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The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Protein C-linked glycosylation differs fundamentally from N - and O-glycosylation and defines a type of glycosylation in which carbohydrate is linked to a protein via carbon atom. In eukaryotes the C-glycosylation was detected in multiple cell lines: mucins, erythropoietin receptor, human RNase 2, IL-12, rat liver microsomes, and proteins of complement system (Hartmann and Hofsteenge, 2000). The biological role of C-glycosylation is still unclear; however, the high interest toward C-glycosylation of protein in pharmaceutical industry is majorly related to its unique resistance to metabolic hydrolysis. For the C-mannosylation the acceptor sequence consists of W-x-x-W where the first Trp becomes C-mannosylated with α-mannopyranose. The alteration of hyaluronidase and lipoprotein lipase enzymes with C-mannosylation showed to be crucial for enzyme secretion-efficiency and overall enzymatic activity (Okamoto et al., 2017; Wang, 2012). The synthesis of C-mannosylated thrombospondin type 1 repeat-derived peptides showed to have a stimulatory effect on lipopolysaccharide-induced signaling in macrophage (Ihara et al., 2010).
The construction of categories in sport: Unfair advantages, equality of opportunity and strict attainability
Published in European Journal of Sport Science, 2021
Silvia Camporesi, Mika Hämäläinen
Eero Mäntyranta (1937–2013) was a Finnish cross-country skier and Olympics medallist active in the 1960s and early 70s. Haematocrit level describes how much individual’s blood contains red blood cells compared to the individual’s total blood volume (Billett, 1990). A study carried out by de La Chapelle, Träskelin, and Juvonen (1993) conducted over 200 members of Mäntyranta’s extended family found that Eero was affected by a rare genetic mutation in the erythropoietin receptor gene (EPOR). This mutation leads to a constitutive activation of EPOR, independent of any signal by the environment, and triggers the activation of the cascade leading to EPO production, resulting in an enhanced production of erythrocytes (red blood cells). This enhanced production of erythrocytes in turn leads to an enhanced oxygen carrying capacity, and conferred to Eero Mäntyranta a property advantage in endurance events. This mutation, by definition, can be considered a stable factor. Mäntyranta, however, did not face regulatory actions related to his haematocrit levels. We have comparatively investigated the regulations at the time when he was an active professional athlete, and now.
Serum iron availability, but not iron stores, is lower in naturally menstruating than in oral contraceptive athletes
Published in European Journal of Sport Science, 2023
Víctor M. Alfaro-Magallanes, Nuria Romero-Parra, Laura Barba-Moreno, Beatriz Rael, Pedro J. Benito, Ángel E. Díaz, Rocío Cupeiro, Ana B. Peinado
The above shifting differences between the studied hormonal profiles are explained by the significant variations found in TSAT, serum iron and transferrin both within the menstrual and OC cycles. In the case of naturally menstruating athletes, the EFP, in which menstrual bleeding occurs, showed a significant reduction in TSAT and iron compared to the non-bleeding phases (MLFP and MLP), to the point that during the EFP mean TSAT levels indicating iron-deficient erythropoiesis (TSAT<16%) were reached (Peeling et al., 2007). Moreover, Chi-squared analysis showed that the occurrence of TSAT levels indicating iron-deficient erythropoiesis was more frequent in the EFP phase, while it was less frequent in the MLFP. Similarly, Lainé et al. (2016) found a reduction in iron and TSAT along with hepcidin during menstruation in a cohort of 90 healthy women pooling both naturally menstruating and OC profiles. These authors also showed a positive correlation between the intensity of menstrual blood loss and the magnitude of hepcidin and iron variations (Lainé et al., 2016). These findings are also consistent with previous studies examining serum iron markers throughout the menstrual cycle (Barba-Moreno et al., 2020; Kim et al., 1993). Therefore, the variations found in TSAT, and iron have the potential to confound its interpretation in athletic population. In addition, it could temporarily impair erythropoiesis due to lack of iron supply during the EFP compared to the MLFP and MLP, as well as stress erythropoiesis, since low levels of plasma iron are reported to upregulate erythropoietic activity by improving the sensibility of erythropoietin receptor to erythropoietin in developing erythrocytes (Camaschella, Nai, & Silvestri, 2020).