Browsing by Subject "Molting"
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- ItemOpen AccessAn angiotensin I-converting enzyme mutation (Y465D) causes a dramatic increase in blood ACE via accelerated ACE shedding(Public Library of Science, 2011) Danilov, Sergei M; Gordon, Kerry; Nesterovitch, Andrew B; Lünsdorf, Heinrich; Chen, Zhenlong; Castellon, Maricela; Popova, Isolda A; Kalinin, Sergey; Mendonca, Emma; Petukhov, Pavel ABACKGROUND: Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. METHODOLOGY/PRINCIPAL FINDINGS: HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE - between Arg1203 and Ser1204 - was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. Conclusions/Significance The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase).
- ItemOpen AccessHand-rearing, release and survival of african penguin chicks abandoned before independence by moulting parents(Public Library of Science, 2014) Sherley, Richard B; Waller, Lauren J; Strauss, Venessa; Geldenhuys, Deon; Underhill, Les G; Parsons, Nola JThe African penguin Spheniscus demersus has an ‘Endangered’ conservation status and a decreasing population. Following abandonment, 841 African penguin chicks in 2006 and 481 in 2007 were admitted to SANCCOB (Southern African Foundation for the Conservation of Coastal Birds) for hand-rearing from colonies in the Western Cape, South Africa, after large numbers of breeding adults commenced moult with chicks still in the nest. Of those admitted, 91% and 73% respectively were released into the wild. There were veterinary concerns about avian malaria, airsacculitis and pneumonia, feather-loss and pododermatitis (bumblefoot). Post-release juvenile (0.32, s.e. = 0.08) and adult (0.76, s.e. = 0.10) survival rates were similar to African penguin chicks reared after oil spills and to recent survival rates recorded for naturally-reared birds. By December 2012, 12 birds had bred, six at their colony of origin, and the apparent recruitment rate was 0.11 (s.e. = 0.03). Hand-rearing of abandoned penguin chicks is recommended as a conservation tool to limit mortality and to bolster the population at specific colonies. The feasibility of conservation translocations for the creation of new colonies for this species using hand-reared chicks warrants investigation. Any such programme would be predicated on adequate disease surveillance programmes established to minimise the risk of disease introduction to wild birds.