Estimation of dominance effects for reproductive, growth and carcass traits of Pannon White rabbits

Authors analysed the reproductive, growth and slaughter records of Pannon White rabbits based on records collected between 1992 and 2014. The examined traits were: average daily gain (ADG), thigh muscle volume (TMV) and litter weight at day 21 (LW21). Genetic parameters were estimated using basic and extended (with dominance effects) single trait animal models using the REML procedure. Heritability estimates ranged between low and moderate for all traits (ADG: 0.25-0.3±0.01, TMV: 0.21-0.24±0.02-0.03, LW21: 0.07-0.19±0.01). Random litter effects were moderate for ADG (0.24-0.25±0.01) but were low for TMV (0.09-0.1±0.01-0.03). Magnitude of permanent environmental effects exceeded that of the heritability values for LW21 in most models. Applying the extended complete models dominance effects were low for ADG and TMV (0.03±0.01-0.02) and moderate for LW21 (0.23±0.01). Among the estimated genetic correlation coefficients, the observed negative value between ADG and TMV (-0.31±0.03) and between TMV and LW21 (-0.38±0.13) were unfavourable. Based on the different models the estimated breeding values showed high stability as their rank correlation coefficients were close to unity (0.93-0.99)

Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, N17A/F32T-AnTx{,} which showed comparable Kv1.3 affinity to the wild-type peptide{,} but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace{,} by chemical synthesis{,} all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly{,} the key pharmacological properties of the Sec-N17A/F32T-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-N17A/F32T-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge