@article{walker_harden_suyemoto_thakur_jacob_borst_2023, title={Draft Genome Sequences of Escherichia coli and Enterococcus faecalis Coisolated from Polymicrobial Extraintestinal Infections of Chickens and Turkeys}, volume={2}, ISSN={["2576-098X"]}, DOI={10.1128/mra.01163-22}, abstractNote={Coinfections by avian pathogenic Escherichia coli (APEC) and Enterococcus faecalis in poultry with colisepticemia have become increasingly recognized. Here, we report draft genome sequences of 18 APEC and 18 E. faecalis strains coisolated from lesions of diseased poultry.}, journal={MICROBIOLOGY RESOURCE ANNOUNCEMENTS}, author={Walker, Grayson K. and Harden, Lyndy and Suyemoto, M. Mitsu and Thakur, Siddhartha and Jacob, Megan and Borst, Luke B.}, year={2023}, month={Feb} }
 @article{sper_proctor_lascina_guo_polkoff_kaeser_simpson_borst_gleason_zhang_et al._2022, title={Allogeneic and xenogeneic lymphoid reconstitution in a RAG2(-/-)IL2RG(y/-) severe combined immunodeficient pig: A preclinical model for intrauterine hematopoietic transplantation}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.965316}, abstractNote={Mice with severe combined immunodeficiency are commonly used as hosts of human cells. Size, longevity, and physiology, however, limit the extent to which immunodeficient mice can model human systems. To address these limitations, we generated RAG2 −/− IL2RG y /− immunodeficient pigs and demonstrate successful engraftment of SLA mismatched allogeneic D42 fetal liver cells, tagged with pH2B-eGFP, and human CD34 + hematopoietic stem cells after in utero cell transplantation. Following intrauterine injection at day 42–45 of gestation, fetuses were allowed to gestate to term and analyzed postnatally for the presence of pig (allogeneic) and human (xenogeneic) B cells, T -cells and NK cells in peripheral blood and other lymphoid tissues. Engraftment of allogeneic hematopoietic cells was detected based on co-expression of pH2B-eGFP and various markers of differentiation. Analysis of spleen revealed robust generation and engraftment of pH2B-eGFP mature B cells (and IgH recombination) and mature T -cells ( and TCR- β recombination), T helper (CD3 + CD4 + ) and T cytotoxic (CD3 + CD8 + ) cells. The thymus revealed engraftment of pH2B-eGFP double negative precursors (CD4 − CD8 − ) as well as double positive (CD4 + , CD8 + ) precursors and single positive T -cells. After intrauterine administration of human CD34 + hematopoietic stem cells, analysis of peripheral blood and lymphoid tissues revealed the presence of human T -cells (CD3 + CD4 + and CD3 + CD8 + ) but no detectable B cells or NK cells. The frequency of human CD45 + cells in the circulation decreased rapidly and were undetectable within 2 weeks of age. The frequency of human CD45 + cells in the spleen also decreased rapidly, becoming undetectable at 3 weeks. In contrast, human CD45 + CD3 + T -cells comprised >70% of cells in the pig thymus at birth and persisted at the same frequency at 3 weeks. Most human CD3 + cells in the pig's thymus expressed CD4 or CD8, but few cells were double positive (CD4 + CD8 + ). In addition, human CD3 + cells in the pig thymus contained human T -cell excision circles (TREC), suggesting de novo development. Our data shows that the pig thymus provides a microenvironment conducive to engraftment, survival and development of human T -cells and provide evidence that the developing T -cell compartment can be populated to a significant extent by human cells in large animals.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Sper, Renan B. and Proctor, Jessica and Lascina, Odessa and Guo, Ling and Polkoff, Kathryn and Kaeser, Tobias and Simpson, Sean and Borst, Luke and Gleason, Katherine and Zhang, Xia and et al.}, year={2022}, month={Oct} }
 @article{downey_mathews_borst_2022, title={Cranial internal hemipelvectomy (iliectomy) with limb sparing for a dog with ilial chondrosarcoma: A case report}, volume={10}, ISSN={["2050-0904"]}, DOI={10.1002/ccr3.5262}, abstractNote={Cranial internal hemipelvectomy can be successful for excision of ilial CSA with minimal complications. Iliectomy with adjuvant radiation therapy was well tolerated in a dog with grade II ilial CSA. The dog survived 1,271 days postoperatively and supposedly succumbed to a disease process unrelated to the CSA.}, number={1}, journal={CLINICAL CASE REPORTS}, author={Downey, Amy C. and Mathews, Kyle G. and Borst, Luke}, year={2022}, month={Jan} }
 @article{vlaming_mathews_hash_keenihan_sommer_borst_vaden_2022, title={Creation of a Continent Urinary Bladder Reservoir Vascularized by Omentum as a Possible Surgical Option for Canine Trigonal/Urethral Urothelial Carcinoma}, volume={35}, ISSN={["1521-0553"]}, DOI={10.1080/08941939.2020.1864797}, abstractNote={Surgical procedures that maintain continence with minimal complication following resection of trigono-urethral urothelial carcinoma (UC) are limited in canines; therefore, palliative options are often pursued. A feasible tumor resection option may improve disease control and survival. The study’s objective was to evaluate a continent urine reservoir created from the urinary bladder body and vascularized solely by omentum. We hypothesized that a viable urine reservoir could be created, and staged omentalization would provide improved vascularity. Nine normal female Beagles were randomized to one of three groups. Group A urinary bladders were transected cranial to the ureteral papillae to create a closed bladder vesicle which was concomitantly omentalized. Group B underwent omentalization two weeks prior to vesicle creation. Based on Group A and B results, Group C underwent neoureterocystostomy and omentalization followed by neoreservoir formation and tube cystostomy 2 weeks later. Serial ultrasounds and histopathology confirmed adequate omental neovascularization in Groups B and C with continent Group C neoreservoirs maintained for 2 months. Some pylectasia and ureteral dilation was documented in all Group C dogs at variable timepoints. Progressive hydroureteronephrosis developed in 2/6 kidneys. Transient azotemia was noted in only 1 Group C dog, although all developed treatable urinary tract infections. The sample size is limited, and the efficacy of this technique in providing disease control for UC is unknown. However, this novel option could allow for primary UC resection while providing continence and limiting complications. Postoperative local or systemic adjuvant therapy, ultrasonographic neoreservoir monitoring, and BRAF analysis would be indicated.}, number={3}, journal={JOURNAL OF INVESTIGATIVE SURGERY}, author={Vlaming, Annemarieke and Mathews, Kyle G. and Hash, Jonathan A. and Keenihan, Erin K. and Sommer, Samantha and Borst, Luke and Vaden, Shelly L.}, year={2022}, month={Feb}, pages={481–495} }
 @article{walker_yustyniuk_shamoun_jacob_correa_vaden_borst_2022, title={Detection of Escherichia coli and Enterococcus spp. in dogs with polymicrobial urinary tract infections: A 5-year retrospective study}, volume={5}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16445}, abstractNote={Urinary tract infections (UTI) caused by Escherichia coli and Enterococcus spp., which are frequently coisolated in polymicrobial UTI, cause morbidity among dogs and warrant antimicrobial therapy.To evaluate clinical features of dogs with polymicrobial E. coli and Enterococcal UTI.Forty-four client-owned dogs with polymicrobial bacteriuria and groups of 100 client-owned dogs with E. coli and Enterococcal monomicrobial bacteriuria.Retrospective cohort study of medical records of dogs at a university teaching hospital from 2014 to 2019. Prevalence of recurrent UTI and isolate antimicrobial resistance were determined. Clinical outcomes of dogs with recurrent UTI from groups including cost and hospital visits were compared.Recurrent UTI was more prevalent (P = .05) in dogs with polymicrobial bacteriuria (57%, 95% confidence interval [95% CI]: 42%-70%) compared to the Enterococcal monomicrobial group (40%, 95% CI: 31%-50%). Escherichia coli from polymicrobial bacteriuria were more frequently resistant to doxycycline (P < .01, 43%, 95% CI: 29%-58%) and gentamicin (P = .03, 17%, 95% CI: 9%-31%) compared to E. coli from monomicrobial bacteriuria (17% and 5%, 95% CI: 11%-26% and 2%-11% for doxycycline and gentamicin, respectively). Dogs with recurrent UTI from the polymicrobial UTI group had significantly (P = .05) more hospital visits (mean = 6 visits, 95% CI: 1.7-9.8) compared to recurrent monomicrobial UTI dogs (mean = 4 and 3 visits, 95% CI: 1.0 to 4.4 and -0.7 to 7.7 for E. coli and Enterococcal monomicrobial UTI, respectively).Escherichia coli and Enterococcus spp. polymicrobial UTI had more frequent adverse clinical outcomes for dogs.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Walker, Grayson K. and Yustyniuk, Valeriia and Shamoun, John and Jacob, Megan E. and Correa, Maria and Vaden, Shelly L. and Borst, Luke B.}, year={2022}, month={May} }
 @article{bauer_murillo_schreeg_borst_watanabe_2022, title={Pathology in Practice}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.03.0119}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bauer, Katherine and Murillo, Daniel Felipe Barrantes and Schreeg, Megan E. and Borst, Luke B. and Watanabe, Tatiane Terumi Negrao}, year={2022}, month={Sep}, pages={1466–1468} }
 @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} }
 @article{walker_suyemoto_hull_gall_jimenez_chen_thakur_crespo_borst_2021, title={Genomic Characterization of a Nalidixic Acid-Resistant Salmonella Enteritidis Strain Causing Persistent Infections in Broiler Chickens}, volume={8}, ISSN={["2297-1769"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85115006803&partnerID=MN8TOARS}, DOI={10.3389/fvets.2021.725737}, abstractNote={Virulent strains of Salmonella enterica subsp. enterica serovar Enteritidis (SE) harbored by poultry can cause disease in poultry flocks and potentially result in human foodborne illness. Two broiler flocks grown a year apart on the same premises experienced mortality throughout the growing period due to septicemic disease caused by SE. Gross lesions predominantly consisted of polyserositis followed by yolk sacculitis, arthritis, osteomyelitis, and spondylitis. Tissues with lesions were cultured yielding 59 SE isolates. These were genotyped by Rep-PCR followed by whole-genome sequencing (WGS) of 15 isolates which were clonal. The strain, SE_TAU19, was further characterized for antimicrobial susceptibility and virulence in a broiler embryo lethality assay. SE_TAU19 was resistant to nalidixic acid and sulfadimethoxine and was virulent to embryos with 100% mortality of all challenged broiler embryos within 3.5 days. Screening the SE_TAU19 whole-genome sequence revealed seven antimicrobial resistance (AMR) genes, 120 virulence genes, and two IncF plasmid replicons corresponding to a single, serovar-specific pSEV virulence plasmid. The pef, spv, and rck virulence genes localized to the plasmid sequence assembly. We report phenotypic and genomic features of a virulent SE strain from persistently infected broiler flocks and present a workflow for SE characterization from isolate collection to genome assembly and sequence analysis. Further SE surveillance and investigation of SE virulence in broiler chickens is warranted.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Walker, Grayson K. K. and Suyemoto, M. Mitsu and Hull, Dawn M. M. and Gall, Sesny and Jimenez, Fernando and Chen, Laura R. R. and Thakur, Siddhartha and Crespo, Rocio and Borst, Luke B. B.}, year={2021}, month={Sep} }
 @article{bomba_sheets_valdivia_khagi_ruterbories_mariani_borst_tokarz_hingtgen_2021, title={Personalized-induced neural stem cell therapy: Generation, transplant, and safety in a large animal model}, volume={6}, ISSN={["2380-6761"]}, DOI={10.1002/btm2.10171}, abstractNote={In this study, we take an important step toward clinical translation by generating the first canine-induced neural stem cells (iNSCs). We explore key aspects of scale-up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation of fibroblasts, iNSCs are known to migrate through the brain, track down invasive cancer foci, and deliver anticancer payloads that significantly reduce tumor burden and extend survival of tumor-bearing mice. Here, skin biopsies were collected from canines and converted into the first personalized canine iNSCs engineered to carry TNFα-related apoptosis-inducing ligand (TRAIL) and thymidine kinase (TK), as well as magnetic resonance imaging (MRI) contrast agents for in vivo tracking. Time-lapse analysis showed canine iNSCs efficiently migrate to human tumor cells, and cell viability assays showed both TRAIL and TK monotherapy markedly reduced tumor growth. Using intraoperative navigation and two delivery methods to closely mimic human therapy, canines received autologous iNSCs either within postsurgical cavities in a biocompatible matrix or via a catheter placed in the lateral ventricle. Both strategies were well tolerated, and serial MRI showed hypointense regions at the implant sites that remained stable through 86 days postimplant. Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC-induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing.}, number={1}, journal={BIOENGINEERING & TRANSLATIONAL MEDICINE}, author={Bomba, Hunter N. and Sheets, Kevin T. and Valdivia, Alain and Khagi, Simon and Ruterbories, Laura and Mariani, Christopher L. and Borst, Luke B. and Tokarz, Debra A. and Hingtgen, Shawn D.}, year={2021}, month={Jan} }
 @article{beachler_gracz_morgan_bembenek bailey_borst_ellis_von dollen_lyle_nebel_andrews_et al._2021, title={Plasma metabolomic profiling of healthy pregnant mares and mares with experimentally induced placentitis}, volume={53}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13262}, abstractNote={Background Metabolomics may represent an avenue for diagnosis of equine ascending placentitis. Objectives To characterise the plasma metabolomic profile in healthy mares and mares with induced ascending placentitis, with the goal of identifying metabolites with potential clinical value for early diagnosis of placentitis. Study design Controlled in vivo experiment. Methods Placentitis was induced in 10 late-term pregnant pony mares via Streptococcal equi subsp. zooepidemicus inoculation in five mares between days 285 and 290 of gestation, while five mares served as healthy controls. Repeated ultrasound examinations and jugular venipuncture were performed to obtain combined thickness of the uterus and placenta (CTUP) and plasma for NMR spectroscopy. Mares with increased CTUP were diagnosed with placentitis and treated in accordance with published therapeutic recommendations. NMR metabolomic analysis was performed to identify and quantify plasma metabolites at each time point. Concentrations were compared using ANOVA with repeated-measures and PLS-DA analysis. Results Four hours post-inoculation, a significant increase was detected in the metabolites alanine, phenylalanine, histidine, pyruvate, citrate, glucose, creatine, glycolate, lactate and 3-hydroxyisobutyrate that returned to baseline by 12 hours. On day 4, a significant reduction in the metabolites alanine, phenylalanine, histidine, tyrosine, pyruvate, citrate, glycolate, lactate and dimethylsulfone was seen in infected mares compared with controls. Main limitations There were small numbers of mares within groups. In addition, this work compares healthy animals with animals treated with multimodal therapeutics following diagnosis of placentitis without an untreated cohort. Conclusions Two phases of metabolite changes were noted after experimental infection: An immediate rise in metabolite concentration involved in energy, nitrogen, hydrogen and oxygen metabolism within 4 hours after inoculation that was followed by a decrease in metabolite concentrations involved in energy and nitrogen metabolism at 4 days, coinciding with ultrasonographic diagnosis of placentitis.}, number={1}, journal={Equine Veterinary Journal}, author={Beachler, T.M. and Gracz, H.S. and Morgan, D.R. and Bembenek Bailey, S.A. and Borst, L. and Ellis, K.E. and Von Dollen, K.A. and Lyle, S.K. and Nebel, A.M. and Andrews, N.C. and et al.}, year={2021}, month={Jan}, pages={85–93} }
 @article{thomas_pontius_borst_breen_2020, title={Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers}, volume={7}, ISSN={["2306-7381"]}, DOI={10.3390/vetsci7030088}, abstractNote={The utility of the domestic cat as a model system for biomedical studies was constrained for many years by the absence of a comprehensive feline reference genome sequence assembly. While such a resource now exists, the cat continues to lag behind the domestic dog in terms of integration into the ‘One Health’ era of molecular medicine. Stimulated by the advances being made within the evolving field of comparative cancer genomics, we developed a microarray platform that allows rapid and sensitive detection of DNA copy number aberrations in feline tumors using comparative genomic hybridization analysis. The microarray comprises 110,456 unique oligonucleotide probes anchored at mean intervals of 22.6 kb throughout the feline reference genome sequence assembly, providing ~350-fold higher resolution than was previously possible using this technique. We demonstrate the utility of this resource through genomic profiling of a feline injection-site sarcoma case, revealing a highly disrupted profile of DNA copy number imbalance involving several key cancer-associated genes including KIT, TP53, PTEN, FAS and RB1. These findings were supported by targeted fluorescence in-situ hybridization analysis, which identified major alterations in chromosome structure, including complex intrachromosomal reorganization events typical of those seen in aggressive soft-tissue sarcomas of other species. We then characterized a second mass that was identified at a nearby site in the same patient almost 12 months later. This mass demonstrated a remarkably conserved genomic profile consistent with a recurrence of the original tumor; however the detection of subtle differences reflected evolution of the tumor over time. These findings exemplify the diverse potential of this microarray platform to incorporate domestic cat cancers into comparative and translational research efforts in molecular oncology.}, number={3}, journal={VETERINARY SCIENCES}, author={Thomas, Rachael and Pontius, Joan U. and Borst, Luke B. and Breen, Matthew}, year={2020}, month={Sep} }
 @article{walker_suyemoto_borst_brake_2020, title={Research Note: Repetitive element-based polymerase chain reaction genotyping improves efficiency of Salmonella surveillance in a model broiler production system}, volume={99}, ISSN={["1525-3171"]}, DOI={10.1016/j.psj.2019.12.048}, abstractNote={The genetic relatedness and antimicrobial susceptibility profiles of Salmonella isolated from poultry and their environment were determined. One broiler breeder flock (BBF1) and 2 broiler flocks (BF1 and BF2) were reared over a 1.75-year period on the same poultry research farm. Hatching eggs were obtained from BBF1 to produce BF1 chicks, while BF2 chicks were progeny of a separate, unsampled broiler breeder flock. BF1 and BF2 were reared in the same housing facilities but 6 mo apart. Salmonella isolates were collected via litter sock sampling (BF1), cecal excision (BF1 and BF2), or cloacal swabs (BBF1). Serotyping identified Salmonella enterica subsp. enterica serovar Altona (SA) in BBF1 and S. enterica subsp. enterica serovar Senftenberg (SS) in BF1 and BF2. Genotypic fingerprinting was achieved with Rep-PCR using the (GTG)5 primer and revealed sequence homology among Senftenberg isolates from BF1 and BF2. For each isolate, the minimum inhibitory concentration was determined for 27 antimicrobial agents using Sensititre plates with formularies specific to antimicrobials used in poultry production or those used to control gram negative pathogens. Isolates from the 3 flocks were resistant to clindamycin, erythromycin, novobiocin, penicillin, and tylosin tartrate and demonstrated intermediate resistance to azithromycin, florfenicol, and spectinomycin. These data demonstrated that serovar Altona and Senftenberg were harbored by poultry, the latter appeared to persist in broiler flocks, and both serotypes shared similar patterns of antimicrobial susceptibility in an integrated research operation. In the case of multiple Salmonella isolates, combining genotypic fingerprinting methods with serotyping of representative isolates would reduce the number of samples required for serotyping and more clearly identify relatedness of isolates. These methods facilitate effective surveillance in poultry production systems, thus allowing for implementation of precise Salmonella control measures.}, number={5}, journal={POULTRY SCIENCE}, author={Walker, G. K. and Suyemoto, M. M. and Borst, L. B. and Brake, J.}, year={2020}, month={May}, pages={2684–2689} }
 @article{walker_suyemoto_gall_chen_thakur_borst_2020, title={The role ofEnterococcus faecalisduring co-infection with avian pathogenicEscherichia coliin avian colibacillosis}, volume={49}, ISSN={["1465-3338"]}, url={http://dx.doi.org/10.1080/03079457.2020.1796926}, DOI={10.1080/03079457.2020.1796926}, abstractNote={Enterococcus spp. (ENT) are frequently co-isolated with avian pathogenic E. coli (APEC) from poultry with colibacillosis, a leading cause of flock mortality. Although largely overlooked, ENT may pl...}, number={6}, journal={AVIAN PATHOLOGY}, publisher={Informa UK Limited}, author={Walker, Grayson K. and Suyemoto, M. Mitsu and Gall, Sesny and Chen, Laura and Thakur, Siddhartha and Borst, Luke B.}, year={2020}, month={Nov}, pages={589–599} }
 @article{beachler_gracz_long_borst_morgan_nebel_andrews_koipillai_frable_bailey_et al._2019, title={Allantoic Metabolites, Progesterone, and Estradiol-17 beta Remain Unchanged After Infection in an Experimental Model of Equine Ascending Placentitis}, volume={73}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2018.11.014}, abstractNote={Abstract The objective of this study was to characterize the metabolomic profile of equine allantoic fluid in the pregnant mare with and without experimentally induced ascending placentitis with the goal of identifying biomarkers of this disease. We compared the onset of metabolomic changes with common modalities for diagnosis of ascending placentitis, including measurement of the combined thickness of the uterus and placenta (CTUP), hormonal profiling, and measurement of serum acute phase proteins. Ten pregnant pony mares were randomly divided into two groups: five healthy control mares (CONT) and five mares induced to develop ascending placentitis (PLAC) via inoculation with Streptococcus equi subsp. zooepidemicus bacteria at Days 280–285 of gestation. Allantoic fluid, whole blood, and serum were collected from both groups at 270–275 days of gestation and at the following time points postinoculation: 4 hours, Days 2, 4, 6, and 10. Differences between groups in identified metabolites, progesterone, estradiol-17β, lactate, and serum amyloid A (SAA) were assessed using an analysis of variance with repeated measures. A total of 27 metabolites were identified in allantoic fluid. No differences were detected between groups at any time point (P > .05) for any identified metabolite, progesterone, estradiol-17β, or lactate concentrations. Significant elevations in CTUP (P = .003) and SAA (P = .0001) were detected by Days 4 and 6 postinoculation, respectively. The results of this study established a database of equine allantoic fluid metabolites and confirmed the utility of uteroplacental ultrasound for detection of placentitis before the onset of hematologic changes.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Beachler, Theresa and Gracz, Hanna and Long, Nathan M. and Borst, Luke and Morgan, David and Nebel, Amber and Andrews, Natalie and Koipillai, Joanna and Frable, Samantha and Bailey, Stasia Bembenek and et al.}, year={2019}, month={Feb}, pages={95–105} }
 @article{beachler_gracz_long_borst_morgan_nebel_andrews_koipillai_frable_bailey_2019, title={Allantoic Metabolites, Progesterone, and Estradiol-17β Remain Unchanged After Infection in an Experimental Model of Equine Ascending Placentitis}, volume={2}, url={http://europepmc.org/abstract/AGR/IND606255595}, journal={Journal of equine veterinary science.}, author={Beachler, T and Gracz, Hanna and Long, Nathan M. and Borst, Luke and Morgan, David and Nebel, Amber and Andrews, Natalie and Koipillai, Joanna and Frable, Samantha and Bailey, Christopher Scott}, year={2019}, month={Feb} }
 @article{megquier_turner-maier_swofford_kim_sarver_wang_sakthikumar_johnson_koltookian_lewellen_et al._2019, title={Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma}, volume={17}, ISSN={["1557-3125"]}, DOI={10.1158/1541-7786.MCR-19-0221}, abstractNote={Abstract Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease. Implications: We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.}, number={12}, journal={MOLECULAR CANCER RESEARCH}, author={Megquier, Kate and Turner-Maier, Jason and Swofford, Ross and Kim, Jong-Hyuk and Sarver, Aaron L. and Wang, Chao and Sakthikumar, Sharadha and Johnson, Jeremy and Koltookian, Michele and Lewellen, Mitzi and et al.}, year={2019}, month={Dec}, pages={2410–2421} }
 @article{megquier_turner-maier_swofford_kim_sarver_wang_sakthikumar_johnson_koltookian_lewellen_et al._2019, title={Genomic analysis reveals shared genes and pathways in human and canine angiosarcoma}, url={http://europepmc.org/abstract/PPR/PPR72592}, DOI={10.1101/570879}, abstractNote={Abstract Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with high fatality and few effective treatment options. It is both rare and heterogenous, making large, well powered genomic studies nearly impossible. In dogs, angiosarcoma is common, with breeds like the golden retriever carrying heritable genetic factors that put them at very high risk. If the clinical similarity of canine and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine angiosarcoma via whole exome sequencing (47 golden retriever angiosarcomas) and RNA sequencing (74 angiosarcomas from multiple breeds). The predominant mutational signature was the age-associated deamination of cytosine to thymine, and somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). We compared the canine data to human data recently released by The Angiosarcoma Project, and found the same genes and many of the same pathways significantly enriched for somatic mutations, most notably protein kinases, glycoproteins, fibronectin Type III domains, EGF-like domains, and cell adhesion proteins such as cadherins. As in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. Canine angiosarcoma closely models human angiosarcoma on a genomic level, and is a powerful tool for investigating the pathogenesis of this devastating disease.}, author={Megquier, K and Turner-Maier, J and Swofford, R and Kim, J and Sarver, AL and Wang, C and Sakthikumar, S and Johnson, J and Koltookian, M and Lewellen, M and et al.}, year={2019}, month={Mar} }
 @article{tuohy_somarelli_borst_eward_lascelles_fogle_2019, title={Immune dysregulation and Osteosarcoma: Staphylococcus aureus downregulates TGF-β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma.}, volume={8}, url={http://europepmc.org/abstract/med/31420936}, DOI={10.1111/vco.12529}, abstractNote={Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti-tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co-cultured with osteosarcoma and S. aureus exhibited increased IFN-γ, TNF-α and IL-12p70 cytokine secretion, decreased TGF-β cytokine secretion and increased mRNA expression of TNF-α when compared with macrophages co-cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN-γ and TNF-α cytokine secretion, decreased TGF-β cytokine secretion, increased mRNA expression of TNF-α and increased surface receptor expression of CD80 when co-cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma-induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti-osteosarcoma macrophage response.}, journal={Veterinary and comparative oncology}, author={Tuohy, JL and Somarelli, JA and Borst, LB and Eward, WC and Lascelles, BDX and Fogle, JE}, year={2019}, month={Aug} }
 @article{lee_daniel_holbrook_brownstein_da_hasapis_ma_borst_badea_kirsch_2019, title={Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice.}, volume={7}, url={http://europepmc.org/abstract/med/31265788}, DOI={10.1667/rr15371.1}, abstractNote={Exposure of the gastrointestinal (GI) tract to ionizing radiation can cause acute and delayed injury. However, critical cellular targets that regulate the development of radiation-induced GI injury remain incompletely understood. Here, we investigated the role of vascular endothelial cells in controlling acute and delayed GI injury after total-abdominal irradiation (TAI). To address this, we used genetically engineered mice in which endothelial cells are sensitized to radiation due to the deletion of the tumor suppressor p53. Remarkably, we found that VE-cadherin-Cre; p53FL/FL mice, in which both alleles of p53 are deleted in endothelial cells, were not sensitized to the acute GI radiation syndrome, but these mice were highly susceptible to delayed radiation enteropathy. Histological examination indicated that VE-cadherin-Cre; p53FL/FL mice that developed delayed radiation enteropathy had severe vascular injury in the small intestine, which was manifested by hemorrhage, loss of microvessels and tissue hypoxia. In addition, using dual-energy CT imaging, we showed that VE-cadherin-Cre; p53FL/FL mice had a significant increase in vascular permeability of the small intestine in vivo 28 days after TAI. Together, these findings demonstrate that while sensitization of endothelial cells to radiation does not exacerbate the acute GI radiation syndrome, it is sufficient to promote the development of late radiation enteropathy.}, journal={Radiation research}, author={Lee, CL and Daniel, AR and Holbrook, M and Brownstein, J and Da, Silva Campos L and Hasapis, S and Ma, Y and Borst, L and Badea, CT and Kirsch, DG}, year={2019}, month={Jul} }
 @article{chen_suyemoto_sarsour_cordova_oviedo-rondon_wineland_barnes_borst_2019, title={Temporal characterization of wooden breast myopathy ("woody breast") severity and correlation with growth rate and lymphocytic phlebitis in three commercial broiler strains and a random-bred broiler strain}, volume={48}, ISSN={["1465-3338"]}, DOI={10.1080/03079457.2019.1598541}, abstractNote={Wooden breast myopathy (WBM), or "woody breast" or "wooden breast" affects modern, rapidly growing, high breast-yield broiler chickens. Decreased meat quality due to undesirable organoleptic properties and condemnation of affected breast meat cause economic losses. The pathogenesis of WBM remains unknown. In this study, WBM lesion development was determined in three modern broiler strains and Athens Canadian Random Bred (ACRB) broilers, a 1950s unselected broiler chicken. Correlations between WBM severity and incubation temperature profile, sex, strain, body weight, and lymphocytic phlebitis were also determined. At 2, 4, 6, and 8 weeks of age, samples of breast muscle from 10 male and 10 female birds from each strain, incubated under optimal or low-early, high-late temperatures, were scored histologically for severity of WBM and lymphocytic phlebitis. WBM lesions, identified as early as 2 weeks, became progressively more severe with age and growth in the three commercial broiler strains. WBM severity was significantly correlated with lymphocytic phlebitis and body weight. Lymphocytic phlebitis and minimal WBM were present in the ACRB broilers at all samplings, but did not progress in severity over time. There were no significant differences in severity of WBM among the commercial broiler strains, between sexes, or between incubation temperature profiles. The positive correlation between WBM severity and lymphocytic phlebitis indicates vascular injury is likely an important factor in the pathogenesis. Mild muscle lesions in ACRB birds without overt clinical signs indicate subclinical muscle disease may have been present in broilers prior to the description of WBM.}, number={4}, journal={AVIAN PATHOLOGY}, author={Chen, Laura R. and Suyemoto, M. Mitsu and Sarsour, Albarra H. and Cordova, H. Alejandro and Oviedo-Rondon, Edgar O. and Wineland, Michael and Barnes, H. John and Borst, Luke B.}, year={2019}, month={Jul}, pages={319–328} }
 @article{borst_suyemoto_chen_barnes_2019, title={Vaccination of breeder hens with a polyvalent killed vaccine for pathogenic Enterococcus cecorum does not protect offspring from enterococcal spondylitis}, volume={48}, ISSN={["1465-3338"]}, url={https://doi.org/10.1080/03079457.2018.1536819}, DOI={10.1080/03079457.2018.1536819}, abstractNote={Pathogenic strains of Enterococcus cecorum cause symmetrical paralysis in broilers due to infection of the free thoracic vertebra. The disease caused by pathogenic E. cecorum, known as enterococcal spondylitis or “kinky-back” continues to be responsible for significant losses to the broiler industry worldwide. In outbreaks of pathogenic E. cecorum, gut colonization and sepsis occur in the first three weeks-of-life. Since maternal antibodies are present during this period, we postulated that vaccination of breeders with a polyvalent killed vaccine would protect chicks from challenge. To test this hypothesis, representative isolates from seven genotype groups of pathogenic E. cecorum circulating in the US were chosen to produce adjuvanted killed vaccines (bacterins) and given to broiler-breeder hens. No single strain produced high titres of antibodies to all other strains; however, the combination of serologic reactivity of pathogenic isolates (designated SA3 and SA7) was sufficient to react with all genotypes. Vaccination of commercial broiler-breeder hens with a bacterin composed of SA3 and SA7 did not have any adverse effects. Vaccinated hens developed E. cecorum specific antibodies; however, no significant difference in survival was observed in infected embryos from hens in vaccine or adjuvant only groups. Chicks from vaccinated hens also failed to resist homologous or heterologous challenge during experimental infection. In a macrophage killing assay, pathogenic E. cecorum were found to evade opsinophagocytosis with elicited antibodies. These data suggest that pathogenic strains of E. cecorum possess virulence mechanisms that confound antibody-mediated opsinophagocytosis, complicating vaccine development for this pathogen of broilers.}, number={1}, journal={AVIAN PATHOLOGY}, author={Borst, Luke B. and Suyemoto, M. Mitsu and Chen, Laura R. and Barnes, H. John}, year={2019}, month={Jan}, pages={17–24} }
 @article{gall_suyemoto_sather_sharpton_barnes_borst_2019, title={Wooden Breast in Commercial Broilers Associated with Mortality, Dorsal Recumbency, and Pulmonary Disease}, volume={63}, ISSN={["1938-4351"]}, DOI={10.1637/11995-111218-Case.1}, abstractNote={Occurrence of mortality, wooden breast, and pulmonary disease in broiler chickens during the last 16 days of production in a teaching flock of 4000 commercial broilers was determined. A new syndrome was identified, in which broilers fell over for an unknown reason and were unable to right themselves (dorsal recumbency). Birds affected by dorsal recumbency were alert and responsive and showed no clinical signs except for occasional mild to moderate dyspnea. When turned over, they resumed normal behavior. Mortality (14 culls; 49 dead) during the last 16 days of production accounted for 1.6% of the flock and 36% of total mortality. Among these, 71% were heavy males, 70% had wooden breast, and 71% had pulmonary congestion and edema. Gross lesions of concurrent wooden breast and pulmonary disease occurred in 68% of the mortality, including 21 of 22 dead birds found on their backs. These findings indicate that wooden breast is associated with mortality prior to processing as a result of pulmonary disease in heavy male broilers. When birds with wooden breast fall onto their backs for unknown reason(s), they are unable to right themselves. If not found and turned over, they may not survive. Based on these findings, wooden breast is likely greater than just a problem with meat quality and should be considered an animal well-being issue.Reporte de caso- Presencia de “pechuga de madera” en pollos de engorde comerciales asociada con mortalidad, recumbencia dorsal y enfermedad pulmonar. Se determinó la presentación de mortalidad, “pechuga de madera” y enfermedad pulmonar en pollos de engorde durante los últimos 16 días de producción en una parvada de 4000 pollos de engorde comerciales. Se identificó un nuevo síndrome en el que los pollos se postraban por una razón desconocida y no podían enderezarse (recumbencia dorsal). Las aves afectadas por la recumbencia dorsal estaban alertas y respondían, y no mostraban signos clínicos, excepto casos de disnea ocasional de leve a moderada. Cuando las aves se colocaban en posición normal, retomaban su comportamiento normal. La mortalidad (14 aves eliminadas; 49 muertas) durante los últimos 16 días de producción representó el 1.6% de la parvada y 36% de la mortalidad total. Entre estos, el 71% eran machos pesados, 70% tenían “pechuga de madera” y 71% tenían congestión pulmonar y edema. Lesiones macroscópicas concurrentes de enfermedad pulmonar y de “pechuga de madera” ocurrieron en el 68% de la mortalidad, incluyendo 21 de las 22 aves muertas que fueron encontradas postradas sobre sus dorsos. Estos hallazgos indican que la “pechuga de madera” se asocia con la mortalidad antes del procesamiento como resultado de enfermedad pulmonar en pollos de engorde machos pesados. Cuando las aves con “pechuga de madera” se caen de espaldas por razones desconocidas, no pueden enderezarse. Si no se encuentran y se colocan en posición normal, pueden no sobrevivir. Según estos hallazgos, la “pechuga de madera” es probablemente más que solo un problema con la calidad de la carne y también debe considerarse un problema de bienestar animal.}, number={3}, journal={AVIAN DISEASES}, author={Gall, Sesny and Suyemoto, M. Mitsu and Sather, Hannah M. L. and Sharpton, A. Richard and Barnes, H. John and Borst, Luke B.}, year={2019}, month={Sep}, pages={514–519} }
 @article{jung_chen_suyemoto_barnes_borst_2018, title={A Review of Enterococcus cecorum Infection in Poultry.}, volume={9}, url={http://europepmc.org/abstract/med/30339512}, DOI={10.1637/11825-030618-review.1}, abstractNote={Enterococcus cecorum was initially identified as a harmless commensal of the gastrointestinal tract of chickens. However, over the past 15 yr, pathogenic strains of E. cecorum have become a significant cause of morbidity and mortality in broiler breeders, and repeated outbreaks occur, but an environmental reservoir for pathogenic E. cecorum has yet to be identified. Genetic analyses of E. cecorum demonstrate that strains with increased pathogenicity are genetically related and share several putative virulence genes. Pathogenic E. cecorum carry increased antimicrobial resistance compared to commensal strains. These pathogenic strains can be recovered from retail meat and may serve as a reservoir for further spread of antimicrobial resistance among other Enterococcus spp. This review presents the current understanding of the pathogenesis of E. cecorum and briefly discusses antimicrobial resistance in E. cecorum due to the role of Enterococcus spp. in nosocomial infections in people.}, journal={Avian diseases}, author={Jung, A and Chen, LR and Suyemoto, MM and Barnes, HJ and Borst, LB}, year={2018}, month={Sep} }
 @article{tuohy_fogle_meichner_borst_petty_griffith_osborne_lascelles_2018, title={Assessment of a novel nanoparticle hyperthermia therapy in a murine model of osteosarcoma}, volume={47}, url={https://doi.org/10.1111/vsu.12959}, DOI={10.1111/vsu.12959}, abstractNote={To evaluate the effects of nanoparticle hyperthermia therapy on monocyte function and tumor-derived factors associated with macrophage polarization in a murine osteosarcoma model.Experimental study.Female C3H mice.Peripheral blood monocyte cell surface phenotype, monocyte chemotaxis, tumor messenger RNA expression, and survival were compared among osteosarcoma (OS)-bearing mice treated with nanoparticle hyperthermia therapy, OS-bearing mice with osteomyelitis, OS-bearing mice, vehicle control mice, and normal control mice.OS-bearing mice with osteomyelitis had a higher proportion of "nonclassical" monocytes (Ly6Clo ) compared with all other experimental groups. There were alterations in monocyte expression of multiple chemokine receptors among experimental groups including CXCR2, CCR2, and CXCR4. Monocytes from OS-bearing mice treated with hyperthermia therapy exhibited greater chemotaxis compared with monocytes from OS-bearing mice with osteomyelitis.OS likely induced alterations in monocyte phenotype and function. Nanoparticle hyperthermia therapy increased in vitro monocyte chemotaxis.Enhancing monocyte/macrophage function in dogs with OS may enhance antitumor immunity.}, number={8}, journal={Vet Surg}, author={Tuohy, J.L. and Fogle, J.E. and Meichner, K. and Borst, L.B. and Petty, C.S. and Griffith, E. and Osborne, J. and Lascelles, B.D.X.}, year={2018}, month={Oct}, pages={1021–1030} }
 @article{borst_mclamb_suyemoto_chen_levy_sarsour_cordova_barnes_oviedo-rondón_2018, title={Coinfection with Eimeria spp. decreases bacteremia and spinal lesions caused by pathogenic Enterococcus cecorum}, volume={250}, ISSN={0377-8401}, url={http://dx.doi.org/10.1016/j.anifeedsci.2018.09.014}, DOI={10.1016/j.anifeedsci.2018.09.014}, abstractNote={Pathogenic strains of Enterococcus cecorum (EC) escape the gut niche to infect the spine of broilers at the free thoracic vertebra (FTV) causing the disease enterococcal spondylitis or ‘kinky-back’. Intestinal barrier damage caused by coinfection with Eimeria spp. has been suggested to play a role in potentiating EC bacteremia and FTV lesion development. To test this hypothesis, 1440 broilers were experimentally infected with EC only, EC and a coinfection of E. acervulina, E. maxima and E. tenella (EC:Cocci), and a saline only control (Sham). Birds were grown for 35 days, spleen cultures, histologic lesions in the FTV and live performance parameters were compared among groups. Coccidian coinfection significantly decreased the prevalence of EC bacteremia and histologic lesions in the FTV. Histologic evaluation of the ceca revealed significantly increased cecal mucosal height and mean inflammatory scores in the EC:Cocci group compared to EC only and sham inoculated controls. These findings indicate that the decrease in pathogenic EC bacteremia observed with coccidia coinfection may be due to increased intestinal epithelial turnover or increased immune surveillance of the intestine. In both infection groups, body weights, body weight gain and feed intake were significantly decreased and feed conversion ratios were significantly increased. These undesirable alterations in live performance parameters were exacerbated by nicarbazin treatment but not zoalene or bacitracin treatment. Further work is needed to determine the mechanism for the observed benefit of coccidian coinfection in decreasing bacteremia and FTV lesions due to pathogenic EC.}, journal={Animal Feed Science and Technology}, publisher={Elsevier BV}, author={Borst, L.B. and McLamb, K.A. and Suyemoto, M.M. and Chen, L.R. and Levy, M.G. and Sarsour, A.H. and Cordova, H.A. and Barnes, H.J. and Oviedo-Rondón, E.O.}, year={2018}, month={Sep}, pages={59–68} }
 @article{fletcher_mansell_martin_borst_barnes_gonzalez_2018, title={Gross Morphometry, Histomorphometry, and Immunohistochemistry Confirm Early and Persistent Jejunal Crypt Hyperplasia in Poults with Enteritis and Depressed Growth}, volume={62}, ISSN={0005-2086 1938-4351}, url={http://dx.doi.org/10.1637/11759-101717-reg.1}, DOI={10.1637/11759-101717-Reg.1}, abstractNote={Phosphorylated histone 3 (PH3) and cleaved caspase 3 (CCASP3) were used to detect proliferating and apoptotic cells, respectively, in the jejunums of female sibling poults, with and without enteritis and depressed growth, from hatch to day 35. Poults that developed enteritis and depressed growth (SIB flock) were raised on a commercial farm in eastern North Carolina, whereas poults with normal growth and no enteritis (TAU flock) were raised in the Teaching Animal Unit at North Carolina State University College of Veterinary Medicine. Beginning on day 5 through day 35 and at processing, TAU poults were significantly heavier than SIB poults. Jejunal weights, relative jejunal weights, and jejunal densities were greater in SIB poults from day 10 through 35. Jejunal efficiency (body weight /jejunal length) was higher in TAU poults at day 5 and days 10 through 35. Mucosal thickness was greater in SIB poults between days 7 and 21 but greater in TAU poults at days 28 and 35. From day 7 to 35, villus-to-crypt ratios were higher for TAU poults and lower for SIB poults because hyperplastic crypts formed a greater percentage of the mucosa in SIB poults. By day 7, PH3- and CCASP3-positive cells were increased in SIB poults, showing that mucosal changes resulted from combined crypt epithelial hyperplasia and increased apoptosis of villous enterocytes. Findings in this study confirm that enteritis, in the absence of clinical signs, and depressed growth in turkey poults begins by day 7, can be identified microscopically, persists for at least 35 days, is associated with lower processing weights, and has a profound negative effect on turkey growth.}, number={2}, journal={Avian Diseases}, publisher={American Association of Avian Pathologists (AAAP)}, author={Fletcher, O. J. and Mansell, R. and Martin, M. P. and Borst, L. B. and Barnes, H. John and Gonzalez, L. M.}, year={2018}, month={Jun}, pages={163–170} }
 @misc{cohen_shive_borst_almeida_2018, title={Lameness in a 3-year-old backyard chicken Response}, volume={252}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Cohen, E. B. and Shive, H. R. and Borst, L. B. and Almeida, S. M. B.}, year={2018}, pages={648–648} }
 @article{lennon_borst_edwards_moeser_2018, title={Mast Cells Exert Anti-Inflammatory Effects in an IL10-/- Model of Spontaneous Colitis.}, url={http://europepmc.org/abstract/med/29849494}, DOI={10.1155/2018/7817360}, abstractNote={Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10 −/− mice to mast cell deficient/IL10 −/− (double knockout (DKO): Kit Wsh/Wsh × IL10 −/− ) mice. Compared with IL10 −/− mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g., Tgfb2 , Bmp2 , Bmp4 , Bmp6 , and Bmp7 ) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10 −/− -mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.}, journal={Mediators of inflammation}, author={Lennon, EM and Borst, LB and Edwards, LL and Moeser, AJ}, year={2018}, month={Apr} }
 @article{lennon_woodrow_thomason_borst_edwards_moeser_2018, title={Mast Cells Play a Protective Role in Spontaneous Colitis}, volume={200}, number={Supplement 1}, journal={Journal of Immunology}, publisher={American Association of Immunologists}, author={Lennon, Elizabeth M. and Woodrow, Jane S. and Thomason, Courtney A. and Borst, Luke B. and Edwards, Laura E. and Moeser, Adam James}, year={2018}, month={May} }
 @article{lennon_borst_edwards_moeser_2018, title={Mast cells exert anti-inflammatory effects in an IL10(-/-) model of spontaneous colitis}, journal={Mediators of Inflammation}, author={Lennon, E. M. and Borst, L. B. and Edwards, L. L. and Moeser, A. J.}, year={2018} }
 @article{royal_hunt_borst_gerard_2018, title={Sleep hygiene among veterinary medical students.}, url={http://europepmc.org/abstract/med/29693028}, DOI={10.4103/jehp.jehp_114_17}, abstractNote={The objective of this study was to better understand veterinary medical students' sleep hygiene and identify the extent to which sleep hygiene behaviors may result in consequences (either positive or negative) for students.A total of 187 doctor of veterinary medicine (DVM) program students at a large College of Veterinary Medicine in the United States.The Epworth Sleep Scale and Daytime Sleepiness Scale were administered to 393 students enrolled in the DVM program.About 55.1% of students reported <7 h of sleep per night, 28.9% reported having trouble sleeping, and 50.3% reported feeling sleepy all day. With respect to sleep quality, 5.3% described it as excellent, 52.4% as good, 34.2% as fair, and 8.0% as poor.A significant percentage of veterinary medical students exhibit poor sleep hygiene habits that may be detrimental to both their health and academic endeavors.}, journal={Journal of education and health promotion}, author={Royal, KD and Hunt, SA and Borst, LB and Gerard, M}, year={2018}, month={Apr} }
 @article{almeida_shive_harvey_borst_cohen_2018, title={What Is your diagnosis? Gallus gallus domesticus}, volume={252}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85040519711&partnerID=MN8TOARS}, DOI={10.2460/javma.252.2.173}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Almeida, M. B. and Shive, H. R. and Harvey, J. B. and Borst, Luke and Cohen, Eli}, year={2018}, pages={173–175} }
 @article{kreilmeier_sampl_deloria_walter_reifinger_hauck_borst_holzmann_kleiter_2017, title={Alternative Lengthening of Telomeres Does Exist in Various Canine Sarcomas}, volume={56}, ISSN={["1098-2744"]}, url={http://europepmc.org/abstract/med/27585244}, DOI={10.1002/mc.22546}, abstractNote={Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) found in some human tumors such as sarcomas. Canine tumors are not characterized for ALT and the study aim was to identify if the ALT phenotype exists in canine sarcomas. Sixty-four canine sarcoma samples (20 snap-frozen, 44 FFPE) as well as six canine sarcoma cell lines were screened for ALT by C-circle assay. ALT was further evaluated by measuring telomere length via qPCR and telomere restriction-fragments including pulsed-field electrophoresis. ALT-associated proteins were validated by immunohistochemistry. Further, telomerase activity (TA) and gene expression were analyzed by TRAP and qPCR. DNA from 20 human neuroblastomas and 8 sarcoma cell lines served as comparative controls. ALT was detected in 9.4% (6/64) canine sarcomas including aggressive subtypes as hemangiosarcoma, osteosarcoma, and histiocytic sarcoma. C-circle levels were comparable with human ALT-positive controls. All ALT tumors demonstrated loss of ATRX expression and 5/6 showed strong p53 expression. TA was detected in 93% (14/15) snap-frozen samples including a sarcoma with ALT activity. This tumor showed long heterogeneous telomeres, and a high level of colocalization of DAXX with telomeres. One sarcoma was ALT and TA negative. All canine and human sarcoma cell lines were ALT negative. In this study, we demonstrated that canine sarcomas use ALT. As in humans, ALT was identified in aggressive sarcomas subtypes and coexisted with TA in one tumor. Overall, canine sarcomas seem to share many similarities with their human counterparts and appear an attractive model for comparative telomere research. © 2016 Wiley Periodicals, Inc.}, number={3}, journal={MOLECULAR CARCINOGENESIS}, author={Kreilmeier, Theresa and Sampl, Sandra and Deloria, Abigail J. and Walter, Ingrid and Reifinger, Martin and Hauck, Marlene and Borst, Luke B. and Holzmann, Klaus and Kleiter, Miriam}, year={2017}, month={Mar}, pages={923–935} }
 @article{suyemoto_barnes_borst_2017, title={Culture methods impact recovery of antibiotic-resistant Enterococci including Enterococcus cecorum from pre- and postharvest chicken}, volume={64}, ISSN={["1472-765X"]}, DOI={10.1111/lam.12705}, abstractNote={Pathogenic strains of Enterococcus cecorum (EC) expressing multidrug resistance have emerged. In National Antimicrobial Resistance Monitoring System (NARMS) data, EC is rarely recovered from chickens. Two NARMS methodologies (FDA and USDA) were compared with standard culture (SC) techniques for recovery of EC. NARMS methods failed to detect EC in 58 caecal samples, 20 chicken breast or six whole broiler samples. EC was recovered from 1 of 38 (2·6%) and 2 of 38 (5·2%) preharvest spinal lesions (USDA and FDA method, respectively). In contrast, using the SC method, EC was recovered from 44 of 53 (83%) caecal samples, all 38 (100%) spinal lesions, 14 of 20 (70%) chicken breast samples, and all three spinal lesions identified in whole carcasses. Compared with other Enterococcus spp., EC isolates had a higher prevalence of resistance to macrolides. The NARMS methods significantly affected recovery of enterococcal species other than EC. When the postharvest FDA method was applied to preharvest caecal samples, isolates of Enterococcus faecium were preferentially recovered. All 11 E. faecium isolates were multidrug resistant, including resistance to penicillin, daptomycin and linezolid. These findings confirm that current methodologies may not accurately identify the amount and range of antimicrobial resistance of enterococci from chicken sources. Enterococci are an important reservoir for antimicrobial resistance. This study demonstrates how current culture methods underreport resistance to macrolides in enterococci by selecting against strains of Enterococcus cecorum in pre‐ and postharvest chicken. Further, the application of postharvest surveillance methods to preharvest samples resulted in selective recovery of Enterococcus faecium over Enterococcus faecalis. Isolates of E. faecium recovered exhibited multidrug resistance including penicillin, daptomycin and linezolid resistance. These findings suggest that culture methodology significantly impacts the range and amount of antimicrobial resistance detected in enterococci isolated from chicken.}, number={3}, journal={LETTERS IN APPLIED MICROBIOLOGY}, author={Suyemoto, M. M. and Barnes, H. J. and Borst, L. B.}, year={2017}, month={Mar}, pages={210–216} }
 @article{jacobi_xi_maltecca_borst_smith_odle_2017, title={Dietary Prebiotics and Arachidonic Acid (ARA) Modulate Intestinal Injury and Microbial Taxa Following Acute Dextran Sodium Sulfate Induced Colitis in Formula-Fed Piglets}, volume={31}, number={1_supplement}, journal={The FASEB Journal}, author={Jacobi, Sheila K. and Xi, Lin and Maltecca, Christian and Borst, Luke and Smith, Andrew and Odle, Jack}, year={2017}, pages={324–324} }
 @article{thomas_demeter_kennedy_borst_singh_valli_le boedec_breen_2017, title={Integrated immunohistochemical and DNA copy number profiling analysis provides insight into the molecular pathogenesis of canine follicular lymphoma}, volume={15}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12227}, abstractNote={Follicular lymphomas (FLs) typically exhibit a chromosome translocation that induces constitutive expression of the anti-apoptotic bcl2 protein and accumulation of additional molecular defects. This rearrangement offers a promising therapeutic target, but its nature as a fundamental driver of FL pathogenesis remains unclear as 15% of cases lack the translocation. We performed an integrated immunohistochemical and genomic investigation of 10 naturally occurring FL cases from domestic dogs, showing that, as with human tumours, they exhibit marked heterogeneity in the frequency and intensity of bcl2 protein expression. Genomic copy number aberrations were infrequent and broadly consistent with those of other canine B-cell lymphoma subtypes. None of the canine FL specimens exhibited a rearrangement consistent with the hallmark translocation of human FL, despite their remarkable histomorphologic similarity. Parallel exploration of canine and human cases may reveal alternative tumour-initiating mechanisms other than BCL2 disruption, yielding a more complete definition of the molecular pathogenesis of FL.}, number={3}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Thomas, R. and Demeter, Z. and Kennedy, K. A. and Borst, L. and Singh, K. and Valli, V. E. and Le Boedec, K. and Breen, M.}, year={2017}, month={Sep}, pages={852–867} }
 @article{chen_suyemoto_sarsour_cordova_oviedo-rondon_barnes_borst_2017, title={Prevalence and severity of osteochondrosis of the free thoracic vertebra in three modern broiler strains and the Athens Canadian Random Bred control broiler}, volume={47}, ISSN={0307-9457 1465-3338}, url={http://dx.doi.org/10.1080/03079457.2017.1388499}, DOI={10.1080/03079457.2017.1388499}, abstractNote={Osteochondrosis (OCD) results from a disturbance of endochondral ossification in articular cartilage and is an important cause of lameness in several animal species, including chickens. OCD lesions in the free thoracic vertebra (FTV) of chickens are essential to the pathogenesis of pathogenic Enterococcus cecorum. The goal of this study was to determine the prevalence of OCD in the FTV among three modern broiler chicken crosses (strains A/A, A/B, and C/C) and Athens Canadian Random Bred (ACRB) chickens, which served as the control group. The effect of sex, age, strain, body weight, and incubation temperature profile on OCD severity for each group was determined. At 2, 4, 6, and 8 weeks of age, the FTV of 10 male and 10 female birds from each strain exposed to either optimal or low-early, high-late incubation temperature profiles were collected and scored histologically for OCD lesion severity. OCD spectrum lesions were detected in >70% of all strain/sex combinations, including the ACRB controls. No association was observed between mean OCD score and broiler strain, incubation temperature profile, sex, age, or body weight. These findings indicate that OCD of the FTV is common in broiler chickens with similar prevalence observed in broilers with modern genetics and the ACRB broilers which represent 1950s broiler genetics. As the parameters examined did not have a statistical correlation with OCD, additional work is needed to understand factors that contribute to development of OCD in chickens.}, number={2}, journal={Avian Pathology}, publisher={Informa UK Limited}, author={Chen, L.R. and Suyemoto, M.M. and Sarsour, A.H. and Cordova, H.A. and Oviedo-Rondon, E.O. and Barnes, H.J. and Borst, L.B.}, year={2017}, pages={1–9} }
 @article{royal_flammer_borst_huckle_barter_neel_2016, title={A Comprehensive Wellness Program for Veterinary Medical Education: Design and Implementation at North Carolina State University}, volume={6}, ISSN={1927-6052 1927-6044}, url={http://dx.doi.org/10.5430/ijhe.v6n1p74}, DOI={10.5430/ijhe.v6n1p74}, abstractNote={Research in veterinary medical education has illustrated the challenges students face with respect to mental and emotional wellness, lack of attention to physical health, and limited opportunities to meaningfully engage with persons from different backgrounds. In response, the North Carolina State University College of Veterinary Medicine has adopted a comprehensive wellness program available to all members of the college community. The wellness program is based on a ‘house system’ learning community model and focuses on five broad outcome categories: intellectual growth; mental and emotional health; social distance reduction; cultural competence; and physical health. This case study paper describes the development and implementation of the model at this institution.}, number={1}, journal={International Journal of Higher Education}, publisher={Sciedu Press}, author={Royal, Kenneth D. and Flammer, Keven and Borst, Luke and Huckle, Jeffrey and Barter, Hillary and Neel, Jennifer}, year={2016}, month={Nov}, pages={74} }
 @article{li_hansen_borst_spears_moeser_2016, title={Dietary Iron Deficiency and Oversupplementation Increase Intestinal Permeability, Ion Transport, and Inflammation in Pigs}, volume={146}, ISSN={["1541-6100"]}, DOI={10.3945/jn.116.231621}, abstractNote={Understanding the influence of dietary iron deficiency and dietary iron oversupplementation on intestinal health is important for both animal production and human health.The aim of this study was to determine whether dietary iron concentration influences intestinal physiology, morphology, and inflammation in the porcine duodenum.Twenty-four male pigs (21 d old) were fed diets containing either 20 mg Fe/kg [low dietary iron (L-Fe)], 120 mg Fe/kg [adequate dietary iron (A-Fe); control], or 520 mg Fe/kg [high dietary iron (H-Fe)] by FeSO4 supplement (dry matter basis). After 32-36 d, the duodenum was harvested from pigs and mounted in Ussing chambers for the measurement of transepithelial electrical resistance (TER), short-circuit current, and (3)H-mannitol permeability. Intestinal morphology and inflammation were assessed by histologic examination, and proinflammatory gene expression was assessed by real-time polymerase chain reaction.Compared with A-Fe-fed pigs, pigs fed L-Fe diets exhibited reduced TER (by 30%; P < 0.05). Compared with that of A-Fe-fed controls, the paracellular flux of (3)H-mannitol across the duodenal mucosa was higher (P < 0.05) in L-Fe-fed (>100%) and H-Fe-fed (∼4-fold) pigs; the L-Fe-fed and H-Fe-fed groups did not differ significantly from one another. Compared with the L-Fe-fed pigs, the A-Fe-fed and H-Fe-fed pigs had malondialdehyde concentrations 1.4- and 2.5-fold higher in the duodenum and 4.4- and 6.6-fold higher in the liver, respectively (P < 0.05). Neutrophil counts were higher in both the L-Fe-fed (by 3-fold) and H-Fe-fed (by 3.3-fold) groups than in the A-Fe-fed group; the L-Fe-fed and H-Fe-fed groups did not significantly differ from one another. Duodenal mucosal tumor necrosis factor α (TNFA), interleukin (IL) 1β, and IL6 relative gene expression was upregulated by 36%, 28%, and 45%, respectively, in H-Fe pigs (P < 0.05), but not in L-Fe pigs, compared with A-Fe pigs.These data suggest that adequate but not oversupplementation of dietary iron in pigs is required to maintain intestinal barrier health and function.}, number={8}, journal={JOURNAL OF NUTRITION}, author={Li, Yihang and Hansen, Stephanie L. and Borst, Luke B. and Spears, Jerry W. and Moeser, Adam J.}, year={2016}, month={Aug}, pages={1499–1505} }
 @article{meichner_kraszeski_durrant_grindem_breuhaus_moore_neel_linder_borst_fogle_et al._2016, title={Extreme lymphocytosis with myelomonocytic morphology in a horse with diffuse large B-cell lymphoma}, volume={46}, ISSN={0275-6382}, url={http://dx.doi.org/10.1111/vcp.12435}, DOI={10.1111/vcp.12435}, abstractNote={An 11-year-old, 443-kg Haflinger mare was presented to the North Carolina State University Veterinary Teaching Hospital with a 2-week history of lethargy and a 3-day duration of anorexia, pyrexia, tachycardia, and ventral edema. Severe pitting edema, peripheral lymphadenopathy, and a caudal abdominal mass were noted on physical examination. An extreme leukocytosis (154.3 × 103 /μL) and microscopic hematologic findings suggestive of myelomonocytic leukemia were observed. Serum protein electrophoresis revealed a monoclonal gammopathy and urine protein electrophoresis revealed a monoclonal light chain proteinuria. Necropsy and histopathology confirmed widespread neoplastic infiltration in many organs with a heterogenous population of cells; there was no apparent evidence of bone marrow involvement. Immunohistochemistry confirmed presence of a majority of B cells with a limited antigen expression, admixed with a lower number of T cells. Molecular clonality analysis of IgH2, IgH3, and kappa-deleting element (KDE, B cell) on whole blood and KDE on infiltrated tissues revealed clonal rearrangements, and the KDE intron clones that amplified in blood and in infiltrated tissue were identical. In contrast, the clonality analysis of T-cell receptor γ revealed no clonality on blood cells and infiltrated tissues. In conjunction with the histopathologic changes, the lesion was interpreted to be composed of neoplastic B cells with a reactive T-cell population. Polymerase chain reaction testing for equine herpes virus 5 was negative. The final diagnosis was diffuse large B-cell lymphoma with a marked hematogenous component.}, number={1}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Meichner, Kristina and Kraszeski, Blaire H. and Durrant, Jessica R. and Grindem, Carol B. and Breuhaus, Babetta A. and Moore, Peter F. and Neel, Jennifer A. and Linder, Keith E. and Borst, Luke B. and Fogle, Jonathan E. and et al.}, year={2016}, month={Dec}, pages={64–71} }
 @inbook{ramos-vara_borst_2016, title={Immunohistochemistry}, ISBN={9781119181200 9780813821795}, url={http://dx.doi.org/10.1002/9781119181200.ch3}, DOI={10.1002/9781119181200.ch3}, booktitle={Tumors in Domestic Animals}, publisher={John Wiley & Sons, Inc.}, author={Ramos-Vara, José A. and Borst, Luke B.}, year={2016}, month={Nov}, pages={44–87} }
 @article{yin_tang_cai_tong_sternberg_yang_dobrucki_borst_kamstock_song_et al._2016, title={Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis}, volume={113}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1603316113}, abstractNote={Significance Malignant osteolysis associated with inoperable primary bone tumors and multifocal skeletal metastases remains a challenging clinical problem in cancer patients. The outgrowth of residual cancer cells within the bone microenvironment despite aggressive multimodality therapies necessitates the discovery and validation of novel strategies for treating osteotropic solid tumors. We report on pamidronate functionalized polylactide nanoparticles for the targeted treatment of focal malignant osteolysis by delivering doxorubicin specifically to the bone tumor microenvironment. Improved efficacy was demonstrated in a preclinical orthotopic mouse model of osteosarcoma. Most importantly, through the inclusion of dogs with naturally developing osteosarcoma, biocompatibility, biodistribution, and anticancer activities at clinically relevant dosages were demonstrated in a large mammalian modeling system.}, number={32}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Yin, Qian and Tang, Li and Cai, Kaimin and Tong, Rong and Sternberg, Rachel and Yang, Xujuan and Dobrucki, Lawrence W. and Borst, Luke B. and Kamstock, Debra and Song, Ziyuan and et al.}, year={2016}, month={Aug}, pages={E4601–E4609} }
 @article{borst_suyemoto_sarsour_harris_martin_strickland_oviedo_barnes_2016, title={Pathogenesis of Enterococcal Spondylitis Caused by Enterococcus cecorum in Broiler Chickens}, volume={54}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985816658098}, DOI={10.1177/0300985816658098}, abstractNote={Enterococcal spondylitis (ES) is a disease of commercial broiler chickens, with a worldwide distribution. Symmetrical hind limb paralysis typical of ES results from infection of the free thoracic vertebra (FTV) by pathogenic strains of Enterococcus cecorum . To determine the pathogenesis of ES, birds with natural and experimental ES were studied over time. In natural disease, case birds (n = 150) from an affected farm and control birds (n = 100) from an unaffected farm were evaluated at weeks 1-6. In control birds, intestinal colonization by E. cecorum began at week 3. In case birds, E. cecorum was detected in intestine and spleen at week 1, followed by infection of the FTV beginning at week 3. E. cecorum isolates recovered from intestine, spleen, and FTV of case birds had matching genotypes, confirming that intestinal colonization with pathogenic strains precedes bacteremia and infection of the FTV. Clinical intestinal disease was not required for E. cecorum bacteremia. In 1- to 3-week-old case birds, pathogenic E. cecorum was observed within osteochondrosis dissecans (OCD) lesions in the FTV. To determine whether OCD of the FTV was a risk factor for ES, 214 birds were orally infected with E. cecorum, and the FTV was evaluated histologically at weeks 1-7. Birds without cartilage clefts of OCD in the FTV did not develop ES; while birds with OCD scores ≥3 were susceptible to lesion development. These findings suggest that intestinal colonization, bacteremia, and OCD of the FTV in early life are crucial to the pathogenesis of ES.}, number={1}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Borst, L. B. and Suyemoto, M. M. and Sarsour, A. H. and Harris, M. C. and Martin, M. P. and Strickland, J. D. and Oviedo, E. O. and Barnes, H. J.}, year={2016}, month={Aug}, pages={61–73} }
 @article{meichner_montgomery_borst_murphy_grindem_2016, title={Pathology in Practice}, volume={249}, ISSN={["1943-569X"]}, DOI={10.2460/javma.249.9.1023}, number={9}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Meichner, Kristina and Montgomery, Stephanie A. and Borst, Luke B. and Murphy, K. Marcia and Grindem, Carol B.}, year={2016}, month={Nov}, pages={1023–1026} }
 @article{holl_shumansky_borst_burnette_sample_ramsburg_sullenger_2016, title={Scavenging nucleic acid debris to combat autoimmunity and infectious disease}, volume={113}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1607011113}, abstractNote={Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal's ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.}, number={35}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Holl, Eda K. and Shumansky, Kara L. and Borst, Luke B. and Burnette, Angela D. and Sample, Christopher J. and Ramsburg, Elizabeth A. and Sullenger, Bruce A.}, year={2016}, month={Aug}, pages={9728–9733} }
 @article{lee_castle_moding_blum_williams_luo_ma_borst_kim_kirsch_et al._2015, title={Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma.}, volume={9}, url={http://europepmc.org/abstract/med/26399548}, DOI={10.1038/ncomms9477}, abstractNote={Abstract Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using Kras LA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic Kras G12D . However, blocking p53 during TBI significantly suppresses the expansion of Kras G12D -expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma.}, journal={Nature communications}, author={Lee, CL and Castle, KD and Moding, EJ and Blum, JM and Williams, N and Luo, L and Ma, Y and Borst, Luke and Kim, Y and Kirsch, DG and et al.}, year={2015}, month={Sep} }
 @article{jacobi_adam_borst_lin_odle_2015, title={Acute Dextran Sodium Sulfate Dose-Dependently Induces Colitis in Formula-Fed Piglets}, volume={29}, number={Supplement 1}, journal={The FASEB Journal}, author={Jacobi, Sheila and Adam, Moeser and Borst, Luke and Lin, Xi and Odle, Jack}, year={2015}, pages={755–758} }
 @article{jackson_kariyawasam_borst_frye_barrett_hiott_woodley_2015, title={Antimicrobial resistance, virulence determinants and genetic profiles of clinical and nonclinical Enterococcus cecorum from poultry}, volume={60}, DOI={10.1111/lam.12374}, abstractNote={Enterococcus cecorum has been implicated as a possible cause of disease in poultry. However, the characteristics that contribute to pathogenesis of Ent. cecorum in poultry have not been defined. In this study, Ent. cecorum from carcass rinsates (n = 75) and diseased broilers and broiler breeders (n = 30) were compared based upon antimicrobial resistance phenotype, the presence of virulence determinants and genetic relatedness using pulsed-field gel electrophoresis (PFGE). Of the 16 antimicrobials tested, Ent. cecorum from carcass rinsates and clinical cases were resistant to ten and six of the antimicrobials, respectively. The majority of Ent. cecorum from carcass rinsates was resistant to lincomycin (54/75; 72%) and tetracycline (46/75; 61·3%) while the highest level of resistance among clinical Ent. cecorum was to tetracycline (22/30; 73·3%) and erythromycin (11/30; 36·7%). Multidrug resistance (resistance to ≥2 antimicrobials) was identified in Ent. cecorum from carcass rinsates (53/75; 70·7%) and diseased poultry (18/30; 60%). Of the virulence determinants tested, efaAfm was present in almost all of the isolates (104/105; 99%). Using PFGE, the majority of clinical isolates clustered together; however, a few clinical isolates grouped with Ent. cecorum from carcass rinsates. These data suggest that distinguishing the two groups of isolates is difficult based upon the characterization criteria used. Significance and Impact of the Study In this study, antimicrobial resistance phenotype, virulence gene profile and genetic relatedness of Enterococcus cecorum isolated from diseased broiler chickens and poultry carcass rinsates were determined. The majority of isolates from both groups were multidrug resistant and harboured few virulence determinants. Results from this study suggest that clinical Ent. cecorum and Ent. cecorum from poultry carcass rinsates may share a common genetic background; clinical Ent. cecorum possess virulence determinants that have not been previously described for this species. Elucidation of those unknown virulence determinants is important for understanding the pathogenesis of Ent. cecorum infections in poultry.}, number={2}, journal={Letters in Applied Microbiology}, author={Jackson, C. R. and Kariyawasam, S. and Borst, Luke and Frye, J. G. and Barrett, J. B. and Hiott, L. M. and Woodley, T. A.}, year={2015}, pages={111–119} }
 @article{coyle_rassnick_borst_rodriguez_northrup_fan_garrett_2015, title={Biological behaviour of canine mandibular osteosarcoma. A retrospective study of 50 cases (1999-2007)}, volume={13}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12020}, abstractNote={The purpose of this retrospective study was to describe the biological behaviour of canine mandibular osteosarcoma (OSA) and to examine factors for their impact on metastasis-free interval (MFI) and survival time (ST). Records from dogs treated with mandibulectomy for OSA (1999-2007) were reviewed. Archived tumour samples were evaluated for mitotic index (MI) and tumour grade. Fifty dogs were included, 21 received chemotherapy. Twenty-nine dogs (58%) developed metastatic disease. The median MFI was 627 days, and median ST was 525 days. In univariate analysis MI > 40 was prognostic for decreased MFI and ST. Grade also influenced MFI and ST, with 5/21 (24%) dogs with grade II/III tumours metastasis-free at one year versus 16/22 (72%) dogs with grade I tumours (P = 0.002); and 5/21 (24%) dogs with grade II/III tumours alive versus 17/22 (77%) dogs with grade I tumours (P = 0.001). In multivariate analysis, histological grade and adjuvant chemotherapy were prognostic for MFI and ST.}, number={2}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Coyle, V. J. and Rassnick, K. M. and Borst, L. B. and Rodriguez, C. O., Jr. and Northrup, N. C. and Fan, T. M. and Garrett, L. D.}, year={2015}, month={Jun}, pages={89–97} }
 @article{borst_suyemoto_scholl_fuller_barnes_2015, title={Comparative Genomic Analysis Identifies Divergent Genomic Features of Pathogenic Enterococcus cecorum Including a Type IC CRISPR-Cas System, a Capsule Locus, an epa-Like Locus, and Putative Host Tissue Binding Proteins}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0121294}, abstractNote={Enterococcus cecorum (EC) is the dominant enteric commensal of adult chickens and contributes to the gut consortia of many avian and mammalian species. While EC infection is an uncommon zoonosis, like other enterococcal species it can cause life-threating nosocomial infection in people. In contrast to other enterococci which are considered opportunistic pathogens, emerging pathogenic strains of EC cause outbreaks of musculoskeletal disease in broiler chickens. Typical morbidity and mortality is comparable to other important infectious diseases of poultry. In molecular epidemiologic studies, pathogenic EC strains were found to be genetically clonal. These findings suggested acquisition of specific virulence determinants by pathogenic EC. To identify divergent genomic features and acquired virulence determinants in pathogenic EC; comparative genomic analysis was performed on genomes of 3 pathogenic and 3 commensal strains of EC. Pathogenic isolates had smaller genomes with a higher GC content, and they demonstrated large regions of synteny compared to commensal isolates. A molecular phylogenetic analysis demonstrated sequence divergence in pathogenic EC genomes. At a threshold of 98% identity, 414 predicted proteins were identified that were highly conserved in pathogenic EC but not in commensal EC. Among these, divergent CRISPR-cas defense loci were observed. In commensal EC, the type IIA arrangement typical for enterococci was present; however, pathogenic EC had a type IC locus, which is novel in enterococci but commonly observed in streptococci. Potential mediators of virulence identified in this analysis included a polysaccharide capsular locus similar to that recently described for E. faecium, an epa-like locus, and cell wall associated proteins which may bind host extracellular matrix. This analysis identified specific genomic regions, coding sequences, and predicted proteins which may be related to the divergent evolution and increased virulence of emerging pathogenic strains of EC.}, number={4}, journal={PLOS ONE}, author={Borst, Luke B. and Suyemoto, M. Mitsu and Scholl, Elizabeth H. and Fuller, Fredrick J. and Barnes, H. John}, year={2015}, month={Apr} }
 @article{poorman_borst_moroff_roy_labelle_motsinger-reif_breen_2015, title={Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization}, volume={23}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-014-9444-6}, abstractNote={Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3–17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.}, number={2}, journal={CHROMOSOME RESEARCH}, author={Poorman, Kelsey and Borst, Luke and Moroff, Scott and Roy, Siddharth and Labelle, Philippe and Motsinger-Reif, Alison and Breen, Matthew}, year={2015}, month={Jun}, pages={171–186} }
 @article{fry_leblanc_suter_borst_reed_2015, title={Cytologic Characteristics and World Health Organization Classification in 45 Dogs With Lymphoma}, volume={44}, number={4}, journal={Veterinary Clinical Pathology}, author={Fry, M. and LeBlanc, C. and Suter, S. and Borst, L. and Reed, G.}, year={2015} }
 @article{boyer_s. d'costa_edwards_milloway_susick_borst_thakur_campbell_crenshaw_polo_et al._2015, title={Early-life dietary spray-dried plasma influences immunological and intestinal injury responses to later-life Salmonella typhimurium challenge}, volume={113}, ISSN={["1475-2662"]}, DOI={10.1017/s000711451400422x}, abstractNote={Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16–17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 10 9 colony-forming units of S. typhimurium . A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S . typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium -challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.}, number={5}, journal={BRITISH JOURNAL OF NUTRITION}, author={Boyer, P. E. and S. D'Costa and Edwards, L. L. and Milloway, M. and Susick, E. and Borst, L. B. and Thakur, S. and Campbell, J. M. and Crenshaw, J. D. and Polo, J. and et al.}, year={2015}, month={Mar}, pages={783–793} }
 @article{maharshak_huh_paiboonrungruang_shanahan_thurlow_herzog_djukic_orlando_pawlinski_ellermann_et al._2015, title={Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2}, volume={83}, ISSN={["1098-5522"]}, DOI={10.1128/iai.00425-15}, abstractNote={Microbial protease-mediated disruption of the intestinal epithelium is a potential mechanism whereby a dysbiotic enteric microbiota can lead to disease. This mechanism was investigated using the colitogenic, protease-secreting enteric microbe Enterococcus faecalis. Caco-2 and T-84 epithelial cell monolayers and the mouse colonic epithelium were exposed to concentrated conditioned media (CCM) from E. faecalis V583 and E. faecalis lacking the gelatinase gene (gelE). The flux of fluorescein isothiocyanate (FITC)-labeled dextran across monolayers or the mouse epithelium following exposure to CCM from parental or mutant E. faecalis strains indicated paracellular permeability. A protease-activated receptor 2 (PAR2) antagonist and PAR2-deficient (PAR2(-/-)) mice were used to investigate the role of this receptor in E. faecalis-induced permeability. Gelatinase (GelE) purified from E. faecalis V583 was used to confirm the ability of this protease to induce epithelial cell permeability and activate PAR2. The protease-mediated permeability of colonic epithelia from wild-type (WT) and PAR2(-/-) mice by fecal supernatants from ulcerative colitis patients was assessed. Secreted E. faecalis proteins induced permeability in epithelial cell monolayers, which was reduced in the absence of gelE or by blocking PAR2 activity. Secreted E. faecalis proteins induced permeability in the colonic epithelia of WT mice that was absent in tissues from PAR2(-/-) mice. Purified GelE confirmed the ability of this protease to induce epithelial cell permeability via PAR2 activation. Fecal supernatants from ulcerative colitis patients induced permeability in the colonic epithelia of WT mice that was reduced in tissues from PAR2(-/-) mice. Our investigations demonstrate that GelE from E. faecalis can regulate enteric epithelial permeability via PAR2.}, number={7}, journal={INFECTION AND IMMUNITY}, author={Maharshak, Nitsan and Huh, Eun Young and Paiboonrungruang, Chorlada and Shanahan, Michael and Thurlow, Lance and Herzog, Jeremy and Djukic, Zorka and Orlando, Roy and Pawlinski, Rafal and Ellermann, Melissa and et al.}, year={2015}, month={Jul}, pages={2762–2770} }
 @article{mariani_jennings_olby_borst_brown_robertson_seiler_mackillop_2015, title={Histiocytic Sarcoma with Central Nervous System Involvement in Dogs: 19 Cases (2006-2012)}, volume={29}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12554}, DOI={10.1111/jvim.12554}, abstractNote={Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1-3 animals.The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement.Nineteen dogs with HS examined at veterinary referral hospitals.Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis.Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days.Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Mariani, C.L. and Jennings, M.K. and Olby, N.J. and Borst, L.B. and Brown, J.C., Jr and Robertson, I.D. and Seiler, G.S. and MacKillop, E.}, year={2015}, month={Feb}, pages={607–613} }
 @article{tang_tong_coyle_yin_pondenis_borst_cheng_fan_2015, title={Targeting Tumor Vasculature with Aptamer-Functionalized Doxorubicin - Polylactide Nanoconjugates for Enhanced Cancer Therapy}, volume={9}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b00166}, abstractNote={An A10 aptamer (Apt)-functionalized, sub-100 nm doxorubicin-polylactide (Doxo-PLA) nanoconjugate (NC) with controlled release profile was developed as an intravenous therapeutic strategy to effectively target and cytoreduce canine hemangiosarcoma (cHSA), a naturally occurring solid tumor malignancy composed solely of tumor-associated endothelium. cHSA consists of a pure population of malignant endothelial cells expressing prostate-specific membrane antigen (PSMA) and is an ideal comparative tumor model system for evaluating the specificity and feasibility of tumor-associated endothelial cell targeting by A10 Apt-functionalized NC (A10 NC). In vitro, A10 NCs were selectively internalized across a panel of PSMA-expressing cancer cell lines, and when incorporating Doxo, A10 Doxo-PLA NCs exerted greater cytotoxic effects compared to nonfunctionalized Doxo-PLA NCs and free Doxo. Importantly, intravenously delivered A10 NCs selectively targeted PSMA-expressing tumor-associated endothelial cells at a cellular level in tumor-bearing mice and dramatically increased the uptake of NCs by endothelial cells within the local tumor microenvironment. By virtue of controlled drug release kinetics and selective tumor-associated endothelial cell targeting, A10 Doxo-PLA NCs possess a desirable safety profile in vivo, being well-tolerated following high-dose intravenous infusion in mice, as supported by the absence of any histologic organ toxicity. In cHSA-implanted mice, two consecutive intravenous infusions of A10 Doxo-PLA NCs exerted rapid and substantial cytoreductive activities within a period of 7 days, resulting in greater than 70% reduction in macroscopic tumor-associated endothelial cell burden as a consequence of enhanced cell death and necrosis.}, number={5}, journal={ACS NANO}, author={Tang, Li and Tong, Rong and Coyle, Virginia J. and Yin, Qian and Pondenis, Holly and Borst, Luke B. and Cheng, Jianjun and Fan, Timothy M.}, year={2015}, month={May}, pages={5072–5081} }
 @article{swisher_grunkemeyer_savage_durrant_borst_2015, title={What’s your diagnosis? Purulent upper respiratory discharge in a rabbit}, url={https://www.dvm360.com/view/whats-your-diagnosis-purulent-upper-respiratory-discharge-rabbit}, journal={DVM 360}, author={Swisher, Samantha D. and Grunkemeyer, Vanessa L. and Savage, Mason Y. and Durrant, Jessica R. and Borst, Luke B.}, year={2015}, month={Sep} }
 @article{borst_suyemoto_keelara_dunningan_guy_barnes_2014, title={A Chicken Embryo Lethality Assay for Pathogenic Enterococcus cecorum}, volume={58}, ISSN={["1938-4351"]}, DOI={10.1637/10687-101113-reg.1}, abstractNote={Pathogenic strains of Enterococcus cecorum cause outbreaks of arthritis and osteomyelitis in chickens worldwide. Enterococcal spondylitis (ES) is a specific manifestation of E. cecorum-associated disease of broilers and broiler breeders characterized by increased flock mortality, resulting from unresolved infection of the free thoracic vertebra by pathogenic E. cecorum. A study of 22 ES outbreaks in the southeast United States revealed that pathogenic E. cecorum strains isolated from spinal lesions were genetically clonal. Here, we compare the virulence of previously genotyped pathogenic strains (n = 8) isolated from spinal lesions and nonpathogenic strains (n = 9) isolated from ceca of unaffected birds in a chicken embryo lethality model. Strains were inoculated into the allantoic cavity of 12-day-old broiler and specific-pathogen-free (SPF) layer embryos; embryo survival was determined by candling eggs daily for 4 days. Significantly decreased survival occurred in both broiler and SPF embryos inoculated with pathogenic genotype strains compared with embryos inoculated with nonpathogenic genotype strains (broiler embryos, 23% vs. 60%; SPF embryos, 9% vs. 61%). Embryos infected with pathogenic strains were unable to control infection and consistently showed gross changes typical of sepsis, including hemorrhage and edema. After 48 hr, similar changes were not observed in embryos infected with nonpathogenic strains. This embryo lethality assay provides a useful tool for understanding the genetic basis of E. cecorum virulence.Ensayo de letalidad en embriones de pollo para cepas de Enterococcus cecorum patogénicas.Las cepas patógenas de Enterococcus cecorum causan brotes de artritis y osteomielitis en pollos a nivel mundial. La espondilitis enterococócica (ES) es una manifestación específica de la enfermedad asociada con E. cecorum en pollos de engorde y en reproductoras pesadas que es caracterizada por alta mortalidad de la parvada, como resultado de la infección no resuelta en la vértebra torácica móvil causada por cepas de E. cecorum patógenas. Un estudio de 22 brotes de espondilitis enterococócica en el sureste de los Estados Unidos reveló que las cepas patógenas de E. cecorum aisladas de lesiones de la médula eran genéticamente provenientes de un clon. En este estudio, se comparó mediante un modelo de letalidad del embrión de pollo, la virulencia de las cepas patógenas previamente genotipificadas (n = 8) aisladas de lesiones de la columna vertebral y cepas no patógenas (n = 9) aisladas del ciego de las aves no afectadas. Las cepas fueron inoculadas en la cavidad alantoidea de embriones de pollo de 12 días de edad, de pollos de engorde y en aves libres de patógenos específicos (SPF); la supervivencia de los embriones se determinó por ovoscopía diariamente por cuatro días. De manera significativa se presentó una disminución en la supervivencia en ambos tipo embriones de pollos de engorde y de aves libres de patógenos específicos inoculados con cepas de genotipo patógeno en comparación con los embriones inoculados con cepas de genotipo no patógeno (embriones de pollos de engorde, 23% contra 60%; y en los embriones libres de patógenos específicos, 9% frente a 61%). Los embriones infectados con cepas patógenas fueron incapaces de controlar la infección y mostraron consistentemente cambios macroscópicos típicos de sepsis, incluyendo hemorragia y edema. Después de 48 horas, no se observaron cambios similares en los embriones infectados con cepas no patógenas. Este ensayo de letalidad del embrión proporciona una herramienta útil para la comprensión de la base genética de la virulencia de E. cecorum.}, number={2}, journal={AVIAN DISEASES}, author={Borst, Luke B. and Suyemoto, M. Mitsu and Keelara, Shivaramu and Dunningan, Sarah E. and Guy, James S. and Barnes, H. John}, year={2014}, month={Jun}, pages={244–248} }
 @article{botham_fan_im_borst_dirikolu_hergenrother_2014, title={Dual Small-Molecule Targeting of Procaspase-3 Dramatically Enhances Zymogen Activation and Anticancer Activity}, volume={136}, ISSN={["0002-7863"]}, DOI={10.1021/ja4124303}, abstractNote={Combination anticancer therapy typically consists of drugs that target different biochemical pathways or those that act on different targets in the same pathway. Here we demonstrate a new concept in combination therapy, that of enzyme activation with two compounds that hit the same biological target, but through different mechanisms. Combinations of procaspase-3 activators PAC-1 and 1541B show considerable synergy in activating procaspase-3 in vitro, stimulate rapid and dramatic maturation of procaspase-3 in multiple cancer cell lines, and powerfully induce caspase-dependent apoptotic death to a degree well exceeding the additive effect. In addition, the combination of PAC-1 and 1541B effectively reduces tumor burden in a murine lymphoma model at dosages for which the compounds alone have minimal or no effect. These data suggest the potential of PAC-1/1541B combinations for the treatment of cancer and, more broadly, demonstrate that differentially acting enzyme activators can potently synergize to give a significantly heightened biological effect.}, number={4}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Botham, Rachel C. and Fan, Timothy M. and Im, Isak and Borst, Luke B. and Dirikolu, Levent and Hergenrother, Paul J.}, year={2014}, month={Jan}, pages={1312–1319} }
 @article{thomas_borst_rotroff_motsinger-reif_lindblad-toh_modiano_breen_2014, title={Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma}, volume={22}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-014-9406-z}, abstractNote={Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however, the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24, and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving CDKN2A, VEGFA, and the SKI oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near twofold lower incidence of VEGFA gain in Golden Retrievers versus other breeds (22 versus 40 %). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly distinct subtypes of canine hemangiosarcoma.}, number={3}, journal={CHROMOSOME RESEARCH}, author={Thomas, Rachael and Borst, Luke and Rotroff, Daniel and Motsinger-Reif, Alison and Lindblad-Toh, Kerstin and Modiano, Jaime F. and Breen, Matthew}, year={2014}, month={Sep}, pages={305–319} }
 @article{steinbach_kobayashi_russo_sheikh_gipson_kennedy_uno_mishima_borst_liu_et al._2014, title={Innate PI3K p110 delta Regulates Th1/Th17 Development and Microbiota-Dependent Colitis}, volume={192}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.1301533}, abstractNote={The p110δ subunit of class IA PI3K modulates signaling in innate immune cells. We previously demonstrated that mice harboring a kinase-dead p110δ subunit (p110δ(KD)) develop spontaneous colitis. Macrophages contributed to the Th1/Th17 cytokine bias in p110δ(KD) mice through increased IL-12 and IL-23 expression. In this study, we show that the enteric microbiota is required for colitis development in germfree p110δ(KD) mice. Colonic tissue and macrophages from p110δ(KD) mice produce significantly less IL-10 compared with wild-type mice. p110δ(KD) APCs cocultured with naive CD4+ Ag-specific T cells also produce significantly less IL-10 and induce more IFN-γ- and IL-17A-producing CD4+ T cells compared with wild-type APCs. Illustrating the importance of APC-T cell interactions in colitis pathogenesis in vivo, Rag1(-/-)/p110δ(KD) mice develop mild colonic inflammation and produced more colonic IL-12p40 compared with Rag1(-/-) mice. However, CD4+ CD45RB(high/low) T cell Rag1(-/-)/p110δ(KD) recipient mice develop severe colitis with increased percentages of IFN-γ- and IL-17A-producing lamina propria CD3+D4+ T cells compared with Rag1(-/-) recipient mice. Intestinal tissue samples from patients with Crohn's disease reveal significantly lower expression of PIK3CD compared with intestinal samples from non-inflammatory bowel disease control subjects (p < 0.05). PIK3CD expression inversely correlates with the ratio of IL12B:IL10 expression. In conclusion, the PI3K subunit p110δ controls homeostatic APC-T cell interactions by altering the balance between IL-10 and IL-12/23. Defects in p110δ expression and/or function may underlie the pathogenesis of human inflammatory bowel disease and lead to new therapeutic strategies.}, number={8}, journal={JOURNAL OF IMMUNOLOGY}, author={Steinbach, Erin C. and Kobayashi, Taku and Russo, Steven M. and Sheikh, Shehzad Z. and Gipson, Gregory R. and Kennedy, Samantha T. and Uno, Jennifer K. and Mishima, Yoshiyuki and Borst, Luke B. and Liu, Bo and et al.}, year={2014}, month={Apr}, pages={3958–3968} }
 @article{tang_yang_yin_cai_wang_chaudhury_yao_zhou_kwon_hartman_et al._2014, title={Investigating the optimal size of anticancer nanomedicine}, volume={111}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1411499111}, abstractNote={Significance Understanding the interdependency of physiochemical properties of nanomedicine (NM) in correlation to its biological response and function is crucial for additional development of anticancer NM. Here, we prepared monodisperse drug–silica nanoconjugates in three distinct sizes (20, 50, and 200 nm) with other physiochemical properties controlled to be identical to investigate size-dependent biodistribution, tumor tissue penetration and clearance, and anticancer efficacy in various tumor models. We also developed a mathematical model of the spatiotemporal distribution of NM within a tumor to gain insight into the size-dependent interaction with tumor. Our studies show clear evidence that there is an optimal size of anticancer NM and that NM with the optimal size has the highest tumor retention integrated over time.}, number={43}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Tang, Li and Yang, Xujuan and Yin, Qian and Cai, Kaimin and Wang, Hua and Chaudhury, Isthier and Yao, Catherine and Zhou, Qin and Kwon, Mincheol and Hartman, James A. and et al.}, year={2014}, month={Oct}, pages={15344–15349} }
 @article{lennon_edwards_borst_moeser_2014, title={Mo1722 Mast Cells Play a Protective Role in Spontaneous Colitis}, volume={146}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/s0016-5085(14)62339-8}, DOI={10.1016/s0016-5085(14)62339-8}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Lennon, Elizabeth M. and Edwards, Laura and Borst, Luke B. and Moeser, Adam J.}, year={2014}, month={May}, pages={S-644} }
 @article{kobayashi_steinbach_russo_matsuoka_nochi_maharshak_borst_hostager_garcia-martinez_rothman_et al._2014, title={NFIL3-Deficient Mice Develop Microbiota-Dependent, IL-12/23-Driven Spontaneous Colitis}, volume={192}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.1301819}, abstractNote={NFIL3 is a transcription factor that regulates multiple immunologic functions. In myeloid cells, NFIL3 is IL-10 inducible and has a key role as a repressor of IL-12p40 transcription. NFIL3 is a susceptibility gene for the human inflammatory bowel diseases. In this article, we describe spontaneous colitis in Nfil3(-/-) mice. Mice lacking both Nfil3 and Il10 had severe early-onset colitis, suggesting that NFIL3 and IL-10 independently regulate mucosal homeostasis. Lymphocytes were necessary for colitis, because Nfil3/Rag1 double-knockout mice were protected from disease. However, Nfil3/Rag1 double-knockout mice adoptively transferred with wild-type CD4(+) T cells developed severe colitis compared with Rag1(-/-) recipients, suggesting that colitis was linked to defects in innate immune cells. Colitis was abrogated in Nfil3/Il12b double-deficient mice, identifying Il12b dysregulation as a central pathogenic event. Finally, germ-free Nfil3(-/-) mice do not develop colonic inflammation. Thus, NFIL3 is a microbiota-dependent, IL-10-independent regulator of mucosal homeostasis via IL-12p40.}, number={4}, journal={JOURNAL OF IMMUNOLOGY}, author={Kobayashi, Taku and Steinbach, Erin C. and Russo, Steven M. and Matsuoka, Katsuyoshi and Nochi, Tomonori and Maharshak, Nitsan and Borst, Luke B. and Hostager, Bruce and Garcia-Martinez, J. Victor and Rothman, Paul B. and et al.}, year={2014}, month={Feb}, pages={1918–1927} }
 @article{portela_fadl-alla_pondenis_byrum_garrett_wycislo_borst_fan_2014, title={Pro-tumorigenic Effects of Transforming Growth Factor Beta 1 in Canine Osteosarcoma}, volume={28}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12348}, abstractNote={Background Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities. Hypothesis Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations. Animals Thirty-three dogs with appendicular OS. Methods Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption. Results Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS-bearing dogs, circulating TGFβ1 concentrations correlate with urine N-telopeptide excretion. Conclusions and Clinical Importance Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Portela, R. F. and Fadl-Alla, B. A. and Pondenis, H. C. and Byrum, M. L. and Garrett, L. D. and Wycislo, K. L. and Borst, L. B. and Fan, T. M.}, year={2014}, month={May}, pages={894–904} }
 @article{campos_borst_cotter_2013, title={B Characterization of BcaA, a putative classical autotransporter protein in Burkholderia pseudomallei}, volume={81}, DOI={10.1128/iai.01453-12}, abstractNote={ABSTRACT Burkholderia pseudomallei is a tier 1 select agent, and the causative agent of melioidosis, a disease with effects ranging from chronic abscesses to fulminant pneumonia and septic shock, which can be rapidly fatal. Autotransporters (ATs) are outer membrane proteins belonging to the type V secretion system family, and many have been shown to play crucial roles in pathogenesis. The open reading frame Bp1026b_II1054 ( bcaA ) in B. pseudomallei strain 1026b is predicted to encode a classical autotransporter protein with an approximately 80-kDa passenger domain that contains a subtilisin-related domain. Immediately 3′ to bcaA is Bp11026_II1055 ( bcaB ), which encodes a putative prolyl 4-hydroxylase. To investigate the role of these genes in pathogenesis, large in-frame deletion mutations of bcaA and bcaB were constructed in strain Bp340, an efflux pump mutant derivative of the melioidosis clinical isolate 1026b. Comparison of Bp340Δ bcaA and Bp340Δ bcaB mutants to wild-type B. pseudomallei in vitro demonstrated similar levels of adherence to A549 lung epithelial cells, but the mutant strains were defective in their ability to invade these cells and to form plaques. In a BALB/c mouse model of intranasal infection, similar bacterial burdens were observed after 48 h in the lungs and liver of mice infected with Bp340Δ bcaA , Bp340Δ bcaB , and wild-type bacteria. However, significantly fewer bacteria were recovered from the spleen of Bp340Δ bcaA -infected mice, supporting the idea of a role for this AT in dissemination or in survival in the passage from the site of infection to the spleen.}, number={4}, journal={Infection and Immunity}, author={Campos, C. G. and Borst, Luke and Cotter, P. A.}, year={2013}, pages={1121–1128} }
 @article{d'costa_borst_kim_2013, title={Bone marrow-derived cells participate in the formation of normal and neoplastic lung stroma.}, volume={3}, url={http://europepmc.org/abstract/med/23482751}, number={3}, journal={Anticancer research}, author={D'Costa, S and Borst, L and Kim, Y}, year={2013}, month={Mar}, pages={831–836} }
 @article{onyiah_sheikh_maharshak_steinbach_russo_kobayashi_mackey_hansen_moeser_rawls_et al._2013, title={Carbon Monoxide and Heme Oxygenase-1 Prevent Intestinal Inflammation in Mice by Promoting Bacterial Clearance}, volume={144}, ISSN={["1528-0012"]}, DOI={10.1053/j.gastro.2012.12.025}, abstractNote={Background & AimsHeme oxygenase-1 (HO-1) and its metabolic by-product, carbon monoxide (CO), protect against intestinal inflammation in experimental models of colitis, but little is known about their intestinal immune mechanisms. We investigated the interactions among CO, HO-1, and the enteric microbiota in mice and zebrafish.MethodsGerm-free, wild-type, and interleukin (Il)10−/− mice and germ-free zebrafish embryos were colonized with specific pathogen-free (SPF) microbiota. Germ-free or SPF-raised wild-type and Il10−/− mice were given intraperitoneal injections of cobalt(III) protoporphyrin IX chloride (CoPP), which up-regulates HO-1, the CO-releasing molecule Alfama-186, or saline (control). Colitis was induced in wild-type mice housed in SPF conditions by infection with Salmonella typhimurium.ResultsIn colons of germ-free, wild-type mice, SPF microbiota induced production of HO-1 via activation of nuclear factor erythroid 2–related factor 2–, IL-10–, and Toll-like receptor–dependent pathways; similar observations were made in zebrafish. SPF microbiota did not induce HO-1 in colons of germ-free Il10−/− mice. Administration of CoPP to Il10−/− mice before transition from germ-free to SPF conditions reduced their development of colitis. In Il10−/− mice, CO and CoPP reduced levels of enteric bacterial genomic DNA in mesenteric lymph nodes. In mice with S typhimurium–induced enterocolitis, CoPP reduced the numbers of live S typhimurium recovered from the lamina propria, mesenteric lymph nodes, spleen, and liver. Knockdown of HO-1 in mouse macrophages impaired their bactericidal activity against E coli, E faecalis, and S typhimurium, whereas exposure to CO or overexpression of HO-1 increased their bactericidal activity. HO-1 induction and CO increased acidification of phagolysosomes.ConclusionsColonic HO-1 prevents colonic inflammation in mice. HO-1 is induced by the enteric microbiota and its homeostatic function is mediated, in part, by promoting bactericidal activities of macrophages. Heme oxygenase-1 (HO-1) and its metabolic by-product, carbon monoxide (CO), protect against intestinal inflammation in experimental models of colitis, but little is known about their intestinal immune mechanisms. We investigated the interactions among CO, HO-1, and the enteric microbiota in mice and zebrafish. Germ-free, wild-type, and interleukin (Il)10−/− mice and germ-free zebrafish embryos were colonized with specific pathogen-free (SPF) microbiota. Germ-free or SPF-raised wild-type and Il10−/− mice were given intraperitoneal injections of cobalt(III) protoporphyrin IX chloride (CoPP), which up-regulates HO-1, the CO-releasing molecule Alfama-186, or saline (control). Colitis was induced in wild-type mice housed in SPF conditions by infection with Salmonella typhimurium. In colons of germ-free, wild-type mice, SPF microbiota induced production of HO-1 via activation of nuclear factor erythroid 2–related factor 2–, IL-10–, and Toll-like receptor–dependent pathways; similar observations were made in zebrafish. SPF microbiota did not induce HO-1 in colons of germ-free Il10−/− mice. Administration of CoPP to Il10−/− mice before transition from germ-free to SPF conditions reduced their development of colitis. In Il10−/− mice, CO and CoPP reduced levels of enteric bacterial genomic DNA in mesenteric lymph nodes. In mice with S typhimurium–induced enterocolitis, CoPP reduced the numbers of live S typhimurium recovered from the lamina propria, mesenteric lymph nodes, spleen, and liver. Knockdown of HO-1 in mouse macrophages impaired their bactericidal activity against E coli, E faecalis, and S typhimurium, whereas exposure to CO or overexpression of HO-1 increased their bactericidal activity. HO-1 induction and CO increased acidification of phagolysosomes. Colonic HO-1 prevents colonic inflammation in mice. HO-1 is induced by the enteric microbiota and its homeostatic function is mediated, in part, by promoting bactericidal activities of macrophages.}, number={4}, journal={GASTROENTEROLOGY}, author={Onyiah, Joseph C. and Sheikh, Shehzad Z. and Maharshak, Nitsan and Steinbach, Erin C. and Russo, Steven M. and Kobayashi, Taku and Mackey, Lantz C. and Hansen, Jonathan J. and Moeser, Adam J. and Rawls, John F. and et al.}, year={2013}, month={Apr}, pages={789–798} }
 @article{moore_mariani_van wettere_borst_2013, title={Chronic Compressive Myelopathy and Progressive Neurologic Signs Associated with Melarsomine Dihydrochloride Administration in a Dog}, volume={49}, ISSN={["1547-3317"]}, url={http://dx.doi.org/10.5326/jaaha-ms-5911}, DOI={10.5326/jaaha-ms-5911}, abstractNote={A 7 yr old castrated male Great Dane presented with a history of progressive myelopathy following the intramuscular injection of melarsomine dihydrochloride 8 wk previously. MRI revealed paraspinal and epidural abscesses at the 13th thoracic (T13) and first lumbar (L1) disc space. The dog’s condition worsened despite medical management, necessitating surgical decompression. Surgical decompression resulted in rapid improvement of the patient’s clinical signs. Histopathologic evaluation of the lesions revealed pyogranulomatous inflammation. Cultures of fluid and tissue within the lesions were negative for bacterial growth, and no infectious organisms were visualized histologically. Melarsomine-associated neurologic signs can be chronic and progressive in nature, presumably secondary to ongoing sterile inflammation that may result in spinal cord compression.}, number={6}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Moore, Sarah A. and Mariani, Christopher L. and Van Wettere, Arnaud and Borst, Luke B.}, year={2013}, pages={389–393} }
 @article{mcclenahan_scherba_borst_fredrickson_uhlenhaut_2013, title={Discovery of a bovine enterovirus in alpaca.}, url={http://europepmc.org/abstract/med/23950875}, DOI={10.1371/journal.pone.0068777}, abstractNote={A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1), but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen.}, journal={PloS one}, author={McClenahan, SD and Scherba, G and Borst, L and Fredrickson, RL and Uhlenhaut, C}, year={2013}, month={Aug} }
 @article{gilor_gilor_graves_borst_labelle_ridge_santoro_dossin_2013, title={Distribution of K and L cells in the feline intestinal tract.}, volume={7}, url={http://europepmc.org/abstract/med/23751572}, DOI={10.1016/j.domaniend.2013.04.004}, abstractNote={Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1–expressing cells were abundant throughout the intestines, GLP-2–expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2– and GLP-1–expressing cells suggests that more than 1 distinct population of L cells is present in cats.}, journal={Domestic animal endocrinology}, author={Gilor, C and Gilor, S and Graves, TK and Borst, LB and Labelle, P and Ridge, TK and Santoro, D and Dossin, O}, year={2013}, month={May} }
 @article{lennon_maharshak_elloumi_borst_plevy_moeser_2013, title={Early Life Stress Triggers Persistent Colonic Barrier Dysfunction and Exacerbates Colitis in Adult IL-10(-/-) Mice}, volume={19}, ISSN={["1078-0998"]}, DOI={10.1097/mib.0b013e3182802a4e}, abstractNote={It has become increasingly evident that disease flares in the human inflammatory bowel diseases are influenced by life stress. It is known that life stress can trigger disturbances in intestinal barrier function and activate proinflammatory signaling pathways, which are important contributors to intestinal inflammation and clinical disease; however, the exact mechanisms of stress-induced inflammatory bowel disease exacerbations remain to be elucidated. Here, we presented a model of early life stress–induced exacerbation of colitis in interleukin (IL)-10−/− mice. C57Bl/6 wild-type and IL-10−/− mice were exposed to neonatal maternal separation (NMS) stress on postnatal days 1 to 18 and reared under normal conditions until 10 to 12 weeks of age. At this time, histopathology, colitis scores, intestinal barrier function, proinflammatory cytokine expression, and mast cell activity were evaluated. NMS increased the severity of colitis IL-10−/− mice indicated by greater colitis scores and colonic proinflammatory cytokine concentrations. NMS and IL-10−/− increased colonic permeability; however, NMS alone did not induce colitis. Increased mast cell activation and colonic tryptase release were observed in IL-10−/− mice exposed to NMS, indicating mast cell activation. This study demonstrates that colitis in IL-10−/− mice can be exacerbated by NMS stress. The precise mechanisms of enhanced colitis severity in NMS IL10−/− mice are unclear but persistent defects in intestinal barrier function likely play a contributing role. NMS serves as a novel model to investigate the mechanisms by which early life stress influences the development and course of inflammatory bowel disease in adulthood.}, number={4}, journal={INFLAMMATORY BOWEL DISEASES}, author={Lennon, E. M. and Maharshak, Nitsan and Elloumi, H. and Borst, L. and Plevy, S. E. and Moeser, Adam J.}, year={2013}, pages={712–719} }
 @article{bailey_hempstead_tobias_borst_clode_posner_2013, title={Evaluation of the effects of tricaine methanesulfonate on retinal structure and function in koi carp (Cyprinus carpio)}, volume={242}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.242.11.1578}, DOI={10.2460/javma.242.11.1578}, abstractNote={To determine whether repeated exposure to clinically relevant concentrations of tricaine methanesulfonate (MS-222) would alter retinal function or induce histologically detectable retinal lesions in koi carp (Cyprinus carpio).Prospective, controlled, experimental study.18 healthy koi carp.2 fish were euthanized at the start of the study, and eyes were submitted for histologic evaluation as untreated controls. Anesthesia was induced in the remaining fish with 200 mg of MS-222/L and maintained with concentrations of 125 to 150 mg/L for a total exposure time of 20 minutes daily on 1 to 13 consecutive days. On days 1, 7, and 13, electroretinography of both eyes was performed in all fish remaining in the study, and 2 fish were euthanized immediately after each procedure for histologic evaluation of the eyes. Median b-wave amplitudes were compared among study days for right eyes and for left eyes via 1-way repeated-measures ANOVA with a Bonferroni correction for multiple comparisons.Median b-wave amplitudes on days 1, 7, and 13 were 17.7, 20.9, and 17.6 μV, respectively, for right eyes and 15.1, 16.9, and 14.3 μV, respectively, for left eyes. No significant differences in b-wave amplitudes were detected among study days. No histopathologic abnormalities were identified in the retinas of any fish treated with MS-222 or in control fish.Short-term exposure of koi carp to clinically relevant concentrations of MS-222 daily for up to 13 days was not associated with changes in retinal structure or function as measured in this study.}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Bailey, Kate M. and Hempstead, Julie E. and Tobias, Jeremy R. and Borst, Luke B. and Clode, Alison B. and Posner, Lysa P.}, year={2013}, month={Jun}, pages={1578–1582} }
 @article{suyemoto_hamrick_spears_horton_washington_havell_borst_orndorff_2013, title={Extrauterine Listeriosis in the Gravid Mouse Influences Embryonic Growth and Development}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0072601}, DOI={10.1371/journal.pone.0072601}, abstractNote={Gravid mice and other rodents inoculated with Listeria monocytogenes typically fail to clear an intrauterine infection and either succumb or expel their intrauterine contents. We took advantage of this property to investigate the effects of an extrauterine infection on parameters of pregnancy success. Pregnant mice were selected for our study if they showed no clinical signs of listeriosis following oral inoculation at 7.5 gestational days (gd), and had no detectable intrauterine colony forming units (cfu) at near term (18.5 gd). The range of oral doses employed was 10⁶-10⁸ cfu per mouse for two listerial serotype strains (4nonb and 1/2a). At all doses, inoculation resulted in a decrease in average near-term (18.5 gd) fetal weight per litter compared to sham inoculated controls. Additionally, embryonic death (indicated by intrauterine resorptions) was exhibited by some inoculated mice but was absent in all sham inoculated animals. In parallel experiments designed to detect possible loss of placental function, gravid uteruses were examined histopathologically and microbiologically 96 h after oral inoculation. Placental lesions were associated with high (> 10⁶), but not low (< 10²) or absent intrauterine cfu. In vitro, mouse embryonic trophoblasts were indistinguishable from mouse enterocytes in terms of their sensitivity to listerial exposure. A model consistent with our observations is one in which products (host or bacterial) generated during an acute infection enter embryos transplacentally and influences embryonic survival and slows normal growth in utero.}, number={8}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Suyemoto, M. Mitsu and Hamrick, Terri S. and Spears, Patricia A. and Horton, John R. and Washington, Ida M. and Havell, Edward A. and Borst, Luke B. and Orndorff, Paul E.}, editor={Roop II, Roy MartinEditor}, year={2013}, month={Aug}, pages={e72601} }
 @article{ghosh_borst_stauffer_suyemoto_moisan_zurek_gookin_2013, title={GI-9 Mortality In Foster-Age Kittens Is Associated With A Shift From Ileum Mucosa-Associated Enterococcus Hirae to Colonization By E. Faecalis and Enteropathogenice E. Coli}, volume={27}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Ghosh, A. and Borst, L. and Stauffer, S. and Suyemoto, M. and Moisan, P. and Zurek, L. and Gookin, J.}, year={2013}, pages={698} }
 @article{richards_motsinger-reif_chen_fedoriw_fan_nielsen_small_thomas_smith_dave_et al._2013, title={Gene Profiling of Canine B-Cell Lymphoma Reveals Germinal Center and Postgerminal Center Subtypes with Different Survival Times, Modeling Human DLBCL}, volume={73}, ISSN={0008-5472 1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.CAN-12-3546}, DOI={10.1158/0008-5472.can-12-3546}, abstractNote={Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-κB pathway genes, mirroring human activated B-cell (ABC)–type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials. Cancer Res; 73(16); 5029–39. ©2013 AACR.}, number={16}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Richards, K. L. and Motsinger-Reif, A. A. and Chen, H.-W. and Fedoriw, Y. and Fan, C. and Nielsen, D. M. and Small, G. W. and Thomas, R. and Smith, C. and Dave, S. S. and et al.}, year={2013}, month={Jun}, pages={5029–5039} }
 @article{hempstead_clode_salmon_gilger_2013, title={Histopathologic features of equine superficial, nonhealing, corneal ulcers}, volume={17}, ISSN={["1463-5224"]}, DOI={10.1111/vop.12117}, abstractNote={Objective To evaluate corneal changes associated with chronic, nonhealing, superficial, corneal ulcers in horses via common histopathological stains. Design Retrospective study. Animals Twenty-four horses diagnosed with chronic, nonhealing, superficial, corneal ulceration. Methods The medical records of horses evaluated at North Carolina State University's Veterinary Teaching Hospital (NCSU-VTH) from 2005 to 2011, diagnosed with a chronic, nonhealing, superficial, corneal ulcer and treated with superficial keratectomy (SK) were reviewed. Inclusion criteria were superficial corneal ulceration, no cellular infiltration via slit-lamp biomicroscopy, no microorganisms evident on corneal cytology, and acquisition of samples for aerobic bacterial and common fungal cultures. Corneal tissue samples were evaluated histopathologically for the presence or absence of a nonadherent epithelial ‘lip’, epithelial dysmaturity, intraepithelial inflammatory cells, an acellular hyaline zone in the anterior stroma, and stromal inflammatory cells, fibrosis and vascularization. Results In the majority of analyzed samples, epithelial cells adjacent to the ulcerated site showed nonadherence to the basement membrane and dysmaturity. Intraepithelial inflammatory cell infiltration was uncommon. Histopathological features of an anterior stromal hyaline zone, intrastromal inflammation, fibrosis and vascularization were variably present. Conclusions The most consistent histopathological characteristics of equine chronic, nonhealing, superficial, corneal ulcers include epithelial nonadherence, epithelial dysmaturity and mild to moderate stromal inflammation; however, one set of histopathological characteristics does not definitively define this syndrome in horses. Additionally, the anterior stromal acellular hyaline zone commonly cited in canine spontaneous chronic corneal epithelial defects (SCCED) is not a consistent finding in equine corneas.}, journal={Veterinary Ophthalmology}, author={Hempstead, J.H. and Clode, A.C. and Salmon, B.H. and Gilger, B.C.}, year={2013}, pages={46–52} }
 @article{thalheim_williams_borst_fogle_suter_2013, title={Lymphoma Immunophenotype of Dogs Determined by Immunohistochemistry, Flow Cytometry, and Polymerase Chain Reaction for Antigen Receptor Rearrangements}, volume={27}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12185}, DOI={10.1111/jvim.12185}, abstractNote={Immunohistochemistry (IHC), flow cytometry (FC), and PCR for antigen receptor rearrangements (PARR) are 3 widely utilized tests to determine immunophenotype in dogs with lymphoma (LSA).This study evaluated the ability of FC and PARR to correctly predict immunophenotype as defined by IHC and to determine the level of agreement among the 3 tests.Sixty-two dogs with lymphoma.Retrospective study. Medical records were searched to identify dogs with LSA that had concurrent IHC, FC, and PARR performed. Immunophenotype results were categorized as B-cell, T-cell, dual immunophenotype (B- and T-cell), or indeterminate. The results of FC and PARR were evaluated for correctly classifying B- and T-cell LSA as compared with IHC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated in addition to concordance between each test.The sensitivity of FC was significantly higher than PARR for both B-cell (91% versus 67%; P < 0.0072) and T-cell (100% versus 75%; P < 0.0312) LSA. The percent agreement between FC and IHC was 94%, between PARR and IHC was 69%, between FC and PARR was 63%, and among all 3 tests was 63%.Flow cytometry is superior to PARR in correctly predicting immunophenotype when evaluating lymph nodes from dogs already diagnosed with B- or T-cell LSA. If fresh samples are not available for FC, PARR is an acceptable assay for determination of immunophenotype given its high specificity.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Thalheim, L. and Williams, L.E. and Borst, L.B. and Fogle, J.E. and Suter, S.E.}, year={2013}, month={Sep}, pages={1509–1516} }
 @article{culver_ito_borst_bell_modiano_breen_2013, title={Molecular characterization of canine BCR-ABL-positive chronic myelomonocytic leukemia before and after chemotherapy}, volume={42}, ISSN={0275-6382}, url={http://dx.doi.org/10.1111/vcp.12055}, DOI={10.1111/vcp.12055}, abstractNote={Genetic aberrations linked to tumorigenesis have been identified in both canine and human hematopoietic malignancies. While the response of human patients to cancer treatments is often evaluated using cytogenetic techniques, this approach has not been used for dogs with comparable neoplasias. The aim of this study was to demonstrate the applicability of cytogenetic techniques to evaluate the cytogenetic response of canine leukemia to chemotherapy. Cytology and flow cytometric techniques were used to diagnose chronic myelomonocytic leukemia in a dog. High-resolution oligonucleotide array comparative genomic hybridization (oaCGH) and multicolor fluorescence in situ hybridization (FISH) were performed to identify and characterize DNA copy number aberrations (CNAs) and targeted structural chromosome aberrations in peripheral blood WBC at the time of diagnosis and following one week of chemotherapy. At the time of diagnosis, oaCGH indicated the presence of 22 distinct CNAs, of which trisomy of dog chromosome 7 (CFA 7) was the most evident. FISH analysis revealed that this CNA was present in 42% of leukemic cells; in addition, a breakpoint cluster region-Abelson murine leukemia viral oncogene homolog (BCR-ABL) translocation was evident in 17.3% of cells. After one week of treatment, the percentage of cells affected by trisomy of CFA7 and BCR-ABL translocation was reduced to 2% and 3.3%, respectively. Chromosome aberrations in canine leukemic cells may be monitored by molecular cytogenetic techniques to demonstrate cytogenetic remission following treatment. Further understanding of the genetic aberrations involved in canine leukemia may be crucial to improve treatment protocols.}, number={3}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Culver, Sarah and Ito, Daisuke and Borst, Luke and Bell, Jerold S. and Modiano, Jaime F. and Breen, Matthew}, year={2013}, month={Jun}, pages={314–322} }
 @article{ghosh_borst_stauffer_suyemoto_moisan_zurek_gookin_2013, title={Mortality in Kittens Is Associated with a Shift in Ileum Mucosa-Associated Enterococci from Enterococcus hirae to Biofilm-Forming Enterococcus faecalis and Adherent Escherichia coli}, volume={51}, ISSN={["1098-660X"]}, DOI={10.1128/jcm.00481-13}, abstractNote={Approximately 15% of foster kittens die before 8 weeks of age, with most of these kittens demonstrating clinical signs or postmortem evidence of enteritis. While a specific cause of enteritis is not determined in most cases, these kittens are often empirically administered probiotics that contain enterococci. The enterococci are members of the commensal intestinal microbiota but also can function as opportunistic pathogens. Given the complicated role of enterococci in health and disease, it would be valuable to better understand what constitutes a "healthy" enterococcal community in these kittens and how this microbiota is impacted by severe illness. In this study, we characterized the ileum mucosa-associated enterococcal community of 50 apparently healthy and 50 terminally ill foster kittens. In healthy kittens, Enterococcus hirae was the most common species of ileum mucosa-associated enterococci and was often observed to adhere extensively to the small intestinal epithelium. These E. hirae isolates generally lacked virulence traits. In contrast, non-E. hirae enterococci, notably Enterococcus faecalis, were more commonly isolated from the ileum mucosa of kittens with terminal illness. Isolates of E. faecalis had numerous virulence traits and multiple antimicrobial resistances. Moreover, the attachment of Escherichia coli to the intestinal epithelium was significantly associated with terminal illness and was not observed in any kitten with adherent E. hirae. These findings identify a significant difference in the species of enterococci cultured from the ileum mucosa of kittens with terminal illness compared to the species cultured from healthy kittens. In contrast to prior case studies that associated enteroadherent E. hirae with diarrhea in young animals, these controlled studies identified E. hirae as more often isolated from healthy kittens and adherence of E. hirae as more common and extensive in healthy kittens than in sick kittens.}, number={11}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Ghosh, Anuradha and Borst, Luke and Stauffer, Stephen H. and Suyemoto, Mitsu and Moisan, Peter and Zurek, Ludek and Gookin, Jody L.}, year={2013}, month={Nov}, pages={3567–3578} }
 @article{wagner_lin_borst_miller_2013, title={YaxAB, a Yersinia enterocolitica Pore-Forming Toxin Regulated by RovA}, volume={81}, ISSN={["1098-5522"]}, DOI={10.1128/iai.00781-13}, abstractNote={ABSTRACT The transcriptional regulator RovA positively regulates transcription of the Yersinia enterocolitica virulence gene inv . Invasin, encoded by inv , is important for establishment of Y. enterocolitica infection. However, a rovA mutant is more attenuated for virulence than an inv mutant, implying that RovA regulates additional virulence genes. When the Y. enterocolitica RovA regulon was defined by microarray analysis, YE1984 and YE1985 were among the genes identified as being upregulated by RovA. Since these genes are homologous to Xenorhabdus nematophila cytotoxin genes xaxA and xaxB , we named them yaxA and yaxB , respectively. In this work, we demonstrate the effects of YaxAB on the course of infection in the murine model. While a yaxAB mutant (Δ yaxAB ) is capable of colonizing mice at the same level as the wild type, it slightly delays the course of infection and results in differing pathology in the spleen. Further, we found that yaxAB encode a probable cytotoxin capable of lysing mammalian cells, that both YaxA and YaxB are required for cytotoxic activity, and that the two proteins associate. YaxAB-mediated cell death occurs via osmotic lysis through the formation of distinct membrane pores. In silico tertiary structural analysis identified predicted structural homology between YaxA and proteins in pore-forming toxin complexes from Bacillus cereus (HBL-B) and Escherichia coli (HlyE). Thus, it appears that YaxAB function as virulence factors by inducing cell lysis through the formation of pores in the host cell membrane. This characterization of YaxAB supports the hypothesis that RovA regulates expression of multiple virulence factors in Y. enterocolitica .}, number={11}, journal={INFECTION AND IMMUNITY}, author={Wagner, Nikki J. and Lin, Carolina P. and Borst, Luke B. and Miller, Virginia L.}, year={2013}, month={Nov}, pages={4208–4219} }
 @article{borst_patterson_lanka_suyemoto_maddox_2013, title={Zebrafish (Danio rerio) as a Screen for Attenuation of Lancefield Group C Streptococci and a Model for Streptococcal Pathogenesis}, volume={50}, ISSN={["1544-2217"]}, DOI={10.1177/0300985811424731}, abstractNote={Group C streptococci are highly contagious pyogenic bacteria responsible for respiratory tract, lymph node, urogenital tract, and wound infections. Wild-type strains of Streptococcus equi ssp equi ( S. equi) and Streptococcus equi ssp zooepidemicus ( S. zoo) as well as a commercially available modified live vaccine strain of S. equi were evaluated for virulence in zebrafish. Survival times, histologic lesions, and relative gene expression were compared among groups. Based on the intramuscular route of infection, significantly shorter survival times were observed in fish infected with wild-type strain when compared to modified live vaccine and S. zoo strains. Histologically, S. zoo–infected fish demonstrated a marked increase in inflammatory infiltrates (predominantly macrophages) at the site of infection, as well as increased cellularity in the spleen and renal interstitium. In contrast, minimal cellular immune response was observed in S. equi–injected fish with local tissue necrosis and edema predominating. Based on whole comparative genomic hybridization, increased transcription of positive acute-phase proteins, coagulation factors, and antimicrobial peptides were observed in S. equi–injected fish relative to S. zoo–injected fish, while mediators of cellular inflammation, including CXC chemokines and granulin, were upregulated in S. zoo–injected fish relative to S. equi–injected fish. In a screen of 11 clinical isolates, S. equi strains with a single nucleotide deletion in the upstream region of szp, a known virulence factor of streptococci, were found to be significantly attenuated in zebrafish. These collective findings underscore the value of the zebrafish as a model of streptococcal pathogenesis.}, number={3}, journal={VETERINARY PATHOLOGY}, author={Borst, L. B. and Patterson, S. K. and Lanka, S. and Suyemoto, M. M. and Maddox, C. W.}, year={2013}, month={May}, pages={457–467} }
 @article{kobayashi_russo_matsuoka_nochi_borst_garcia_rothman_kashiwada_plevy_2012, title={867 NFIL3 Deficient Mice Develop Severe Innate Immune Mediated Spontaneous Colitis}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/s0016-5085(12)60563-0}, DOI={10.1016/s0016-5085(12)60563-0}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Kobayashi, Taku and Russo, Steven and Matsuoka, Katsuyoshi and Nochi, Tomonori and Borst, Luke B. and Garcia, J Victor and Rothman, Paul B. and Kashiwada, Masaki and Plevy, Scott E.}, year={2012}, month={May}, pages={S-149} }
 @article{robbins_suyemoto_lyman_martin_barnes_borst_2012, title={An Outbreak and Source Investigation of Enterococcal Spondylitis in Broilers Caused by Enterococcus cecorum}, volume={56}, ISSN={["0005-2086"]}, DOI={10.1637/10253-052412-case.1}, abstractNote={Enterococcus cecorum was isolated from spondylitis lesions in broilers from two flocks in North Carolina that were experiencing increased mortality. Affected birds showed paresis and paralysis, clinical signs characteristic of enterococcal spondylitis (ES). Affected birds rested on their hocks and caudal abdomens with legs extended forward and were unable to stand or walk. Necropsy examination of affected birds revealed firm to hard inflammatory masses involving the vertebral bodies at the level of the free thoracic vertebra that bulged dorsally and compressed the spinal cord. When opened, lesions contained pale, tan to yellow caseonecrotic material. Microscopically, necrosis and fibrinoheterophilic spondylitis with intralesional gram-positive bacteria were seen. Heavy growth of E. cecorum recovered from vertebral lesions confirmed the diagnosis of ES. To investigate possible sources of the organism for one of the flocks bacterial cultures were made from the environment, water lines, mice trapped on the farm, cecal/cloacal swabs from one of the parent broiler breeder flocks, egg residue, hatching eggs, and the hatchery environment. Except for cecal/cloacal swabs from the breeders, E. cecorum was not isolated from any of these samples. When compared phenotypically and genotypically, cecal/cloacal isolates of E. cecorum from the breeders differed from isolates from spondylitis lesions in the broilers. The source of E. cecorum for the broiler flocks was not determined, but vertical transmission appears unlikely.}, number={4}, journal={AVIAN DISEASES}, author={Robbins, Kabel M. and Suyemoto, M. Mitsu and Lyman, Roberta L. and Martin, Michael P. and Barnes, H. John and Borst, Luke B.}, year={2012}, month={Dec}, pages={768–773} }
 @article{bailey_heitzman_buchanan_bare_sper_borst_macpherson_archibald_whitacre_2012, title={B-mode and Doppler ultrasonography in pony mares with experimentally induced ascending placentitis}, volume={44}, ISSN={["2042-3306"]}, DOI={10.1111/j.2042-3306.2012.00658.x}, abstractNote={Early, accurate diagnosis of ascending placentitis in mares remains a key challenge for successful treatment of the disease. Doppler ultrasonography has shown promise as a tool to diagnose pregnancy abnormalities and is becoming more available to equine clinicians. However, to date, no studies have prospectively compared this technique to standard B-mode measurement of the combined thickness of the uterus and placenta (CTUP).The objective of the current study was to compare Doppler and B-mode ultrasonography for the detection of experimentally-induced ascending placentitis in mares.Eleven healthy pony mares in late gestation were used in this study. Placentitis was induced in 6 mares between Days 280 and 295, while 5 mares served as negative controls. All mares were intensively monitored until delivery. Fetal heart rate, CTUP, uterine artery blood flow (resistance index, pulsatility index, arterial diameter and total arterial blood flow) and physical examination findings were recorded at each examination. Mares with an increased CTUP above published values were treated in accordance with published recommendations. Foals and fetal membranes were examined at birth. Ultrasonographic parameters were compared between groups using ANOVA. Foal viability and histological presence of placentitis were compared using a Fisher's exact test.The CTUP was increased above normal in 5 of 6 inoculated mares within 3 days after inoculation (P = 0.05). The sixth inoculated mare was excluded from subsequent data analysis. Uterine artery blood flow, physical examination findings and fetal heart rate were not different between groups. Gradual increases in CTUP, arterial diameter and total arterial blood flow were detected with increasing gestational age in the control mares (P = 0.02, P = 0.00001 and P = 0.00001, respectively).The CTUP, but not uterine blood flow, was different between groups (P = 0.00001). Recorded CTUP values for control pony mares were similar to previously published values for light breed horses.}, journal={EQUINE VETERINARY JOURNAL}, author={Bailey, C. S. and Heitzman, J. M. and Buchanan, C. N. and Bare, C. A. and Sper, R. B. and Borst, L. B. and Macpherson, M. and Archibald, K. and Whitacre, M.}, year={2012}, month={Dec}, pages={88–94} }
 @article{schmit_pondenis_barger_borst_garrett_wypij_neumann_fan_2012, title={Cathepsin K Expression and Activity in Canine Osteosarcoma}, volume={26}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2011.00834.x}, abstractNote={Background Cathepsin K (CatK) is a lysosomal protease with collagenolytic activity, and its secretion by osteoclasts is responsible for degrading organic bone matrix. People with pathologic bone resorption have higher circulating CatK concentrations. Hypothesis Canine osteosarcoma (OS) cells will possess CatK, and its secretion will be cytokine inducible. Circulating CatK concentrations will be increased in dogs with OS, and will be a surrogate marker of bone resorption. Animals Fifty-one dogs with appendicular OS and 18 age- and weight-matched healthy control dogs. Methods In a prospective study, expressions of CatK mRNA and protein were investigated in OS cells. The inducible secretion and proteolytic activity of CatK from OS cells was assessed in vitro. Serum CatK concentrations were quantified in normal dogs and dogs with OS and its utility as a bone resorption marker was evaluated in dogs with OS treated with palliative radiation and antiresorptive agents. Results Canine OS cells contain preformed CatK within cytoplasmic vesicles. In OS cells, TGFβ1 induced the secretion of CatK, which degraded bone-derived type I collagen in vitro. CatK concentrations were higher in dogs with OS than healthy dogs (11.3 ± 5.2 pmol/L versus 8.1 ± 5.0 pmol/L, P = .03). In a subset of dogs with OS, pretreatment CatK concentrations gradually decreased after palliative radiation and antiresorptive treatment, from 9.3 ± 3.2 pmol/L to 5.0 ± 3.1 pmol/L, P = .03. Conclusions and Clinical Importance Canine OS is associated with pathologic bone resorption, and CatK inhibitors might aid in the management of canine OS-related malignant osteolysis.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Schmit, J. M. and Pondenis, H. C. and Barger, A. M. and Borst, L. B. and Garrett, L. D. and Wypij, J. M. and Neumann, Z. L. and Fan, T. M.}, year={2012}, pages={126–134} }
 @article{boozer_davis_borst_zseltvay_olby_mariani_2012, title={Characterization of Immune Cell Infiltration Into Canine Intracranial Meningiomas}, volume={49}, ISSN={["1544-2217"]}, url={http://dx.doi.org/10.1177/0300985811417249}, DOI={10.1177/0300985811417249}, abstractNote={Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (αD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3 + T cells. Large numbers of CD18 + microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d + . Scattered macrophages at the tumor–brain interface were TLR4 + and TLR9 + . Rare CD79a + B cells were noted in only a small subset of tumors. Lesser numbers of lymphocytes that were CD11d + , CD45RA + , or FoxP3 + were noted in a number of the meningiomas. Although the function of these cells is not yet clear, work in other species suggests that evaluation of this immune cell infiltrate may provide important prognostic information and may be useful in the design of novel therapies.}, number={5}, journal={VETERINARY PATHOLOGY}, author={Boozer, L. B. and Davis, T. W. and Borst, L. B. and Zseltvay, K. M. and Olby, N. J. and Mariani, C. L.}, year={2012}, month={Sep}, pages={784–795} }
 @article{moeser_borst_overman_pittman_2012, title={Defects in small intestinal epithelial barrier function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine}, volume={93}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2012.01.003}, abstractNote={The objective of this study was to investigate intestinal function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine. Jejunum and distal ileum from control and pigs exhibiting PFTS was harvested at weaning, 4 and 11 days post-weaning (PW) for intestinal barrier function studies and histological analyses (n=6 pigs per group). Marked disturbances in intestinal barrier function was observed in PFTS pigs, compared with controls, indicated by lower (p<0.05) TER and increased (p<0.01) permeability to FITC dextran (4 kDa). Intestines from weaned pigs, subjected to a 4-day fast, exhibited minor disturbances in intestinal barrier function. Villus atrophy and crypt hyperplasia were observed in the PFTS intestine compared with control and fasted pigs. These data demonstrate that PFTS is associated with profound disturbances in intestinal epithelial barrier function and alterations in mucosal and epithelial morphology in which anorexia is not the sole factor.}, number={2}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Moeser, Adam J. and Borst, Luke B. and Overman, Beth L. and Pittman, Jeremy S.}, year={2012}, month={Oct}, pages={975–982} }
 @article{stoermer_burrack_oko_montgomery_borst_gill_morrison_2012, title={Genetic Ablation of Arginase 1 in Macrophages and Neutrophils Enhances Clearance of an Arthritogenic Alphavirus}, volume={189}, ISSN={["0022-1767"]}, DOI={10.4049/jimmunol.1201240}, abstractNote={Chikungunya virus (CHIKV) and Ross River virus (RRV) cause a debilitating, and often chronic, musculoskeletal inflammatory disease in humans. Macrophages constitute the major inflammatory infiltrates in musculoskeletal tissues during these infections. However, the precise macrophage effector functions that affect the pathogenesis of arthritogenic alphaviruses have not been defined. We hypothesized that the severe damage to musculoskeletal tissues observed in RRV- or CHIKV-infected mice would promote a wound-healing response characterized by M2-like macrophages. Indeed, we found that RRV- and CHIKV-induced musculoskeletal inflammatory lesions, and macrophages present in these lesions, have a unique gene-expression pattern characterized by high expression of arginase 1 and Ym1/Chi3l3 in the absence of FIZZ1/Relmα that is consistent with an M2-like activation phenotype. Strikingly, mice specifically deleted for arginase 1 in neutrophils and macrophages had dramatically reduced viral loads and improved pathology in musculoskeletal tissues at late times post-RRV infection. These findings indicate that arthritogenic alphavirus infection drives a unique myeloid cell activation program in inflamed musculoskeletal tissues that inhibits virus clearance and impedes disease resolution in an arginase 1-dependent manner.}, number={8}, journal={JOURNAL OF IMMUNOLOGY}, author={Stoermer, Kristina A. and Burrack, Adam and Oko, Lauren and Montgomery, Stephanie A. and Borst, Luke B. and Gill, Ronald G. and Morrison, Thomas E.}, year={2012}, month={Oct}, pages={4047–4059} }
 @article{borst_suyemoto_robbins_lyman_martin_barnes_2012, title={Molecular epidemiology of Enterococcus cecorum isolates recovered from enterococcal spondylitis outbreaks in the southeastern United States}, volume={41}, ISSN={["1465-3338"]}, DOI={10.1080/03079457.2012.718070}, abstractNote={Enterococcus cecorum, a normal intestinal inhabitant, is increasingly responsible for outbreaks of arthritis and osteomyelitis in chickens worldwide. Enterococcal spondylitis (ES) is a specific manifestation of E. cecorum-associated disease in which increased flock morbidity and mortality result from chronic infection involving the free thoracic vertebra. In this study the genetic relatedness and antimicrobial resistance of isolates recovered from ES-affected flocks in the southeastern United States were determined. ES outbreaks from 2007 to 2011 were investigated in North Carolina (15 flocks, 13 farms, four integrators), South Carolina (one flock, one farm, one integrator) and Alabama (six flocks, six farms, one integrator). From these 22 epidemiologically distinct outbreaks, 326 isolates of E. cecorum were recovered. Isolates from spinal lesions and caeca of affected birds (cases) and caeca of unaffected birds (controls) were genotyped using pulsed-field gel electrophoresis; phenotyped using both GenIII MicroPlate™ (Biolog; Hayward, CA, USA) microbial identification plates and antimicrobial sensitivity testing; and compared with each other. Isolates from spinal lesions were incapable of mannitol metabolism and the majority of these isolates were genetically clonal. In contrast, caecal isolates from control birds varied in their ability to metabolize mannitol and were genetically diverse. Isolates from both case and control birds had high levels of antimicrobial resistance. These findings indicate that the increase in E. cecorum-associated disease in the southeast United States is due to the emergence of new clones with increased pathogenicity and multidrug resistance.}, number={5}, journal={AVIAN PATHOLOGY}, author={Borst, Luke B. and Suyemoto, M. Mitsu and Robbins, Kabel M. and Lyman, Roberta L. and Martin, Michael P. and Barnes, H. John}, year={2012}, pages={479–485} }
 @article{jain_pitoc_holl_zhang_borst_leong_lee_sullenger_2012, title={Nucleic acid scavengers inhibit thrombosis without increasing bleeding}, volume={109}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1204928109}, abstractNote={Development of effective, yet safe, antithrombotic agents has been challenging because such agents increase the propensity of patients to bleed. Recently, naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphates have been shown to activate blood coagulation. In this report, we evaluate the anticoagulant and antithrombotic activity of nucleic acid-binding polymers in vitro and in vivo. Such polymers bind to DNA, RNA, and inorganic polyphosphate molecules with high affinity and inhibit RNA- and polyphosphate-induced clotting and the activation of the intrinsic pathway of coagulation in vitro. Moreover, [NH 2 (CH 2 ) 2 NH 2 ]∶(G = 3);dendri PAMAM(NH 2 ) 32 (PAMAM G-3) prevents thrombosis following carotid artery injury and pulmonary thromboembolism in mice without significantly increasing blood loss from surgically challenged animals. These studies indicate that nucleic acid-binding polymers are able to scavenge effectively prothrombotic nucleic acids and other polyphosphates in vivo and represent a new and potentially safer class of antithrombotic agents.}, number={32}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Jain, Shashank and Pitoc, George A. and Holl, Eda K. and Zhang, Ying and Borst, Luke and Leong, Kam W. and Lee, Jaewoo and Sullenger, Bruce A.}, year={2012}, month={Aug}, pages={12938–12943} }
 @article{bailey_fallon_wang_borst_timoney_2012, title={Serum and Colostral Antibody Responses of Pregnant Mares to Salmonella Bacterins and Colostral Antibody Transfer to Their Foals}, volume={32}, ISSN={["0737-0806"]}, url={http://europepmc.org/abstract/AGR/IND44713884}, DOI={10.1016/j.jevs.2012.02.001}, abstractNote={Abstract Salmonella spp. are well-recognized foal pathogens. However, prevention of neonatal salmonellosis by vaccinating pregnant mares has not been reported previously. A formalinized adjuvanted bacterin of Salmonella enterica, serovar typhimurium (S typhimurium) and serovar newport (S newport), was given to pregnant mares to determine its safety (study 1) and potency in enhancing Salmonella-specific antibody for colostral transfer to foals (study 2). Antibody levels to S typhimurium (lysate and lipopolysaccharide [LPS]) and S newport (lysate) were determined by enzyme-linked immunoassay and reported as optical density measures. The mares in study 1 (n = 16) exhibited minimal reactions to the bacterin, and pregnancy was maintained in all mares throughout the study period. In study 2, serum antibody levels to both S typhimurium and S newport increased significantly in vaccinated mares (mean OD increase: 0.83 ± 0.58 [lysate of S typhimurium], 1.27 ± 0.82 [LPS of S typhimurium], and 0.67 ± 0.74 [lysate of S newport], respectively; n = 28). Elevated serum antibody levels on day 28 correlated with high antibody levels in colostrum (r2 = 0.62-0.75; P}, number={9}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Bailey, Christopher Scott and Fallon, Luke and Wang, Wei and Borst, Luke and Timoney, John}, year={2012}, month={Sep}, pages={575–578} }
 @article{tang_fan_borst_cheng_2012, title={Synthesis and Biological Response of Size-Specific, Monodisperse Drug-Silica Nanoconjugates}, volume={6}, ISSN={["1936-0851"]}, DOI={10.1021/nn300149c}, abstractNote={Drug-containing nanoparticles (NPs) with monodisperse, controlled particle sizes are highly desirable for drug delivery. Accumulating evidence suggests that NPs with sizes less than 50 nm demonstrate superior performance in vitro and in vivo. However, it is difficult to fabricate monodisperse, drug-containing NPs with discrete sizes required for studying and characterizing existing relationships among particle size, biologic processing, and therapeutic functionality. Here, we report a scalable process of fabricating drug-silica conjugated nanoparticles, termed drug-silica nanoconjugates (drug-NCs), which possess monodisperse size distributions and desirable particle sizes as small as 20 nm. We find that 20 nm NCs are superior to their 50 and 200 nm NC analogues by 2-5- and 10-20-fold, respectively, with regard to tumor accumulation and penetration and cellular internalization. These fundamental findings underscore the importance and necessity of further miniaturizing nanomedicine size for optimized drug delivery applications.}, number={5}, journal={ACS NANO}, author={Tang, Li and Fan, Timothy M. and Borst, Luke B. and Cheng, Jianjun}, year={2012}, month={May}, pages={3954–3966} }
 @article{neihaus_locke_barger_borst_goring_2011, title={A Novel Method of Core Aspirate Cytology Compared to Fine-Needle Aspiration for Diagnosing Canine Osteosarcoma}, volume={47}, ISSN={["1547-3317"]}, DOI={10.5326/jaaha-ms-5676}, abstractNote={There is little information in veterinary literature regarding the diagnostic accuracy of aspirate cytology for the diagnosis of canine osteosarcoma (OSA). The authors compared the diagnostic accuracy of a novel method of cytologic collection, termed core aspirate cytology (CA), with fine needle aspiration (FNA) and histopathology in 27 dogs with lytic and/or proliferative bone lesions. Alkaline phosphatase (ALP) staining was performed to confirm the diagnosis of OSA cytologically. OSA was accurately diagnosed in 85% and 95% of FNA and CA, respectively. ALP staining was 100% sensitive for the diagnosis of OSA. CA using a bone marrow biopsy needle allowed for penetration of cortical bone and aspirate cytology with a larger bore needle than FNA; however, there was no significant difference in diagnostic accuracy between techniques. Aspirate cytology with ALP staining was a safe, accurate, and minimally invasive diagnostic test for the evaluation of suspected OSA lesions in dogs.}, number={5}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Neihaus, Steven A. and Locke, Jennifer E. and Barger, Anne M. and Borst, Luke B. and Goring, Robert L.}, year={2011}, pages={317–323} }
 @article{ardente_christian_borst_lewbart_2011, title={CLINICAL CHALLENGE}, volume={42}, ISSN={["1042-7260"]}, DOI={10.1638/2011-0028.1}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Ardente, Amanda J. and Christian, Larry S. and Borst, Luke B. and Lewbart, Gregory A.}, year={2011}, month={Dec}, pages={770–773} }
 @article{borst_patterson_lanka_barger_fredrickson_maddox_2011, title={Evaluation of a commercially available modified-live Streptococcus equi subsp equi vaccine in ponies}, volume={72}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.72.8.1130}, abstractNote={To evaluate a commercially available modified-live Streptococcus equi subsp equi vaccine for safety and persistence in vaccinated ponies and to detect recombination or reversion events in the vaccine strain.5 ponies that were 1.5 to 8 years old (group 1) and 4 ponies that were 6 months old (group 2).Ponies were vaccinated, with a subsequent booster vaccination 2 to 3 weeks later, and monitored for 50 days. At booster vaccination, an equal amount of a tetracycline-resistant wild-type strain of S equiwas administered. Recovery of all strains was performed by use of bacteriologic culture and PCR assays.Ponies in group 1 had background antibody titers against S equi antigen before vaccination despite the lack of known exposure to S equi. Ponies in group 2 were immunologically naïve. Increases in anti-S equi antibody titers were detected in both groups. Ponies in group 1 did not have clinical signs of disease caused by S equi. In group 2, all ponies developed abscesses in retropharyngeal lymph nodes; 1 pony developed severe clinical disease and was euthanized. The vaccine strain was recovered from ponies in group 2 for up to 24 days after vaccination.Although the vaccine was successful in inducing IgG antibodies against S equi in all ponies, findings suggested that the vaccine may have caused substantial morbidity and some deaths in the young ponies. In young ponies, the vaccine strain persisted in tissues for weeks; however, no evidence of recombination was detected.}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Borst, Luke B. and Patterson, Sheila K. and Lanka, Saraswathi and Barger, Anne M. and Fredrickson, Richard L. and Maddox, Carol W.}, year={2011}, month={Aug}, pages={1130–1138} }
 @article{thomas_seiser_motsinger-reif_borst_valli_kelley_suter_argyle_burgess_bell_et al._2011, title={Refining tumor-associated aneuploidy through ‘genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas}, volume={52}, ISSN={1042-8194 1029-2403}, url={http://dx.doi.org/10.3109/10428194.2011.559802}, DOI={10.3109/10428194.2011.559802}, abstractNote={Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. 'Genomic recoding' of canine NHL data into a 'virtual human' chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.}, number={7}, journal={Leukemia & Lymphoma}, publisher={Informa UK Limited}, author={Thomas, Rachael and Seiser, Eric L. and Motsinger-Reif, Alison and Borst, Luke and Valli, Victor E. and Kelley, Kathryn and Suter, Steven E. and Argyle, David and Burgess, Kristine and Bell, Jerold and et al.}, year={2011}, month={Mar}, pages={1321–1335} }
 @article{lanka_borst_patterson_maddox_2010, title={A multiphasic typing approach to subtype Streptococcus equi subspecies equi}, volume={22}, ISSN={["1040-6387"]}, DOI={10.1177/104063871002200612}, abstractNote={The objective of the present investigation was to differentiate between strains of Streptococcus equi subspecies equi implicated in abscess formation in vaccinated horses. Streptococcus equi isolates recovered from clinical specimens associated with equine strangles cases submitted to the University of Illinois Veterinary Diagnostic Laboratory were compared with S. equi isolates representing at least 12 lots of a commercial modified live vaccine (MLV) to determine whether the isolates obtained from the abscesses were vaccine or wild type. Genotyping techniques evaluated included enterobacterial repetitive intergenic consensus polymerase chain reaction (PCR), repetitive extragenic palindrome PCR, BOX element PCR, ribotyping, and pulsed-field gel electrophoresis (PFGE). Phenotypic evaluations were performed using the Biolog GP2 Microplate (hereafter, Biolog). In cases where Biolog and PFGE results did not coincide, a single nucleotide polymorphism located in the upstream regulatory region of szp gene was used to identify the S. equi strains. PFGE and Biolog successfully differentiated wild-type S. equi strains isolated from clinical submissions from isolates of the MLV. PFGE genotyping enabled further subtyping of the wild-type strains, whereas Biolog combined with szp sequencing was useful in differentiating the MLV strain from its wild-type progenitor. Deletion of a single guanine residue located in the upstream regulatory region of the szp gene appears to be conserved among vaccine isolates, and shows a 98.5% correlation to Biolog identification. This multiphasic approach can be used to answer specific diagnostic questions pertaining to the source of infection and/or outbreak, or to address quarantine concerns.}, number={6}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Lanka, Saraswathi and Borst, Luke B. and Patterson, Sheila K. and Maddox, Carol W.}, year={2010}, month={Nov}, pages={928–936} }
 @article{hillman_garrett_lorimier lp_charney_borst_fan_2010, title={Biological behavior of oral and perioral mast cell tumors in dogs: 44 cases (1996-2006).}, volume={10}, url={http://europepmc.org/abstract/med/20946081}, DOI={10.2460/javma.237.8.936}, abstractNote={To describe clinical outcome of dogs with mast cell tumors (MCTs) arising from the oral mucosa, oral mucocutaneous junction, or perioral region of the muzzle and evaluate the potential role of the chemokine receptor type 7 (CCR7) in the biological behavior of these tumors.Retrospective case series.44 dogs with MCTs of the oral mucosa (n=14), oral mucocutaneous junction (19), or perioral region of the muzzle (11).Medical records were reviewed for information on signalment, regional metastasis, treatments, cause of death, and survival time. Twenty of the 44 cases had stored histologic samples available for immunohistochemical staining for CCR7For all dogs, median survival time was 52 months. Twenty-six (59%) dogs had regional lymph node metastasis on admission. Median survival time for dogs with lymph node metastasis was 14 months, whereas median survival time was not reached for dogs without lymph node metastasis. Intensity of staining for CCR7 was not significantly associated with the presence of regional lymph node metastasis or survival time.Results suggested that in dogs with MCTs arising from the oral mucosa, oral mucocutaneous junction, or perioral region of the muzzle, the presence of regional lymph node metastasis at the time of diagnosis was a negative prognostic factor. However, prolonged survival times could be achieved with treatment. In addition, CCR7 expression in the primary tumor was not significantly associated with the presence of regional lymph node metastasis or survival time.}, journal={Journal of the American Veterinary Medical Association}, author={Hillman, LA and Garrett, LD and Lorimier LP and Charney, SC and Borst, LB and Fan, TM}, year={2010}, month={Oct} }
 @article{tennent-brown_solis_foreman_goetz_fredrickson_borst_flaminio_2010, title={Common variable immunodeficiency in a horse with chronic peritonitis}, volume={22}, number={8}, journal={Equine Veterinary Education}, author={Tennent-Brown, B. S. and Solis, C. N. and Foreman, J. H. and Goetz, T. E. and Fredrickson, R. L. and Borst, L. B. and Flaminio, M. J. B. F.}, year={2010}, pages={393–399} }
 @inproceedings{robbins_borst_martin_jay_suyemoto_barnes_2010, place={Schaumburg, IL}, title={Phenotypic analysis of Enterococcus cecorum field isolates associated with vertebral osteoarthritis}, booktitle={AAAP Scientific Program}, publisher={American Veterinary Medical Association}, author={Robbins, Kabel and Borst, Luke and Martin, Michael P. and Jay, Paula and Suyemoto, Mitsu and Barnes, H.John}, year={2010} }
 @phdthesis{borst_2009, title={Investigations into a rationally designed modified live vaccine for equine strangles}, school={University of Illinois at Urbana-Champaign}, author={Borst, Luke B.}, year={2009} }
 @article{clark_ness_baldrighi_borst_maddox_payne_2008, title={10 INOCULATION OF CULTURE-NEGATIVE PORCINE SEMEN WITH NOVEL BIOFILM-FORMING BACTERIA}, volume={20}, ISSN={1031-3613}, url={http://dx.doi.org/10.1071/rdv20n1ab10}, DOI={10.1071/rdv20n1ab10}, abstractNote={With the growing number of boar studs having semen analysis performed by reproductive specialists, a growing number of diagnostic challenges are encountered. Semen analysis classically involves evaluation of sperm cell motility, morphology, and concentration; however, culture of the extended semen sample for bacterial contamination has become routine. Two isolates, Achromobacter xylosoxidans and Ralstonia pickettii, have recently been identified in the water distillation system of a boar stud facility that uses this water to extend the raw semen in various semen extenders. Insemination of sows with contaminated semen has resulted in severe pyometras diagnosed on necropsy. The effect of these bacteria on sperm motility has not been examined in a controlled setting. The objective of this study was to determine the effects of A. xylosoxidans (AX) and R. pickettii (RP) on pH and motility in culture-negative semen samples over a 7-day period at 16�C. Banked clinical isolates of AX and RP were plated on Columbia blood agar and incubated for 48 h at 37�C. For each isolate, a single colony was selected and transferred to 10 mL of Luria broth. The broth was then incubated for 24 h at 37�C. Optical density measurements were performed at 24 and 48 h of growth, followed by quantification of bacteria by plate counts of serially diluted broth cultures (colony forming units). At 24 h, AX and RP reached levels of 1 � 108 and 1 � 107 [colony-forming units (cfu) mL–1], respectively. Concentration of bacteria in clinical infection was determined to be approximately 1 � 104 and 102 for AX and RP, respectively. In order to attain concentrations similar to those in clinical infection, dilution of the bacteria was necessary. Centrifugation of broth culture at 4000 rpm for 5 min was performed and the bacterial pellet was re-suspended in culture-negative semen in Modena (SGI, LTD, Cambridge, IA, USA) extender to concentrations mimicking those in clinical infection. The samples were then incubated at 16�C and rotated once daily. Motility and morphology, viewed using computer-assisted sperm analysis (CASA: Spermvision; Minitube of America, Verona, WI, USA), and pH (Accumet AB15, Fisher Scientific, Hanover Park, IL, USA) were measured daily for each sample at 25�C. Data from 4 replicates were used in the analysis. For motility, ANOVA revealed no significant differences (P < 0.05) between the control and inoculated samples. A PROX MIXED analysis (SAS, SAS Institute, Inc., Cary, NC, USA) revealed no treatment-by-time interaction with sperm motility after inoculation. For sample pH, statistically significant differences (P < 0.05) were noted between all of the samples, primarily contributed by a treatment-by-time effect. The pH of the control sample became more basic over the 7-day period (from 6.94 to 7.32). This phenomenon was also observed in all of samples; however, semen inoculated with AX appeared to remain closer to neutral pH than did the RP samples. Although statistically significant differences were noted in pH, the addition of biofilm bacteria did not negatively affect the motility of extended porcine semen during this time period. Further experiments need to be performed in relation to different concentrations, time period of bacterial growth, and determination of final cfu mL–1.}, number={1}, journal={Reproduction, Fertility and Development}, publisher={CSIRO Publishing}, author={Clark, S. and Ness, A. and Baldrighi, J. and Borst, L. and Maddox, C. and Payne, B.}, year={2008}, pages={85} }
 @article{lowe_campbell_barger_schaeffer_borst_2008, title={Clinical, clinicopathological and histological changes observed in 14 cats treated with glucocorticoids.}, volume={6}, url={http://europepmc.org/abstract/med/18552328}, DOI={10.1136/vr.162.24.777}, abstractNote={Fourteen cats were given immunosuppressive doses of either prednisolone (4·4 mg/kg/day) or dexamethasone (0·55 mg/kg/day) for 56 days. Complete blood counts, serum biochemistry profiles and urinalyses were performed on days 0 and 56, and liver biopsies were taken laparoscopically on day 56, because of evidence of hepatic disease on the serum biochemistry profiles. There were significant increases in the cats' mean white blood cell counts, neutrophil counts and monocyte counts, and significant decreases in their mean lymphocyte counts and eosinophil counts. There were consistent increases in the serum concentrations of albumin, glucose, triglycerides and cholesterol. Glycogen deposition, consistent with a steroid hepatopathy, was present to varying degrees in all the liver biopsies. One of the cats developed adverse clinical signs including anorexia, icterus, pruritus and medial curling of the pinnae, some of which were suspected to be related to the glucocorticoid therapy.}, journal={The Veterinary record}, author={Lowe, AD and Campbell, KL and Barger, A and Schaeffer, DJ and Borst, L}, year={2008}, month={Jun} }
 @article{clark_ness_payne_borst_maddox_2007, title={DESCRIPTION OF GROWTH DYNAMICS OF BIOFILM BACTERIA FOUND IN EXTENDED PORCINE SEMEN}, volume={77}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1093/biolreprod/77.s1.84c}, DOI={10.1093/biolreprod/77.s1.84c}, number={Suppl_1}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Clark, Sherrie and Ness, Amanda and Payne, Brian and Borst, Luke and Maddox, Carol}, year={2007}, month={Jul}, pages={84–85} }
 @article{krug_manfra marretta_lorimier_white_borst_2006, title={Diagnosis and management of Wegener's granulomatosis in a dog}, volume={23}, ISSN={["2470-4083"]}, url={http://europepmc.org/abstract/med/17286129}, DOI={10.1177/089875640602300406}, abstractNote={A four-year-old male/neutered mixed-breed dog was presented for severe, multifocal, proliferative gingivitis. Histopathologic examination of incisional biopsies supported a diagnosis of Wegener's granulomatosis, an autoimmune vasculitis previously unreported in the veterinary literature. Diagnostic investigations for infectious, neoplastic, or other inflammatory conditions all provided negative results. Management with a combination of immunosuppressive agents resulted in complete resolution and remission of the presenting lesions and associated clinical signs.}, number={4}, journal={JOURNAL OF VETERINARY DENTISTRY}, author={Krug, William and Manfra Marretta, Sandra and Lorimier, Louis-Philippe and White, Dean K. and Borst, Luke}, year={2006}, month={Dec}, pages={231–236} }