@misc{stern_mozdziak_2019, title={Differential ammonia metabolism and toxicity between avian and mammalian species, and effect of ammonia on skeletal muscle: A comparative review}, volume={103}, ISSN={["1439-0396"]}, DOI={10.1111/jpn.13080}, abstractNote={Abstract}, number={3}, journal={JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION}, author={Stern, Rachel A. and Mozdziak, Paul E.}, year={2019}, month={May}, pages={774–785} }
 @article{stern_mozdziak_2019, title={Glutamine synthetase in avian muscle contributes to a positive myogenic response to ammonia compared with mammalian muscle}, volume={317}, ISSN={["1522-1490"]}, DOI={10.1152/ajpregu.00232.2018}, abstractNote={In mammalian models of cirrhosis, plasma ammonia concentration increases, having numerous adverse effects, including sarcopenia. The objective of this study was to identify differences between avian and mammalian myogenic response to applied ammonia and glutamine. Primary chicken breast and thigh, primary rat, and C2C12myotubes were treated with ammonium acetate (AA, 10 mM) or glutamine (10 mM) for 24 h and compared with sodium acetate (10 mM) and untreated controls. Myostatin mRNA was significantly higher in C2C12and rat myotubes treated with AA compared with glutamine and controls ( P < 0.01), whereas myostatin was unchanged in chicken myotubes. AA-treated C2C12myotubes had significantly higher glutamine synthetase (GS) mRNA expression compared with controls, but GS protein expression was unchanged. In contrast, GS mRNA expression was unchanged in thigh myotubes, but GS protein expression was significantly higher in AA-treated thigh myotubes ( P < 0.05). In both breast and thigh myotubes, intracellular glutamine concentration was significantly increased in AA- and glutamine-treated myotubes compared with controls but was only increased in glutamine-treated C2C12and rat myotubes ( P < 0.05). Glutamine concentration was significantly higher in all treatment media collected from avian myotube cultures compared with both C2C12and rat media ( P < 0.01). Myotube diameter was significantly larger in avian myotubes after treatment with both AA and glutamine ( P < 0.05). C2C12and rat myotubes had a significantly smaller myotube diameter after AA treatment ( P < 0.001). Altogether, these data support species differences in skeletal muscle ammonia metabolism and suggest that glutamine synthesis is a mechanism of ammonia utilization in avian muscle.}, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY}, author={Stern, Rachel Allysa and Mozdziak, Paul E.}, year={2019}, month={Jul}, pages={R214–R221} }
 @article{chen_song_chen_zhu_cai_sun_stern_mozdziak_ge_means_et al._2018, title={Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing}, volume={9}, ISSN={["2073-4425"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85042059878&partnerID=MN8TOARS}, DOI={10.3390/genes9020086}, abstractNote={Titin (TTN) is a major disease-causing gene in cardiac muscle. Titin (TTN) contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mainly by RNA binding motif 20 (RBM20). Three isoforms of TTN protein are produced by mutually exclusive exons 45 (Novex 1), 46 (Novex 2), and 48 (Novex 3). Alternatively splicing in Novex isoforms across species and whether Novex isoforms are associated with heart disease remains completely unknown. Cross-species exon comparison with the mVISTA online tool revealed that exon 45 is more highly conserved across all species than exons 46 and 48. Importantly, a conserved region between exons 47 and 48 across species was revealed for the first time. Reverse transcript polymerase chain reaction (RT-PCR) and DNA sequencing confirmed a new exon named as 48′ in Novex 3. In addition, with primer pairs for Novex 1, a new truncated form preserving introns 44 and 45 was discovered. We discovered that Novex 2 is not expressed in the pig, mouse, and rat with Novex 2 primer pairs. Unexpectedly, three truncated forms were identified. One TTN variant with intron 46 retention is mainly expressed in the human and frog heart, another variant with co-expression of exons 45 and 46 exists predominantly in chicken and frog heart, and a third with retention of introns 45 and 46 is mainly expressed in pig, mouse, rat, and chicken. Using Rbm20 knockout rat heart, we revealed that RBM20 is not a splicing regulator of Novex variants. Furthermore, the expression levels of Novex variants in human hearts with cardiomyopathies suggested that Novexes 2 and 3 could be associated with dilated cardiomyopathy (DCM) and/or arrhythmogenic right ventricular cardiomyopathy (ARVC). Taken together, our study reveals that splicing diversity of Novex exons across species and Novex variants might play a role in cardiomyopathy.}, number={2}, journal={GENES}, author={Chen, Zhilong and Song, Jiangping and Chen, Liang and Zhu, Chaoqun and Cai, Hanfang and Sun, Mingming and Stern, Allysa and Mozdziak, Paul and Ge, Ying and Means, Warrie J. and et al.}, year={2018}, month={Feb} }
 @article{stern_dasarathy_mozdziak_2017, title={Ammonia elicits a different myogenic response in avian and murine myotubes}, volume={53}, ISSN={["1543-706X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84984622681&partnerID=MN8TOARS}, DOI={10.1007/s11626-016-0088-z}, abstractNote={Increased myostatin expression, resulting in muscle loss, has been associated with hyperammonemia in mammalian models of cirrhosis. However, there is evidence that hyperammonemia in avian embryos results in a reduction of myostatin expression, suggesting a proliferative myogenic environment. The present in vitro study examines species differences in myotube and liver cell response to ammonia using avian and murine-derived cells. Primary myoblasts and liver cells were isolated from embryonic day 15 and 17 chick embryos to be compared with mouse myoblasts (C2C12) and liver (AML12) cells. Cells were exposed to varying concentrations of ammonium acetate (AA; 2.5, 5, or 10 mM) to determine the effects of ammonia on the cells. Relative expression of myostatin mRNA, determined by quantitative real-time PCR, was significantly increased in AA (10 mM) treated C2C12 myotubes compared to both ages of chick embryonic myotube cultures after 48 h (P < 0.02). Western blot analysis of myostatin protein confirmed an increase in myostatin expression in AA-treated C2C12 myotubes compared to the sodium acetate (SA) controls, while myostatin expression was decreased in the chick embryonic myotube cultures when treated with AA. Myotube diameter was significantly decreased in AA-treated C2C12 myotubes compared to controls, while avian myotube diameter increased with AA treatment (P < 0.001). There were no significant differences between avian and murine liver cell viability, assessed using 2', 7'- bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein, acetoxymethyl ester, when treated with AA. However, after 24 h, AA-treated avian myotubes showed a significant increase in cell viability compared to the C2C12 myotubes (P < 0.05). Overall, it appears that there is a positive myogenic response to hyperammonemia in avian myotubes compared to murine myotubes, which supports a proliferative myogenic environment.}, number={2}, journal={IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL}, author={Stern, Rachel A. and Dasarathy, Srinivasan and Mozdziak, Paul E.}, year={2017}, month={Feb}, pages={99–110} }
 @article{mocka_stern_fletcher_anderson_petitte_mozdziak_2017, title={Chemoprevention of spontaneous ovarian cancer in the domestic hen}, volume={96}, ISSN={0032-5791}, url={http://dx.doi.org/10.3382/ps/pew422}, DOI={10.3382/ps/pew422}, abstractNote={&NA; The hen is an attractive animal model for in vivo testing of agents that thwart ovarian carcinogenesis because ovarian cancer in the domestic hen features clinical and molecular alterations that are similar to ovarian cancer in humans, including a high incidence of p53 mutations. The objective of the study was to test the potential ovarian cancer chemopreventive effect of the p53 stabilizing compound CP‐31398 on hens that spontaneously present the ovarian cancer phenotype. Beginning at 79 wk of age, 576 egg‐laying hens (Gallus domesticus) were randomized to diets containing different amounts of CP‐31398 for 94 wk, 5 d, comprising a control group (C) (n = 144), which was fed a diet containing 0 ppm (mg/kg) of CP‐31398; a low‐dose treatment (LDT) group (n = 144), which was fed a diet containing 100 ppm of CP‐31398; a moderate‐dose treatment (MDT) group (n = 144) which was fed a diet containing 200 ppm of CP‐31398; and a high‐dose treatment (HDT) group (n = 144), which was fed a diet containing 300 ppm of CP‐31398. Hens were killed at 174 wk of age to determine the incidence of ovarian and oviductal adenocarcinomas. Whereas the incidence of localized and metastatic ovarian cancers in the MDT and HDT groups was significantly lower (up to 77%) compared to levels in the C and LDT groups (P < 0.05), the incidence of oviductal cancer was unaffected by CP‐31398. CP‐31398 appears to be an effective tool for chemoprevention against ovarian malignancies, but does not appear to affect oviductal malignancies.}, number={6}, journal={Poultry Science}, publisher={Elsevier BV}, author={Mocka, E.H. and Stern, R.A. and Fletcher, O.J. and Anderson, K.E. and Petitte, J.N. and Mozdziak, P.E.}, year={2017}, month={Jun}, pages={1901–1909} }
 @article{stern_ashwell_dasarathy_mozdziak_2015, title={The effect of hyperammonemia on myostatin and myogenic regulatory factor gene expression in broiler embryos}, volume={9}, ISSN={["1751-732X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84929513015&partnerID=MN8TOARS}, DOI={10.1017/s1751731115000117}, abstractNote={Myogenesis is facilitated by four myogenic regulatory factors and is significantly inhibited by myostatin. The objective of the current study was to examine embryonic gene regulation of myostatin/myogenic regulatory factors, and subsequent manipulations of protein synthesis, in broiler embryos under induced hyperammonemia. Broiler eggs were injected with ammonium acetate solution four times over 48 h beginning on either embryonic day (ED) 15 or 17. Serum ammonia concentration was significantly higher (P<0.05) in ammonium acetate injected embryos for both ED17 and ED19 collected samples when compared with sham-injected controls. Expression of mRNA, extracted from pectoralis major of experimental and control embryos, was measured using real-time quantitative PCR for myostatin, myogenic regulatory factors myogenic factor 5, myogenic determination factor 1, myogenin, myogenic regulatory factor 4 and paired box 7. A significantly lower (P<0.01) myostatin expression was accompanied by a higher serum ammonia concentration in both ED17 and ED19 collected samples. Myogenic factor 5 expression was higher (P<0.05) in ED17 collected samples administered ammonium acetate. In both ED17 and ED19 collected samples, myogenic regulatory factor 4 was lower (P⩽0.05) in ammonium acetate injected embryos. No significant difference was seen in myogenic determination factor 1, myogenin or paired box 7 expression between treatment groups for either age of sample collection. In addition, there was no significant difference in BrdU staining of histological samples taken from treated and control embryos. Myostatin protein levels were evaluated by Western blot analysis, and also showed lower myostatin expression (P<0.05). Overall, it appears possible to inhibit myostatin expression through hyperammonemia, which is expected to have a positive effect on embryonic myogenesis and postnatal muscle growth.}, number={6}, journal={ANIMAL}, author={Stern, R. A. and Ashwell, C. M. and Dasarathy, S. and Mozdziak, P. E.}, year={2015}, month={Jun}, pages={992–999} }