger, Shannon L Carpenter, Christine M. Knoll, Michael Wang, Guy Young, Courtney D Thornburg, Joseph L Lasky, Tiffany Lin Lucas, Nina Hwang, Deborah Vehec, Dana Ivanco, Tamara L. Haller, Marnie Bertolet, Maria M Brooks
Journal: Blood (2020)
Response to: ‘Correspondence on ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’’ by Yang<i>et al</i>
Authors: Shintaro Akiyama, Shadi Hamdeh, Dejan Micic, Atsushi Sakuraba
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> Longitudinal studies of development and disease in the human brain have motivated the acquisition of large neuroimaging data sets and the concomitant development of robust methodological and statistical tools for quantifying neurostructural changes. Longitudinal-specific strategies for acquisition and processing have potentially significant benefits including more consistent estimates of intra-subject measurements while retaining predictive power. In this work, we introduce the open-source Advanced Normalization Tools (ANTs) registration-based cortical thickness longitudinal processing pipeline and its application to the first phase of the Alzheimer’s Disease Neuroimaging Initiative (ADNI-1) comprising over 600 subjects with multiple time points from baseline to 36 months. We demonstrate in these data that the single-subject template construction and same orientation processing results in a simultaneous minimization of residual variability and maximization of between-subject variability immediately estimable from a longitudinal mixed-effects modeling strategy. It is known from the statistical literature that optimizing these dual criteria leads to greater scientific interpretability in terms of tighter confidence intervals in calculated mean trends, smaller prediction intervals, and narrower confidence intervals for determining cross-sectional effects. This strategy is evaluated over the entire cortex, as defined by the Desikan-Killiany-Tourville labeling protocol, where comparisons are made with the cross-sectional and longitudinal FreeSurfer processing streams. Subsequent linear mixed effects modeling for identifying diagnostic groupings within the ADNI cohort is provided as supporting evidence for the utility of the proposed ANTs longitudinal framework which provides unbiased structural neuroimage processing and competitive to superior power for longitudinal structural change detection.
Molecular and Phenotypic Profiling of Drug Product and Post-Infusion Samples from CRB-402, an Ongoing: Phase I Clinical Study of bb21217 a BCMA-Directed CAR T Cell Therapy
Authors: Olivia C Finney, Ashish Yeri, Pingping Mao, Chetanya Pandya, Eric Alonzo, Gregory Hopkins, Sebastian Hymson, Tiffany Hu, Marianna Foos, Sneha Bhadoriya, Stephanie Hintzen, Maple Gioia, Alison Timm, Monica Massaro, Ron Hause, Shari Kaiser, Nathan Martin, Melissa Alsina, Nina Shah, Noopur S. Raje, Jesus G. Berdeja, Shannon Grande, Hans Bitter, Fabio Petrocca, Kevin M. Friedman, Dipen Sangurdekar
Journal: Blood (2020)
Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia
Authors: Sofie Gottschalk Højfeldt, Kathrine Grell, Jonas Abrahamsson, Bendik Lund, Kim Vettenranta, Ólafur G. Jónsson, Thomas L. Frandsen, Benjamin O. Wolthers, Hanne Vibeke Marquart, Goda Vaitkeviciene, Kristi Lepik, Mats Heyman, Kjeld Schmiegelow, Birgitte Klug Albertsen
Journal: Blood (2020)
Clinical Exome Sequencing in B-Cell Ph-Negative ALL Patient Demonstrates Clonal Changes at Different Stages of the Disease
Authors: Kseniia I. Zarubina, Elena N. Parovichnikova, Vadim L. Surin, Olesya S. Pshenichnikova, Ekaterina Y. Demidova, Bella V. Biderman, Andrey B. Sudarikov, Galina A. Baskhaeva, Olga A. Gavrilina, Ekaterina S. Kotova, Andrey N. Sokolov, Vera V. Troitskaya, Valeriy G. Savchenko
Journal: Blood (2020)
Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model
Authors: Jennifer M. Panlilio, Neelakanteswar Aluru, Mark E. Hahn
Journal: Environmental Health Perspectives (2020)

Background: Harmful algal blooms (HABs) produce potent neurotoxins that threaten human health, but current regulations may not be protective of sensitive populations. Early life exposure to low levels of the HAB toxin domoic acid (DomA) produces long-lasting behavioral deficits in rodent and primate models; however, the mechanisms involved are unknown. The zebrafish is a powerful in vivo vertebrate model system for exploring cellular processes during development and thus may help to elucidate mechanisms of DomA developmental neurotoxicity. Objectives: We used the zebrafish model to investigate how low doses of DomA affect the developing nervous system, including windows of susceptibility to DomA exposure, structural and molecular changes in the nervous system, and the link to behavioral alterations. Methods: To identify potential windows of susceptibility, DomA (0.09–0.18 ng) was delivered to zebrafish through caudal vein microinjection during distinct periods in early neurodevelopment. Following exposure, structural and molecular targets were identified using live imaging of transgenic fish and RNA sequencing. To assess the functional consequences of exposures, we quantified startle behavior in response to acoustic/vibrational stimuli. Results: Larvae exposed to DomA at 2 d postfertilization (dpf), but not at 1 or 4 dpf, showed consistent deficits in startle behavior at 7 dpf, including lower responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure at 2 dpf but not 1 or 4 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA exposure at 2 dpf down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton. Discussion: These results in zebrafish reveal a developmental window of susceptibility to DomA-induced behavioral deficits and identify altered gene expression and disrupted myelin structure as possible mechanisms. The results establish a zebrafish model for investigating the mechanisms of developmental DomA toxicity, including effects with potential relevance to exposed sensitive human populations. https://doi.org/10.1289/EHP6652