@article{parzygnat_dunn_koci_crespo_harden_thakur_2024, title={Fluoroquinolone-resistant Campylobacter in backyard and commercial broiler production systems in the United States}, volume={6}, ISSN={["2632-1823"]}, DOI={10.1093/jacamr/dlae102}, abstractNote={Abstract Objectives Campylobacter spp. are one of the leading foodborne pathogens in the world, and chickens are a known reservoir. This is significant considering broiler chicken is the top consumed meat worldwide. In the USA, backyard poultry production is increasing, but little research has been done to investigate prevalence and antimicrobial resistance associated with Campylobacter in these environments. Methods Our study encompasses a farm-to-genome approach to identify Campylobacter and investigate its antimicrobial resistance phenotypically and genotypically. We travelled to 10 backyard and 10 integrated commercial broiler farms to follow a flock throughout production. We sampled at days 10, 31 and 52 for backyard and 10, 24 and 38 for commercial farms. Bird faecal (n = 10) and various environmental samples (soil n = 5, litter/compost n = 5, and feeder and waterer swabs n = 6) were collected at each visit and processed for Campylobacter. Results Our results show a higher prevalence of Campylobacter in samples from backyard farms (21.9%) compared to commercial (12.2%). Most of our isolates were identified as C. jejuni (70.8%) and the remainder as C. coli (29.2%). Antimicrobial susceptibility testing reveals phenotypic resistance to ciprofloxacin (40.2%), an important treatment drug for Campylobacter infection, and tetracycline (46.6%). A higher proportion of resistance was found in C. jejuni isolates and commercial farms. Whole-genome sequencing revealed resistance genes, such as tet(O) and gyrA_T86I point mutation, that may confer resistance. Conclusion Overall, our research emphasizes the need for interventions to curb prevalence of resistant Campylobacter spp. on broiler production systems.}, number={4}, journal={JAC-ANTIMICROBIAL RESISTANCE}, author={Parzygnat, Jessica L. and Dunn, Robert R. and Koci, Matthew D. and Crespo, Rocio and Harden, Lyndy and Thakur, Siddhartha}, year={2024}, month={Jul} } @article{fu_wang_guo_koci_lu_zeng_wang_tang_ma_ji_et al._2024, title={Pleurotus eryngii polysaccharides alleviate aflatoxin B 1-induced liver inflammation in ducks involving in remodeling gut microbiota and regulating SCFAs transport via the gut-liver axis}, volume={271}, ISSN={["1879-0003"]}, DOI={10.1016/j.ijbiomac.2024.132371}, abstractNote={Aflatoxin B}, journal={INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES}, author={Fu, Yutong and Wang, Qianqian and Guo, Yongpeng and Koci, Matthew and Lu, Zhengda and Zeng, Xiangfang and Wang, Yanan and Tang, Yu and Ma, Qiugang and Ji, Cheng and et al.}, year={2024}, month={Jun} } @article{wang_wang_wang_zhang_guo_su_tang_koci_zhang_ma_et al._2024, title={Rutin, a natural flavonoid glycoside, ameliorates zearalenone induced liver inflammation via inhibiting lipopolysaccharide gut leakage and NF-κB signaling pathway in mice}, volume={191}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2024.114887}, abstractNote={Zearalenone (ZEN) poses a potential threat on human and animal health partly through the nuclear factor (NF)-κB signaling pathway. In silico study suggested that rutin effective against TLR4 and NF-κB. A wetting test was designed to evaluate the effect and underlying mechanism of rutin in alleviating ZEN-induced inflammation in animals. Twenty-four female mice were randomly divided into 4 groups: control (basal diet), ZEN group (basal diet + ZEN), rutin group (basic diet + rutin), Z + R group (basal diet + rutin + ZEN). Results showed that rutin effectively alleviated ZEN-induced inflammation and damage of liver and jejunum in mice. Rutin addition reduced the content of lipopolysaccharide (LPS) in serum and liver mainly by improving the intestinal barrier function resulted from the production increase of short-chain fatty acids (SCFA). In sum, this study showed that rutin alleviated ZEN-induced liver inflammation and injury by modulating the gut microbiota, increasing the production of SCFA and improving intestinal barrier function, leading to the decrease of LPS in liver and the inhibition of MyD88 independent NF-κB signaling pathway in mice. Specifically, these findings may provide useful insights into the screening of functional natural compounds and its action mechanism to alleviate ZEN induced liver inflammation.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Wang, Yanan and Wang, Qianqian and Wang, Gaigai and Zhang, Qiongqiong and Guo, Yongpeng and Su, Xin and Tang, Yu and Koci, Matthew and Zhang, Jianyun and Ma, Qiugang and et al.}, year={2024}, month={Sep} } @article{parzygnat_crespo_koci_dunn_harden_fosnaught_thakur_2024, title={Widespread prevalence of plasmid-mediated blaCTX-M type extended-spectrum beta-lactamase Escherichia coli in backyard broiler production systems in the United States}, volume={19}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0304599}, DOI={10.1371/journal.pone.0304599}, abstractNote={Extended-spectrum beta-lactamase (ESBL) Escherichia coli ( E . coli ) is an emerging pathogen of high concern given its resistance to extended-spectrum cephalosporins. Broiler chicken, which is the number one consumed meat in the United States and worldwide, can be a reservoir of ESBL E . coli . Backyard poultry ownership is on the rise in the United States, yet there is little research investigating prevalence of ESBL E . coli in this setting. This study aims to identify the prevalence and antimicrobial resistance profiles (phenotypically and genotypically) of ESBL E . coli in some backyard and commercial broiler farms in the U.S. For this study ten backyard and ten commercial farms were visited at three time-points across flock production. Fecal (n = 10), litter/compost (n = 5), soil (n = 5), and swabs of feeders and waterers (n = 6) were collected at each visit and processed for E . coli . Assessment of ESBL phenotype was determined through using disk diffusion with 3 rd generation cephalosporins, cefotaxime and ceftazidime, and that with clavulanic acid. Broth microdilution and whole genome sequencing were used to investigate both phenotypic and genotypic resistance profiles, respectively. ESBL E . coli was more prevalent in backyard farms with 12.95% of samples testing positive whereas 0.77% of commercial farm samples were positive. All isolates contained a bla CTX-M gene, the dominant variant being bla CTX-M-1 , and its presence was entirely due to plasmids. Our study confirms concerns of growing resistance to fourth generation cephalosporin, cefepime, as roughly half (51.4%) of all isolates were found to be susceptible dose-dependent and few were resistant. Resistance to non-beta lactams, gentamicin and ciprofloxacin, was also detected in our samples. Our study identifies prevalence of bla CTX-M type ESBL E . coli in U.S. backyard broiler farms, emphasizing the need for interventions for food and production safety.}, number={6}, journal={PLOS ONE}, author={Parzygnat, Jessica L. and Crespo, Rocio and Koci, Matthew D. and Dunn, Robert R. and Harden, Lyndy and Fosnaught, Mary and Thakur, Siddhartha}, editor={Trueba, GabrielEditor}, year={2024}, month={Jun} } @article{koci_2023, title={Beyond Better Medicines}, url={https://doi.org/10.52750/677629}, DOI={10.52750/677629}, author={Koci, Matt}, year={2023}, month={Aug} } @article{wang_liu_koci_wang_fu_ma_ma_zhao_2023, title={Chlorogenic Acid Alleviated AFB1-Induced Hepatotoxicity by Regulating Mitochondrial Function, Activating Nrf2/HO-1, and Inhibiting Noncanonical NF-κB Signaling Pathway}, volume={12}, ISSN={["2076-3921"]}, DOI={10.3390/antiox12122027}, abstractNote={Aflatoxin B1 (AFB1), a kind of mycotoxin, imposes acute or chronic toxicity on humans and causes great public health concerns. Chlorogenic acid (CGA), a natural phenolic substance, shows a powerful antioxidant and anti-inflammatory effect. This study was conducted to investigate the effect and mechanism of CGA on alleviating cytotoxicity induced by AFB1 in L-02 cells. The results showed that CGA (160 μM) significantly recovered cell viability and cell membrane integrity in AFB1-treated (8 μM) cells. Furthermore, it was found that CGA reduced AFB1-induced oxidative injury by neutralizing reactive oxygen species (ROS) and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In addition, CGA showed anti-inflammatory effects as it suppressed the expression of inflammation-related genes (IL-6, IL-8, and TNF-α) and AFB1-induced noncanonical nuclear factor kappa-B (NF-κB) activation. Moreover, CGA mitigated AFB1-induced apoptosis by maintaining the mitochondrial membrane potential (MMP) and inhibiting mRNA expressions of Caspase-3, Caspase-8, Bax, and Bax/Bcl-2. These findings revealed a possible mechanism: CGA prevents AFB1-induced cytotoxicity by maintaining mitochondrial membrane potential, activating Nrf2/HO-1, and inhibiting the noncanonical NF-κB signaling pathway, which may provide a new direction for the application of CGA.}, number={12}, journal={ANTIOXIDANTS}, author={Wang, Qianqian and Liu, Tianxu and Koci, Matthew and Wang, Yanan and Fu, Yutong and Ma, Mingxin and Ma, Qiugang and Zhao, Lihong}, year={2023}, month={Dec} } @article{zhang_wei_wang_liu_hou_xu_su_koci_yin_zhang_2023, title={NF-KB activation enhances STING signaling by altering microtubule-mediated STING trafficking}, volume={42}, ISSN={["2211-1247"]}, DOI={10.1016/j.celrep.2023.112185}, abstractNote={It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.}, number={3}, journal={CELL REPORTS}, author={Zhang, Lulu and Wei, Xubiao and Wang, Zhimeng and Liu, Peiyuan and Hou, Yanfei and Xu, Yifang and Su, Huili and Koci, Matthew D. and Yin, Hang and Zhang, Conggang}, year={2023}, month={Mar} } @article{swords_porter_hawkins_li_rowland-goldsmith_koci_tansey_woitowich_2023, title={Science Communication Training Imparts Confidence and Influences Public Engagement Activity}, ISSN={["1935-7885"]}, url={https://doi.org/10.1128/jmbe.00037-23}, DOI={10.1128/jmbe.00037-23}, abstractNote={The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental understanding of science is necessary.}, journal={JOURNAL OF MICROBIOLOGY & BIOLOGY EDUCATION}, author={Swords, Christina M. and Porter, Jerlym S. and Hawkins, Amy J. and Li, Edwin and Rowland-Goldsmith, Melissa and Koci, Matthew D. and Tansey, John T. and Woitowich, Nicole C.}, editor={Brancaccio-Taras, LorettaEditor}, year={2023}, month={Jul} } @article{koci_2022, title={COVID-19: The Beginning of The Beginning}, url={https://doi.org/10.52750/209905}, DOI={10.52750/209905}, abstractNote={In his podcast The Beginning of The Beginning, Matt zooms in on the story of COVID-19.What is it?How did this start?Where did it come from?As we're still in the early phase of this pandemic, there's still a lot we don't know about this virus and about the disease.Much of this COVID-19 story remains to be written.How this story unfolds depends a lot on you.In the short-term, we all have a role to play in protecting those around us who are the most vulnerable.In the longer-term, as future leaders in North Carolina, the country, and the world, what role are you going to play to make sure we learn from the lessons of COVID-19 and are better prepared for future pandemics, and other Wicked Problems.}, author={Koci, Matt}, year={2022}, month={Jun} } @article{wei_zhang_yang_hou_xu_wang_su_han_han_liu_et al._2022, title={LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity}, volume={39}, ISSN={["2211-1247"]}, DOI={10.1016/j.celrep.2022.110880}, abstractNote={

Summary

Cyclic 2′,3′-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.}, number={9}, journal={CELL REPORTS}, author={Wei, Xubiao and Zhang, Lulu and Yang, Yinlong and Hou, Yanfei and Xu, Yifang and Wang, Zhimeng and Su, Huili and Han, Fangping and Han, Jing and Liu, Peiyuan and et al.}, year={2022}, month={May} } @article{koci_2022, title={Viruses: The Most Abundant Thing You’ve Never Seen}, url={https://doi.org/10.52750/205120}, DOI={10.52750/205120}, abstractNote={In his video, Matt Koci, Ph.D. will introduce himself, how he came to work on poultry diseases, and why viruses are fascinating biological paradoxes.He'll explain what a virus is, how common viruses are, and the basics of a virus life cycle, even though viruses aren't alive.All of this will introduce you to what we know about viruses, and how much we still have to learn, so we can make sense of how something so small ends up being so consequential.Matt Koci, Ph.D., grew up in the Richmond, VA area playing soccer and developing an interest in science and math.He attended Virginia Tech with the original goal of becoming an engineer, but thanks to an undergraduate research experience in a tumor immunology lab, he ended up majoring in biology with a concentration in microbiology and immunology.After Virginia Tech, he went to the University of Georgia where he got his master's degree and Ph.D. focused on viral pathogenesis.After a short post-doctoral research position at the University of Wisconsin studying how viruses evade antiviral drugs, he joined the at NC State.His lab works to understand the immune mechanisms which allow an animal to recognize, respond, eliminate and develop resistance to pathogens.}, author={Koci, Matt}, year={2022}, month={Jun} } @article{zhang_wei_zhang_koci_si_ahmad_guo_hou_2021, title={C-Terminal Amination of a Cationic Anti-Inflammatory Peptide Improves Bioavailability and Inhibitory Activity Against LPS-Induced Inflammation}, volume={11}, ISSN={["1664-3224"]}, DOI={10.3389/fimmu.2020.618312}, abstractNote={Lipopolysaccharide (LPS) has been implicated as a major cause of inflammation and an uncontrolled LPS response increases the risk of localized inflammation and sepsis. While some native peptides are helpful in the treatment of LPS-induced inflammation, the use of these peptides is limited due to their potential cytotoxicity and poor anti-inflammatory activity. Hybridization is an effective approach for overcoming this problem. In this study, a novel hybrid anti-inflammatory peptide that combines the active center of Cathelicidin 2 (CATH2) with thymopentin (TP5) was designed [CTP, CATH2 (1–13)-TP5]. CTP was found to have higher anti-inflammatory effects than its parental peptides through directly LPS neutralization. However, CTP scarcely inhibited the attachment of LPS to cell membranes or suppressed an established LPS-induced inflammation due to poor cellular uptake. The C-terminal amine modification of CTP (CTP-NH2) was then designed based on the hypothesis that C-terminal amidation can enhance the cell uptake by increasing the hydrophobicity of the peptide. Compared with CTP, CTP-NH2 showed enhanced anti-inflammatory activity and lower cytotoxicity. CTP-NH2 not only has strong LPS neutralizing activity, but also can significantly inhibit the LPS attachment and the intracellular inflammatory response. The intracellular anti-inflammatory effect of CTP-NH2 was associated with blocking of LPS binding to the Toll-like receptor 4-myeloid differentiation factor 2 complex and inhibiting the nuclear factor-kappa B pathway. In addition, the anti-inflammatory effect of CTP-NH2 was confirmed using a murine LPS-induced sepsis model. Collectively, these findings suggest that CTP-NH2 could be developed into a novel anti-inflammatory drug. This successful modification provides a design strategy to improve the cellular uptake and anti-inflammatory activity of peptide agents.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Zhang, Lulu and Wei, Xubiao and Zhang, Rijun and Koci, Matthew and Si, Dayong and Ahmad, Baseer and Guo, Henan and Hou, Yanfei}, year={2021}, month={Feb} } @article{wei_zhang_zhang_koci_si_ahmad_cheng_wang_aihemaiti_zhang_2020, title={A Novel Cecropin-LL37 Hybrid Peptide Protects Mice Against EHEC Infection-Mediated Changes in Gut Microbiota, Intestinal Inflammation, and Impairment of Mucosal Barrier Functions}, volume={11}, ISSN={["1664-3224"]}, DOI={10.3389/fimmu.2020.01361}, abstractNote={Intestinal inflammation can cause impaired epithelial barrier function and disrupt immune homeostasis, which increases the risks of developing many highly fatal diseases. Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes intestinal infections worldwide and is a major pathogen that induces intestinal inflammation. Various antibacterial peptides have been described as having the potential to suppress and treat pathogen-induced intestinal inflammation. Cecropin A (1–8)-LL37 (17–30) (C-L), a novel hybrid peptide designed in our laboratory that combines the active center of C with the core functional region of L, shows superior antibacterial properties and minimized cytotoxicity compared to its parental peptides. Herein, to examine whether C-L could inhibit pathogen-induced intestinal inflammation, we investigated the anti-inflammatory effects of C-L in EHEC O157:H7-infected mice. C-L treatment improved the microbiota composition and microbial community balance in mouse intestines. The hybrid peptide exhibited improved anti-inflammatory effects than did the antibiotic, enrofloxacin. Hybrid peptide treated infected mice demonstrated reduced clinical signs of inflammation, reduced weight loss, reduced expression of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)], reduced apoptosis, and reduced markers of jejunal epithelial barrier function. The peptide also affected the MyD88–nuclear factor κB signaling pathway, thereby modulating inflammatory responses upon EHEC stimulation. Collectively, these findings suggest that the novel hybrid peptide C-L could be developed into a new anti-inflammatory agent for use in animals or humans.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Wei, Xubiao and Zhang, Lulu and Zhang, Rijun and Koci, Matthew and Si, Dayong and Ahmad, Baseer and Cheng, Junhao and Wang, Junyong and Aihemaiti, Maierhaba and Zhang, Manyi}, year={2020}, month={Jun} } @article{troxell_mendoza_ali_koci_hassan_2020, title={Attenuated Salmonella enterica Serovar Typhimurium, Strain NC983, Is Immunogenic, and Protective against Virulent Typhimurium Challenges in Mice}, volume={8}, ISSN={["2076-393X"]}, DOI={10.3390/vaccines8040646}, abstractNote={Non-typhoidal Salmonella (NTS) serovars are significant health burden worldwide. Although much effort has been devoted to developing typhoid-based vaccines for humans, currently there is no NTS vaccine available. Presented here is the efficacy of a live attenuated serovar Typhimurium strain (NC983). Oral delivery of strain NC983 was capable of fully protecting C57BL/6 and BALB/c mice against challenge with virulent Typhimurium. Strain NC983 was found to elicit an anti-Typhimurium IgG response following administration of vaccine and boosting doses. Furthermore, in competition experiments with virulent S. Typhimurium (ATCC 14028), NC983 was highly defective in colonization of the murine liver and spleen. Collectively, these results indicate that strain NC983 is a potential live attenuated vaccine strain that warrants further development.}, number={4}, journal={VACCINES}, author={Troxell, Bryan and Mendoza, Mary and Ali, Rizwana and Koci, Matthew and Hassan, Hosni}, year={2020}, month={Dec} } @article{hassan_mendoza_rezvani_koci_dickey_scholl_2020, title={Complete Genome Sequences of Lactobacillus Strains C25 and P38, Isolated from Chicken Cecum}, volume={9}, url={https://doi.org/10.1128/MRA.00501-20}, DOI={10.1128/MRA.00501-20}, abstractNote={ We report the complete circular genome sequences of Lactobacillus crispatus strain C25, its plasmid, and Lactobacillus animalis strain P38; both strains were isolated from the cecum of 4-week-old chickens. These isolates represent potential probiotic strains for poultry. }, number={39}, journal={Microbiology Resource Announcements}, publisher={American Society for Microbiology}, author={Hassan, Hosni M. and Mendoza, Mary and Rezvani, Morvarid and Koci, Matthew D. and Dickey, Allison N. and Scholl, Elizabeth H.}, editor={Rasko, DavidEditor}, year={2020}, month={Sep} } @article{koci_ballou_wei_zhang_liew_ali_2020, title={Connecting the microbiome to host metabolites: understanding how the microbiome controls immune activity in birds}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.00747}, abstractNote={The gastrointestinal (GI) microbiome plays an important role in the development and function not only of the GI, but also the immune system. Products such as probiotics represent promising treatments for improving animal health through the GI, but their modes of action are largely still unknown. Previous research in our laboratory has demonstrated supplementation with a lactic acid bacteria probiotic product alters host energy partitioning in immune tissues, including increased ATP production and consumption in circulating leukocytes; and was associated with a more rapid antibody response to antigen. To better understand the communication between probiotics and the immune system our laboratory has focused on characterizing how supplementation affects the microbiome and host systems. We hypothesized that the changes previously observed in immune tissue activity and energy metabolism were regulated by a probiotic‐stimulated factor in the serum. We examined the ability of serum isolated from probiotic‐fed animals to augment ATP production in vitro. Chicken lymphocyte cell lines were cultured for 4 days in media supplemented with serum from treated and control birds. Cells cultured in serum from probiotic‐fed birds had higher levels of ATP (P < 0.05) compared to controls. Transcriptomic analysis of these cells suggest an increase in genes associated with cell survival and differentiation, and signaling via TGF‐β, IFN‐γ, IL‐7, and IL‐1β. Analysis of the metabolites in serum and digesta from these animals identified several metabolite changes correlate with the change in ATP levels in lymphocytes and putative changes in pro‐ and anti‐inflammatory cytokine production.}, journal={FASEB JOURNAL}, author={Koci, Matthew and Ballou, Anne and Wei, Xubiao and Zhang, Lulu and Liew, Zie and Ali, Rizwana}, year={2020}, month={Apr} } @article{zhang_wei_zhang_koci_si_ahmad_cheng_wang_2019, title={Development of a Highly Efficient Hybrid Peptide That Increases Immunomodulatory Activity Via the TLR4-Mediated Nuclear Factor-κB Signaling Pathway}, url={https://doi.org/10.3390/ijms20246161}, DOI={10.3390/ijms20246161}, abstractNote={Immunity is a defensive response that fights disease by identifying and destroying harmful substances or microbiological toxins. Several factors, including work-related stress, pollution, and immunosuppressive agents, contribute to low immunity and poor health. Native peptides, a new class of immunoregulatory agents, have the potential for treating immunodeficiencies, malignancies, and infections. However, the potential cytotoxicity and low immunoregulatory activity and stability of native peptides have prevented their development. Therefore, we designed three hybrid peptides (LTAa, LTAb, and LTAc) by combining a characteristic fragment of LL-37 with an active Tα1 center that included Tα1 (17–24), Tα1 (20–25), and Tα1 (20–27). The best hybrid peptide (LTAa), according to molecule docking and in vitro experiments, had improved immunoregulatory activity and stability with minimal cytotoxicity. We investigated the immunoregulatory effects and mechanisms of LTAa using a cyclophosphamide-immunosuppressed murine model. LTAa effectively reversed immunosuppression by enhancing immune organ development, activating peritoneal macrophage phagocytosis, regulating T lymphocyte subsets, and increasing cytokine (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immunoglobulin (IgA, IgG, and IgM) contents. The immunomodulatory effects of LTAa may be associated with binding to the TLR4/MD-2 complex and activation of the NF-κB signaling pathway. Therefore, LTAa could be an effective therapeutic agent for improving immune function.}, journal={International Journal of Molecular Sciences}, author={Zhang, Lulu and Wei, Xubiao and Zhang, Rijun and Koci, Matthew and Si, Dayong and Ahmad, Baseer and Cheng, Junhao and Wang, Junyong}, year={2019}, month={Dec} } @article{allali_arnold_roach_cadenas_butz_hassan_koci_ballou_mendoza_ali_et al._2017, title={A comparison of sequencing platforms and bioinformatics pipelines for compositional analysis of the gut microbiome}, volume={17}, ISSN={["1471-2180"]}, DOI={10.1186/s12866-017-1101-8}, abstractNote={Advancements in Next Generation Sequencing (NGS) technologies regarding throughput, read length and accuracy had a major impact on microbiome research by significantly improving 16S rRNA amplicon sequencing. As rapid improvements in sequencing platforms and new data analysis pipelines are introduced, it is essential to evaluate their capabilities in specific applications. The aim of this study was to assess whether the same project-specific biological conclusions regarding microbiome composition could be reached using different sequencing platforms and bioinformatics pipelines. Chicken cecum microbiome was analyzed by 16S rRNA amplicon sequencing using Illumina MiSeq, Ion Torrent PGM, and Roche 454 GS FLX Titanium platforms, with standard and modified protocols for library preparation. We labeled the bioinformatics pipelines included in our analysis QIIME1 and QIIME2 (de novo OTU picking [not to be confused with QIIME version 2 commonly referred to as QIIME2]), QIIME3 and QIIME4 (open reference OTU picking), UPARSE1 and UPARSE2 (each pair differs only in the use of chimera depletion methods), and DADA2 (for Illumina data only). GS FLX+ yielded the longest reads and highest quality scores, while MiSeq generated the largest number of reads after quality filtering. Declines in quality scores were observed starting at bases 150–199 for GS FLX+ and bases 90–99 for MiSeq. Scores were stable for PGM-generated data. Overall microbiome compositional profiles were comparable between platforms; however, average relative abundance of specific taxa varied depending on sequencing platform, library preparation method, and bioinformatics analysis. Specifically, QIIME with de novo OTU picking yielded the highest number of unique species and alpha diversity was reduced with UPARSE and DADA2 compared to QIIME. The three platforms compared in this study were capable of discriminating samples by treatment, despite differences in diversity and abundance, leading to similar biological conclusions. Our results demonstrate that while there were differences in depth of coverage and phylogenetic diversity, all workflows revealed comparable treatment effects on microbial diversity. To increase reproducibility and reliability and to retain consistency between similar studies, it is important to consider the impact on data quality and relative abundance of taxa when selecting NGS platforms and analysis tools for microbiome studies.}, journal={BMC MICROBIOLOGY}, author={Allali, Imane and Arnold, Jason W. and Roach, Jeffrey and Cadenas, Maria Belen and Butz, Natasha and Hassan, Hosni M. and Koci, Matthew and Ballou, Anne and Mendoza, Mary and Ali, Rizwana and et al.}, year={2017}, month={Sep} } @article{azcarate-peril_butz_cadenas_koci_ballou_mendoza_ali_hassan_2017, title={An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome}, volume={84}, ISSN={0099-2240 1098-5336}, url={http://dx.doi.org/10.1128/AEM.02526-17}, DOI={10.1128/aem.02526-17}, abstractNote={ABSTRACT Salmonella is estimated to cause one million foodborne illnesses in the United States every year. Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota in Salmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. In Salmonella , the global regulator gene fnr ( f umarate n itrate r eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant of Salmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-type Salmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-type Salmonella serovar 4,[5],12:r:− (Nal r ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuated Salmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases of Alistipes and undefined Lactobacillus , while GOS increased Christensenellaceae and Lactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after a Salmonella challenge. IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated that Salmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota in Salmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuated Salmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance to Salmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment. }, number={5}, journal={Applied and Environmental Microbiology}, publisher={American Society for Microbiology}, author={Azcarate-Peril, M. Andrea and Butz, Natasha and Cadenas, Maria Belen and Koci, Matthew and Ballou, Anne and Mendoza, Mary and Ali, Rizwana and Hassan, Hosni}, editor={Schottel, Janet L.Editor}, year={2017}, month={Dec} } @inbook{astrovirus_2017, booktitle={Food Microbiology Series: Laboratory Models for Foodborne Infections}, year={2017} } @article{efficacy of feed additives to reduce the effect of naturally occurring mycotoxins fed to turkey hen poults reared to 6 weeks of age_2017, DOI={10.3382/ps/pex214}, abstractNote={&NA; Corn with naturally occurring aflatoxin (AF), wheat with naturally occurring doxynivalenol (DON), and barley with naturally occurring zearalenone (ZEA) were used to make rations for feeding turkey hen poults to 6 weeks of age. Control rations with equal amounts of corn, wheat, and barley were also fed. The control rations did contain some DON while both sets of rations contained ZEA. Within each grain source, there were 4 treatments: the control ration plus 3 rations each with a different feed additive which were evaluated for the potential to lessen potential mycotoxin effects on bird performance and physiology. The additives were Biomin BioFix (2 lb/ton), Kemin Kallsil (4 lb/ton), and Nutriad UNIKE (3 lb/ton). The mycotoxin rations reduced poult body weight (2.31 vs. 2.08 ± 0.02 kg) and increased (worsened) poult feed conversion (1.47 vs. 1.51 ± 0.01) at 6 wk. Feeding the poults the mycotoxin feed also resulted in organ and physiological changes typical of feeding dietary aflatoxin although a combined effect of AF, DON, and ZEA which cannot be dismissed. The feed additives resulted in improved feed conversion to 6 wk in both grain treatment groups. The observed physiological effect of feeding the additives was to reduce relative gizzard weight for both groups and to lessen the increase in relative kidney weight for the birds fed the mycotoxin feed. In conclusion, the feed additives used in this study did alleviate the effect of dietary mycotoxins to some degree, especially with respect to feed conversion. Further studies of longer duration are warranted.}, journal={Poult. Sci}, year={2017}, month={Sep} } @article{hughes_ali_mendoza_hassan_koci_2017, title={Impact of Dietary Galacto-Oligosaccharide (GOS) on Chicken’s Gut Microbiota, Mucosal Gene Expression, and Salmonella Colonization}, volume={4}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2017.00192}, DOI={10.3389/fvets.2017.00192}, abstractNote={Preventing Salmonella colonization in young birds is key to reducing contamination of poultry products for human consumption (eggs and meat). While several Salmonella vaccines have been developed that are capable of yielding high systemic antibodies, it is not clear how effective these approaches are at controlling or preventing Salmonella colonization of the intestinal tract. Effective alternative control strategies are needed to help supplement the bird’s ability to prevent Salmonella colonization, specifically by making the cecum less hospitable to Salmonella. In this study, we investigated the effect of the prebiotic galacto-oligosaccharide (GOS) on the cecal microbiome and ultimately the carriage of Salmonella. Day-old pullet chicks were fed control diets or diets supplemented with GOS (1% w/w) and then challenged with a cocktail of Salmonella Typhimurium and Salmonella Enteritidis. Changes in cecal tonsil gene expression, cecal microbiome, and levels of cecal and extraintestinal Salmonella were assessed at 1, 4, 7, 12, and 27 days post infection. While the Salmonella counts were generally lower in the GOS-treated birds, the differences were not significantly different at the end of the experiment. However, these data demonstrated that treatment with the prebiotic GOS can modify both cecal tonsil gene expression and the cecal microbiome, suggesting that this type of treatment may be useful as a tool for altering the carriage of Salmonella in poultry.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Hughes, Rebecca-Ayme and Ali, Riawana A. and Mendoza, Mary A. and Hassan, Hosni M. and Koci, Matthew D.}, year={2017}, month={Nov} } @article{ballou_ali_mendoza_ellis_hassan_croom_koci_2016, title={Development of the Chick Microbiome: How Early Exposure Influences Future Microbial Diversity}, volume={3}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2016.00002}, DOI={10.3389/fvets.2016.00002}, abstractNote={The concept of improving animal health through improved gut health has existed in food animal production for decades; however, only recently have we had the tools to identify microbes in the intestine associated with improved performance. Currently, little is known about how the avian microbiome develops or the factors that affect its composition. To begin to address this knowledge gap, the present study assessed the development of the cecal microbiome in chicks from hatch to 28 days of age with and without a live Salmonella vaccine and/or probiotic supplement; both are products intended to promote gut health. The microbiome of growing chicks develops rapidly from days 1–3, and the microbiome is primarily Enterobacteriaceae, but Firmicutes increase in abundance and taxonomic diversity starting around day 7. As the microbiome continues to develop, the influence of the treatments becomes stronger. Predicted metagenomic content suggests that, functionally, treatment may stimulate more differences at day 14, despite the strong taxonomic differences at day 28. These results demonstrate that these live microbial treatments do impact the development of the bacterial taxa found in the growing chicks; however, additional experiments are needed to understand the biochemical and functional consequences of these alterations.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Ballou, Anne L. and Ali, Rizwana A. and Mendoza, Mary A. and Ellis, J. C. and Hassan, Hosni M. and Croom, W. J. and Koci, Matthew D.}, year={2016}, month={Jan} } @article{rezvani_mendoza_koci_daron_levy_hassan_2016, title={Draft Genome Sequence of Lactobacillus crispatus C25 Isolated from Chicken Cecum}, volume={4}, ISSN={2169-8287}, url={http://dx.doi.org/10.1128/genomeA.01223-16}, DOI={10.1128/genomeA.01223-16}, abstractNote={ABSTRACT Lactic acid bacteria are important members of the gut microbiota of humans and animals. Here, we present the genome sequence of Lactobacillus crispatus strain C25, originally isolated from the cecum of 4-week-old chicken fed a standard diet. This isolate represents a potential probiotic strain for poultry. }, number={6}, journal={Genome Announcements}, publisher={American Society for Microbiology}, author={Rezvani, Morvarid and Mendoza, Mary and Koci, Matthew D. and Daron, Caitlyn and Levy, Josh and Hassan, Hosni M.}, year={2016}, month={Dec} } @article{rezvani_mendoza_koci_daron_levy_hassan_2016, title={Draft Genome Sequences of Lactobacillus animalis Strain P38 and Lactobacillus reuteri Strain P43 Isolated from Chicken Cecum}, volume={4}, ISSN={2169-8287}, url={http://dx.doi.org/10.1128/genomeA.01229-16}, DOI={10.1128/genomeA.01229-16}, abstractNote={ABSTRACT Here, we present the genome sequence of Lactobacillus animalis strain P38 and Lactobacillus reuteri strain P43, both isolated from the cecum content of a 4-week old chicken fed a diet supplemented with the prebiotic β(1-4)galacto-oligosaccharide (GOS). These indigenous Lactobacillus isolates are potential probiotic organisms for poultry. }, number={6}, journal={Genome Announcements}, publisher={American Society for Microbiology}, author={Rezvani, Morvarid and Mendoza, Mary and Koci, Matthew D. and Daron, Caitlyn and Levy, Josh and Hassan, Hosni M.}, year={2016}, month={Dec} } @article{meliopoulos_marvin_freiden_moser_nighot_ali_blikslager_reddivari_heath_koci_et al._2016, title={Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo}, volume={7}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mBio.01494-16}, DOI={10.1128/mBio.01494-16}, abstractNote={ABSTRACT The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction. IMPORTANCE Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity. }, number={6}, journal={mBio}, publisher={American Society for Microbiology}, author={Meliopoulos, Victoria A. and Marvin, Shauna A. and Freiden, Pamela and Moser, Lindsey A. and Nighot, Prashant and Ali, Rizwana and Blikslager, Anthony and Reddivari, Muralidhar and Heath, Richard J. and Koci, Matthew D. and et al.}, year={2016}, month={Nov} } @article{troxell_petri_daron_pereira_mendoza_hassan_koci_2015, title={Poultry Body Temperature Contributes to Invasion Control through Reduced Expression of Salmonella Pathogenicity Island 1 Genes in Salmonella enterica Serovars Typhimurium and Enteritidis}, volume={81}, ISSN={0099-2240 1098-5336}, url={http://dx.doi.org/10.1128/AEM.02622-15}, DOI={10.1128/aem.02622-15}, abstractNote={ABSTRACT Salmonella enterica serovars Typhimurium ( S . Typhimurium) and Enteritidis ( S . Enteritidis) are foodborne pathogens, and outbreaks are often associated with poultry products. Chickens are typically asymptomatic when colonized by these serovars; however, the factors contributing to this observation are uncharacterized. Whereas symptomatic mammals have a body temperature between 37°C and 39°C, chickens have a body temperature of 41°C to 42°C. Here, in vivo experiments using chicks demonstrated that numbers of viable S . Typhimurium or S . Enteritidis bacteria within the liver and spleen organ sites were ≥4 orders of magnitude lower than those within the ceca. When similar doses of S . Typhimurium or S . Enteritidis were given to C3H/HeN mice, the ratio of the intestinal concentration to the liver/spleen concentration was 1:1. In the avian host, this suggested poor survival within these tissues or a reduced capacity to traverse the host epithelial layer and reach liver/spleen sites or both. Salmonella pathogenicity island 1 (SPI-1) promotes localization to liver/spleen tissues through invasion of the epithelial cell layer. Following in vitro growth at 42°C, SPI-1 genes sipC , invF , and hilA and the SPI-1 rtsA activator were downregulated compared to expression at 37°C. Overexpression of the hilA activators fur , fliZ , and hilD was capable of inducing hilA-lacZ at 37°C but not at 42°C despite the presence of similar levels of protein at the two temperatures. In contrast, overexpression of either hilC or rtsA was capable of inducing hilA and sipC at 42°C. These data indicate that physiological parameters of the poultry host, such as body temperature, have a role in modulating expression of virulence. }, number={23}, journal={Applied and Environmental Microbiology}, publisher={American Society for Microbiology}, author={Troxell, Bryan and Petri, Nicholas and Daron, Caitlyn and Pereira, Rafaela and Mendoza, Mary and Hassan, Hosni M. and Koci, Matthew D.}, editor={Elkins, C. A.Editor}, year={2015}, month={Sep}, pages={8192–8201} } @article{fulton_arango_ali_bohorquez_lund_ashwell_settar_o'sullivan_koci_2014, title={Genetic Variation within the Mx Gene of Commercially Selected Chicken Lines Reveals Multiple Haplotypes, Recombination and a Protein under Selection Pressure}, volume={9}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0108054}, DOI={10.1371/journal.pone.0108054}, abstractNote={The Mx protein is one of the best-characterized interferon-stimulated antiviral mediators. Mx homologs have been identified in most vertebrates examined; however, their location within the cell, their level of activity, and the viruses they inhibit vary widely. Recent studies have demonstrated multiple Mx alleles in chickens and some reports have suggested a specific variant (S631N) within exon 14 confers antiviral activity. In the current study, the complete genome of nine elite egg-layer type lines were sequenced and multiple variants of the Mx gene identified. Within the coding region and upstream putative promoter region 36 SNP variants were identified, producing a total of 12 unique haplotypes. Each elite line contained from one to four haplotypes, with many of these haplotypes being found in only one line. Observation of changes in haplotype frequency over generations, as well as recombination, suggested some unknown selection pressure on the Mx gene. Trait association analysis with either individual SNP or haplotypes showed a significant effect of Mx haplotype on several egg production related traits, and on mortality following Marek's disease virus challenge in some lines. Examination of the location of the various SNP within the protein suggests synonymous SNP tend to be found within structural or enzymatic regions of the protein, while non-synonymous SNP are located in less well defined regions. The putative resistance variant N631 was found in five of the 12 haplotypes with an overall frequency of 47% across the nine lines. Two Mx recombinants were identified within the elite populations, indicating that novel variation can arise and be maintained within intensively selected lines. Collectively, these results suggest the conflicting reports in the literature describing the impact of the different SNP on chicken Mx function may be due to the varying context of haplotypes present in the populations studied.}, number={9}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Fulton, Janet E. and Arango, Jesus and Ali, Rizwana A. and Bohorquez, Elaine B. and Lund, Ashlee R. and Ashwell, Chris M. and Settar, Petek and O'Sullivan, Neil P. and Koci, Matthew D.}, editor={Arez, Ana PaulaEditor}, year={2014}, month={Sep}, pages={e108054} } @article{sample_hudak_barefoot_koci_wanyonyi_abraham_staat_ramsburg_2013, title={A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses}, volume={48}, ISSN={["1873-5169"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84886937495&partnerID=MN8TOARS}, DOI={10.1016/j.peptides.2013.07.014}, abstractNote={Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cationic, peptides that have direct antimicrobial activity, and which in some instances activate cell-mediated antiviral immune responses. Although mNHP have potent activity in vitro, efficacy trials in vivo of exogenously provided mNHP have been largely disappointing, and no mNHP are currently licensed for human use. Mastoparan is an invertebrate host defense peptide that penetrates lipid bilayers, and we reasoned that a mastoparan analog might interact with the lipid component of virus membranes and thereby reduce infectivity of enveloped viruses. Our objective was to determine whether mastoparan-derived peptide MP7-NH2 could inactivate viruses of multiple types, and whether it could stimulate cell-mediated antiviral activity. We found that MP7-NH2 potently inactivated a range of enveloped viruses. Consistent with our proposed mechanism of action, MP7-NH2 was not efficacious against a non-enveloped virus. Pre-treatment of cells with MP7-NH2 did not reduce the amount of virus recovered after infection, which suggested that the primary mechanism of action in vitro was direct inactivation of virus by MP7-NH2. These results demonstrate for the first time that a mastoparan derivative has broad-spectrum antiviral activity in vitro and suggest that further investigation of the antiviral properties of mastoparan peptides in vivo is warranted.}, journal={PEPTIDES}, publisher={Elsevier BV}, author={Sample, Christopher J. and Hudak, Kathryn E. and Barefoot, Brice E. and Koci, Matthew D. and Wanyonyi, Moses S. and Abraham, Soman and Staat, Herman F. and Ramsburg, Elizabeth A.}, year={2013}, month={Oct}, pages={96–105} } @article{oviedo-rondon_leandro_ali_koci_moraes_brake_2013, title={Broiler breeder feeding programs and trace minerals on maternal antibody transfer and broiler humoral immune response1}, volume={22}, ISSN={1056-6171 1537-0437}, url={http://dx.doi.org/10.3382/japr.2012-00708}, DOI={10.3382/japr.2012-00708}, abstractNote={SUMMARY Breeder feed restriction may negatively affect broiler progeny immunity. Sources of trace minerals (TM) with higher bioavailability in breeder diets have been reported to enhance humoral and cellular immunity in broiler progeny. An experiment was conducted to examine the effects of breeder feeding programs and TM dietary sources on maternal antibody transfer and humoral immune response of progeny to a live vaccine against Newcastle disease virus (NDV). Cobb 500 breeders were fed according to 2 feed allocation programs, sigmoid late fast and sigmoid late slow, from 14 to 29 wk of age. From 56 to 62 wk of age, breeders were fed with either inorganic TM or an organic source (OTM) to replace 30% of Cu, Zn, and Mn. Progeny broilers were vaccinated intraocularly with La Sota NDV vaccine at 7 d of age. Blood samples were collected at hatching, 4, and 14 d postvaccination. Serum antibody levels against NDV were assessed by ELISA and cytokine expression by real time PCR. At hatching, late slow breeder progeny fed diets with 30% OTM had higher antibody titers as compared with progeny of breeders fed 100% inorganic TM. Similar results were observed 2 wk postvaccination. Breeder feeding programs and TM sources affected the expression level of IL-4 in NDV vaccinated broiler progeny. It was concluded that breeder feeding programs influenced humoral immune response to NDV vaccine in the broiler progeny, and 30% OTM may increase these responses.}, number={3}, journal={The Journal of Applied Poultry Research}, publisher={Oxford University Press (OUP)}, author={Oviedo-Rondon, E. O. and Leandro, N. M. and Ali, R. and Koci, M. and Moraes, V. and Brake, J.}, year={2013}, month={Sep}, pages={499–510} } @inbook{krishna_koci_guix_2013, title={Astrovirus Immunity}, volume={9781461447351}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84948144983&partnerID=MN8TOARS}, DOI={10.1007/978-1-4614-4735-1_5}, booktitle={Astrovirus Research: Essential Ideas, Everyday Impacts, Future Directions}, publisher={Springer Science \mathplus Business Media}, author={Krishna, Neel K. and Koci, Matthew D. and Guix, Susana}, year={2013}, pages={79–95} } @inbook{pantin-jackwood_todd_koci_2013, title={Avian Astroviruses}, volume={9781461447351}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84948148046&partnerID=MN8TOARS}, DOI={10.1007/978-1-4614-4735-1_9}, booktitle={Astrovirus Research: Essential Ideas, Everyday Impacts, Future Directions}, publisher={Springer Science \mathplus Business Media}, author={Pantin-Jackwood, Mary and Todd, Daniel and Koci, Matthew D.}, year={2013}, pages={151–180} } @article{meyerhoff_nighot_ali_blikslager_koci_2012, title={Characterization of turkey inducible nitric oxide synthase and identification of its expression in the intestinal epithelium following astrovirus infection}, volume={35}, ISSN={0147-9571}, url={http://dx.doi.org/10.1016/j.cimid.2011.10.002}, DOI={10.1016/j.cimid.2011.10.002}, abstractNote={The inducible nitric oxide synthase (iNOS) enzyme has long been recognized as a key mediator of innate immune responses to infectious diseases across the phyla. Its role in killing or inactivating bacterial, parasitic, and viral pathogens has been documented in numerous host systems. iNOS, and its innate immune mediator NO has also been described to have negative consequence on host tissues as well; therefore understanding the pathogenesis of any infectious agent which induces iNOS expression requires a better understanding of the role iNOS and NO play in that disease. Previous studies in our laboratory and others have demonstrated evidence for increased levels of iNOS and activity of its innate immune mediator NO in the intestine of turkeys infected with astrovirus. To begin to characterize the role iNOS plays in the innate immune response to astrovirus infection, we identified, characterized, developed tkiNOS specific reagents, and demonstrated that the intestinal epithelial cells induce expression of iNOS following astrovirus infection. These data are the first to our knowledge to describe the tkiNOS gene, and demonstrate that astrovirus infection induces intestinal epithelial cells to express iNOS, suggesting these cells play a key role in the antiviral response to enteric infections.}, number={1}, journal={Comparative Immunology, Microbiology and Infectious Diseases}, publisher={Elsevier BV}, author={Meyerhoff, R. Ryan and Nighot, Prashant K. and Ali, Rizwana A. and Blikslager, Anthony T. and Koci, Matthew D.}, year={2012}, month={Jan}, pages={63–69} } @article{meyerhoff_ali_liu_huang_koci_2012, title={Comprehensive analysis of commercially available mouse antichicken monoclonal antibodies for cross-reactivity with peripheral blood leukocytes from commercial turkeys}, volume={91}, ISSN={["1525-3171"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84855963731&partnerID=MN8TOARS}, DOI={10.3382/ps.2011-01846}, abstractNote={In the United States, turkey production contributes approximately $14.4 billion to the US economy; however, the number of reagents specifically developed to study the immune system of this economically important species is limited. To compensate for this, laboratories focused on the turkey system have each empirically tested various chicken-specific reagents for cross-reactivity with turkeys. The result is a patchwork of reports using different genetic lines and different ages, and in many cases, leading to inconsistent conclusions about the cross-reactivity of the reagents tested. In the current study, we investigated a large panel of commercially available monoclonal antibodies specific for chicken leukocyte markers for their ability to specifically recognize the turkey homolog of their respective ligand using 2 different genetic lines of commercial turkeys. The results of these studies identify 8 chicken-specific monoclonal antibodies (F21-21, F21-2, CT4, EP96, 3-298, AV7, c264, and AV6) as demonstrating strong evidence for cross-reactivity with turkey peripheral blood mononuclear cells from both commercial lines, 3 of which (F21-2, EP96, and c264), to our knowledge, have not previously been reported. In addition, characterization of the anti-CD8α monoclonal antibody 3-298 provides evidence that turkeys, like chickens, have a relatively high percentage of CD4CD8 double-positive T-cells in circulation and have at least 5 alleles of the CD8α gene. Collectively, the results from these experiments strengthen our understanding of the turkey immune system, its relative level of conservation with the chicken system, and adds to the list of reagents that can be reliably used to assess immune responses in commercial turkeys.}, number={2}, journal={POULTRY SCIENCE}, author={Meyerhoff, R. R. and Ali, R. A. and Liu, K. and Huang, G. -Q. and Koci, M. D.}, year={2012}, month={Feb}, pages={383–392} } @article{meyerhoff_ali_liu_huang_koci_2012, title={Comprehensive analysis of commercially available mouse antichicken monoclonal antibodies for cross-reactivity with peripheral blood leukocytes from commercial turkeys (vol 91, pg 383, 2012)}, volume={91}, ISSN={["0032-5791"]}, DOI={10.3382/ps.2012-91-4-1043}, number={4}, journal={POULTRY SCIENCE}, author={Meyerhoff, R. R. and Ali, R. A. and Liu, K. and Huang, G. -Q. and Koci, M. D.}, year={2012}, month={Apr}, pages={1043–1043} } @article{qiu_croom_ali_ballou_smith_ashwell_hassan_chiang_koci_2012, title={Direct fed microbial supplementation repartitions host energy to the immune system}, volume={90}, ISSN={["1525-3163"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84865634686&partnerID=MN8TOARS}, DOI={10.2527/jas.2011-4611}, abstractNote={Direct fed microbials and probiotics are used to promote health in livestock and poultry; however, their mechanism of action is still poorly understood. We previously reported that direct fed microbial supplementation in young broilers reduced ileal respiration without changing whole-body energy expenditure. The current studies were conducted to further investigate the effects of a direct fed microbial on energy metabolism in different tissues of broilers. One hundred ninety-two 1-d-old broiler chicks (16 chicks/pen) were randomly assigned to 2 dietary groups: standard control starter diet (CSD) and CSD plus direct fed microbial (DFMD; 0.3%) with 6 pens/treatment. Body weight, feed consumption, whole-body energy expenditure, organ mass, tissue respiration rates, and peripheral blood mononuclear cell (PBMC) ATP concentrations were measured to estimate changes in energy metabolism. No differences in whole body energy expenditure or BW gain were observed; however, decreased ileal O(2) respiration (P < 0.05) was measured in DFMD fed broilers. In contrast, the respiration rate of the thymus in those broilers was increased (P < 0.05). The PBMC from DFMD fed broilers had increased ATP concentrations and exhibited increased ATP turnover (P < 0.01). To determine if the increased energy consumption by PBMC corresponded with an altered immune response, broilers were immunized with sheep red blood cells (SRBC) and assayed for differences in their humoral response. The DFMD-fed broilers had a faster rate of antigen specific IgG production (P < 0.05) and an increase in total IgA (P < 0.05). Collectively, these data indicate that supplementation with the direct fed microbial used in this study resulted in energy re-partitioning to the immune system and an increase in antibody production independent of changes in whole body metabolism or growth performance.}, number={8}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Qiu, R. and Croom, J. and Ali, R. A. and Ballou, A. L. and Smith, C. D. and Ashwell, C. M. and Hassan, H. M. and Chiang, C. -C. and Koci, M. D.}, year={2012}, month={Aug}, pages={2639–2651} } @inbook{schultz-cherry_koci_2011, title={Avastrovirus, Astroviridae}, DOI={10.1007/978-0-387-95919-1_10}, booktitle={The Springer Index of Viruses. 2nd Edition}, publisher={Springer Science \mathplus Business Media}, author={Schultz-Cherry, Stacey L. and Koci, Matthew}, year={2011}, pages={89–95} } @article{leandro_ali_koci_moraes_malheiros_wineland_oviedo-rondon_2011, title={Effects of broiler breeder genetic, diet type, and feeding program on maternal antibody transfer and development of lymphoid tissues in chicken progeny}, volume={20}, ISSN={1056-6171 1537-0437}, url={http://dx.doi.org/10.3382/japr.2010-00268}, DOI={10.3382/japr.2010-00268}, abstractNote={SUMMARY Maternal antibody (MatAb) transfer is important for early chicken survivability. Diet composition and the amount of feed given to breeder pullets during rearing may affect the development of immunity and the transfer of MatAb to progeny, and could affect progeny performance and resistance to disease. The effects of broiler breeder nutrition and feeding management practices were evaluated for the transfer of MatAb to progeny and for spleen and bursa development at hatching in 2 genetic strains (A and B). In this experiment, the levels of MatAb against Newcastle disease virus were assessed by enzyme-linked immunosorbent assays in serum samples taken of pedigreed chicken progeny from hatching to 13 d of age. Chickens were fed corn- and wheat-based diets, as were their parents. The breeder feeding program and diet type altered the Newcastle disease virus MatAb found in progeny at hatching and affected how long these antibodies were maintained in circulation. Bursal follicle size at hatching was influenced by an interaction among all factors evaluated. Percentage of white pulp in the spleen was affected mainly by genetic strain and diet type, but responses varied according to the breeder feeding program. It was concluded that breeder feeding programs influence MatAb transfer and half-life, and may also affect the early development of lymphoid tissues.}, number={4}, journal={The Journal of Applied Poultry Research}, publisher={Oxford University Press (OUP)}, author={Leandro, N. M. and Ali, R. and Koci, M. and Moraes, V. and Malheiros, R. D. and Wineland, M. J. and Oviedo-Rondon, E. O.}, year={2011}, month={Dec}, pages={474–484} } @article{leandro_ali_koci_moraes_eusebio-balcazar_jornigan_malheiros_wineland_brake_oviedo-rondón_2011, title={Maternal antibody transfer to broiler progeny varies among strains and is affected by grain source and cage density}, volume={90}, ISSN={0032-5791}, url={http://dx.doi.org/10.3382/ps.2011-01573}, DOI={10.3382/ps.2011-01573}, abstractNote={Two experiments were conducted to examine the effects of broiler breeder dietary grain source and cage density on maternal antibody (MatAb) transfer to progeny in 2 genetic strains (A and B). Broiler breeders were assigned to 16 litter floor pens and fed either corn- or wheat-based diets. Breeders were administered 4 live vaccines against Newcastle disease virus (NDV). At 23 wk of age, pullets and cocks, which reflected the full BW distribution from each treatment, were moved to a cage breeder house and placed at 1 or 2 hens/cage. Breeders were artificially inseminated at 44 wk (experiment 1) and 52 wk of age (experiment 2). Eggs were collected for 8 d, incubated, and placed in individual pedigree bags at d 19 of incubation. Blood samples from 5 chicks per treatment combination were collected at hatch in both experiments. Spleen and bursa were collected from the same chicks for histomorphometry analyses in experiment 2. In the second experiment, 12 chicks per treatment were placed in cages. Progeny were provided diets based on the same grain (corn or wheat) as their parents. Serum samples were collected at 5, 9, and 13 d of age and analyzed for anti-NDV MatAb. Data were analyzed as a 2 × 2 × 2 factorial design considering strain, dietary grain source, and cage density as main factors. Interaction effects were observed in breeders and progeny. Experiment 1 showed that strain A chicks had lower levels of MatAb when hens were housed at 2 hens/cage rather than 1 hen/cage. The MatAb levels of strain B chickens were not affected by cage density in either experiment. Experiment 2 demonstrated similar effects of cage density on MatAb levels and the area of bursa follicles for both strains. Progeny of breeders fed corn-based diets had smaller spleen white pulp only when hens were housed at 2 hens/cage compared with 1 hen/cage. The results of these experiments suggest that breeder strain and cage-density conditions affected MatAb transfer to progeny and embryo development of spleen and bursa.}, number={12}, journal={Poultry Science}, publisher={Elsevier BV}, author={Leandro, N.M. and Ali, R. and Koci, M. and Moraes, V. and Eusebio-Balcazar, P.E. and Jornigan, J. and Malheiros, R.D. and Wineland, M.J. and Brake, J. and Oviedo-Rondón, E.O.}, year={2011}, month={Dec}, pages={2730–2739} } @article{nighot_moeser_ali_blikslager_koci_2010, title={Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanger expression}, volume={401}, ISSN={0042-6822}, url={http://dx.doi.org/10.1016/j.virol.2010.02.004}, DOI={10.1016/j.virol.2010.02.004}, abstractNote={Astroviruses are known to be a leading cause of diarrhea in infants and the immunocompromised; however, our understanding of this endemic pathogen is limited. Histological analyses of astrovirus pathogenesis demonstrate clinical disease is not associated with changes to intestinal architecture, inflammation, or cell death. Recent studies in vitro have suggested that astroviruses induce actin rearrangement leading to loss of barrier function. The current study used the type-2 turkey astrovirus (TAstV-2) and turkey poult model of astrovirus disease to examine how astrovirus infection affects the ultrastructure and electrophysiology of the intestinal epithelium. These data demonstrate that infection results in changes to the epithelial ultrastructure, rearrangement of F-actin, decreased absorption of sodium, as well as redistribution of the sodium/hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm. Collectively, these data suggest astrovirus infection induces sodium malabsorption, possibly through redistribution of specific sodium transporters, which results in the development of an osmotic diarrhea.}, number={2}, journal={Virology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Moeser, Adam and Ali, Rizwana A. and Blikslager, Anthony T. and Koci, Matthew D.}, year={2010}, month={Jun}, pages={146–154} } @article{grimes_koci_stark_smith_nighot_middleton_2010, title={Biological Effect of Naturally Occurring Mycotoxins Fed to Poults Reared to 21 Days of Age}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78650548809&partnerID=MN8TOARS}, DOI={10.3923/ijps.2010.871.874}, abstractNote={3 Abstract: A trial was conducted to observe potential changes in turkey poults reared to 21 d by feeding diets with naturally occurring mycotoxins. Two sources of corn, one each with Aflatoxin (AFL) and Deoxynevalenol (DON), were obtained. Treatments (T) were: 1) clean corn (C), 2) AFL (A), 3) DON (D) and 4) ½A+½D (AD). A marker (celite, 1.5%) was added for 21 d AMEn determination. A basal ration with ingredients except corn was mixed. The basal and corn were mixed for T feeds. Feed was pelleted and crumbled. Male poults were placed into 24 pens in petersyme batteries (7 birds/pen; 6 pens/T). Feed consumption, by pen and BW were determined by wk. At 21 d, birds were euthanized. Heart (H), spleen (S), gizzard (G), liver (L) and bursa of fabricious (B) were weighed and Breast Muscle (BM) collected for color analysis. Light microscopic analysis of HE AD = 2,758±29). Relative (R) S weight of D (0.11) fed birds was reduced versus A (0.14) but not C or AD (0.12, 0.13±0.006 g/g). The RL weight of birds fed A (2.26) and AD (2.52) were reduced versus C (2.68±0.07g/g). The A fed birds had reduced SA (by OD). Mortality, RH, RB and RG weights, G score and BM colors were not affected. There were no differences in AB. The L of the A fed birds had hepatic parenchyma with diffuse degenerative changes. The hepatocytic nuclei were swollen and had condensed nucleoli. Some hepatic cords had hepatocyte necrosis. There was some sinusoidal congestion with dilatation/congestion of few central veins. These lesions were suggestive of aflatoxin toxicity. The effects of AFL and DON in this study were reflective of what has been reported in the literature. Feeding naturally occurring mycotoxins to poults can be used as a model to study interventions.}, number={9}, journal={International J. of Poultry Science}, publisher={Science Alert}, author={Grimes, Jesse L. and Koci, Matthew D. and Stark, Charles R. and Smith, Doug P. and Nighot, Prashant K. and Middleton, Teena}, year={2010}, month={Sep}, pages={871–874} } @article{croom_chichlowski_froetschel_mcbride_qui_koci_2009, title={The effects of direct-fed microbial, primalac®, or salinomycin supplementation on intestinal lactate isomers and cecal volatile fatty acid concentrations in broilers}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67649336776&partnerID=MN8TOARS}, DOI={10.3923/ijps.2009.128.132}, abstractNote={Direct-Fed Microbials (DFM) are a putative alternative to the feeding of sub-therapeutic levels of antibiotics in the production of poultry and other livestock species. This study was designed to examine the effects of a commercial DFM (Primalac®), or salinomycin (SAL), a commonly used antibiotic and coccidiostat supplement, on fermentation patterns and lactate production in the cecum and the lower intestinal tract of broiler chickens. L-lactate and total lactate concentrations in the digesta fluid of the ileum decreased (P<0.01) with the DFM feeding in comparison to CON and SAL treatments while d-lactate concentration increased (P<0.04) in comparison to CON. Total cecal VFA concentration was lower (P<0.003) with DFM feeding and SAL than the CON. In the present study both dietary supplements, DFM and SAL, altered lactic acid and VFA concentrations in the cecum and intestines of experimental animals; however the full spectrum of mechanisms responsible for antibacterial properties and growth promotion associated with those changes remains to be elucidated.}, number={2}, journal={International Journal of Poultry Science}, author={Croom, J. and Chichlowski, M. and Froetschel, M. and McBride, B.W. and Qui, R. and Koci, M.D.}, year={2009}, pages={128–132} } @article{oviedo-rondon_small_wineland_christensen_mozdziak_koci_funderburk_ort_mann_2008, title={Broiler embryo bone development is influenced by incubator temperature, oxygen concentration and eggshell conductance at the plateau stage in oxygen consumption}, volume={49}, ISSN={["1466-1799"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-57849128060&partnerID=MN8TOARS}, DOI={10.1080/00071660802433149}, abstractNote={1. Four experiments were conducted to evaluate the effects of temperature (TEM) and oxygen (O2) concentrations during the last 4 d of incubation on bone development. Fertile eggs from two strains were obtained that either exhibited Low or High eggshell conductance (G). 1The mention of trade names in this publication does not imply endorsement of the products mentioned nor criticism of similar products not mentioned. 2. Four experimental cabinets provided either four TEM (36, 37, 38 or 39°C) or four O2 concentrations (17, 19, 21 or 23% O2). Data were analysed as a 2 × 2 factorial design. In the fourth experiment, two temperatures (36 and 39°C), two O2 concentrations (17 and 23%) and the same Low and High G strains were evaluated in a 2 × 2 × 2 factorial design. 3. Body weights (BW) and residual yolks were obtained, both legs were dissected. Femur, tibia and shank weights, length and thickness were recorded. Relative asymmetry (RA) of each leg section was calculated. 4. The results indicated that elevated TEM during incubation increased RA between the two legs, mainly in the Low G strain. Chickens at the lowest O2 concentrations had lighter and shorter tibias, lighter shanks, and increased RA of femur length compared to chickens in the 23% O2. In the fourth experiment no interactions were observed between O2 and TEM. High TEM depressed BW of Low G broilers, but no significant effect of treatments was observed on BW of High G broilers. Nevertheless, the high TEM or low O2 independently caused reduced femur and tibia weights and length, shank length and thickness, and both low O2 and high TEM together increased RA in shank weight. 5. These results suggest that late incubation conditions affect long bone development in broilers.}, number={6}, journal={BRITISH POULTRY SCIENCE}, author={Oviedo-Rondon, E. O. and Small, J. and Wineland, M. J. and Christensen, V. L. and Mozdziak, P. S. and Koci, M. D. and Funderburk, S. V. L. and Ort, D. T. and Mann, K. M.}, year={2008}, pages={666–676} } @article{chichlowski_croom_qui_mcbride_koci_2008, title={Direct fed microbial, Primalac®, supplementation and jejunal glucose and proline transport in broiler chickens}, volume={7}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-58849094009&partnerID=MN8TOARS}, DOI={10.3923/ijps.2008.1163.1166}, number={12}, journal={International Journal of Poultry Science}, author={Chichlowski, M. and Croom, J. and Qui, R. and McBride, B.W. and Koci, M.D.}, year={2008}, pages={1163–1166} } @article{strain_kelley_schultz-cherry_muse_koci_2008, title={Genomic analysis of closely related astroviruses}, volume={82}, ISSN={["0022-538X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-43249085073&partnerID=MN8TOARS}, DOI={10.1128/JVI.01993-07}, abstractNote={ABSTRACT To understand astrovirus biology, it is essential to understand factors associated with its evolution. The current study reports the genomic sequences of nine novel turkey astrovirus (TAstV) type 2-like clinical isolates. This represents, to our knowledge, the largest genomic-length data set available for any one astrovirus type. The comparison of these TAstV sequences suggests that the TAstV species contains multiple subtypes and that recombination events have occurred across the astrovirus genome. In addition, the analysis of the capsid gene demonstrated evidence for both site-specific positive selection and purifying selection.}, number={10}, journal={JOURNAL OF VIROLOGY}, author={Strain, Errol and Kelley, Laura A. and Schultz-Cherry, Stacey and Muse, Spencer V. and Koci, Matthew D.}, year={2008}, month={May}, pages={5099–5103} } @article{nighot_koci_moeser_ali_blikslager_2008, title={W1268 Mechanism of Astrovirus Induced Diarrhea}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)63119-4}, DOI={10.1016/s0016-5085(08)63119-4}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Koci, Matthew D. and Moeser, Adam J. and Ali, Rizwana and Blikslager, Anthony T.}, year={2008}, month={Apr}, pages={A-668} } @article{chichlowski_croom_mcbride_daniel_davis_koci_2007, title={Direct-fed microbial PrimaLac and salinomycin modulate whole-body and intestinal oxygen consumption and intestinal mucosal cytokine production in the broiler chick}, volume={86}, ISSN={["1525-3171"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547665641&partnerID=MN8TOARS}, DOI={10.1093/ps/86.6.1100}, abstractNote={The current study investigated whole-body O2 consumption, intestinal O2 consumption, and intestinal inflammation status through mucosal cytokine production on broiler chicks fed the direct-fed microbial PrimaLac. One hundred twenty 1-d-old broiler chicks were randomly assigned to 1 of 3 experimental diets: standard starter diet (control), standard starter diet with added salinomycin (SAL), and standard starter diet with added PrimaLac (DFM). Birds were housed in 2 separate rooms, the control and SAL treatments in one room and the DFM in another. Intact ileal and cecal samples were collected on d 19, 20, and 21 after measuring whole-body O2 consumption using indirect calorimetry. The O2 up-take of ileal tissue was measured using an in vitro O2 monitor. Analysis of intestinal immune status of broilers was measured by the relative differences in mRNA of both pro- and antiinflammatory cytokines: interleukin-(IL) 1beta, IL-6, and IL-10 using real-time reverse transcription-PCR. Broilers exhibited a 6 to 16% decrease in whole-body energy expenditures and up to a 47% decrease (P<0.05) in ileal energy expenditures in the DFM group compared with other treatments. The reverse transcription-PCR data demonstrated that DFM consortium numerically altered both pro- and antiinflammatory cytokines within the ileum of 19-d posthatch broilers. These data suggest that direct-fed microbials like PrimaLac increase metabolic efficiency via changes in intestinal physiology and metabolism.}, number={6}, journal={POULTRY SCIENCE}, author={Chichlowski, M. and Croom, J. and McBride, B. W. and Daniel, L. and Davis, G. and Koci, M. D.}, year={2007}, month={Jun}, pages={1100–1106} } @article{chichlowski_croom_mcbride_havenstein_koci_2007, title={Metabolic and physiological impact of probiotics or direct-fed-microbials on poultry: A brief review of current knowledge}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-36048940317&partnerID=MN8TOARS}, number={10}, journal={International Journal of Poultry Science}, author={Chichlowski, M. and Croom, J. and McBride, B.W. and Havenstein, G.B. and Koci, M.D.}, year={2007}, pages={694–704} } @article{chichlowski_croom_edens_mcbride_qiu_chiang_daniel_havenstein_koci_2007, title={Microarchitecture and spatial relationship between bacteria and ileal, cecal, and colonic epithelium in chicks fed a direct-fed microbial, PrimaLac, and salinomycin}, volume={86}, ISSN={["1525-3171"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547680556&partnerID=MN8TOARS}, DOI={10.1093/ps/86.6.1121}, abstractNote={Direct-fed microbials (DFM) could serve as a potential alternative to the feeding of antibiotics in poultry production. In this study, the effects of providing a DFM were compared with the feeding of salinomycin on intestinal histomorphometrics, and microarchitecture was examined. Broiler chicks (n=18 per treatment; trials 1 and 2) were fed a standard starter diet (control), control+PrimaLac (DFM; 0.3% wt/wt), and control+salinomycin (SAL; 50 ppm) from hatch to 21d. The birds were euthanized on d 21, and the ileal, jejunal, cecal, and colon tissues were dissected. Samples were examined by light microscopy (jejunum and ileum; trial 1) and scanning electron microscopy (ileum, cecum, and colon; trial 2). Feeding of the DFM increased intestinal muscle thickness (P<0.05) up to 33% compared with the control treatment. The DFM group also had increased villus height and perimeter (P=0.009 and 0.003, respectively) in jejunum. Segmented filamentous-like bacteria were less numerous in DFM-treated chicks than in the control chicks. Very few segmented filamentous-like bacteria were found near other microbes in the ileum. The DFM chicks had a larger number of bacteria positioned over or near goblet cells and in intervilli spaces. Bacteria in the colon were observed to be attached primarily around and within the crypts. Mucous thickness was less, and the density of bacteria embedded in the mucous blanket appeared to be lower in DFM-treated animals than in the control in all intestinal segments. The birds fed SAL had fewer bacteria and enterocytes in the ileum than in the control-and DFM-treated birds, and they had thicker and fewer microvilli. Because gastrointestinal track colonization by the DFM organisms can prevent the attachment of pathogens to the epithelium, spatial relationships, in this study, demonstrate the functionality of DFM and probiotics in preventing disease. It also supports previous observations that the feeding of salinomycin may alter intestinal function.}, number={6}, journal={POULTRY SCIENCE}, author={Chichlowski, M. and Croom, W. J. and Edens, F. W. and McBride, B. W. and Qiu, R. and Chiang, C. C. and Daniel, L. R. and Havenstein, G. B. and Koci, M. D.}, year={2007}, month={Jun}, pages={1121–1132} } @article{effect of genotype on whole-body and intestinal metabolic response to monensin in mice_2006, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33645764643&partnerID=MN8TOARS}, number={4}, journal={Asian-Australasian Journal of Animal Sciences}, year={2006}, pages={554–562} } @misc{koci_2005, title={Immunity and resistance to astrovirus infection}, volume={18}, ISSN={["0882-8245"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-17844369466&partnerID=MN8TOARS}, DOI={10.1089/vim.2005.18.11}, abstractNote={Astroviruses are one of the leading causes of acute viral enteritis in infants, and are recognized as a clinically important pathogen in the elderly and the immunocompromised. In spite of this, we still know very little about the immune response to astrovirus infection. Clinical observations and human volunteer studies have indicated a role for the humoral response and suggest neutralizing antibodies are important in limiting infection. Studies of human intestinal biopsies have suggested that cellular immunity; specifically CD4(+) T-cells may also be involved in the anti-astrovirus response. Additionally, various animal models have indicated potential roles for the innate immune system in controlling infections. How these various effector arms of the immune system collaborate to result in immunity and resistance to astrovirus infection is still unknown. This review summarizes our current understanding of the immune response to this pathogen and highlights the key concepts that still need to be addressed. Until we understand the role of the immune system in astrovirus infection or other enteric viruses, we will continue to be limited in our ability to treat and control gastrointestinal diseases.}, number={1}, journal={VIRAL IMMUNOLOGY}, publisher={Mary Ann Liebert Inc}, author={Koci, MD}, year={2005}, pages={11–16} } @article{koci_kelley_larsen_schultz-cherry_2004, title={Astrovirus-Induced Synthesis of Nitric Oxide Contributes to Virus Control during Infection}, volume={78}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0346373575&partnerID=MN8TOARS}, DOI={10.1128/JVI.78.3.1564-1574.2004}, abstractNote={ABSTRACTAstrovirus is one of the major causes of infant and childhood diarrhea worldwide. Our understanding of astrovirus pathogenesis trails behind our knowledge of its molecular and epidemiologic properties. Using a recently developed small-animal model, we investigated the mechanisms by which astrovirus induces diarrhea and the role of both the adaptive and innate immune responses to turkey astrovirus type-2 (TAstV-2) infection. Astrovirus-infected animals were analyzed for changes in total lymphocyte populations, alterations in CD4+/CD8+ratios, production of virus-specific antibodies (Abs), and macrophage activation. There were no changes in the numbers of circulating or splenic lymphocytes or in CD4+/CD8+ratios compared to controls. Additionally, there was only a modest production of virus-specific Abs. However, adherent spleen cells from infected animals produced more nitric oxide (NO) in response to ex vivo stimulation with lipopolysaccharide. In vitro analysis demonstrated that TAstV-2 induced macrophage production of inducible nitric oxide synthase. Studies using NO donors and inhibitors in vivo demonstrated, for the first time, that NO inhibited astrovirus replication. These studies suggest that NO is important in limiting astrovirus replication and are the first, to our knowledge, to describe the potential role of innate immunity in astrovirus infection.}, number={3}, journal={Journal of Virology}, author={Koci, M.D. and Kelley, L.A. and Larsen, D. and Schultz-Cherry, S.}, year={2004}, pages={1564–1574} } @article{sellers_koci_linnemann_kelley_schultz-cherry_2004, title={Development of a Multiplex Reverse Transcription–Polymerase Chain Reaction Diagnostic Test Specific for Turkey Astrovirus and Coronavirus}, volume={48}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-13744254372&partnerID=MN8TOARS}, DOI={10.1637/7128}, abstractNote={Abstract A multiplex reverse transcription–polymerase chain reaction (RT-PCR) assay was developedfor the simultaneous detection of two enteric viruses of poultry: turkey enteric coronavirus (TCV) and turkey astrovirus (TAstV). PCR primers were designed to conserved regions within the nucleocapsid gene of TCV and to the polymerase gene of TAstV-2. The primer pairs were successfully used in a multiplex RT-PCR to detect nucleic acid of TAstV-2 and TCV. The test was optimized for use with intestines/feces from naturally infected turkeys. The primers were specific and did not amplify other common RNA or DNA avian viruses. The detection limit was determined to be 10 ng of RNA used as starting template. The use of this specific test allows the rapid and early diagnosis of two financially costly viruses affecting the commercial turkey industry.}, number={3}, journal={Avian Diseases}, publisher={American Association of Avian Pathologists (AAAP)}, author={Sellers, Holly S. and Koci, Matthew D. and Linnemann, Erich and Kelley, Laura A. and Schultz-Cherry, Stacey}, year={2004}, month={Sep}, pages={531–538} } @article{koci_moser_kelley_larsen_brown_schultz-cherry_2003, title={Astrovirus Induces Diarrhea in the Absence of Inflammation and Cell Death}, volume={77}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0142060825&partnerID=MN8TOARS}, DOI={10.1128/JVI.77.21.11798-11808.2003}, abstractNote={ABSTRACTAstroviruses are a leading cause of infantile viral gastroenteritis worldwide. Very little is known about the mechanisms of astrovirus-induced diarrhea. One reason for this is the lack of a small-animal model. Recently, we isolated a novel strain of astrovirus (TAstV-2) from turkeys with the emerging infectious disease poult enteritis mortality syndrome. In the present studies, we demonstrate that TAstV-2 causes growth depression, decreased thymus size, and enteric infection in infected turkeys. Infectious TAstV-2 can be recovered from multiple tissues, including the blood, suggesting that there is a viremic stage during infection. In spite of the severe diarrhea, histopathologic changes in the intestine were mild and there was a surprising lack of inflammation. This may be due to the increased activation of the potent immunosuppressive cytokine transforming growth factor beta during astrovirus infection. These studies suggest that the turkey will be a useful small-animal model with which to study astrovirus pathogenesis and immunity.}, number={21}, journal={Journal of Virology}, author={Koci, M.D. and Moser, L.A. and Kelley, L.A. and Larsen, D. and Brown, C.C. and Schultz-Cherry, S.}, year={2003}, pages={11798–11808} } @article{schultz-cherry_koci_thompson_tumpey_2003, title={Examining the cellular pathways involved in influenza virus induced apoptosis}, volume={47}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0141677673&partnerID=MN8TOARS}, number={SPEC. ISS.}, journal={Avian Diseases}, author={Schultz-Cherry, S. and Koci, M. and Thompson, E. and Tumpey, T.M.}, year={2003}, pages={968–971} } @article{koci_schultz-cherry_2002, title={Avian astroviruses}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036281220&partnerID=MN8TOARS}, DOI={10.1080/03079450220136521}, abstractNote={As poultry becomes more important in the world economy, it is increasingly important to fully understand the mechanisms of disease and poor production that affect the industry. To more accurately and reasonably treat these diseases, a more sophisticated understanding of interrelatedness is required. This review focuses on avian astroviruses (AAstVs), in particular the recent advances in our understanding of AAstV molecular biology, and also history, diagnosis, treatment and control. The known AastVs comprise duck astrovirus 1, turkey astrovirus 1 and 2, and avian nephritis virus of chickens. Nucleotide and amino acid identities between the avian and mammalian (human, ovine, bovine) astroviruses is very low (e.g. 20 to 25% and 12 to 15%, respectively) in open reading frame (ORF) 1a. There is also variation among the avian astroviruses, including between the two known types of turkey astrovirus. The ORF 1b sequence contains a number of conserved amino acid motifs; these could be the basis of degnerate oligonucleotide primers. A nomenclature for astroviruses is also proposed, based on: host species-astrovirus-type number/country(state)/reference number/year of isolation. For example, turkey astrovirus 2/North Carolina/034/1999.}, number={3}, journal={Avian Pathology}, publisher={Informa UK Limited}, author={Koci, Matthew D. and Schultz-Cherry, Stacey}, year={2002}, month={Jun}, pages={213–227} } @article{behling-kelly_schultz-cherry_koci_kelley_larsen_brown_2002, title={Localization of astrovirus in experimentally infected turkeys as determined by in situ hybridization.}, volume={39}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036728382&partnerID=MN8TOARS}, number={5}, journal={Veterinary Pathology}, author={Behling-Kelly, E. and Schultz-Cherry, S. and Koci, M. and Kelley, L. and Larsen, D. and Brown, C.}, year={2002}, pages={595–598} } @article{schultz-cherry_king_koci_2001, title={Inactivation of an Astrovirus Associated with Poult Enteritis Mortality Syndrome}, volume={45}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035066975&partnerID=MN8TOARS}, DOI={10.2307/1593014}, abstractNote={Outbreaks of poult enteritis mortality syndrome (PEMS) continue to cause financial losses to the turkey industry. Clinically, PEMS is defined by mortality profiles, diarrhea, flock unevenness, and immunosuppression. PEMS is a very difficult disease to control and prevent. Depopulation of PEMS-affected flocks and thorough cleaning of the contaminated housing have failed to prevent infection (disease) in subsequent flock placements. The relationship of PEMS to other enteric disease complexes of young turkeys is unknown, partly because the causative agent of PEMS remains unknown. Recently, we isolated a unique astrovirus strain from the thymus and intestines of PEMS-infected poults. This strain is molecularly and serologically distinct from the astrovirus that circulated in turkeys in the 1980s. Mammalian astroviruses are very resistant to inactivation. In these studies, we examined the stability of partially purified PEMS-associated astrovirus to inactivation with heat, laboratory disinfectants, and commercial disinfectants used in commercial turkey houses in an embryonated egg model system. Similar to mammalian astroviruses, the PEMS-associated astrovirus is resistant to inactivation by heat, acidification, detergent treatment, and treatment with phenolic, quaternary ammonium, or benzalkonium chloride-based products. Only treatment with formaldehyde, beta-propriolactone, or the peroxymonosulfate-based product Virkon S completely inactivated the astrovirus in the embryo model. These studies provide an alternate means to potentially control at least one virus associated with PEMS through the use of specific disinfectants.}, number={1}, journal={Avian Diseases}, publisher={JSTOR}, author={Schultz-Cherry, Stacey and King, Daniel J. and Koci, Matthew D.}, year={2001}, month={Jan}, pages={76} } @article{koci_seal_schultz-cherry_2000, title={Development of an RT-PCR diagnostic test for an avian astrovirus}, volume={90}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033813102&partnerID=MN8TOARS}, DOI={10.1016/s0166-0934(00)00228-7}, abstractNote={Astroviruses are small round viruses that cause enteric disease in the young of several species. Detection and diagnosis of astrovirus infection in non-human hosts relies heavily on electron microscopy and fluorescent antibody tests. Recently, our laboratory isolated and sequenced an avian astrovirus from poult enteritis mortality syndrome affected turkeys. These studies describe the development of RT-PCR methods, which specifically detect regions of the viral capsid and polymerase genes, and demonstrate their use in detecting astrovirus infection in commercial turkey flocks.}, number={1}, journal={Journal of Virological Methods}, publisher={Elsevier BV}, author={Koci, Matthew D and Seal, Bruce S and Schultz-Cherry, Stacey}, year={2000}, month={Oct}, pages={79–83} } @article{schultz-cherry_kapczynski_simmons_koci_brown_barnes_2000, title={Identifying agent(s) associated. with poult enteritis mortality syndrome: Importance of the thymus}, volume={44}, ISSN={["0005-2086"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034088250&partnerID=MN8TOARS}, DOI={10.2307/1592538}, abstractNote={Poult enteritis mortality syndrome (PEMS), a highly infectious disease of young turkeys, causes serious financial losses to the turkey industry. Clinically, PEMS is defined by mortality profiles, diarrhea, growth depression, and immunosuppression. Although many viruses, bacteria, and parasites are found in PEMS-infected birds, the inciting agent remains unknown. Experimentally, PEMS can be reproduced by exposing naïve poults to the intestinal contents from infected birds. Previous reports suggest that extraintestinal tissues fail to reproduce the disease. Histopathologic examination of tissues from PEMS-infected poults suggested that the thymus exhibited the earliest signs of pathology. On the basis of these observations, we hypothesized that the thymus harbors an agent(s) involved in PEMS. In these studies, naïve turkey poults were orally inoculated with a bacteria-free filtrate composed of either the intestines and feces or the thymus from PEMS-infected birds and were monitored for clinical signs of PEMS. Poults exposed to a filtrate composed solely of the thymus from PEMS-infected birds exhibited diarrhea, growth depression, mortality, pathology, and, most importantly, immunosuppression similar to poults exposed to the intestinal filtrate. The results of this study suggest that the thymus of infected birds harbors the agent(s) that can reproduce a PEMS-like disease in turkey poults.}, number={2}, journal={AVIAN DISEASES}, publisher={JSTOR}, author={Schultz-Cherry, S and Kapczynski, DR and Simmons, VM and Koci, MD and Brown, C and Barnes, HJ}, year={2000}, pages={256–265} } @article{koci_seal_schultz-cherry_2000, title={Molecular characterization of an avian astrovirus}, volume={74}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034123772&partnerID=MN8TOARS}, DOI={10.1128/JVI.74.13.6173-6177.2000}, abstractNote={ABSTRACT Astroviruses are known to cause enteric disease in several animal species, including turkeys. However, only human astroviruses have been well characterized at the nucleotide level. Herein we report the nucleotide sequence, genomic organization, and predicted amino acid sequence of a turkey astrovirus isolated from poults with an emerging enteric disease.}, number={13}, journal={Journal of Virology}, author={Koci, M.D. and Seal, B.S. and Schultz-Cherry, S.}, year={2000}, pages={6173–6177} } @article{mullins_koci_burger_elgert_1998, title={Interleukin-12 Overcomes Paclitaxel-Mediated Suppression of T-Cell Proliferation}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031751801&partnerID=MN8TOARS}, DOI={10.3109/08923979809031511}, abstractNote={The antineoplastic agent paclitaxel (TAXOL) is a potent inhibitor of tumor cell division and a useful chemotherapeutic for the treatment of refractory ovarian and breast carcinoma. Multiple immune system actions have been ascribed to paclitaxel, including the capacity to induce macrophage antitumor cytotoxic molecule production. However, T-cells are susceptible to paclitaxel's cytostatic functions, and no studies have investigated the effects of direct paclitaxel administration on lymphocyte function in the tumor-bearing host (TBH). Because paclitaxel is currently used as an antitumor chemotherapeutic agent and tumor growth alters leukocyte functions, we assessed T-cell function following chemotherapeutic-type paclitaxel treatment. Paclitaxel administration significantly compromised the proliferative capacity of both normal host and TBH lymphocytes in vitro. Although tumor growth impaired T-cell interferon-gamma (IFN-gamma) production, paclitaxel treatment did not alter IFN-gamma. We speculate that the immunostimulatory cytokine interleukin-12 (IL-12), which promoted T-cell activation and proliferation, was capable of reversing paclitaxel-mediated immunosuppression. Exogenous IL-12 fully reconstituted proliferative reactivity and enhanced IFN-gamma production by both normal host and TBH lymphocytes in vitro. Collectively, these data suggest that chemotherapeutic paclitaxel regimens impart significant but reversible inhibition of lymphocyte populations, and IL-12 may be a useful ancillary immunotherapeutic to overcome paclitaxel-induced modulation of lymphocyte activities.}, number={4}, journal={Immunopharmacology and Immunotoxicology}, publisher={Informa UK Limited}, author={Mullins, David W. and Koci, Matthew D. and Burger, Carol J. and Elgert, Klaus D.}, year={1998}, month={Jan}, pages={473–492} } @article{salmonella-attenuated strain and galacto-oligosaccharides accelerate clearance of salmonella infections in poultry through modifications to the gut microbiome. , url={https://www.ncbi.nlm.nih.gov/pubmed/29269490} }