Apomorphine as an emetic for insectivorous songbirds: effectiveness and post‐release effects on survival and mass change

Emetics can be used to obtain food samples from birds, but they can harm birds during or after treatment. Studies to date suggest that apomorphine is a safe emetic for songbirds, but information is needed about possible post‐release deleterious effects. From March to July 2012, we collected food samples from insectivorous songbirds using apomorphine. We treated 67 Moustached Warblers (Acrocephalus melanopogon), 56 Reed Warblers (Acrocephalus scirpaceus), 15 Great Reed Warblers (Acrocephalus arundinaceus), and 12 Savi's Warblers (Locustella luscinoides). Effectiveness in inducing regurgitation was high (76.7%) and varied among species, being significantly more effective with Reed Warblers (91.1%). No birds died during treatment. To check for possible post‐release negative effects, we considered 53 treated Moustached Warblers and 37 treated Reed Warblers and selected an equal number of untreated individuals (simply captured, banded, and measured). We found no support for differences in survival or recapture probabilities between treated and untreated birds of either species within 21 d after administering apomorphine. We calculated body mass changes of all Moustached Warblers subsequently recaptured (within 21 d) and found no difference between treated (N = 8) and untreated (N = 22) birds, suggesting normal foraging activity after release. Our results suggest that apomorphine is a safe emetic, with no negative effect on survival at least in the short term. The effectiveness of apomorphine with insectivorous songbirds in our study contrasts with the results of some previous studies and confirms the differences in effectiveness among different taxa of songbirds. As with differences in effectiveness among species in our study, this variability in sensitivity to the emetic could be caused by morphological and physiological differences among different taxa.     

Design of enhanced agonists through the use of a new virtual screening method: application to peptides that bind class I major histocompatibility complex (MHC) molecules

A new screening procedure is described that uses docking calculations to design enhanced agonist peptides that bind to major histocompatibility complex (MHC) class I receptors. The screening process proceeds via single mutations of one amino acid at the positions that directly interact with the MHC receptor. The energetic and structural effects of these mutations have been studied using fragments of the original ligand that vary in length. The results of these docking studies indicate that the mutant affinity ranking of long peptides can be practically reproduced with a screening approach performed using fragments of six residues. Fragments of four and five residues could mimic, in some cases, the structural arrangement of the side chains of the full-length peptide. We have compared the structural and energetic results of the docking calculations with experimental data using three unrelated ligand peptides that differ greatly in their affinity for the MHC complex. Analysis of the affinity of the fragments led to the identification of three important parameters in the construction of fragments that mimic the structural and energetic properties of the full-length ligand: the length of the fragment; its intermolecular energy; and the number and localization, internal or terminal, of the anchor residues. The results of this new peptide-design methodology have been applied to suggest new peptides derived from the MUC1-8 peptide that could be used as murine vaccines that trigger the immune response through the MHC class I protein H-2K(b).     

The serine 2481-autophosphorylated form of mammalian Target Of Rapamycin (mTOR) is localized to midzone and midbody in dividing cancer cells

Using a high-resolution, automated confocal high-content imaging system, we investigated the sub-cellular localization of the Serine 2481-autophosphorylated form of mTOR (PP-mTOR^Ser2481) during mitosis and cytokinesis in human cancer cells. PP-mTOR^Ser2481 exhibited a punctate nuclear distribution in interphase cancer cells, with the number of PP-mTOR^Ser2481 nuclear speckles positively relating with the proliferative capacity of cancer cells. PP-mTOR^Ser2481 expression dynamically rearranged within the cytoplasm in a close association near and between separating chromosomes during early stages of mitosis. Towards the end of anaphase and in telophase, PP-mTOR^Ser2481 drastically focused on the midzone and ultimately in the centre of the midbody at the presumptive cleavage furrow. In cells at cytokinesis, PP-mTOR^Ser2481 appeared as a doublet facing each other at the apical ends of two daughter cells. Three-dimensional analysis confirmed that PP-mTOR^Ser2481 positioned at a ring structure wrapped round by microtubule bundles to connect daughter cells. These results reveal for the first time that PP-mTOR^Ser2481 may be unexpectedly involved in the terminal stages of cytokinesis.     

Global distribution of IRC7 alleles in Saccharomyces cerevisiae populations: a genomic and phenotypic survey within the wine clade

The adaptation to the different biotic and abiotic factors of wine fermentation has led to the accumulation of numerous genomic hallmarks in Saccharomyces cerevisiae wine strains. IRC7, a gene encoding a cysteine-S-β-lyase enzyme related volatile thiols production in wines, has two alleles: a full-length allele (IRC7^F) and a mutated one (IRC7^S), harbouring a 38 bp-deletion. Interestingly, IRC7^S-encoding a less active enzyme – appears widespread amongst wine populations. Studying the global distribution of the IRC7^S allele in different yeast lineages, we confirmed its high prevalence in the Wine clade and demonstrated a minority presence in other domesticated clades (Wine-PDM, Beer and Bread) while it is completely missing in wild clades. Here, we show that IRC7^S-homozygous (HS) strains exhibited both fitness and competitive advantages compared with IRC7^F-homozygous (HF) strains. There are some pieces of evidence of the direct contribution of the IRC7^S allele to the outstanding behaviour of HS strains (i.e., improved response to oxidative stress conditions and higher tolerance to high copper levels); however, we also identified a set of sequence variants with significant co-occurrence patterns with the IRC7^S allele, which can be co-contributing to the fitness and competitive advantages of HS strains in wine fermentations.     

BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells

Background  

Accumulation of amyloid β-peptide (Aβ) in the plaques is one of the major pathological features in Alzheimer's disease (AD). Sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE-1) and γ-secretase results in the formation of Aβ peptides. Preventing Aβ formation is believed to attenuate AD progression and BACE-1 and γ-secretase are thus attractive targets for AD drug development.