Biology subjects

Zahn, S.

Publications and source records attributed to Zahn, S..

2 recordsLinked to original sources

bioRxiv2023

Early-life environmental effects on mitochondrial aerobic metabolism: an experimental brood size manipulation in wild great tits

Parental care (including postnatal provisioning) is a major component of the offsprings early-life environment. In avian species, the number of chicks in the nest and subsequent sibling competition for food are known to affect chicks growth, leading in some cases to long-lasting effects for the offspring. Because of its central role in converting energy, variation in the offsprings mitochondrial metabolism could be an important pathway underlying variation in growth patterns. Here, we performed a brood size manipulation in great tits (Parus major) to unravel its impact on offsprings mitochondrial metabolism and reactive oxygen species (ROS) production in red blood cells. We investigated the effects of brood size on chicks growth and survival, and tested for long-lasting effects on juvenile mitochondrial metabolism and phenotype. As expected, chicks raised in reduced broods had a higher body mass compared to enlarged and control groups. However, mitochondrial metabolism and ROS production were not significantly affected by the treatment either at chick or juvenile stages. Chicks in very small broods were smaller in size and had higher mitochondrial metabolic rates. The nest of rearing has a significant effect on nestling mitochondrial metabolism, yet variation in mitochondrial metabolism at the early-life stages are not associated with survival chances. The contribution of the rearing environment in determining offspring mitochondrial metabolism emphasizes the plasticity of mitochondrial metabolism in changing environments. Further studies would be needed to closely investigate what are the major environmental cues affecting the offspring mitochondrial metabolism during the growth period.

physiology↗

bioRxiv2021

Prolonging coagulant activity of factor Xa under hemophilic conditions by site-specific N-glycosylation of the surface-exposed autolysis loop

The regulation of Factor X (FX) is critical to maintain hemostasis. To gain insights to the regulation of the active and zymogen form of coagulation FX, we probed specific molecular interactions by introducing novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX. Introduction of N-glycans in the autolysis loop of these FX variants decreased Factor VIIa (FVIIa)-mediated activation ~3-fold and prothrombin activation 2- to 10-fold presumably through steric hinderance. Prothrombin activation was, however, recovered in presence of cofactor Factor Va (FVa) despite a reduced prothrombinase assembly. The introduced N-glycans exhibited position-specific effects on the interaction with two FXa inhibitors: tissue factor pathway inhibitor (TFPI) and antithrombin (ATIII). Ki for the inhibition by full-length TFPI of these FXa variants was increased by 7- to 1150-fold, while ATIII inhibition in the presence of the heparin-analogue Fondaparinux was modestly increased by 2- to 15-fold compared to wild type. To probe the in vitro hemostatic effect of the FX variants, the thrombin generation potential in FX-depleted plasma was evaluated. When supplemented in zymogen form, the FX variants exhibited reduced thrombin generation activity relative to wild-type FX, whereas enhanced procoagulant activity was measured for activated FX variants with N-glycosylation at positions 148-150. These results indicate that residues of the surface-exposed autolysis loop and residues close by participate in FX activation, proteolytic activity and inhibition of FXa by TFPI and ATIII. In plasma-based assays, a modest decrease in FX-activation rate appeared to compensate for the collective reduction in inhibitor interactions.

biochemistry↗