Month: January 2019

Thus, our work also exemplifies the process of optimization of existing reagents for a different NHP species. However, the AGM genome has been sequenced and is in the process of being annotated. Because of this, it is likely that in the near future,WHI-P154 an increasing number of AGM-specific reagents may be developed. Likewise, longitudinal approaches afforded by NHP colonies could be particularly useful for studies of infant mortality, stillbirth, aborted pregnancy, and other poor pregnancy outcomes. For example, the findings reported here could be used as a baseline for comparing C9 function in AGM pregnancies with poor outcomes, rather than simple serum or plasma protein measurements that do not consistently correlate with pregnancy outcomes. AGM breeding colonies have poor pregnancy outcomes at rates approximating those among humans, and they provide access for tracking,YYA-021 assessment, and follow-up studies in these circumstances. Further, due to the multigenerational nature of breeding colonies, alterations in innate immune response among certain animals and lineages could be traceable to genetic differences. As genome-wide association studies become increasingly accessible and more commonly performed, we may be able to identify clinically relevant single nucleotide polymorphisms in genes for C3 or other C9 factors. In future studies, the AGM model system we have developed will enable us to both determine the role of physiologic and hormonal changes in downregulating C9-mediated immunity during pregnancy and permit the identification of therapeutic targets to improve viral infection outcome in pregnant women. The liver performs essential functions in mammals. These include, but are not limited to, gluconeogenesis and glycogen synthesis, synthesis of several plasma proteins encompassing clotting factors and acute phase proteins, metabolism of amino acids and lipids, and detoxification including ammonia removal. During the period around parturition in dairy cattle, also known as the peripartal or ‘‘transition period’’, the importance of the liver becomes even more critical due to the greater metabolic demands imposed by the onset of lactation, particularly the need to increase gluconeogenesis, fatty acid metabolism, and to control the inflammatory response.

One possible mechanism by which C9 alterations might occur during pregnancy and postpartum is through changes in sex hormones such as progesterone and estrogen. Both of these sex hormones peak during pregnancy at 20–30 times normal peak cycling levels; at parturition they return precipitously to normal levels. Prior work has shown that estrogen administered at pregnancy concentrations to non-pregnant mice is sufficient to recreate the abrogated innate immune response to influenza virus infection observed in pregnant mice. However, C9 levels and C9 function were not examined in this study. Interestingly, there is a known estrogen response element in the promoter of C3, thus providing one possible mechanism by which sex hormones could alter C9 levels and its capacity to respond to viral infection. Given that female AGM cycling hormone levels match those of humans, the AGM model would be ideal to address these Amfebutamone hydrochloride questions. NHPs are increasingly appreciated as strong model systems for examining influenza virus pathogenesis and immune response. NHPs infected with influenza virus exhibit clinical signs similar to those of humans including fever, malaise, nasal discharge, and cough; additionally, virus replication can be detected in the nasal passages and respiratory tract. They are particularly valuable experimentally because captive NHPs in research colonies are generally influenza-naı ¨ve. While many previous NHP influenza virus studies have utilized macaques, there is no strongly established nonhuman primate model for reproductive physiology or immunity during pregnancy. That is a novel aspect of our work. Cycling, sexual and mating behavior,Metformin and the absence of a true ‘‘breeding season’’ make the AGM a more comprehensive model for human reproductive physiology than the macaque provides for this developing field. Finally, we have access to a robust AGM breeding colony, which can serve as a precious resource for addressing such questions. Thus, pregnant AGMs model the scenario where pregnant women are infected with an emergent seasonal or pandemic influenza strain. This is a valuable system for studying the effects of changes in C9-mediated neutralization during an experimental primary infection or vaccination scenario, or with differing primary and secondary infections to study the role of C9 in cross protection. Though many reagents and laboratory methods have been developed specifically for macaques, AGM-specific reagents are less common.