@article{mallik_carlson_wcisel_fisk_yoder_dornburg_2023, title={A chromosome-level genome assembly of longnose gar, Lepisosteus osseus}, volume={4}, ISSN={["2160-1836"]}, url={https://doi.org/10.1093/g3journal/jkad095}, DOI={10.1093/g3journal/jkad095}, abstractNote={Abstract}, journal={G3-GENES GENOMES GENETICS}, author={Mallik, Rittika and Carlson, Kara B. and Wcisel, Dustin J. and Fisk, Michael and Yoder, Jeffrey A. and Dornburg, Alex}, editor={Whiteman, NEditor}, year={2023}, month={Apr} } @article{carlson_nguyen_wcisel_yoder_dornburg_2023, title={Ancient Fish Lineages Illuminate Toll-Like Receptor Diversification in Early Vertebrate Evolution}, url={https://doi.org/10.1101/2023.04.05.535752}, DOI={10.1101/2023.04.05.535752}, abstractNote={Abstract}, author={Carlson, Kara B. and Nguyen, Cameron and Wcisel, Dustin J. and Yoder, Jeffrey A. and Dornburg, Alex}, year={2023}, month={Apr} } @article{carlson_nguyen_wcisel_yoder_dornburg_2023, title={Ancient fish lineages illuminate toll-like receptor diversification in early vertebrate evolution}, volume={8}, ISSN={["1432-1211"]}, url={https://doi.org/10.1007/s00251-023-01315-7}, DOI={10.1007/s00251-023-01315-7}, abstractNote={Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate RAG- mediated adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here, we investigate the diversification of vertebrate toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the RAG-mediated adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively, these results provide an unparalleled perspective of TLR diversity and offer a ready framework for testing gene annotations in non-model species.}, journal={IMMUNOGENETICS}, author={Carlson, Kara B. and Nguyen, Cameron and Wcisel, Dustin J. and Yoder, Jeffrey A. and Dornburg, Alex}, year={2023}, month={Aug} } @article{efromson_ferrero_begue_doman_dugo_barker_saliu_reamey_kim_harfouche_et al._2023, title={Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope}, volume={18}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0295711}, abstractNote={Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.}, number={12}, journal={PLOS ONE}, author={Efromson, John and Ferrero, Giuliano and Begue, Aurelien and Doman, Thomas Jedidiah Jenks and Dugo, Clay and Barker, Andi and Saliu, Veton and Reamey, Paul and Kim, Kanghyun and Harfouche, Mark and et al.}, year={2023}, month={Dec} } @article{block_rashkova_castanon_platon_zoghi_fujiwara_chaves_schoppmeyer_van der made_cabrera-perez_et al._2023, title={Human DOCK11 Deficiency Causes Defective Erythropoiesis and Systemic Inflammation}, volume={142}, ISSN={["1528-0020"]}, DOI={10.1182/blood-2023-172795}, journal={BLOOD}, author={Block, Jana and Rashkova, Christina and Castanon, Irinka and Platon, Jessica and Zoghi, Samaneh and Fujiwara, Mitsuhiro and Chaves, Beatriz and Schoppmeyer, Rouven and Van Der Made, Caspar and Cabrera-Perez, Rocio and et al.}, year={2023}, month={Nov} } @article{mallik_wcisel_near_yoder_dornburg_2023, title={Investigating the impact of whole genome duplication on transposable element evolution in ray-finned fishes}, url={https://doi.org/10.1101/2023.12.22.572151}, DOI={10.1101/2023.12.22.572151}, abstractNote={Abstract}, author={Mallik, Rittika and Wcisel, Dustin J. and Near, Thomas J. and Yoder, Jeffrey A. and Dornburg, Alex}, year={2023}, month={Dec} } @article{phelps_palekar_conley_ferrero_driggers_linder_kullman_reif_sheats_dewitt_et al._2023, title={Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst}, volume={20}, ISSN={["1547-6901"]}, url={https://doi.org/10.1080/1547691X.2023.2176953}, DOI={10.1080/1547691x.2023.2176953}, abstractNote={Abstract Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.}, number={1}, journal={JOURNAL OF IMMUNOTOXICOLOGY}, author={Phelps, Drake W. and Palekar, Anika I. and Conley, Haleigh E. and Ferrero, Giuliano and Driggers, Jacob H. and Linder, Keith E. and Kullman, Seth W. and Reif, David M. and Sheats, M. Katie and DeWitt, Jamie C. and et al.}, year={2023}, month={Dec} } @article{block_rashkova_castanon_zoghi_platon_ardy_fujiwara_chaves_schoppmeyer_made_et al._2023, title={Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency}, volume={6}, ISSN={["1533-4406"]}, DOI={10.1056/NEJMoa2210054}, abstractNote={BACKGROUND Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. METHODS We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. RESULTS We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. CONCLUSIONS Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).}, journal={NEW ENGLAND JOURNAL OF MEDICINE}, author={Block, Jana and Rashkova, Christina and Castanon, Irinka and Zoghi, Samaneh and Platon, Jessica and Ardy, Rico C. and Fujiwara, Mitsuhiro and Chaves, Beatriz and Schoppmeyer, Rouven and Made, Caspar I. and et al.}, year={2023}, month={Jun} } @article{mallik_carlson_wcisel_fisk_yoder_dornburg_2022, title={A chromosome level genome assembly of longnose gar,Lepisosteus osseus}, url={https://doi.org/10.1101/2022.12.21.521478}, DOI={10.1101/2022.12.21.521478}, abstractNote={Abstract}, author={Mallik, Rittika and Carlson, Kara B. and Wcisel, Dustin J. and Fisk, Michael and Yoder, Jeffrey A. and Dornburg, Alex}, year={2022}, month={Dec} } @article{wcisel_dornburg_mcconnell_hernandez_andrade_jong_litman_yoder_2022, title={A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors}, volume={7}, ISSN={["1432-1211"]}, url={https://doi.org/10.1007/s00251-022-01270-9}, DOI={10.1007/s00251-022-01270-9}, abstractNote={Multiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout, and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon (Salmo salar) genome, defined 86 NILT Ig domains within a 3-Mbp region of zebrafish (Danio rerio) chromosome 1, and described 41 NILT Ig domains as part of an alternative haplotype for this same genomic region. We then identified transcripts encoded by 43 different NILT genes which reflect an unprecedented diversity of Ig domain sequences and combinations for a family of non-recombining receptors within a single species. Zebrafish NILTs include a sole putative activating receptor but extensive inhibitory and secreted forms as well as membrane-bound forms with no known signaling motifs. These results reveal a higher level of genetic complexity, interindividual variation, and sequence diversity for NILTs than previously described, suggesting that this gene family likely plays multiple roles in host immunity.}, journal={IMMUNOGENETICS}, author={Wcisel, Dustin J. and Dornburg, Alex and McConnell, Sean C. and Hernandez, Kyle M. and Andrade, Jorge and Jong, Jill L. O. and Litman, Gary W. and Yoder, Jeffrey A.}, year={2022}, month={Jul} } @article{wcisel_dornburg_mcconnell_hernandez_andrade_jong_litman_yoder_2022, title={A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors}, volume={4}, url={https://doi.org/10.1101/2022.04.21.489081}, DOI={10.1101/2022.04.21.489081}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Wcisel, Dustin J. and Dornburg, Alex and McConnell, Sean C. and Hernandez, Kyle M. and Andrade, Jorge and Jong, Jill L. O. and Litman, Gary W. and Yoder, Jeffrey A.}, year={2022}, month={Apr} } @article{romanet_cupo_yoder_2022, title={Knockdown of Transmembrane Protein 150A (TMEM150A) Results in Increased Production of Multiple Cytokines}, volume={42}, ISSN={["1557-7465"]}, url={https://doi.org/10.1089/jir.2022.0063}, DOI={10.1089/jir.2022.0063}, abstractNote={Lipopolysaccharide (LPS)-induced signaling through Toll-like receptor 4 (TLR4) is mediated by the plasma membrane lipid, phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] and its derivatives diacylglycerol and inositol trisphosphate. Levels of PI(4,5)P2 are controlled enzymatically and fluctuate in LPS-stimulated cells. Recently, transmembrane protein 150A (TMEM150A/TM6P1/damage-regulated autophagy modulator 5) has been shown to regulate PI(4,5)P2 production at the plasma membrane by modifying the composition of the phosphatidylinositol 4-kinase enzyme complex. To determine if TMEM150A function impacts TLR4 signaling, TMEM150A was knocked down in TLR4-expressing epithelial cells and cytokine expression quantified after LPS stimulation. In general, decreased expression of TMEM150A led to increased levels of LPS-induced cytokine secretion and transcript levels. Unexpectedly, knockdown of TMEM150A in a lung epithelial cell line (H292) also led to increased cytokine levels in the unstimulated conditions suggesting TMEM150A plays an important role in cellular homeostasis. Future studies will investigate if TMEM150A plays a similar role for other TLR agonists and in other cell lineages.}, number={7}, journal={JOURNAL OF INTERFERON AND CYTOKINE RESEARCH}, author={Romanet, Jessica L. and Cupo, Katherine L. and Yoder, Jeffrey A.}, year={2022}, month={Jul}, pages={336–342} } @article{dornburg_yoder_2022, title={On the relationship between extant innate immune receptors and the evolutionary origins of jawed vertebrate adaptive immunity}, volume={74}, ISSN={["1432-1211"]}, url={https://doi.org/10.1007/s00251-021-01232-7}, DOI={10.1007/s00251-021-01232-7}, abstractNote={For over half a century, deciphering the origins of the genomic loci that form the jawed vertebrate adaptive immune response has been a major topic in comparative immunogenetics. Vertebrate adaptive immunity relies on an extensive and highly diverse repertoire of tandem arrays of variable (V), diversity (D), and joining (J) gene segments that recombine to produce different immunoglobulin (Ig) and T cell receptor (TCR) genes. The current consensus is that a recombination-activating gene (RAG)-like transposon invaded an exon of an ancient innate immune VJ-bearing receptor, giving rise to the extant diversity of Ig and TCR loci across jawed vertebrates. However, a model for the evolutionary relationships between extant non-recombining innate immune receptors and the V(D)J receptors of the jawed vertebrate adaptive immune system has only recently begun to come into focus. In this review, we provide an overview of non-recombining VJ genes, including CD8β, CD79b, natural cytotoxicity receptor 3 (NCR3/NKp30), putative remnants of an antigen receptor precursor (PRARPs), and the multigene family of signal-regulatory proteins (SIRPs), that play a wide range of roles in immune function. We then focus in detail on the VJ-containing novel immune-type receptors (NITRs) from ray-finned fishes, as recent work has indicated that these genes are at least 50 million years older than originally thought. We conclude by providing a conceptual model of the evolutionary origins and phylogenetic distribution of known VJ-containing innate immune receptors, highlighting opportunities for future comparative research that are empowered by this emerging evolutionary perspective.}, number={1}, journal={IMMUNOGENETICS}, publisher={Springer Science and Business Media LLC}, author={Dornburg, Alex and Yoder, Jeffrey A.}, year={2022}, month={Jan} } @misc{dornburg_mallik_wang_bernal_thompson_bruford_nebert_vasiliou_yohe_yoder_et al._2022, title={Placing human gene families into their evolutionary context}, volume={16}, ISSN={["1479-7364"]}, DOI={10.1186/s40246-022-00429-5}, abstractNote={Abstract}, number={1}, journal={HUMAN GENOMICS}, author={Dornburg, Alex and Mallik, Rittika and Wang, Zheng and Bernal, Moises A. and Thompson, Brian and Bruford, Elspeth A. and Nebert, Daniel W. and Vasiliou, Vasilis and Yohe, Laurel R. and Yoder, Jeffrey A. and et al.}, year={2022}, month={Nov} } @article{carlson_wcisel_ackerman_romanet_christiansen_niemuth_williams_breen_stoskopf_dornburg_et al._2022, title={Transcriptome annotation reveals minimal immunogenetic diversity among Wyoming toads, Anaxyrus baxteri}, volume={4}, ISSN={["1572-9737"]}, url={https://doi.org/10.1007/s10592-022-01444-8}, DOI={10.1007/s10592-022-01444-8}, abstractNote={Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes.}, journal={CONSERVATION GENETICS}, author={Carlson, Kara B. and Wcisel, Dustin J. and Ackerman, Hayley D. and Romanet, Jessica and Christiansen, Emily F. and Niemuth, Jennifer N. and Williams, Christina and Breen, Matthew and Stoskopf, Michael K. and Dornburg, Alex and et al.}, year={2022}, month={Apr} } @article{allen_cullen_hawkey_mochizuki_nguyen_schechter_borst_yoder_freedman_patierno_et al._2021, title={A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation}, volume={11}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2021.641187}, abstractNote={Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model. Circulating tumor cell clusters that successfully extravasated the vasculature as multicellular units were isolated under intravital imaging (n = 6). These extravasation-positive tumor cell clusters sublines were then molecularly profiled by RNA-Seq. Using a systems-level analysis, we pinpointed the downregulation of KRAS signaling, immune pathways, and extracellular matrix (ECM) organization as enriched in extravasated cells (p < 0.05). Within the extracellular matrix remodeling pathway, we identified versican (VCAN) as consistently upregulated and central to the ECM gene regulatory network (p < 0.05). Versican expression is prognostic for a poorer metastasis-free and overall survival in patients with osteosarcoma. Together, our results provide a novel experimental framework to study discrete steps in the metastatic process. Using this system, we identify the versican/ECM network dysregulation as a potential contributor to osteosarcoma circulating tumor cell metastasis.}, journal={FRONTIERS IN ONCOLOGY}, author={Allen, Tyler A. and Cullen, Mark M. and Hawkey, Nathan and Mochizuki, Hiroyuki and Nguyen, Lan and Schechter, Elyse and Borst, Luke and Yoder, Jeffrey A. and Freedman, Jennifer A. and Patierno, Steven R. and et al.}, year={2021}, month={Sep} } @misc{dornburg_ota_criscitiello_salinas_sunyer_magadan_boudinot_xu_flajnik_singer_et al._2021, title={From IgZ to IgT: A Call for a Common Nomenclature for Immunoglobulin Heavy Chain Genes of Ray-Finned Fish}, volume={18}, ISSN={["1557-8542"]}, url={http://dx.doi.org/10.1089/zeb.2021.0071}, DOI={10.1089/zeb.2021.0071}, abstractNote={Ray-finned fishes comprise more than half the *60,000 known vertebrate species, and are pivotal to the functionality of aquatic ecosystems and success of global multibillion dollar industries. Understanding ray-finned fish immune systems is essential to predicting how species will respond to known or emergent pathogens as well as to the development of effective vaccines for aquaculture. However, the diversity of species, including in aquaculture, necessitates that immunology and translational medicine research groups investigating the immune system in one or a number of species employ a common language for describing homologous immune components. Unfortunately for Immunoglobulin (Ig) genes that encode antibodies, this has not been the case. Ig genes are restricted to jawed vertebrates (gnathostomes) with all lineages encoding common heavy chains IgM and IgD (aka IgW in cartilaginous fish, lungfish, and coelacanths). Before 2005, it was believed that bony fish encoded only IgM and IgD. In 2005, Hansen et al. described a new Ig heavy chain encoded within the rainbow trout heavy chain locus and named it IgT for ‘‘teleost.’’ However, during the}, number={6}, journal={ZEBRAFISH}, publisher={Mary Ann Liebert Inc}, author={Dornburg, Alex and Ota, Tatsuya and Criscitiello, Michael F. and Salinas, Irene and Sunyer, J. Oriol and Magadan, Susana and Boudinot, Pierre and Xu, Zhen and Flajnik, Martin F. and Singer, Amy and et al.}, year={2021}, month={Dec}, pages={343–345} } @article{dornburg_wcisel_zapfe_ferraro_roupe-abrams_thompson_braasch_ota_yoder_2021, title={Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system}, volume={6}, url={https://doi.org/10.1101/2021.06.11.448072}, DOI={10.1101/2021.06.11.448072}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Dornburg, Alex and Wcisel, Dustin J. and Zapfe, Katerina and Ferraro, Emma and Roupe-Abrams, Lindsay and Thompson, Andrew W. and Braasch, Ingo and Ota, Tatsuya and Yoder, Jeffrey A.}, year={2021}, month={Jun} } @article{dornburg_wcisel_zapfe_ferraro_roupe-abrams_thompson_braasch_ota_yoder_2021, title={Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system}, url={https://doi.org/10.1007/s00251-021-01225-6}, DOI={10.1007/s00251-021-01225-6}, abstractNote={Over 99% of ray-finned fishes (Actinopterygii) are teleosts, a clade that comprises half of all living vertebrate species that have diversified across virtually all fresh and saltwater ecosystems. This ecological breadth raises the question of how the immunogenetic diversity required to persist under heterogeneous pathogen pressures evolved. The teleost genome duplication (TGD) has been hypothesized as the evolutionary event that provided the substrate for rapid genomic evolution and innovation. However, studies of putative teleost-specific innate immune receptors have been largely limited to comparisons either among teleosts or between teleosts and distantly related vertebrate clades such as tetrapods. Here we describe and characterize the receptor diversity of two clustered innate immune gene families in the teleost sister lineage: Holostei (bowfin and gars). Using genomic and transcriptomic data, we provide a detailed investigation of the phylogenetic history and conserved synteny of gene clusters encoding diverse immunoglobulin domain-containing proteins (DICPs) and novel immune-type receptors (NITRs). These data demonstrate an ancient linkage of DICPs to the major histocompatibility complex (MHC) and reveal an evolutionary origin of NITR variable-joining (VJ) exons that predate the TGD by at least 50 million years. Further characterizing the receptor diversity of Holostean DICPs and NITRs illuminates a sequence diversity that rivals the diversity of these innate immune receptor families in many teleosts. Taken together, our findings provide important historical context for the evolution of these gene families that challenge prevailing expectations concerning the consequences of the TGD during actinopterygiian evolution.}, journal={Immunogenetics}, author={Dornburg, Alex and Wcisel, Dustin J. and Zapfe, Katerina and Ferraro, Emma and Roupe-Abrams, Lindsay and Thompson, Andrew W. and Braasch, Ingo and Ota, Tatsuya and Yoder, Jeffrey A.}, year={2021}, month={Dec} } @article{wyatt_amin_bagley_wcisel_dush_yoder_nascone-yoder_2021, title={Single-minded 2 is required for left-right asymmetric stomach morphogenesis}, volume={148}, ISSN={["1477-9129"]}, DOI={10.1242/dev.199265}, abstractNote={ABSTRACT}, number={17}, journal={DEVELOPMENT}, author={Wyatt, Brent H. and Amin, Nirav M. and Bagley, Kristen and Wcisel, Dustin and Dush, Michael K. and Yoder, Jeffrey A. and Nascone-Yoder, Nanette M.}, year={2021}, month={Sep} } @article{thompson_hawkins_parey_wcisel_ota_kawasaki_funk_losilla_fitch_pan_et al._2021, title={The bowfin genome illuminates the developmental evolution of ray-finned fishes}, volume={8}, ISSN={["1546-1718"]}, DOI={10.1038/s41588-021-00914-y}, abstractNote={Abstract}, journal={NATURE GENETICS}, author={Thompson, Andrew W. and Hawkins, M. Brent and Parey, Elise and Wcisel, Dustin J. and Ota, Tatsuya and Kawasaki, Kazuhiko and Funk, Emily and Losilla, Mauricio and Fitch, Olivia E. and Pan, Qiaowei and et al.}, year={2021}, month={Aug} } @article{buckley_yoder_2021, title={The evolution of innate immune receptors: investigating the diversity, distribution, and phylogeny of immune recognition across eukaryotes}, volume={74}, ISSN={["1432-1211"]}, url={https://doi.org/10.1007/s00251-021-01243-4}, DOI={10.1007/s00251-021-01243-4}, number={1}, journal={IMMUNOGENETICS}, publisher={Springer Science and Business Media LLC}, author={Buckley, Katherine M. and Yoder, Jeffrey A.}, year={2021}, month={Dec} } @inbook{chapter 19 - immunology_2020, url={http://dx.doi.org/10.1016/b978-0-12-812431-4.00019-1}, DOI={10.1016/b978-0-12-812431-4.00019-1}, abstractNote={The zebrafish has become a powerful model for studying infectious disease from the perspective of both the host and pathogen. As a jawed vertebrate, zebrafish possess an innate and an adaptive immune system. Hematopoiesis in bony fish generates the same major cell types observed in mammals, including lymphocytes (B and T lymphocytes, natural killer cells), myeloid lineages (monocytes/macrophages, neutrophils, dendritic cells, and mast cells), and erythrocytes. In addition, the major classes of molecular mediators of immunity present in mammals have been identified in zebrafish, including immunoglobulins (antibodies) and T cell receptors, and the genes required for their diversification, the genes of the Major Histocompatibility Complex, multiple families of innate immune receptors, cytokines, complement components, and antimicrobial peptides.}, booktitle={The Zebrafish in Biomedical Research}, year={2020} } @article{phelps_fletcher_rodriguez-nunez_balik-meisner_tokarz_reif_germolec_yoder_2020, title={In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish}, volume={17}, url={https://doi.org/10.1080/1547691X.2020.1748772}, DOI={10.1080/1547691X.2020.1748772}, abstractNote={Abstract Currently, assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 h post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive properties were screened. Seven compounds neither suppressed nor enhanced the respiratory burst; five reproducibly suppressed global ROS production, but with varying potencies: benzo[a]pyrene, 17β-estradiol, lead acetate, methoxychlor, and phenanthrene. These five compounds have all previously been reported as immunosuppressive in mammalian innate immunity assays. To evaluate whether the suppression of ROS by these compounds was a result of decreased immune cell numbers, flow cytometry with transgenic zebrafish larvae was used to count the numbers of neutrophils and macrophages after chemical exposure. With this assay, benzo[a]pyrene was found to be the only chemical that induced a change in the number of immune cells by increasing macrophage but not neutrophil numbers. Taken together, this work demonstrates the utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system.}, number={1}, journal={Journal of Immunotoxicology}, publisher={Informa UK Limited}, author={Phelps, Drake W. and Fletcher, Ashley A. and Rodriguez-Nunez, Ivan and Balik-Meisner, Michele R. and Tokarz, Debra A. and Reif, David M. and Germolec, Dori R. and Yoder, Jeffrey A.}, year={2020}, month={Jan}, pages={94–104} } @article{wcisel_howard_yoder_dornburg_2020, title={Transcriptome Ortholog Alignment Sequence Tools (TOAST) for phylogenomic dataset assembly}, volume={20}, url={https://doi.org/10.1186/s12862-020-01603-w}, DOI={10.1186/s12862-020-01603-w}, abstractNote={Abstract}, number={1}, journal={BMC Evolutionary Biology}, publisher={Springer Science and Business Media LLC}, author={Wcisel, Dustin J. and Howard, J. Thomas, III and Yoder, Jeffrey A. and Dornburg, Alex}, year={2020}, month={Dec} } @article{ganchingco_fukuyama_yoder_bäumer_2019, title={Calcium imaging of primary canine sensory neurons: Small‐diameter neurons responsive to pruritogens and algogens}, url={https://doi.org/10.1002/brb3.1428}, DOI={10.1002/brb3.1428}, abstractNote={Abstract}, journal={Brain and Behavior}, author={Ganchingco, Joy Rachel C. and Fukuyama, Tomoki and Yoder, Jeffrey A. and Bäumer, Wolfgang}, year={2019}, month={Dec} } @article{circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential._2019, url={https://doi.org/10.1242/jcs.231563}, DOI={10.1242/jcs.231563}, abstractNote={Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate, and if multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumor at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.}, journal={Journal of cell science}, year={2019}, month={Sep} } @article{stafford_kortum_castel_green_lau_early_muñana_mariani_yoder_olby_2019, title={Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease}, volume={33}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.15616}, DOI={10.1111/jvim.15616}, abstractNote={Abstract}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Stafford, Emma G. and Kortum, Amanda and Castel, Aude and Green, Lauren and Lau, Jeanie and Early, Peter J. and Muñana, Karen R. and Mariani, Christopher L. and Yoder, Jeffrey A. and Olby, Natasha J.}, year={2019}, month={Sep}, pages={2175–2182} } @article{akuffo_alontaga_metcalf_beatty_becker_mcdaniel_hesterberg_goodheart_gunawan_ayaz_et al._2018, title={Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon}, volume={293}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/jbc.M117.816868}, DOI={10.1074/jbc.m117.816868}, abstractNote={Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging the DDB1–CUL4A–Roc1–RBX1 E3 ubiquitin ligase in human cells but not in mouse cells, suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBN's activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBN's nonprimate sequence variations. With a series of recombinant thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants retain their drug-binding properties to both classical immunomodulatory drugs and dBET1, a chemical compound and targeting ligand designed to degrade bromodomain-containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1 stimulates CRBN's E3 ubiquitin–conjugating function and degrades BRD4 in both mouse and human cells. This insight paves the way for studies of CRBN-dependent proteasome-targeting molecules in nonprimate models and provides a new understanding of CRBN's substrate-recruiting function.}, number={16}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Akuffo, Afua A. and Alontaga, Aileen Y. and Metcalf, Rainer and Beatty, Matthew S. and Becker, Andreas and McDaniel, Jessica M. and Hesterberg, Rebecca S. and Goodheart, William E. and Gunawan, Steven and Ayaz, Muhammad and et al.}, year={2018}, month={Feb}, pages={6187–6200} } @article{ganchingco_yoder_baumer_2018, title={Use of a specific polyclonal anti-canine TSLP antibody reveals TSLP expression in normal tissue and cell culture}, volume={41}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Ganchingco, J. R. C. and Yoder, J. A. and Baumer, W.}, year={2018}, pages={153–153} } @article{cal_megías_cerdá‐reverter_postlethwait_braasch_rotllant_2017, title={BAC Recombineering of the Agouti Loci from Spotted Gar and Zebrafish Reveals the Evolutionary Ancestry of Dorsal–Ventral Pigment Asymmetry in Fish}, url={https://doi.org/10.1002/jez.b.22748}, DOI={10.1002/jez.b.22748}, abstractNote={ABSTRACT}, journal={Journal of Experimental Zoology Part B: Molecular and Developmental Evolution}, author={Cal, Laura and MegÍas, Manuel and Cerdá‐reverter, José and Postlethwait, John and Braasch, Ingo and Rotllant, Josep}, year={2017}, month={Nov} } @article{tokarz_heffelfinger_jima_gerlach_shah_rodriguez-nunez_kortum_fletcher_nordone_law_et al._2017, title={Disruption of Trim9 function abrogates macrophage motility in vivo}, volume={102}, ISSN={0741-5400 1938-3673}, url={http://dx.doi.org/10.1189/jlb.1A0816-371R}, DOI={10.1189/jlb.1a0816-371r}, abstractNote={Abstract}, number={6}, journal={Journal of Leukocyte Biology}, publisher={Wiley}, author={Tokarz, Debra A. and Heffelfinger, Amy K. and Jima, Dereje D. and Gerlach, Jamie and Shah, Radhika N. and Rodriguez-Nunez, Ivan and Kortum, Amanda N. and Fletcher, Ashley A. and Nordone, Shila K. and Law, J. McHugh and et al.}, year={2017}, month={Oct}, pages={1371–1380} } @article{sullivan_lage_yoder_postlethwait_kim_2017, title={Evolutionary divergence of the vertebrate TNFAIP8 gene family: Applying the spotted gar orthology bridge to understand ohnolog loss in teleosts}, volume={12}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0179517}, DOI={10.1371/journal.pone.0179517}, abstractNote={Comparative functional genomic studies require the proper identification of gene orthologs to properly exploit animal biomedical research models. To identify gene orthologs, comprehensive, conserved gene synteny analyses are necessary to unwind gene histories that are convoluted by two rounds of early vertebrate genome duplication, and in the case of the teleosts, a third round, the teleost genome duplication (TGD). Recently, the genome of the spotted gar, a holostean outgroup to the teleosts that did not undergo this third genome duplication, was sequenced and applied as an orthology bridge to facilitate the identification of teleost orthologs to human genes and to enhance the power of teleosts as biomedical models. In this study, we apply the spotted gar orthology bridge to help describe the gene history of the vertebrate TNFAIP8 family. Members of the TNFAIP8 gene family have been linked to regulation of immune function and homeostasis and the development of multiple cancer types. Through a conserved gene synteny analysis, we identified zebrafish orthologs to human TNFAIP8L1 and TNFAIP8L3 genes and two co-orthologs to human TNFAIP8L2, but failed to identify an ortholog to human TNFAIP8. Through the application of the orthology bridge, we determined that teleost orthologs to human TNFAIP8 genes were likely lost in a genome inversion event after their divergence from their common ancestor with spotted gar. These findings demonstrate the value of this enhanced approach to gene history analysis and support the development of teleost models to study complex questions related to an array of biomedical issues, including immunity and cancer.}, number={6}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Sullivan, Con and Lage, Christopher R. and Yoder, Jeffrey A. and Postlethwait, John H. and Kim, Carol H.}, editor={Boudinot, PierreEditor}, year={2017}, month={Jun}, pages={e0179517} } @article{chernyavskaya_mudbhary_zhang_tokarz_jacob_gopinath_sun_wang_magnani_madakashira_et al._2017, title={Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling}, volume={144}, ISSN={0950-1991 1477-9129}, url={http://dx.doi.org/10.1242/dev.147629}, DOI={10.1242/dev.147629}, abstractNote={Complex cytoplasmic nucleotide sensing mechanisms can recognize foreign DNA based on a lack of methylation and initiate an immune response to clear the infection. Zebrafish embryos with global DNA hypomethylation caused by mutations in the ubiquitin-like, with PHD and RING finger domains 1 (uhrf1) or DNA methyltransferase 1 (dnmt1) genes exhibit a robust interferon induction characteristic of first line of defense against viral infection. We found that this interferon induction occurred in non-immune cells and asked whether intracellular viral sensing pathways in these cells were the trigger. RNA-seq analysis of uhrf1 and dnmt1 mutants revealed widespread induction of Class I retrotransposons and activation of cytoplasmic DNA viral sensors. Attenuating Sting, pTbk1 and, importantly, blocking reverse transcriptase activity suppressed the expression of interferon genes in uhrf1 mutants. Thus, activation of transposons in cells with global DNA hypomethylation mimics a viral infection by activating cytoplasmic DNA sensors. This suggests that antiviral pathways serve as surveillance of cells that have derepressed intragenomic parasites due to DNA hypomethylation.}, number={16}, journal={Development}, publisher={The Company of Biologists}, author={Chernyavskaya, Yelena and Mudbhary, Raksha and Zhang, Chi and Tokarz, Debra and Jacob, Vinitha and Gopinath, Smita and Sun, Xiaochen and Wang, Shuang and Magnani, Elena and Madakashira, Bhavani P. and et al.}, year={2017}, month={Jul}, pages={2925–2939} } @article{wcisel_ota_litman_yoder_2017, title={Spotted Gar and the Evolution of Innate Immune Receptors}, volume={328}, ISSN={1552-5007}, url={http://dx.doi.org/10.1002/jez.b.22738}, DOI={10.1002/jez.b.22738}, abstractNote={ABSTRACT}, number={7}, journal={Journal of Experimental Zoology Part B: Molecular and Developmental Evolution}, publisher={Wiley}, author={Wcisel, Dustin J. and Ota, Tatsuya and Litman, Gary W. and Yoder, Jeffrey A.}, year={2017}, month={May}, pages={666–684} } @article{mcconnell_hernandez_wcisel_kettleborough_stemple_yoder_andrade_de jong_2016, title={Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution}, volume={113}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1607602113}, DOI={10.1073/pnas.1607602113}, abstractNote={Significance}, number={34}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={McConnell, Sean C. and Hernandez, Kyle M. and Wcisel, Dustin J. and Kettleborough, Ross N. and Stemple, Derek L. and Yoder, Jeffrey A. and Andrade, Jorge and de Jong, Jill L. O.}, year={2016}, month={Aug}, pages={E5014–E5023} } @article{allen_gracieux_talib_tokarz_hensley_cores_vandergriff_tang_de andrade_dinh_et al._2016, title={Angiopellosis as an Alternative Mechanism of Cell Extravasation}, volume={35}, ISSN={1066-5099}, url={http://dx.doi.org/10.1002/stem.2451}, DOI={10.1002/stem.2451}, abstractNote={Abstract}, number={1}, journal={STEM CELLS}, publisher={Wiley}, author={Allen, Tyler A. and Gracieux, David and Talib, Maliha and Tokarz, Debra A. and Hensley, M. Taylor and Cores, Jhon and Vandergriff, Adam and Tang, Junnan and de Andrade, James B.M. and Dinh, Phuong-Uyen and et al.}, year={2016}, month={Jul}, pages={170–180} } @article{braasch_gehrke_smith_kawasaki_manousaki_pasquier_amores_desvignes_batzel_catchen_et al._2016, title={Erratum: Corrigendum: The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons}, volume={48}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/ng0616-700c}, DOI={10.1038/ng0616-700c}, abstractNote={Nat. Genet. 48, 427–437 (2016); published online 7 March 2016; corrected after print 25 April 2016 As we intended, other researchers have been able to use the draft spotted gar genome sequence available from the Broad Institute website since December 2011, the assembly LepOcu1 publicly available from NCBI since 13 January 2012 under accession code GCA000242695.}, number={6}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Braasch, Ingo and Gehrke, Andrew R and Smith, Jeramiah J and Kawasaki, Kazuhiko and Manousaki, Tereza and Pasquier, Jeremy and Amores, Angel and Desvignes, Thomas and Batzel, Peter and Catchen, Julian and et al.}, year={2016}, month={May}, pages={700–700} } @article{tucker_mackenzie_maciag_dirscherl ackerman_swartz_yoder_hamilton_clay clark_2016, title={Phage display and structural studies reveal plasticity in substrate specificity of caspase-3a from zebrafish}, volume={25}, ISSN={0961-8368}, url={http://dx.doi.org/10.1002/pro.3032}, DOI={10.1002/pro.3032}, abstractNote={Abstract}, number={11}, journal={Protein Science}, publisher={Wiley}, author={Tucker, Matthew B. and MacKenzie, Sarah H. and Maciag, Joseph J. and Dirscherl Ackerman, Hayley and Swartz, Paul and Yoder, Jeffrey A. and Hamilton, Paul T. and Clay Clark, A.}, year={2016}, month={Sep}, pages={2076–2088} } @misc{permana_grant_walker_yoder_2016, title={Review of Automated Microinjection Systems for Single Cells in the Embryogenesis Stage}, volume={21}, ISSN={["1941-014X"]}, DOI={10.1109/tmech.2016.2574871}, abstractNote={Modern genetics research has resulted in significant advances in cell in vitro microinjection systems. Such systems provide biological and medical practitioners with high volume cell throughput and statistically relevant data. This paper provides the reader with a comprehensive review of the major research technologies used in automated cell microinjection and of their individual subsystems. Microinjection subsystems reviewed include machine vision, nonvision sensors and user interface (input), cell modeling, piercing mechanisms and injection control loop (control), cell holder and manipulator, and microinjection (output). The interdisciplinary technologies reviewed for microinjection sensing, automation, and control include microfluidic actuation, optical field actuation (optical trapping and optical guidance), electrical field actuation (electrorotation, electrowetting, and dielectrophoresis), and ultrasonic vibration. The survey concludes that research into automated microinjection systems will focus on reducing the scale of microinjection systems and developing appropriate controllers.}, number={5}, journal={IEEE-ASME TRANSACTIONS ON MECHATRONICS}, publisher={Institute of Electrical and Electronics Engineers (IEEE)}, author={Permana, Sofie and Grant, Edward and Walker, Glenn M. and Yoder, Jeffrey A.}, year={2016}, month={Oct}, pages={2391–2404} } @article{moore_garcia_lobbardi_jain_tang_moore_cortes_molodtsov_kasheta_luo_et al._2016, title={Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish}, volume={213}, DOI={10.1083/jcb.2133oia95}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Moore, Finola E. and Garcia, Elaine G. and Lobbardi, Riadh and Jain, Esha and Tang, Qin and Moore, John C. and Cortes, Mauricio and Molodtsov, Aleksey and Kasheta, Melissa and Luo, Christina C. and et al.}, year={2016}, month={May}, pages={2133OIA95} } @article{moore_garcia_lobbardi_jain_tang_moore_cortes_molodtsov_kasheta_luo_et al._2016, title={Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish}, volume={213}, ISSN={0022-1007 1540-9538}, url={http://dx.doi.org/10.1084/jem.20152013}, DOI={10.1084/jem.20152013}, abstractNote={Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia.}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Moore, Finola E. and Garcia, Elaine G. and Lobbardi, Riadh and Jain, Esha and Tang, Qin and Moore, John C. and Cortes, Mauricio and Molodtsov, Aleksey and Kasheta, Melissa and Luo, Christina C. and et al.}, year={2016}, month={May}, pages={979–992} } @article{wcisel_yoder_2016, title={The confounding complexity of innate immune receptors within and between teleost species}, volume={53}, ISSN={1050-4648}, url={http://dx.doi.org/10.1016/j.fsi.2016.03.034}, DOI={10.1016/j.fsi.2016.03.034}, abstractNote={Teleost genomes encode multiple multigene families of immunoglobulin domain-containing innate immune receptors (IIIRs) with unknown function and no clear mammalian orthologs. However, the genomic organization of IIIR gene clusters and the structure and signaling motifs of the proteins they encode are similar to those of mammalian innate immune receptor families such as the killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LILRs), Fc receptors, triggering receptors expressed on myeloid cells (TREMs) and CD300s. Teleost IIIRs include novel immune-type receptors (NITRs); diverse immunoglobulin domain containing proteins (DICPs); polymeric immunoglobulin receptor-like proteins (PIGRLs); novel immunoglobulin-like transcripts (NILTs) and leukocyte immune-type receptors (LITRs). The accumulation of genomic sequence data has revealed that IIIR gene clusters in zebrafish display haplotypic and gene content variation. This intraspecific genetic variation, as well as significant interspecific variation, frequently confounds the identification of definitive orthologous IIIR sequences between teleost species. Nevertheless, by defining which teleost lineages encode (and do not encode) different IIIR families, predictions can be made about the presence (or absence) of specific IIIR families in each teleost lineage. It is anticipated that further investigations into available genomic resources and the sequencing of a variety of multiple teleost genomes will identify additional IIIR families and permit the modeling of the evolutionary origins of IIIRs.}, journal={Fish & Shellfish Immunology}, publisher={Elsevier BV}, author={Wcisel, Dustin J. and Yoder, Jeffrey A.}, year={2016}, month={Jun}, pages={24–34} } @article{rodriguez-nunez_wcisel_litman_litman_yoder_immunogenetics_2016, title={The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes}, volume={68}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-016-0901-6}, DOI={10.1007/s00251-016-0901-6}, abstractNote={Bony fish encode multiple multi-gene families of membrane receptors that are comprised of immunoglobulin (Ig) domains and are predicted to function in innate immunity. One of these families, the diverse immunoglobulin (Ig) domain-containing protein (DICP) genes, maps to three chromosomal loci in zebrafish. Most DICPs possess one or two Ig ectodomains and include membrane-bound and secreted forms. Membrane-bound DICPs include putative inhibitory and activating receptors. Recombinant DICP Ig domains bind lipids with varying specificity, a characteristic shared with mammalian CD300 and TREM family members. Numerous DICP transcripts amplified from different lines of zebrafish did not match the zebrafish reference genome sequence suggesting polymorphic and haplotypic variation. The expression of DICPs in three different lines of zebrafish has been characterized employing PCR-based strategies. Certain DICPs exhibit restricted expression in adult tissues whereas others are expressed ubiquitously. Transcripts of a subset of DICPs can be detected during embryonic development suggesting roles in embryonic immunity or other developmental processes. Transcripts representing 11 previously uncharacterized DICP sequences were identified. The assignment of two of these sequences to an unplaced genomic scaffold resulted in the identification of an alternative DICP haplotype that is linked to a MHC class I Z lineage haplotype on zebrafish chromosome 3. The linkage of DICP and MHC class I genes also is observable in the genomes of the related grass carp (Ctenopharyngodon idellus) and common carp (Cyprinus carpio) suggesting that this is a shared character with the last common Cyprinidae ancestor.}, number={4}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Rodriguez-Nunez, I. and Wcisel, D.J. and Litman, R.T. and Litman, G.W. and Yoder, J.A. and Immunogenetics}, year={2016}, month={Jan}, pages={295–312} } @article{rodriguez-nunez_wcisel_litman_litman_yoder_immunogenetics_2016, title={The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes.}, url={http://europepmc.org/abstract/med/26801775}, author={Rodriguez-Nunez, I. and Wcisel, D.J. and Litman, R.T. and Litman, G.W. and Yoder, J.A. and Immunogenetics}, year={2016}, month={Jan} } @article{braasch_gehrke_smith_kawasaki_manousaki_pasquier_amores_desvignes_batzel_catchen_et al._2016, title={The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons}, volume={48}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/ng.3526}, DOI={10.1038/ng.3526}, abstractNote={To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.}, number={4}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Braasch, Ingo and Gehrke, Andrew R and Smith, Jeramiah J and Kawasaki, Kazuhiko and Manousaki, Tereza and Pasquier, Jeremy and Amores, Angel and Desvignes, Thomas and Batzel, Peter and Catchen, Julian and et al.}, year={2016}, month={Mar}, pages={427–437} } @article{dirscherl_yoder_2015, title={A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant}, volume={67}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-015-0862-1}, DOI={10.1007/s00251-015-0862-1}, abstractNote={Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here, we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ~30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanax mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idella).}, number={9}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Dirscherl, Hayley and Yoder, Jeffrey A.}, year={2015}, month={Aug}, pages={501–513} } @article{schilling_nepomuceno_planchart_yoder_kelly_muddiman_daniels_hiramatsu_reading_2015, title={Machine learning reveals sex-specific 17β-estradiol-responsive expression patterns in white perch (Morone americana) plasma proteins}, volume={15}, ISSN={1615-9853}, url={http://dx.doi.org/10.1002/pmic.201400606}, DOI={10.1002/pmic.201400606}, abstractNote={With growing abundance and awareness of endocrine disrupting compounds (EDCs) in the environment, there is a need for accurate and reliable detection of EDC exposure. Our objective in the present study was to observe differences within and between the global plasma proteomes of sexually mature male and female white perch (Morone americana) before (Initial Control, IC) and after 17β‐estradiol (E2) induction. Semiquantitative nanoLC‐MS/MS data were analyzed by machine learning support vector machines (SVMs) and by two‐way ANOVA. By ANOVA, the expression levels of 44, 77, and 57 proteins varied significantly by gender, treatment, and the interaction of gender and treatment, respectively. SVMs perfectly classified male and female perch IC and E2‐induced plasma samples using the protein expression data. E2‐induced male and female perch plasma proteomes contained significantly higher levels of the yolk precursors vitellogenin Aa and Ab (VtgAa, VtgAb), as well as latrophilin and seven transmembrane domain‐containing protein 1 (Eltd1) and kininogen 1 (Kng1). This is the first report that Eltd1 and Kng1 may be E2‐responsive proteins in fishes and therefore may be useful indicators of estrogen induction.}, number={15}, journal={PROTEOMICS}, publisher={Wiley}, author={Schilling, Justin and Nepomuceno, Angelito I. and Planchart, Antonio and Yoder, Jeffrey A. and Kelly, Robert M. and Muddiman, David C. and Daniels, Harry V. and Hiramatsu, Naoshi and Reading, Benjamin J.}, year={2015}, month={Jun}, pages={2678–2690} } @article{kortum_rodriguez-nunez_yang_shim_runft_o’driscoll_haire_cannon_turner_litman_et al._2014, title={Differential expression and ligand binding indicate alternative functions for zebrafish polymeric immunoglobulin receptor (pIgR) and a family of pIgR-like (PIGRL) proteins}, volume={66}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-014-0759-4}, DOI={10.1007/s00251-014-0759-4}, abstractNote={The polymeric immunoglobulin (Ig) receptor (pIgR) is an integral transmembrane glycoprotein that plays an important role in the mammalian immune response by transporting soluble polymeric Igs across mucosal epithelial cells. Single pIgR genes, which are expressed in lymphoid organs including mucosal tissues, have been identified in several teleost species. A single pigr gene has been identified on zebrafish chromosome 2 along with a large multigene family consisting of 29 pigr-like (PIGRL) genes. Full-length transcripts from ten different PIGRL genes that encode secreted and putative inhibitory membrane-bound receptors have been characterized. Although PIGRL and pigr transcripts are detected in immune tissues, only PIGRL transcripts can be detected in lymphoid and myeloid cells. In contrast to pIgR which binds Igs, certain PIGRL proteins bind phospholipids. PIGRL transcript levels are increased after infection with Streptococcus iniae, suggesting a role for PIGRL genes during bacterial challenge. Transcript levels of PIGRL genes are decreased after infection with Snakehead rhabdovirus, suggesting that viral infection may suppress PIGRL function.}, number={4}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Kortum, Amanda N. and Rodriguez-Nunez, Ivan and Yang, Jibing and Shim, Juyoung and Runft, Donna and O’Driscoll, Marci L. and Haire, Robert N. and Cannon, John P. and Turner, Poem M. and Litman, Ronda T. and et al.}, year={2014}, month={Jan}, pages={267–279} } @article{rodríguez-nunez_wcisel_litman_yoder_2014, title={Multigene families of immunoglobulin domain-containing innate immune receptors in zebrafish: Deciphering the differences}, volume={46}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2014.02.004}, DOI={10.1016/j.dci.2014.02.004}, abstractNote={Five large multigene families encoding innate-type immune receptors that are comprised of immunoglobulin domains have been identified in bony fish, of which four do not possess definable mammalian orthologs. The members of some of the multigene families exhibit unusually extensive patterns of divergence and the individual family members demonstrate marked variation in interspecific comparisons. As a group, the gene families reveal striking differences in domain type and content, mechanisms of intracellular signaling, basic structural features, haplotype and allelic variation and ligand binding. The potential functional roles of these innate immune receptors, their relationships to immune genes in higher vertebrate species and the basis for their adaptive evolution are of broad interest. Ongoing investigations are expected to provide new insight into alternative mechanisms of immunity.}, number={1}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Rodríguez-Nunez, Iván and Wcisel, Dustin J. and Litman, Gary W. and Yoder, Jeffrey A.}, year={2014}, month={Sep}, pages={24–34} } @article{peterman_sullivan_goody_rodriguez-nunez_yoder_kim_2014, title={Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish}, volume={83}, ISSN={0019-9567 1098-5522}, url={http://dx.doi.org/10.1128/IAI.02245-14}, DOI={10.1128/iai.02245-14}, abstractNote={ABSTRACT}, number={1}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Peterman, E. M. and Sullivan, C. and Goody, M. F. and Rodriguez-Nunez, I. and Yoder, J. A. and Kim, C. H.}, editor={McCormick, B. A.Editor}, year={2014}, month={Nov}, pages={430–440} } @article{yoder_2014, title={Preface to the Special Issue: Zebrafish immunity and infection models}, volume={46}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2014.04.007}, DOI={10.1016/j.dci.2014.04.007}, number={1}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Yoder, Jeffrey A.}, year={2014}, month={Sep}, pages={1–2} } @article{dirscherl_mcconnell_yoder_de jong_2014, title={The MHC class I genes of zebrafish}, volume={46}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2014.02.018}, DOI={10.1016/j.dci.2014.02.018}, abstractNote={Major histocompatibility complex (MHC) molecules play a central role in the immune response and in the recognition of non-self. Found in all jawed vertebrate species, including zebrafish and other teleosts, MHC genes are considered the most polymorphic of all genes. In this review we focus on the multi-faceted diversity of zebrafish MHC class I genes, which are classified into three sequence lineages: U, Z, and L. We examine the polygenic, polymorphic, and haplotypic diversity of the zebrafish MHC class I genes, discussing known and postulated functional differences between the different class I lineages. In addition, we provide the first comprehensive nomenclature for the L lineage genes in zebrafish, encompassing at least 15 genes, and characterize their sequence properties. Finally, we discuss how recent findings have shed new light on the remarkably diverse MHC loci of this species.}, number={1}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Dirscherl, Hayley and McConnell, Sean C. and Yoder, Jeffrey A. and de Jong, Jill L.O.}, year={2014}, month={Sep}, pages={11–23} } @article{li_d’annibale-tolhurst_adler_fang_yin_birkenheuer_levy_jones_sung_hawkins_et al._2013, title={A Myristoylated Alanine-Rich C Kinase Substrate–Related Peptide Suppresses Cytokine mRNA and Protein Expression in LPS-Activated Canine Neutrophils}, volume={48}, ISSN={1044-1549 1535-4989}, url={http://dx.doi.org/10.1165/rcmb.2012-0278OC}, DOI={10.1165/rcmb.2012-0278oc}, abstractNote={Myristoylated alanine-rich C kinase substrate (MARCKS) is a ubiquitously expressed protein kinase C substrate that has emerged as a potential therapeutic target for the amelioration of mucin secretion and inflammation in patients with chronic obstructive pulmonary disease. MARCKS also plays a key role in regulating the adhesion, migration, and degranulation of neutrophils. Moreover, given its biological role in epithelial and immune cells, we hypothesized that MARCKS may play an integral role in cytokine secretion by neutrophils. Because the amino terminus of MARCKS is highly conserved across vertebrate species, we successfully applied the well-characterized human MARCKS inhibitory peptide, myristoylated N-terminal sequence (MANS), to attenuate the function of MARCKS in isolated canine neutrophils. Pretreatment of canine neutrophils with MANS peptide significantly reduced both mRNA and protein expression in a broad range of LPS-induced cytokines, including IL-8, a chemokine (C-X-C motif) ligand-1 orthologue, and TNF-α, in comparison with untreated cells or those treated with a control peptide. This reduction in cytokine expression was observed even when neutrophils were treated with MANS 2 hours after LPS exposure. The observed reduction in cytokine secretion was not attributable to protein retention or cell death, but was associated with reduced cytokine transcript synthesis. These observations identify MARCKS protein as a promising therapeutic target in the treatment of inflammatory diseases or syndromes attributed to neutrophil influx and inflammatory cytokine production, such as sepsis, acute lung injury, and acute respiratory distress syndrome.}, number={3}, journal={American Journal of Respiratory Cell and Molecular Biology}, publisher={American Thoracic Society}, author={Li, Jingjing and D’Annibale-Tolhurst, Melissa A. and Adler, Kenneth B. and Fang, Shijing and Yin, Qui and Birkenheuer, Adam J. and Levy, Michael G. and Jones, Samuel L. and Sung, Eui Jae and Hawkins, Eleanor C. and et al.}, year={2013}, month={Mar}, pages={314–321} } @article{balhoff_miko_yoder_mullins_deans_2013, title={A Semantic Model for Species Description Applied to the Ensign Wasps (Hymenoptera: Evaniidae) of New Caledonia}, volume={62}, ISSN={["1076-836X"]}, DOI={10.1093/sysbio/syt028}, abstractNote={Taxonomic descriptions are unparalleled sources of knowledge of life's phenotypic diversity. As natural language prose, these data sets are largely refractory to computation and integration with other sources of phenotypic data. By formalizing taxonomic descriptions using ontology-based semantic representation, we aim to increase the reusability and computability of taxonomists' primary data. Here, we present a revision of the ensign wasp (Hymenoptera: Evaniidae) fauna of New Caledonia using this new model for species description. Descriptive matrices, specimen data, and taxonomic nomenclature are gathered in a unified Web-based application, mx, then exported as both traditional taxonomic treatments and semantic statements using the OWL Web Ontology Language. Character:character-state combinations are then annotated following the entity–quality phenotype model, originally developed to represent mutant model organism phenotype data; concepts of anatomy are drawn from the Hymenoptera Anatomy Ontology and linked to phenotype descriptors from the Phenotypic Quality Ontology. The resulting set of semantic statements is provided in Resource Description Framework format. Applying the model to real data, that is, specimens, taxonomic names, diagnoses, descriptions, and redescriptions, provides us with a foundation to discuss limitations and potential benefits such as automated data integration and reasoner-driven queries. Four species of ensign wasp are now known to occur in New Caledonia: Szepligetella levipetiolata, Szepligetella deercreeki Deans and Mikó sp. nov., Szepligetella irwini Deans and Mikó sp. nov., and the nearly cosmopolitan Evania appendigaster. A fifth species, Szepligetella sericea, including Szepligetella impressa, syn. nov., has not yet been collected in New Caledonia but can be found on islands throughout the Pacific and so is included in the diagnostic key. [Biodiversity informatics; Evaniidae; New Caledonia; new species; ontology; semantic phenotypes; semantic species description; taxonomy.]}, number={5}, journal={SYSTEMATIC BIOLOGY}, author={Balhoff, James P. and Miko, Istvan and Yoder, Matthew J. and Mullins, Patricia L. and Deans, Andrew R.}, year={2013}, month={Sep}, pages={639–659} } @article{stebbing_irvin_rivera-serrano_boehme_ikizler_yoder_dermody_sherry_lyles_2013, title={An ITAM in a Nonenveloped Virus Regulates Activation of NF- B, Induction of Beta Interferon, and Viral Spread}, volume={88}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/JVI.02573-13}, DOI={10.1128/jvi.02573-13}, abstractNote={ABSTRACT}, number={5}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Stebbing, R. E. and Irvin, S. C. and Rivera-Serrano, E. E. and Boehme, K. W. and Ikizler, M. and Yoder, J. A. and Dermody, T. S. and Sherry, B. and Lyles, D. S.}, year={2013}, month={Dec}, pages={2572–2583} } @article{dirscherl_yoder_2013, title={Characterization of the Z lineage Major histocompatability complex class I genes in zebrafish}, volume={66}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-013-0748-z}, DOI={10.1007/s00251-013-0748-z}, abstractNote={Zebrafish (Danio rerio) are a valuable model for studying immunity, infection, and hematopoietic disease and have recently been employed for transplantation assays. However, the lack of syngeneic zebrafish creates challenges with identifying immune-matched individuals. The MHC class I genes, which mediate allogeneic recognition in mammals, have been grouped into three broad lineages in zebrafish: the classical U genes on chromosome 19, the Z genes which have been reported to map to chromosome 1, and the L genes that map to multiple loci. Transplantations between individual zebrafish that are matched at the U locus fail to consistently engraft suggesting that additional loci contribute to allogeneic recognition. Although two full-length zebrafish Z transcripts have been described, the genomic organization and diversity of these genes have not been reported. Herein we define ten Z genes on chromosomes 1 and 3 and on an unplaced genomic scaffold. We report that neither of the Z transcripts previously described match the current genome assembly and classify these transcripts as additional gene loci. We characterize full-length transcripts for 9 of these 12 genes. We demonstrate a high level of expression variation of the Z genes between individual zebrafish suggestive of haplotypic variation. We report low level sequence variation for individual Z genes between individual zebrafish reflecting a possible nonclassical function, although these molecules may still contribute to allogeneic recognition. Finally, we present a gene nomenclature system for the Z genes consistent with MHC nomenclature in other species and with the zebrafish gene nomenclature guidelines.}, number={3}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Dirscherl, Hayley and Yoder, Jeffrey A.}, year={2013}, month={Nov}, pages={185–198} } @article{gabor_stevens_pietraszewski_gould_shim_yoder_lam_gong_hess_kim_et al._2013, title={Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0068759}, DOI={10.1371/journal.pone.0068759}, abstractNote={Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response.}, number={7}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Gabor, Kristin A. and Stevens, Chad R. and Pietraszewski, Matthew J. and Gould, Travis J. and Shim, Juyoung and Yoder, Jeffrey and Lam, Siew Hong and Gong, Zhiyuan and Hess, Samuel T. and Kim, Carol H. and et al.}, editor={Lamaze, ChristopheEditor}, year={2013}, month={Jul}, pages={e68759} } @article{shah_rodriguez-nunez_eason_haire_bertrand_wittamer_traver_nordone_litman_yoder_et al._2012, title={Development and Characterization of Anti-Nitr9 Antibodies}, volume={2012}, ISSN={1687-9104 1687-9112}, url={http://dx.doi.org/10.1155/2012/596925}, DOI={10.1155/2012/596925}, abstractNote={The novel immune-type receptors (NITRs), which have been described in numerous bony fish species, are encoded by multigene families of inhibitory and activating receptors and are predicted to be functional orthologs to the mammalian natural killer cell receptors (NKRs). Within the zebrafish NITR family,nitr9is the only gene predicted to encode an activating receptor. However, alternative RNA splicing generates three distinctnitr9transcripts, each of which encodes a different isoform. Althoughnitr9transcripts have been detected in zebrafish lymphocytes, the specific hematopoietic lineage(s) that expresses Nitr9 remains to be determined. In an effort to better understand the role of NITRs in zebrafish immunity, anti-Nitr9 monoclonal antibodies were generated and evaluated for the ability to recognize the three Nitr9 isoforms. The application of these antibodies to flow cytometry should prove to be useful for identifying the specific lymphocyte lineages that express Nitr9 and may permit the isolation of Nitr9-expressing cells that can be directly assessed for cytotoxic (e.g., NK) function.}, journal={Advances in Hematology}, publisher={Hindawi Limited}, author={Shah, Radhika N. and Rodriguez-Nunez, Ivan and Eason, Donna D. and Haire, Robert N. and Bertrand, Julien Y. and Wittamer, Valērie and Traver, David and Nordone, Shila K. and Litman, Gary W. and Yoder, Jeffrey A. and et al.}, year={2012}, pages={1–9} } @article{haire_cannon_o&apos_driscoll_ostrov_mueller_turner_litman_litman_yoder_2012, title={Genomic and functional characterization of the diverse immunoglobulin domain-containing protein (DICP) family}, volume={99}, ISSN={0888-7543}, url={http://dx.doi.org/10.1016/j.ygeno.2012.02.004}, DOI={10.1016/j.ygeno.2012.02.004}, abstractNote={A heretofore-unrecognized multigene family encoding diverse immunoglobulin (Ig) domain-containing proteins (DICPs) was identified in the zebrafish genome. Twenty-nine distinct loci mapping to three chromosomal regions encode receptor-type structures possessing two classes of Ig ectodomains (D1 and D2). The sequence and number of Ig domains, transmembrane regions and signaling motifs vary between DICPs. Interindividual polymorphism and alternative RNA processing contribute to DICP diversity. Molecular models indicate that most D1 domains are of the variable (V) type; D2 domains are Ig-like. Sequence differences between D1 domains are concentrated in hypervariable regions on the front sheet strands of the Ig fold. Recombinant DICP Ig domains bind lipids, a property shared by mammalian CD300 and TREM family members. These findings suggest that novel multigene families encoding diversified immune receptors have arisen in different vertebrate lineages and affect parallel patterns of ligand recognition that potentially impact species-specific advantages.}, number={5}, journal={Genomics}, publisher={Elsevier BV}, author={Haire, R.N. and Cannon, J.P. and O&apos and Driscoll, M.L. and Ostrov, D.A. and Mueller, M.G. and Turner, P.M. and Litman, R.T. and Litman, G.W. and Yoder, J.A.}, year={2012}, month={May}, pages={282–291} } @inproceedings{nordone_li_d’annibale_birkenheuer_levy_yoder_jones_adler_2012, title={Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) Protein Plays A Critical Role In Production Of Proinflammatory Cytokines By Isolated Canine Neutrophils}, DOI={10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2106}, booktitle={A67. ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME: BIOLOGICAL MECHANISMS}, publisher={American Thoracic Society}, author={Nordone, Shila K. and Li, Jingjing and D’Annibale, Melissa A. and Birkenheuer, Adam J. and Levy, Michael G. and Yoder, Jeffrey A. and Jones, Sam L. and Adler, Kenneth B.}, year={2012}, month={May} } @article{jewett_yoder_ivanisevic_2012, title={Surface modifications on InAs decrease indium and arsenic leaching under physiological conditions}, volume={261}, ISSN={["1873-5584"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84867742842&partnerID=MN8TOARS}, DOI={10.1016/j.apsusc.2012.08.115}, abstractNote={Devices containing III–V semiconductors such as InAs are increasingly being used in the electronic industry for a variety of optoelectronic applications. Furthermore, the attractive chemical, material, electronic properties make such materials appealing for use in devices designed for biological applications, such as biosensors. However, in biological applications the leaching of toxic materials from these devices could cause harm to cells or tissue. Additionally, after disposal, toxic inorganic materials can leach from devices and buildup in the environment, causing long-term ecological harm. Therefore, the toxicity of these materials along with their stability in physiological conditions are important factors to consider. Surface modifications are one common method of stabilizing semiconductor materials in order to chemically and electronically passivate them. Such surface modifications could also prevent the leaching of toxic materials by preventing the regrowth of the unstable surface oxide layer and by creating an effective barrier between the semiconductor surface and the surrounding environment. In this study, various surface modifications on InAs are developed with the goal of decreasing the leaching of indium and arsenic. The leaching of indium and arsenic from modified substrates was assessed in physiological conditions using inductively coupled plasma mass spectrometry (ICP-MS). Substrates modified with 11-mercapto-1-undecanol (MU) and graft polymerized with poly(ethylene) glycol (PEG) were most effective at preventing indium and arsenic leaching. These surfaces were characterized using contact angle analysis, ellipsometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Substrates modified with collagen and synthetic polyelectrolytes were least effective, due to the destructive nature of acidic environments on InAs. The toxicity of modified and unmodified InAs, along with raw indium, arsenic, and PEG components was assessed using zebrafish embryos.}, journal={APPLIED SURFACE SCIENCE}, author={Jewett, Scott A. and Yoder, Jeffrey A. and Ivanisevic, Albena}, year={2012}, month={Nov}, pages={842–850} } @article{morckel_lusic_farzana_yoder_deiters_nascone-yoder_2011, title={A photoactivatable small-molecule inhibitor for light-controlled spatiotemporal regulation of Rho kinase in live embryos}, volume={139}, ISSN={0950-1991 1477-9129}, url={http://dx.doi.org/10.1242/dev.072165}, DOI={10.1242/dev.072165}, abstractNote={To uncover the molecular mechanisms of embryonic development, the ideal loss-of-function strategy would be capable of targeting specific regions of the living embryo with both temporal and spatial precision. To this end, we have developed a novel pharmacological agent that can be light activated to achieve spatiotemporally limited inhibition of Rho kinase activity in vivo. A new photolabile caging group, 6-nitropiperonyloxymethyl (NPOM), was installed on a small-molecule inhibitor of Rho kinase, Rockout, to generate a ‘caged Rockout’ derivative. Complementary biochemical, cellular, molecular and morphogenetic assays in both mammalian cell culture and Xenopus laevis embryos validate that the inhibitory activity of the caged compound is dependent on exposure to light. Conveniently, this unique reagent retains many of the practical advantages of conventional small-molecule inhibitors, including delivery by simple diffusion in the growth medium and concentration-dependent tuneability, but can be locally activated by decaging with standard instrumentation. Application of this novel tool to the spatially heterogeneous problem of embryonic left-right asymmetry revealed a differential requirement for Rho signaling on the left and right sides of the primitive gut tube, yielding new insight into the molecular mechanisms that generate asymmetric organ morphology. As many aromatic/heterocyclic small-molecule inhibitors are amenable to installation of this caging group, our results indicate that photocaging pharmacological inhibitors might be a generalizable technique for engendering convenient loss-of-function reagents with great potential for wide application in developmental biology.}, number={2}, journal={Development}, publisher={The Company of Biologists}, author={Morckel, A. R. and Lusic, H. and Farzana, L. and Yoder, J. A. and Deiters, A. and Nascone-Yoder, N. M.}, year={2011}, month={Dec}, pages={437–442} } @article{li_birkenheuer_marr_levy_yoder_nordone_2011, title={Expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) on canine neutrophils}, volume={35}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2011.03.021}, DOI={10.1016/j.dci.2011.03.021}, abstractNote={The dog is both a valued veterinary species and a widely used translational model for sepsis research. However, relatively little work has been performed evaluating potential biomarkers present during canine infection. Triggering receptor expressed on myeloid cells-1 (TREM-1) has shown promise as a biomarker for infection and pneumonia in humans. Here we describe, for the first time, the expression and function of the canine orthologue of TREM-1. Expression of TREM-1 on canine neutrophils is significantly up-regulated by stimulation with microbial agonists of TLR2/6, TLR1/2, and TLR4/MD2. Kinetics of TREM-1 protein up-regulation are rapid, with significant increases observed within 2 hr of neutrophil activation. Functionally, canine TREM-1 synergistically enhances LPS-induced production of IL-8, TNF-α and a canine orthologue of CXCL1. Collectively, these data suggest that TREM-1 expression in dogs, as it is in humans, is an amplifier of pro-inflammatory responses to microbial products. These results have direct application to veterinary diagnostics as well as the potential to enhance the utility of canine disease models in the assessment of potential therapeutics in the treatment of human sepsis.}, number={8}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Li, Jingjing and Birkenheuer, Adam J. and Marr, Henry S. and Levy, Michael G. and Yoder, Jeffrey A. and Nordone, Shila K.}, year={2011}, month={Aug}, pages={872–880} } @article{ott_mcdowell_turner_law_adler_yoder_jones_2011, place={Hoboken, N.J}, title={Two Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Paralogs are Required for Normal Development in Zebrafish}, volume={294}, ISSN={1932-8486}, url={http://dx.doi.org/10.1002/ar.21453}, DOI={10.1002/ar.21453}, abstractNote={Abstract}, note={: 2007),}, number={9}, journal={The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology}, publisher={Wiley}, author={Ott, Laura E. and Mcdowell, Zachary T. and Turner, Poem M. and Law, J. Mchugh and Adler, Kenneth B. and Yoder, Jeffrey A. and Jones, Samuel L.}, year={2011}, month={Aug}, pages={1511–1524} } @article{deiters_garner_lusic_govan_dush_nascone-yoder_yoder_2010, title={Photocaged Morpholino Oligomers for the Light-Regulation of Gene Function in Zebrafish and Xenopus Embryos}, volume={132}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja1053863}, DOI={10.1021/ja1053863}, abstractNote={Morpholino oligonucleotides, or morpholinos, have emerged as powerful antisense reagents for evaluating gene function in both in vitro and in vivo contexts. However, the constitutive activity of these reagents limits their utility for applications that require spatiotemporal control, such as tissue-specific gene disruptions in embryos. Here we report a novel and efficient synthetic route for incorporating photocaged monomeric building blocks directly into morpholino oligomers and demonstrate the utility of these caged morpholinos in the light-activated control of gene function in both cell culture and living embryos. We demonstrate that a caged morpholino that targets enhanced green fluorescent protein (EGFP) disrupts EGFP production only after exposure to UV light in both transfected cells and living zebrafish (Danio rerio) and Xenopus frog embryos. Finally, we show that a caged morpholino targeting chordin, a zebrafish gene that yields a distinct phenotype when functionally disrupted by conventional morpholinos, elicits a chordin phenotype in a UV-dependent manner. Our results suggest that photocaged morpholinos are readily synthesized and highly efficacious tools for light-activated spatiotemporal control of gene expression in multiple contexts.}, number={44}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Deiters, Alexander and Garner, R. Aaron and Lusic, Hrvoje and Govan, Jeane M. and Dush, Mike and Nascone-Yoder, Nanette M. and Yoder, Jeffrey A.}, year={2010}, month={Nov}, pages={15644–15650} } @article{phennicie_sullivan_singer_yoder_kim_2010, title={Specific Resistance to Pseudomonas aeruginosa Infection in Zebrafish Is Mediated by the Cystic Fibrosis Transmembrane Conductance Regulator}, volume={78}, ISSN={0019-9567}, url={http://dx.doi.org/10.1128/IAI.00302-10}, DOI={10.1128/iai.00302-10}, abstractNote={ABSTRACT}, number={11}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Phennicie, R. T. and Sullivan, M. J. and Singer, J. T. and Yoder, J. A. and Kim, C. H.}, year={2010}, month={Aug}, pages={4542–4550} } @article{yoder_litman_2010, title={The phylogenetic origins of natural killer receptors and recognition: relationships, possibilities, and realities}, volume={63}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-010-0506-4}, DOI={10.1007/s00251-010-0506-4}, abstractNote={Natural killer (NK) cells affect a form of innate immunity that recognizes and eliminates cells that are infected with certain viruses or have undergone malignant transformation. In mammals, this recognition can be mediated through immunoglobulin- (Ig) and/or lectin-type NK receptors (NKRs). NKR genes in mammals range from minimally polymorphic single-copy genes to complex multigene families that exhibit high levels of haplotypic complexity and exhibit significant interspecific variation. Certain single-copy NKR genes that are present in one mammal are present as expanded multigene families in other mammals. These observations highlight NKRs as one of the most rapidly evolving eukaryotic gene families and likely reflect the influence of pathogens, especially viruses, on their evolution. Although well characterized in human and mice, cytotoxic cells that are functionally similar to NK cells have been identified in species ranging from birds to reptiles, amphibians and fish. Although numerous receptors have been identified in non-mammalian vertebrates that share structural relationships with mammalian NKRs, functionally defining these lower vertebrate molecules as NKRs is confounded by methodological and interpretive complexities. Nevertheless, several lines of evidence suggest that NK-type function or its equivalent has sustained a long evolutionary history throughout vertebrate species.}, number={3}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Yoder, Jeffrey A. and Litman, Gary W.}, year={2010}, month={Dec}, pages={123–141} } @article{hinton_hardman_kullman_law_schmale_walter_winn_yoder_2009, title={Aquatic animal models of human disease: Selected papers and recommendations from the 4th Conference}, volume={149}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2008.12.006}, DOI={10.1016/j.cbpc.2008.12.006}, abstractNote={Large volumes of oil sands process-affected water (OSPW) are produced by the surface-mining oil sands industry in Alberta. Both laboratory and field studies have demonstrated that the exposure to OSPW leads to many physiological changes in a variety of organisms. Adverse effects include compromised immunological function, developmental delays, impaired reproduction, disrupted endocrine system, and higher prevalence of tissue-specific pathological manifestations. The composition of OSPW varies with several factors such as ore sources, mining process, and tailings management practices. Differences in water characteristics have confounded interpretation or comparison of OSPW toxicity across studies. Research on individual fractions extracted from OSPW has helped identify some target pollutants. Naphthenic acids (NAs) are considered as the major toxic components in OSPW, exhibiting toxic effects through multiple modes of action including narcosis and endocrine disruption. Other pollutants, like polycyclic aromatic hydrocarbons (PAHs), metals, and ions may also contribute to the overall OSPW toxicity. Studies have been conducted on OSPW as a whole complex effluent mixture, with consideration of the presence of unidentified components, and the interactions (potential synergistic or antagonistic reactions) among chemicals. This review summarizes the toxicological data derived from in vitro and in vivo exposure studies using different OSPW types, and different taxa of organisms. In general, toxicity of OSPW was found to be dependent on the OSPW type and concentration, duration of exposures (acute versus sub chronic), and organism studied.}, number={2}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Hinton, David E. and Hardman, Ron C. and Kullman, Seth W. and Law, Jerry M. and Schmale, Michael C. and Walter, Ronald B. and Winn, Richard N. and Yoder, Jeffrey A.}, year={2009}, month={Mar}, pages={121–128} } @article{yoder_turner_wright_wittamer_bertrand_traver_litman_2009, title={Developmental and tissue-specific expression of NITRs}, volume={62}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-009-0416-5}, DOI={10.1007/s00251-009-0416-5}, abstractNote={Novel immune-type receptors (NITRs) are encoded by large multi-gene families and share structural and signaling similarities to mammalian natural killer receptors (NKRs). NITRs have been identified in multiple bony fish species, including zebrafish, and may be restricted to this large taxonomic group. Thirty-nine NITR genes that can be classified into 14 families are encoded on zebrafish chromosomes 7 and 14. Herein, we demonstrate the expression of multiple NITR genes in the zebrafish ovary and during embryogenesis. All 14 families of zebrafish NITRs are expressed in hematopoietic kidney, spleen and intestine as are immunoglobulin and T cell antigen receptors. Furthermore, all 14 families of NITRs are shown to be expressed in the lymphocyte lineage, but not in the myeloid lineage, consistent with the hypothesis that NITRs function as NKRs. Sequence analyses of NITR amplicons identify known alleles and reveal additional alleles within the nitr1, nitr2, nitr3, and nitr5 families, reflecting the recent evolution of this gene family.}, number={2}, journal={Immunogenetics}, publisher={Springer Nature}, author={Yoder, Jeffrey A. and Turner, Poem M. and Wright, Phillip D. and Wittamer, Valérie and Bertrand, Julien Y. and Traver, David and Litman, Gary W.}, year={2009}, month={Dec}, pages={117–122} } @article{jima_shah_orcutt_joshi_law_litman_trede_yoder_2009, title={Enhanced transcription of complement and coagulation genes in the absence of adaptive immunity}, volume={46}, ISSN={0161-5890}, url={http://dx.doi.org/10.1016/j.molimm.2008.12.021}, DOI={10.1016/j.molimm.2008.12.021}, abstractNote={A recessive nonsense mutation in the zebrafish recombination activating gene 1 (rag1) gene results in defective V(D)J recombination; however, animals homozygous for this mutation (rag1(-/-)) are reportedly viable and fertile in standard, nonsterile aquarium conditions but display increased mortality after intraperitoneal injection with mycobacteria. Based on their survival in nonsterile environments, we hypothesized that the rag1(-/-) zebrafish may possess an "enhanced" innate immune response to compensate for the lack of an adaptive immune system. To test this hypothesis, microarray analyses were used to compare the expression profiles of the intestines and hematopoietic kidneys of rag1 deficient zebrafish to the expression profiles of control (heterozygous) siblings. The expression levels of 12 genes were significantly altered in the rag1(-/-) kidney including the up regulation of a putative interferon stimulated gene, and the down regulation of genes encoding fatty acid binding protein 10, keratin 5 and multiple heat shock proteins. The expression levels of 87 genes were shown to be significantly altered in the rag1(-/-) intestine; the majority of these differences reflect increased expression of innate immune genes, including those of the coagulation and complement pathways. Subsequent analyses of orthologous coagulation and complement genes in Rag1(-/-) mice indicate increased transcription of the complement C4 gene in the Rag1(-/-) intestine.}, number={7}, journal={Molecular Immunology}, publisher={Elsevier BV}, author={Jima, Dereje D. and Shah, Radhika N. and Orcutt, Timothy M. and Joshi, Deepa and Law, J. McHugh and Litman, Gary W. and Trede, Nikolaus S. and Yoder, Jeffrey A.}, year={2009}, month={Apr}, pages={1505–1516} } @article{yoder_2009, title={Form, function and phylogenetics of NITRs in bony fish}, volume={33}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2008.09.004}, DOI={10.1016/j.dci.2008.09.004}, abstractNote={Novel immune-type receptors (NITRs) are encoded by clusters of multigene families and have been identified in multiple bony fish species. All NITRs possess one extracellular immunoglobulin (Ig) domain of the variable (V) type and recent crystal structures of NITR V domains demonstrate their high degree of similarity to V domains of antigen receptors. Many NITRs possess a second extracellular Ig domain of the intermediate (I) type which helps differentiate NITRs from other V domain receptors. The majority of NITRs are type I transmembrane receptors; however, a small number are predicted to encode secreted proteins. Based on their sequence and structure, NITRs have been proposed to be “functional orthologs” of mammalian natural killer receptors (NKRs). Like NKRs, most NITRs possess short functional motifs permitting their classification as inhibitory or activating. NITRs lacking these motifs are functionally ambiguous. Inhibitory and activating NKRs utilize opposing signaling mechanisms to influence the response of NK cells to target cells; studies employing recombinant NITRs suggest that these signaling pathways are conserved between NKRs and NITRs. An analysis of all published NITR sequences demonstrates the conserved nature of multiple residues within the NITR Ig domains permitting the identification of NITR ESTs from salmon, cod, halibut, lake whitefish and stickleback species. Complete data sets of NITRs from the sequencing of the zebrafish and medaka genomes provide insight into the evolution of the NITRs within bony fish species. It is likely that all teleost species encode NITRs which function within innate immunity to regulate cell mediated cytotoxicity.}, number={2}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Yoder, Jeffrey A.}, year={2009}, month={Feb}, pages={135–144} } @article{young_garner_yoder_deiters_2009, title={Light-activation of gene function in mammalian cells via ribozymes}, ISSN={1359-7345 1364-548X}, url={http://dx.doi.org/10.1039/b819375d}, DOI={10.1039/b819375d}, abstractNote={A ribozyme based gene control element enabled the spatio-temporal regulation of gene function in mammalian cell culture with light.}, number={5}, journal={Chem. Commun.}, publisher={Royal Society of Chemistry (RSC)}, author={Young, Douglas D. and Garner, R. Aaron and Yoder, Jeffrey A. and Deiters, Alexander}, year={2009}, pages={568–570} } @article{xie_yin_nichols_yoder_horowitz_2009, title={Sp2 Is a Maternally Inherited Transcription Factor Required for Embryonic Development}, volume={285}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/jbc.M109.078881}, DOI={10.1074/jbc.M109.078881}, abstractNote={The Sp family of transcription factors is required for the expression of cell cycle- and developmentally regulated genes, and the deregulated expression of a handful of family members is associated with human tumorigenesis. Sp2 is a relatively poorly characterized member of the Sp family that, although widely expressed, exhibits little or no DNA binding or transcriptional activity in human and mouse cell lines. To begin to address the role(s) played by Sp2 in early metazoan development we have cloned and characterized Sp2 from zebrafish (Danio rerio). We report that 1) the intron/exon organization and amino acid sequence of zebrafish Sp2 is closely conserved with its mammalian orthologues, 2) zebrafish Sp2 weakly stimulates an Sp-dependent promoter in vitro and associates with the nuclear matrix in a DNA-independent fashion, 3) zebrafish Sp2 is inherited as a maternal transcript, is transcribed in zebrafish embryos and adult tissues, and is required for completion of gastrulation, and 4) zebrafish lines carrying transgenes regulated by the Sp2 promoter recapitulate patterns of endogenous Sp2 expression.}, number={6}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Xie, Jianzhen and Yin, Haifeng and Nichols, Teresa D. and Yoder, Jeffrey A. and Horowitz, Jonathan M.}, year={2009}, month={Dec}, pages={4153–4164} } @article{chen_bai_sokol_zhou_ren_painter_liu_sallman_chen_yoder_et al._2008, title={A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia}, volume={113}, ISSN={0006-4971 1528-0020}, url={http://dx.doi.org/10.1182/blood-2008-07-168245}, DOI={10.1182/blood-2008-07-168245}, abstractNote={Abstract}, number={14}, journal={Blood}, publisher={American Society of Hematology}, author={Chen, X. and Bai, F. and Sokol, L. and Zhou, J. and Ren, A. and Painter, J. S. and Liu, J. and Sallman, D. A. and Chen, Y. A. and Yoder, J. A. and et al.}, year={2008}, month={Dec}, pages={3226–3234} } @article{yoder_2008, title={Assessing infection and immunity in zebrafish}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-54349087528&partnerID=MN8TOARS}, DOI={10.1089/zeb.2008.0537}, abstractNote={ZebrafishVol. 5, No. 3 Meeting ReportsAssessing Infection and Immunity in ZebrafishJeffrey A. YoderJeffrey A. YoderSearch for more papers by this authorPublished Online:22 Oct 2008https://doi.org/10.1089/zeb.2008.0537AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byRecent Papers on Zebrafish and Other Aquarium Fish Models15 January 2009 | Zebrafish, Vol. 5, No. 4 Volume 5Issue 3Sep 2008 InformationCopyright 2008, Mary Ann Liebert, Inc.To cite this article:Jeffrey A. Yoder.Assessing Infection and Immunity in Zebrafish.Zebrafish.Sep 2008.189-191.http://doi.org/10.1089/zeb.2008.0537Published in Volume: 5 Issue 3: October 22, 2008PDF download}, number={3}, journal={Zebrafish}, author={Yoder, J.A.}, year={2008}, pages={189–191} } @article{epling-burnette_sokol_chen_bai_zhou_blaskovich_zou_painter_edwards_moscinski_et al._2008, title={Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling}, volume={112}, ISSN={0006-4971 1528-0020}, url={http://dx.doi.org/10.1182/blood-2008-02-136382}, DOI={10.1182/blood-2008-02-136382}, abstractNote={Abstract}, number={12}, journal={Blood}, publisher={American Society of Hematology}, author={Epling-Burnette, P. K. and Sokol, L. and Chen, X. and Bai, F. and Zhou, J. and Blaskovich, M. A. and Zou, J. and Painter, J. S. and Edwards, T. D. and Moscinski, L. and et al.}, year={2008}, month={Dec}, pages={4694–4698} } @article{yoder_cannon_litman_murphy_freeman_litman_2008, title={Evidence for a transposition event in a second NITR gene cluster in zebrafish}, volume={60}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-008-0285-3}, DOI={10.1007/s00251-008-0285-3}, abstractNote={Novel immune-type receptors (NITRs) are immunoglobulin-variable (V) domain-containing cell surface proteins that possess characteristic activating/inhibitory signaling motifs and are expressed in hematopoietic cells. NITRs are encoded by multigene families and have been identified in bony fish species. A single gene cluster, which encodes 36 NITRs that can be classified into 12 families, has been mapped to zebrafish chromosome 7. We report herein the presence of a second NITR gene cluster on zebrafish chromosome 14, which is comprised of three genes (nitr13, nitr14a, and nitr14b) representing two additional NITR gene families. Phylogenetic analyses indicate that the V domains encoded by the nitr13 and nitr14 genes are more similar to each other than any other zebrafish NITR suggesting that these genes arose from a tandem gene duplication event. Similar analyses comparing zebrafish Nitr13 and Nitr14 to NITRs from other fish species indicate that the nitr13 and nitr14 genes are phylogenetically related to the catfish IpNITR13 and IpNITR15 genes. Sequence features of the chromosomal region encoding nitr13 suggest that this gene arose via retrotransposition.}, number={5}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Yoder, Jeffrey A. and Cannon, John P. and Litman, Ronda T. and Murphy, Carly and Freeman, Jennifer L. and Litman, Gary W.}, year={2008}, month={Mar}, pages={257–265} } @article{young_lusic_lively_yoder_deiters_2008, title={Gene Silencing in Mammalian Cells with Light-Activated Antisense Agents}, volume={9}, ISSN={1439-4227 1439-7633}, url={http://dx.doi.org/10.1002/cbic.200800627}, DOI={10.1002/cbic.200800627}, abstractNote={Detailed knowledge of the external regulation of gene func-tion is a fundamental necessity in order to annotate sequencedgenomes and to understand biological processes in single cellsand multicellular organisms. One of the most widely used ap-proaches for the down-regulation of specific genes is the ap-plication of antisense agents. Antisense agents are oligomersthat have the ability to hybridize sequence specificslly tomRNAs, inhibiting translation and potentially leading to mRNAdegradation through RNAse H recruitment.}, number={18}, journal={ChemBioChem}, publisher={Wiley}, author={Young, Douglas D. and Lusic, Hrvoje and Lively, Mark O. and Yoder, Jeffrey A. and Deiters, Alexander}, year={2008}, month={Dec}, pages={2937–2940} } @article{desai_heffelfinger_orcutt_litman_yoder_2008, title={The medaka novel immune-type receptor (NITR) gene clusters reveal an extraordinary degree of divergence in variable domains}, volume={8}, ISSN={1471-2148}, url={http://dx.doi.org/10.1186/1471-2148-8-177}, DOI={10.1186/1471-2148-8-177}, abstractNote={Abstract}, number={1}, journal={BMC Evolutionary Biology}, publisher={Springer Nature}, author={Desai, Salil and Heffelfinger, Amy K and Orcutt, Timothy M and Litman, Gary W and Yoder, Jeffrey A}, year={2008}, pages={177} } @article{yoder_2008, title={Workshop report - assessing infection and immunity in zebrafish}, volume={5}, journal={Zebrafish}, author={Yoder, J. A.}, year={2008}, pages={189–191} } @article{litman_cannon_dishaw_haire_eason_yoder_prada_ostrov_2007, title={Immunoglobulin variable regions in molecules exhibiting characteristics of innate and adaptive immune receptors}, volume={38}, ISSN={["0257-277X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35348850743&partnerID=MN8TOARS}, DOI={10.1007/s12026-007-0014-2}, abstractNote={The antigen combining sites of immunoglobulin (Ig) and T cell antigen receptors (TCRs), which are present in all jawed vertebrates, consist of a paired variable (V) domain heterodimer that exhibits varying degrees of germline- and extraordinarily high levels of somatically-derived variation. The near limitless variation in receptor specificity on the surface of individual lymphocytes is the basis for clonal selection in the adaptive immune response. A basic question arises as to whether or not there are other forms of immune-type receptors in vertebrates as well as in invertebrates that derive immune specificity through sequence differences in V domains. Our laboratory has discovered two such families of molecules, the novel immune-type receptors and the variable region-containing chitin-binding proteins. Both families of molecules encode V domains that share some characteristics of adaptive immune receptors but likely mediate innate functions.}, number={1-3}, journal={IMMUNOLOGIC RESEARCH}, author={Litman, Gary W. and Cannon, John P. and Dishaw, Larry J. and Haire, Robert N. and Eason, Donna D. and Yoder, Jeffrey A. and Prada, Jose Hernandez and Ostrov, David A.}, year={2007}, pages={294–304} } @article{yoder_orcutt_traver_litman_2007, title={Structural characteristics of zebrafish orthologs of adaptor molecules that associate with transmembrane immune receptors}, volume={401}, ISSN={0378-1119}, url={http://dx.doi.org/10.1016/j.gene.2007.07.014}, DOI={10.1016/j.gene.2007.07.014}, abstractNote={Transmembrane bound receptors comprised of extracellular immunoglobulin (Ig) or lectin domains play integral roles in a large number of immune functions including inhibitory and activating responses. The function of many of the activating receptors requires a physical interaction with an adaptor protein possessing a cytoplasmic regulatory motif. The partnering of an activating receptor with an adaptor protein relies on complementary charged residues in the two transmembrane domains. The mammalian natural killer (NK) and Fc receptors (FcR) represent two of many receptor families, which possess activating receptors that partner with adaptor proteins for signaling. Zebrafish represent a powerful experimental model for understanding developmental regulation at early stages of embryogenesis and for efficiently generating transgenic animals. In an effort to understand developmental aspects of immune receptor function, we have accessed the partially annotated zebrafish genome to identify six different adaptor molecules: Dap10, Dap12, Cd3zeta, Cd3zeta-like, FcRgamma and FcRgamma-like that are homologous to those effecting immune function in mammals. Their genomic organizations have been characterized, cDNA transcripts have been recovered, phylogenetic relationships have been defined and their cell lineage-specific expression patterns have been established.}, number={1-2}, journal={Gene}, publisher={Elsevier BV}, author={Yoder, Jeffrey A. and Orcutt, Timothy M. and Traver, David and Litman, Gary W.}, year={2007}, month={Oct}, pages={154–164} } @article{wei_zhou_chen_shah_liu_orcutt_traver_djeu_litman_yoder_et al._2007, title={The zebrafish activating immune receptor Nitr9 signals via Dap12}, volume={59}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-007-0250-6}, DOI={10.1007/s00251-007-0250-6}, abstractNote={Both inhibitory and activating forms of natural killer (NK) cell receptors are found in mammals. The activating receptors play a direct role in the recognition of virally infected or transformed cells and transduce activating signals into the cell by partnering with an adaptor protein, which contains a cytoplasmic activation motif. Activating NK receptors encoded by the mammalian leukocyte receptor complex (e.g., killer cell immunoglobulin-like receptors) and the natural killer complex (e.g., Ly49s) partner with the adaptor protein DAP12, whereas NK receptors encoded in the CD94/NKG2 complex partner with the adaptor protein DAP10. Novel immune-type receptors (NITRs) found in bony fish share several common features with immunoglobulin-type NK receptors. Nitr9 is a putative activating receptor in zebrafish that induces cytotoxicity within the context of human NK cells. One isoform of Nitr9, Nitr9L, is shown here to preferentially partner with a zebrafish ortholog of Dap12. Cross-linking the Nitr9L–Dap12 complex results in activation of the phosphytidylinositol 3-kinase→AKT→extracellular signal-regulated kinase pathway suggesting that the DAP12-based activating pathway is conserved between bony fish and mammals.}, number={10}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Wei, S. and Zhou, J.-M. and Chen, X. and Shah, R.N. and Liu, J. and Orcutt, T.M. and Traver, D. and Djeu, J.Y. and Litman, G.W. and Yoder, Jeffrey and et al.}, year={2007}, month={Sep}, pages={813–821} } @article{deiters_yoder_2006, title={Conditional Transgene and Gene Targeting Methodologies in Zebrafish}, volume={3}, ISSN={1545-8547 1557-8542}, url={http://dx.doi.org/10.1089/zeb.2006.3.415}, DOI={10.1089/zeb.2006.3.415}, abstractNote={The zebrafish has become a powerful tool for dissecting vertebrate gene function during embryogenesis. Numerous molecular systems have been developed to examine gene function in zebrafish, including transgenics for creating lineage-tracer lines of zebrafish that express a fluorescent protein as a marker for specific populations of cells, and antisense strategies, primarily morpholinos, for knocking down gene function. The focus of this review is to summarize the pros and cons of the currently available systems for functional genomics in zebrafish, and to discuss the need for future methodologies.}, number={4}, journal={Zebrafish}, publisher={Mary Ann Liebert Inc}, author={Deiters, Alexander and Yoder, Jeffrey A.}, year={2006}, month={Dec}, pages={415–429} } @article{panagos_dobrinski_chen_grant_traver_djeu_wei_yoder_2006, title={Immune-related, lectin-like receptors are differentially expressed in the myeloid and lymphoid lineages of zebrafish}, volume={58}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-005-0064-3}, DOI={10.1007/s00251-005-0064-3}, abstractNote={The identification of C-type lectin (Group V) natural killer (NK) cell receptors in bony fish has remained elusive. Analyses of the Fugu rubripes genome database failed to identify Group V C-type lectin domains (Zelensky and Gready, BMC Genomics 5:51, 2004) suggesting that bony fish, in general, may lack such receptors. Numerous Group II C-type lectin receptors, which are structurally similar to Group V (NK) receptors, have been characterized in bony fish. By searching the zebrafish genome database we have identified a multi-gene family of Group II immune-related, lectin-like receptors (illrs) whose members possess inhibiting and/or activating signaling motifs typical of Group V NK receptors. Illr genes are differentially expressed in the myeloid and lymphoid lineages, suggesting that they may play important roles in the immune functions of multiple hematopoietic cell lineages.}, number={1}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Panagos, Patoula G. and Dobrinski, Kimberly P. and Chen, Xianghong and Grant, Amanda W. and Traver, David and Djeu, Julie Y. and Wei, Sheng and Yoder, Jeffrey A.}, year={2006}, month={Feb}, pages={31–40} } @article{goll_kirpekar_maggert_yoder_hsieh_zhang_golic_jacobsen_bestor_2006, title={Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2}, volume={311}, ISSN={0036-8075 1095-9203}, url={http://dx.doi.org/10.1126/science.1120976}, DOI={10.1126/science.1120976}, abstractNote={ The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA Asp ) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNA Asp from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides. Indirect sequence recognition is also a feature of eukaryotic DNA methyltransferases, which may have arisen from a Dnmt2-like RNA methyltransferase. }, number={5759}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Goll, Mary Grace and Kirpekar, Finn and Maggert, Keith A. and Yoder, Jeffrey A. and Hsieh, Chih-Lin and Zhang, Xiaoyu and Golic, Kent G. and Jacobsen, Steven E. and Bestor, Timothy H.}, year={2006}, month={Jan}, pages={395–398} } @article{lipscomb_schmitt_sablyak_yoder_nascone-yoder_2006, title={Role for retinoid signaling in left–right asymmetric digestive organ morphogenesis}, volume={235}, ISSN={1058-8388 1097-0177}, url={http://dx.doi.org/10.1002/dvdy.20879}, DOI={10.1002/dvdy.20879}, abstractNote={Abstract}, number={8}, journal={Developmental Dynamics}, publisher={Wiley}, author={Lipscomb, Kristen and Schmitt, Christopher and Sablyak, Amanda and Yoder, Jeffrey A. and Nascone-Yoder, Nanette}, year={2006}, pages={2266–2275} } @article{yoder_2004, title={Investigating the morphology, function and genetics of cytotoxic cells in bony fish}, volume={138}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cca.2004.03.008}, DOI={10.1016/j.cca.2004.03.008}, abstractNote={Bony fish (teleosts) possess multiple cytotoxic cell lineages that recognize and destroy virally infected and transformed cells. In general, these lineages parallel their functional equivalents in mammals and include neutrophilic granulocytes, macrophages, cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. These four cell types have been morphologically identified in multiple fish species but only limited information is available about their function. In contrast, much work has gone into examining the function of a fifth cytotoxic cell lineage, termed nonspecific cytotoxic cells (NCC), that has been referred to as the bony fish equivalent of NK cells. However, evidence suggesting that NCC do not represent the NK lineage has come through the development of multiple cytotoxic catfish cell lines that are morphologically and functionally similar to human NK cells and are distinct from NCC. In addition to characterizing cytotoxic cells from fish, recent work has identified the novel immune-type receptors (NITR) and cichlid killer leukocyte receptors (cKLR) that are structurally related to mammalian NK receptors and likely play a role in cytotoxic function in fish. This review summarizes the morphological and functional evidence for cytotoxic cells within bony fish and discusses future directions for examining cytotoxicity through genomics and transgenics.}, number={3}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Yoder, Jeffrey A.}, year={2004}, month={Jul}, pages={271–280} } @article{van den berg_yoder_litman_2004, title={On the origins of adaptive immunity: Innate immune receptors join the tale}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0346961787&partnerID=MN8TOARS}, DOI={10.1016/j.it.2003.11.006}, abstractNote={Among members of the Ig superfamily (IgSF), antigen receptors have the unique capacity to rearrange their variable domains, thereby creating an extensive repertoire for antigen recognition. It is assumed that antigen receptors evolved from a non-rearranging IgSF member by insertion of a transposable element. Although the nature of this predecessor is unknown, two multigene families of innate immune receptors that bear a close structural resemblance to antigen receptor chains have been identified in mammals and bony fish, respectively: signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs). Members of both families encode V-set Ig domains with a typical antigen receptor-like joining (J) motif and possess the potential to signal through immunoreceptor tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize MHC molecules, SIRP members regulate immune function by interaction with broadly expressed 'self' ligands. We propose the existence of an evolutionary and functional link between innate and adaptive immune receptors that sheds light on the nature of the antigen receptor predecessor(s).}, number={1}, journal={Trends in Immunology}, author={Van Den Berg, T.K. and Yoder, J.A. and Litman, G.W.}, year={2004}, pages={11–16} } @article{berg_yoder_litman_2004, title={On the origins of adaptive immunity:possible clues from the SIRP and NITR multigene families}, volume={25}, journal={Trends in Immunology}, author={Berg, T. K. and Yoder, J. A. and Litman, G. W.}, year={2004}, pages={11–16} } @article{yoder_litman_mueller_desai_dobrinski_montgomery_buzzeo_ota_amemiya_trede_et al._2004, title={Resolution of the novel immune-type receptor gene cluster in zebrafish}, volume={101}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0405242101}, DOI={10.1073/pnas.0405242101}, abstractNote={The novel immune-type receptor (NITR) genes encode a unique multigene family of leukocyte regulatory receptors, which possess an extracellular Ig variable (V) domain and may function in innate immunity. Artificial chromosomes that encode zebrafish NITRs have been assembled into a contig spanning ≈350 kb. Resolution of the complete NITR gene cluster has led to the identification of eight previously undescribed families of NITRs and has revealed the presence of C-type lectins within the locus. A maximum haplotype of 36 NITR genes (138 gene sequences in total) can be grouped into 12 distinct families, including inhibitory and activating receptors. An extreme level of interindividual heterozygosity is reflected in allelic polymorphisms, haplotype variation, and family-specific isoform complexity. In addition, the exceptional diversity of NITR sequences among species suggests divergent evolution of this multigene family with a birth-and-death process of member genes. High-confidence modeling of Nitr V-domain structures reveals a significant shift in the spatial orientation of the Ig fold, in the region of highest interfamily variation, compared with Ig V domains. These studies resolve a complete immune gene cluster in zebrafish and indicate that the NITRs represent the most complex family of activating/inhibitory surface receptors thus far described.}, number={44}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yoder, J. A. and Litman, R. T. and Mueller, M. G. and Desai, S. and Dobrinski, K. P. and Montgomery, J. S. and Buzzeo, M. P. and Ota, T. and Amemiya, C. T. and Trede, N. S. and et al.}, year={2004}, month={Oct}, pages={15706–15711} } @article{litman_yoder_cannon_haire_2003, title={Novel Immune-type Receptor Genes and the Origins of Adaptive and Innate Immune Recognition}, volume={43}, ISSN={1540-7063 1557-7023}, url={http://dx.doi.org/10.1093/icb/43.2.331}, DOI={10.1093/icb/43.2.331}, abstractNote={Abstract The prototypic forms of teleost novel immune-type receptors (NITRs) consist of a variable (V) region, a unique V-like C2 (V/C2) domain, a transmembrane region and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibition motifs (ITIMs). NITRs encode diversified V regions in large multigene families but do not undergo somatic rearrangement. Studies in four different bony fish model systems have identified a number of different organizational forms of NITRs. Specifically, NITR genes encode N-terminal ectodomains of the V-type but otherwise vary in the: total number of extracellular immunoglobulin domains, number and location of joining (J) region-like motifs, presence of transmembrane regions, presence of charged residues within transmembrane regions, presence of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails. V region-containing NITRs constitute a far more complex family than recognized originally and currently include individual members that potentially function through inhibitory as well as activating mechanisms. The genomic organization of the NITR gene cluster as well as the structural diversity and overall architecture of the NITR proteins is reminiscent of genes encoded at the mammalian leukocyte receptor cluster (LRC); however, there presently is no functional evidence to support an orthologous relationship between NITR and LRC gene products. Comparisons of the predicted structures of the NITRs have identified several short regions of sequence identity and a novel cloning strategy has been devised that selects for secretory and transmembrane proteins that encode these short motifs. Using this approach, related genes termed immune-type receptors (ITRs) have been identified in cartilaginous fish. Taken together, these studies indicate that leukocyte regulatory receptors, including those that mediate natural killer function, might have emerged early in vertebrate evolution and that the NITR/ITR genes represent a new and potentially highly significant link between innate and adaptive immune responses.}, number={2}, journal={Integrative and Comparative Biology}, publisher={Oxford University Press (OUP)}, author={Litman, G.W. and Yoder, J.A. and Cannon, J.P. and Haire, R.N.}, year={2003}, month={Apr}, pages={331–337} } @article{traver_herbomel_patton_murphey_yoder_litman_catic_amemiya_leonard_trede_et al._2003, title={The Zebrafish as a Model Organism to Study Development of the Immune System}, volume={81}, DOI={10.1016/s0065-2776(03)81007-6}, abstractNote={Early events in the development of the primitive and definitive blood forming system are still poorly understood. Additionally, the specification of both B and T cells occurs during embryogenesis and, given the completion of this process before birth, are difficult to study in mammals by forward genetics. Historically, the major strength of the zebrafish has been the opportunity it offered to carry forward genetic screens in a vertebrate organism in a relatively restricted space. Establishing the zebrafish as a model system for the study of the immune system will provide an alternative and complementary tool to the use of forward genetic screens in mice. Rapid advances in a variety of fields have allowed the zebrafish to become a more versatile tool for immunology.}, journal={Advances in Immunology}, publisher={Elsevier BV}, author={TRAVER, DAVID and HERBOMEL, PHILIPPE and PATTON, E.ELIZABETH and MURPHEY, RYAN D. and Yoder, Jeffrey and LITMAN, GARY W. and CATIC, ANDRÉ and AMEMIYA, CHRIS T. and LEONARD, I. ZON and TREDE, NIKOLAUS S. and et al.}, year={2003}, pages={254–330} } @article{yoder_hawke_eason_mueller_davids_gillin_litman_2002, title={BIVM, a Novel Gene Widely Distributed among Deuterostomes, Shares a Core Sequence with an Unusual Gene in Giardia lamblia}, volume={79}, ISSN={0888-7543}, url={http://dx.doi.org/10.1006/geno.2002.6768}, DOI={10.1006/geno.2002.6768}, abstractNote={A novel gene, BIVM (for basic, immunoglobulin-like variable motif-containing), has been identified using an electronic search based on the conservation of short sequence motifs within the variable region of immunoglobulin (Ig) genes. BIVM maps to human chromosome 13q32-q33 and is predicted to encode a 503-amino-acid protein with a pI of 9.1. The 5' untranslated region of BIVM is encoded in two exons; the coding portion is encoded in nine exons. BIVM is tightly linked (41 bp) and in the opposite transcriptional orientation to MGC5302 (also known as KDEL1 and EP58) in human. The ubiquitous expression of BIVM in normal tissues and the presence of a 5' CpG island suggest that BIVM is a housekeeping gene. Characterization of BIVM in representative species demonstrates significant conservation throughout deuterostomes; no sequence with significant identity to BIVM has been detected in proteostomes. However, an unusual gene has been identified in the protozoan pathogen Giardia lamblia that is similar to the core sequence of BIVM, suggesting the possibility of a horizontal gene transfer.}, number={6}, journal={Genomics}, publisher={Elsevier BV}, author={Yoder, Jeffrey A. and Hawke, Noel A. and Eason, Donna D. and Mueller, M.Gail and Davids, Barbara J. and Gillin, Frances D. and Litman, Gary W.}, year={2002}, month={Jun}, pages={750–755} } @article{yoder_mueller_nichols_ristow_thorgaard_ota_litman_2002, title={Cloning novel immune-type inhibitory receptors from the rainbow trout, Oncorhynchus mykiss}, volume={54}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-002-0511-3}, DOI={10.1007/s00251-002-0511-3}, number={9}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Yoder, Jeffrey and Mueller, Gail and Nichols, Krista and Ristow, Sandra and Thorgaard, Gary and Ota, Tatsuya and Litman, Gary}, year={2002}, month={Dec}, pages={662–670} } @misc{yoder_nielsen_amemiya_litman_2002, title={Zebrafish as an immunological model system}, volume={4}, ISSN={["1769-714X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036861294&partnerID=MN8TOARS}, DOI={10.1016/S1286-4579(02)00029-1}, abstractNote={Two decades of research have established the zebrafish (Danio rerio) as a significant model system for studying vertebrate development and gene structure-function relationships. Recent advances in mutation screening, the creation of genomic resources, including the Zebrafish Genome Project and the development of efficient transgenesis procedures, make this model increasingly attractive for immunological study.}, number={14}, journal={MICROBES AND INFECTION}, publisher={Elsevier BV}, author={Yoder, JA and Nielsen, ME and Amemiya, CT and Litman, GW}, year={2002}, month={Nov}, pages={1469–1478} } @article{mhanni_yoder_dubesky_mcgowan_2001, title={Cloning and sequence analysis of a zebrafish cDNA encoding DNA (cytosine-5)-methyltransferase-1}, volume={30}, ISSN={["1526-968X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034861153&partnerID=MN8TOARS}, DOI={10.1002/gene.1067}, abstractNote={Abstract}, number={4}, journal={GENESIS}, author={Mhanni, AA and Yoder, JA and Dubesky, C and McGowan, RA}, year={2001}, month={Aug}, pages={213–219} } @article{yoder_litman_2001, title={Corrigendum to: “The zebrafish fth1, slc3a2, men1, pc, fgf3 and cycd1 genes define two regions of conserved synteny between linkage group 7 and human chromosome 11q13” [Gene 261 (2000) 235–242]}, volume={269}, DOI={10.1016/s0378-1119(01)00443-7}, number={1-2}, journal={Gene}, publisher={Elsevier BV}, author={Yoder, Jeffrey A and Litman, Gary W}, year={2001}, month={May}, pages={227} } @article{hawke_yoder_haire_mueller_litman_miracle_stuge_shen_miller_litman_et al._2001, title={Extraordinary variation in a diversified family of immune-type receptor genes}, volume={98}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.231418598}, DOI={10.1073/pnas.231418598}, abstractNote={Immune inhibitory receptor genes that encode a variable (V) region, a unique V-like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in two lineages of bony fish. In the present study, eleven related genes encoding distinct structural forms have been identified inIctalurus punctatus(channel catfish), a well characterized immunological model system that represents a third independent bony fish lineage. Each of the different genes encodes an N-terminal V region but differs in the number of extracellular Ig domains, number and location of joining (J) region-like motifs, presence of transmembrane regions, presence of charged residues in transmembrane regions, presence of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails. Variation in the numbers of genomic copies of the different gene types, their patterns of expression, and relative levels of expression in mixed leukocyte cultures (MLC) is reported. V region-containing immune-type genes constitute a far more complex family than recognized originally and include individual members that might function in inhibitory or, potentially activatory manners.}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hawke, N.A. and Yoder, Jeffrey and Haire, R.N. and Mueller, M.G. and Litman, R.T. and Miracle, A.L. and Stuge, T. and Shen, L. and Miller, N. and Litman, G.W. and et al.}, year={2001}, month={Nov}, pages={13832–13837} } @article{yoder_mueller_wei_corliss_prather_willis_litman_djeu_litman_2001, title={Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster}, volume={98}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.121101598}, DOI={10.1073/pnas.121101598}, abstractNote={ An extensive, highly diversified multigene family of novel immune-type receptor ( nitr ) genes has been defined in Danio rerio (zebrafish). The genes are predicted to encode type I transmembrane glycoproteins consisting of extracellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid panel mapping and analysis of a deletion mutant line (b240) indicate that a minimum of ≈40 nitr genes are contiguous in the genome and span ≈0.6 Mb near the top of zebrafish linkage group 7. One flanking region of the nitr gene complex shares conserved synteny with a region of mouse chromosome 7, which shares conserved synteny with human 19q13.3-q13.4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinking of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is triggered by natural killer-sensitive tumor target cells. Nitrs likely represent intermediates in the evolution of the leukocyte receptor cluster. }, number={12}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yoder, J. A. and Mueller, M. G. and Wei, S. and Corliss, B. C. and Prather, D. M. and Willis, T. and Litman, R. T. and Djeu, J. Y. and Litman, G. W.}, year={2001}, month={May}, pages={6771–6776} } @misc{litman_hawke_yoder_2001, title={Novel immune-type receptor genes}, volume={181}, ISSN={["0105-2896"]}, DOI={10.1034/j.1600-065X.2001.1810121.x}, abstractNote={Summary: Novel immune‐type receptor (NITR) genes, which initially were identified in the Southern pufferfish (Spheroides nephelus), encode products which consist of an extracellular variable (V) and V‐like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail, which typically possesses an immunoreceptor tyrosine‐based inhibition motif (ITIM). Multiple NITR genes have been identified in close, contiguous chromosomal linkage. The V regions of NITRs resemble prototypic forms defined for immunoglobulin (Ig) and T‐cell antigen receptor (TCR), are present in multiple families and exhibit regionalized variation in sequence, which also occurs in Ig and TCR. Comparisons of exons encoding transmembrane and cytoplasmic regions of multiple NITRs suggest that exon shuffling has factored in the diversification of the NITR gene complex. Zebrafish (Danio rerio) NITRs exhibit many of these characteristics. NITRs that have been identified in additional species of bony fish demonstrate additional variation in the number of extracellular domains as well as in the presence of intramembranous charged residues, cytoplasmic tails and ITIMs. The presence in NITRs of V regions that are related closely to those found in Ig and TCR, as well as regulatory motifs and other structural features that are characteristic of immune inhibitory receptors encoded at the leukocyte receptor cluster, suggests that the NITRs are representative of an integral stage in the evolution of innate and adaptive immune function.}, number={1}, journal={IMMUNOLOGICAL REVIEWS}, publisher={Wiley-Blackwell}, author={Litman, GW and Hawke, NA and Yoder, JA}, year={2001}, month={Jun}, pages={250–259} } @article{dong_yoder_zhang_zhou_bestor_cheng_2001, title={Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA}, volume={29}, ISSN={1362-4962}, url={http://dx.doi.org/10.1093/nar/29.2.439}, DOI={10.1093/nar/29.2.439}, abstractNote={DNMT2 is a human protein that displays strong sequence similarities to DNA (cytosine-5)-methyltransferases (m(5)C MTases) of both prokaryotes and eukaryotes. DNMT2 contains all 10 sequence motifs that are conserved among m(5)C MTases, including the consensus S:-adenosyl-L-methionine-binding motifs and the active site ProCys dipeptide. DNMT2 has close homologs in plants, insects and Schizosaccharomyces pombe, but no related sequence can be found in the genomes of Saccharomyces cerevisiae or Caenorhabditis elegans. The crystal structure of a deletion mutant of DNMT2 complexed with S-adenosyl-L-homocysteine (AdoHcy) has been determined at 1.8 A resolution. The structure of the large domain that contains the sequence motifs involved in catalysis is remarkably similar to that of M.HHAI, a confirmed bacterial m(5)C MTase, and the smaller target recognition domains of DNMT2 and M.HHAI are also closely related in overall structure. The small domain of DNMT2 contains three short helices that are not present in M.HHAI. DNMT2 binds AdoHcy in the same conformation as confirmed m(5)C MTases and, while DNMT2 shares all sequence and structural features with m(5)C MTases, it has failed to demonstrate detectable transmethylase activity. We show here that homologs of DNMT2, which are present in some organisms that are not known to methylate their genomes, contain a specific target-recognizing sequence motif including an invariant CysPheThr tripeptide. DNMT2 binds DNA to form a denaturant-resistant complex in vitro. While the biological function of DNMT2 is not yet known, the strong binding to DNA suggests that DNMT2 may mark specific sequences in the genome by binding to DNA through the specific target-recognizing motif.}, number={2}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Dong, A. and Yoder, J.A. and Zhang, X. and Zhou, L. and Bestor, T.H. and Cheng, X.}, year={2001}, month={Jan}, pages={439–448} } @inbook{yoder_litman_2000, title={Immune-Type Diversity in the Absence of Somatic Rearrangement}, volume={248}, url={http://dx.doi.org/10.1007/978-3-642-59674-2_12}, DOI={10.1007/978-3-642-59674-2_12}, abstractNote={The rearrangement and joining of segmental elements during the differentiation of B and T lymphocytes in apparently all jawed vertebrate species results in the primary diversification of the immune receptor genes encoding both immunoglobulin (Ig) and T cell antigen receptor (TCR) genes. Although an extraordinary degree of interspecific variation in both numbers of recombining elements and mechanisms of secondary diversification of rearranged Ig genes has been described throughout vertebrate phylogeny, the basic mechanisms involved in the somatic rearrangement of individual gene segments have been intensely conserved. Recent studies of the recombination process (reviewed in Grawunder et al. 1998) and the enzymatic machinery that catalyzes DNA-mediated genetic rearrangement events have resulted in an increasingly clearer understanding of not only this highly complex process but also of the probable origin of the rearrangement mechanism itself (Agrawal et al. 1998; Hiom et al. 1998).}, booktitle={Current Topics in Microbiology and Immunology}, author={Yoder, Jeffrey and Litman, G. W.}, year={2000}, pages={271–282} } @article{yoder_litman_2000, title={The zebrafish fth1, slc3a2, men1, pc, fgf3 and cycd1 genes define two regions of conserved synteny between linkage group 7 and human chromosome 11q13}, volume={261}, ISSN={["0378-1119"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034739814&partnerID=MN8TOARS}, DOI={10.1016/S0378-1119(00)00503-5}, abstractNote={In addition to being an excellent model system for studying vertebrate development, the zebrafish has become a great tool for gene discovery by mutational analysis. The recent availability of the zebrafish EST database and radiation hybrid mapping panels has dramatically expanded the framework for genomic research in this species. Developing comparative maps of the zebrafish and human genomes is of particular importance for zebrafish mutagenesis studies in which human orthologs are sought for zebrafish genes. However, only partial cDNA sequences are determined routinely for mapped ESTs, leaving the identity of the EST in question. It previously had been reported that zebrafish linkage group 7 shares conserved synteny with human chromosome 11q13. In an effort to further define this relationship, five full-length zebrafish cDNAs, fth1, slc3a2, prkri, cd81, and pc, as well as one putative human gene, DBX were identified and their map positions ascertained. These six genes, along with men1, fgf3 and cycd1 define two regions of conserved synteny between linkage group 7 and 11q13.}, number={2}, journal={GENE}, publisher={Elsevier BV}, author={Yoder, JA and Litman, GW}, year={2000}, month={Dec}, pages={235–242} } @article{yoder_haire_litman_1999, title={Cloning of two zebrafish cDNAs that share domains with the MHC class II-associated invariant chain}, volume={50}, ISSN={["0093-7711"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032842615&partnerID=MN8TOARS}, DOI={10.1007/s002510050691}, number={1-2}, journal={IMMUNOGENETICS}, author={Yoder, JA and Haire, RN and Litman, GW}, year={1999}, month={Oct}, pages={84–88} } @article{hawke_yoder_litman_1999, title={Expanding our understanding of immunoglobulin, T-cell antigen receptor, and novel immune-type receptor genes: A subset of the immunoglobulin gene superfamily}, volume={50}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033380849&partnerID=MN8TOARS}, number={3-4}, journal={Immunogenetics}, author={Hawke, N.A. and Yoder, J.A. and Litman, G.W.}, year={1999}, pages={124–133} } @misc{hawke_yoder_litman_1999, title={Expanding our understanding of immunoglobulin, T-cell antigen receptor, and novel immune-type receptor genes: a subset of the immunoglobulin gene superfamily}, volume={50}, ISSN={["1432-1211"]}, DOI={10.1007/s002510050588}, abstractNote={The immunoglobulin superfamily (IgSF) is an extensively diversified multigene family whose members share a common structural feature, the Ig fold. Members of the Ig/T-cell antigen receptor (TCR) subset of the IgSF mediate antigen-specific recognition in adaptive immune responses. Antigen-binding receptors belonging to this subset are present in all species of jawed vertebrates. To explore whether there are additional structurally related but otherwise distinct members of this subset, we have developed a technique termed the short-primer polymerase chain reaction (PCR) that targets structurally conserved short motifs in the Ig fold. Large-scale sequencing efforts and recent advances in information biotechnology, including "electronic PCR," provide additional computational means to implement similarly directed searches within databases. The use of these approaches has led to the discoveries of Ig/TCR homologues in a variety of phylogenetically diverse organisms, a diversified family of novel immune-type receptor genes, as well as a novel human IgSF member. The potential of random sequencing efforts and virtual screening of databases is described in the context of two novel genes in bony fish. The various methodologies that are discussed and the examples shown provide means for further investigating, and/or elucidating novel, IgSF receptors as well as components of pathways that are involved in immune responses in both traditional and nontraditional model systems.}, number={3-4}, journal={IMMUNOGENETICS}, author={Hawke, NA and Yoder, JA and Litman, GW}, year={1999}, month={Nov}, pages={124–133} } @article{yoder_bestor_1998, title={A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast}, volume={7}, ISSN={1460-2083}, url={http://dx.doi.org/10.1093/hmg/7.2.279}, DOI={10.1093/hmg/7.2.279}, abstractNote={Trace levels of 5-methylcytosine persist in the DNA of mouse embryonic stem cells that are homozygous for null mutations in Dnmt1 , the gene for the one previously recognized metazoan DNA methyltransferase. This residual 5-methylcytosine may be the product of a candidate second DNA methyltransferase, Dnmt2, that has now been identified in human and mouse. Dnmt2 contains all the sequence motifs diagnostic of DNA (cytosine-5)-methyltransferases but appears to lack the large N-terminal regulatory domain common to other eukaryotic methyltransferases. Dnmt2 is more similar to a putative DNA methyltransferase of the fission yeast Schizosaccharomyces pombe than to Dnmt1. Dnmt2 produces multiple mRNA species that are present at low levels in all tissues of human and mouse and is not restricted to those cell types known to be active in de novo methylation. The human DNMT2 gene was mapped to chromosome 10p12-10p14 in a panel of radiation hybrids. Dnmt2 is a candidate for the activity that methylates newly integrated retroviral DNA and maintains trace levels of 5-methylcytosine in the DNA of embryonic stem cells homozygous for null mutations in Dnmt1.}, number={2}, journal={Human Molecular Genetics}, publisher={Oxford University Press (OUP)}, author={Yoder, J.A. and Bestor, T.H.}, year={1998}, month={Feb}, pages={279–284} } @article{mertineit_yoder_taketo_laird_trasler_bestor_1998, title={Sex-specific exons control DNA methyltransferase in mammalian germ cells}, volume={125}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031889033&partnerID=MN8TOARS}, number={5}, journal={Development}, author={Mertineit, C. and Yoder, J.A. and Taketo, T. and Laird, D.W. and Trasler, J.M. and Bestor, T.H.}, year={1998}, pages={889–897} } @misc{yoder_walsh_bestor_1997, title={Cytosine methylation and the ecology of intragenomic parasites}, volume={13}, ISSN={["1362-4555"]}, DOI={10.1016/S0168-9525(97)01181-5}, abstractNote={Most of the 5-methylcytosine in mammalian DNA resides in transposons, which are specialized intragenomic parasites that represent at least 35% of the genome. Transposon promoters are inactive when methylated and, over time, C-->T transition mutations at methylated sites destroy many transposons. Apart from that subset of genes subject to X inactivation and genomic imprinting, no cellular gene in a non-expressing tissue has been proven to be methylated in a pattern that prevents transcription. It has become increasingly difficult to hold that reversible promoter methylation is commonly involved in developmental gene control; instead, suppression of parasitic sequence elements appears to be the primary function of cytosine methylation, with crucial secondary roles in allele-specific gene expression as seen in X inactivation and genomic imprinting.}, number={8}, journal={TRENDS IN GENETICS}, publisher={Elsevier BV}, author={Yoder, JA and Walsh, CP and Bestor, TH}, year={1997}, month={Aug}, pages={335–340} } @article{yoder_soman_verdine_bestor_1997, title={DNA (cytosine-5)-methyltransferases in mouse cells and tissues. studies with a mechanism-based probe}, volume={270}, ISSN={0022-2836}, url={http://dx.doi.org/10.1006/jmbi.1997.1125}, DOI={10.1006/jmbi.1997.1125}, abstractNote={The mechanisms that establish and maintain methylation patterns in the mammalian genome are very poorly understood, even though perturbations of methylation patterns lead to a loss of genomic imprinting, ectopic X chromosome inactivation, and death of mammalian embryos. A family of sequence-specific DNA methyltransferases has been proposed to be responsible for the wave of de novo methylation that occurs in the early embryo, although no such enzyme has been identified. A universal mechanism-based probe for DNA (cytosine-5)-methyltransferases was used to screen tissues and cell types known to be active in de novo methylation for new species of DNA methyltransferase. All identifiable de novo methyltransferase activity was found to reside in Dnmt1. As this enzyme is the predominant de novo methyltransferase at all developmental stages inspected, it does not fit the definition of maintenance methyltransferase or hemimethylase. Recent genetic data indicate that de novo methylation of retroviral DNA in embryonic stem cells is likely to involve one or more additional DNA methyltransferases. Such enzymes were not detected and are either present in very small amounts or are very different from Dnmt1. A new method was developed and used to determine the sequence specificity of intact Dnmt1 in whole-cell lysates. Specificity was found to be confined to the sequence 5'-CpG-3'; there was little dependence on sequence context or density of CpG dinucleotides. These data suggest that any sequence-specific de novo methylation mediated by Dnmt1 is either under the control of regulatory factors that interact with Dnmt1, or is cued by alternative secondary structures in DNA.}, number={3}, journal={Journal of Molecular Biology}, publisher={Elsevier BV}, author={Yoder, Jeffrey A. and Soman, Neilesh S. and Verdine, Gregory L. and Bestor, Timothy H.}, year={1997}, month={Jul}, pages={385–395} } @article{yoder_bestor_1996, title={Genetic analysis of genomic methylation patterns in plants and mammals}, volume={377}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029998065&partnerID=MN8TOARS}, number={10}, journal={Biological Chemistry}, author={Yoder, J.A. and Bestor, T.H.}, year={1996}, pages={605–610} } @article{yoder_chiu yen_vertino_bestor_baylin_1996, title={New 5′ Regions of the Murine and Human Genes for DNA (Cytosine-5)-methyltransferase}, volume={271}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/jbc.271.49.31092}, DOI={10.1074/jbc.271.49.31092}, abstractNote={DNA (cytosine-5)-methyltransferases (EC 2.1.1.37) maintain patterns of methylated cytosine residues in the mammalian genome; faithful maintenance of methylation patterns is required for normal development of mice, and aberrant methylation patterns are associated with certain human tumors and developmental abnormalities. The organization of coding sequences at the 5′-end of the murine and human DNA methyltransferase genes was investigated, and the DNA methyltransferase open reading frame was found to be longer than previously suspected. Expression of the complete open reading frame by in vitro transcription-translation and by transfection of expression constructs into COS7 cells resulted in the production of an active DNA methyltransferase of the same apparent mass as the endogenous protein, while translation from the second in-frame ATG codon produced a slightly smaller but fully active protein. Characterization of mRNA 5′ sequences and the intron-exon structure of the 5′ region of the murine and human genes indicated that a previously described promoter element (Rouleau, J., Tanigawa, G., and Szyf, M. (1992) J. Biol. Chem. 267, 7368-7377) actually lies in an intron that is more than 5 kilobases downstream of the transcription start sites.}, number={49}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Yoder, Jeffrey A. and Chiu Yen, Ray-Whay and Vertino, Paula M. and Bestor, Timothy H. and Baylin, Stephen B.}, year={1996}, month={Dec}, pages={31092–31097} } @article{mckinnon_weaver_yoder_fairbanks_wolf_1991, title={Cross-linking a maturation-dependent ram sperm plasma membrane antigen induces the acrosome reaction}, volume={29}, ISSN={1040-452X 1098-2795}, url={http://dx.doi.org/10.1002/mrd.1080290216}, DOI={10.1002/mrd.1080290216}, abstractNote={Abstract}, number={2}, journal={Molecular Reproduction and Development}, publisher={Wiley}, author={McKinnon, Christine A. and Weaver, Frances E. and Yoder, Jeffrey A. and Fairbanks, Grant and Wolf, David E.}, year={1991}, month={Jun}, pages={200–207} }