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  • faah inhibitor Despite the association with asthma it is not

    2021-10-14

    Despite the association with asthma, it is not surprising that we did not find a relation between the percent predicted FEV1 and SNPs in GSNOR. FEV1 measured on a routine clinic visit is likely to be normal in most asthmatic children. FEV1 in children reflects a complex mix of factors in the growth and development of the child, of which faah inhibitor status is only one factor. The likelihood that asthma candidate SNPs would have a major association with FEV1 measured at a single point in time in a child would seem to be low. Our asthmatic patients were given diagnoses by pediatric allergists at a pediatric allergy specialty clinic of a large public hospital. Referral to this pediatric allergy clinic is a tertiary referral, and thus the children in our study had already been seen by a generalist and a pediatrician over time for recurrent asthma symptoms. Diagnoses were made on clinical grounds, according to previous guidelines. We did not have tests of bronchial hyperreactivity. However, physician diagnosis of asthma is a valid outcome compared with objective measurements. Of note, physician diagnosis of asthma has been used as the major end point in linkage studies resulting in the positional cloning of asthma genes. We had objective data on atopy; skin prick tests revealed the vast majority of these children with asthma (92%) to be atopic to aeroallergens. In a large case-parent triad study of a Mexican childhood asthmatic population, we found that the rs1154404 and rs28730619 SNPs and the most common haplotype across the GSNOR gene were associated with childhood asthma risk. Although we have data from only one population, given the strong biologic rationale for an important role of GSNOR in asthma pathogenesis, these findings are of interest.
    Introduction The establishment of a dormancy state was an evolutionary strategy, permitting plants to avoid unfavourable environmental conditions. Seed dormancy is commonly defined as a temporal arrest of growth and development of viable organs (Hilhorst, 2007). The strength of this physiological state is under control of different endogenous and exogenous factors (Finch-Savage and Leubner-Metzger, 2006; Krasuska et al., 2015a, 2015b). Dormancy release “opens the window” for metabolic events which initiate seed germination (Finch-Savage and Leubner-Metzger, 2006). Seed germination sensu stricto is described as the termination of embryo activation with visible effect of an embryonic root protrusion throughout seed covering layers (Finch-Savage and Leubner-Metzger, 2006; Lewak, 2011). Seeds imbibition (at the initial phase of germination) is accompanied by enhanced production of reactive oxygen species (ROS) (Bailly et al., 2008) and reactive nitrogen species (RNS), which is observed also in germinating apple embryos (Malus domestica Borkh.) (Gniazdowska et al., 2010a, 2010b). This is linked to a stimulation of cellular antioxidant system (Krasuska and Gniazdowska, 2012). Seeds of apple belong to the orthodox type characterised by a deep physical and physiological dormancy (Lewak, 2011). Embryos isolated from dormant seeds (after removal of seed coat and endosperm) germinate very slowly (even under favourable conditions) and develop abnormal seedlings with shortened embryonic axes/roots and asynchronously greening cotyledons. Dormancy of apple seeds can be removed by 90 days long cold stratification (Dębska et al., 2013; Lewak, 2011) or after short term (3–6 h) pre-treatment of isolated embryos with donors of nitric oxide (NO) or hydrogen cyanide (HCN) (Bogatek and Gniazdowska, 2006; Gniazdowska et al., 2010b). Cold stratification is a commonly used practice consisting of imbibition of dormant seeds at chilling temperature (above 0 °C) for the period that varies, depending on the plant species. Non-dormant apple embryos (stratified/treated with NO or HCN) germinate fast (Gniazdowska et al., 2007, 2010a; 2010b) with chloroplasts developing in both cotyledons and of an equal size (Krasuska et al., 2015b). Elevated HCN (Lewak, 2011 and references herein), ROS and RNS generation is observed in apple seeds (Dębska et al., 2013) during cold stratification. While, application of NO scavengers keeps embryos at the dormancy state (Gniazdowska et al., 2007; Krasuska et al., 2016).