KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies

1. Download : Download high-res image (150KB)
2. Download : Download full-size image

     

A theoretical and experimental case study of the hydrogen bonding predilection of S-methylcysteine

S-containing amino acids can lead to two types of local NH···S interactions which bridge backbone NH sites to the side chain to form either intra- or inter-residue H-bonds. The present work reports on the conformational preferences of S-methyl-l-cysteine, Cys(Me), using a variety of investigating tools, ranging from quantum chemistry simulations, gas-phase UV and IR laser spectroscopy, and solution state IR and NMR spectroscopies, on model compounds comprising one or two Cys(Me) residues. We demonstrate that in gas phase and in low polarity solution, the C- and N-capped model compound for one Cys(Me) residue adopts a preferred C5–C6γ conformation which combines an intra-residue N–H···O=C backbone interaction (C5) and an inter-residue N–H···S interaction implicating the side-chain sulfur atom (C6γ). In contrast, the dominant conformation of the C- and N-capped model compound featuring two consecutive Cys(Me) residues is a regular type I β-turn. This structure is incompatible with concomitant C6γ interactions, which are no longer in evidence. Instead, C5γ interactions occur, that are fully consistent with the turn geometry and additionally stabilize the structure. Comparison with the thietane amino acid Attc, which exhibits a rigid cyclic side chain, pinpoints the significance of side chain flexibility for the specific conformational behavior of Cys(Me).

     

Genetic analysis of emotional reactivity in sheep: effects of the genotypes of the lambs and of their dams

A total of 1347 weaned lambs from eight genotypes were tested over five consecutive years: Romanov (ROM) and Lacaune (LAC) pure breeds, the two F1 crossbreeds (RL and LR) and the offspring of ewes from these four genotypes sired with Berrichon-du-Cher rams (BCF). The lambs were individually exposed to three challenging tests involving novelty, human contact and social isolation. Ten synthetic variables were used to express social reactivity (i.e., active vs. passive strategy), exploratory activity and reactivity to humans. BCF crossbreds were more active (i.e., high bleats, locomotion and attempts to escape) than purebreds and F1. In contrast, ROM expressed more passive responses (i.e., low bleats and vigilance postures) than LAC and BCF crossbreds. In addition, ROM approached a motionless human less and had longer flight distances to an approaching human than did LAC and BCF crossbreds. When restrained, ROM, and to a lesser extent B×ROM and B×LR, avoided human contact more than did LAC, RL and B×LAC. Most of these differences were explained by direct additive genetic effects while maternal influences or heterosis effects were rarely significant. The highest heritability was for high bleats (h² = 0.48). Females were more active and avoided human contact more than did males.     

Gene expression modulation and the molecular mechanisms involved in Nelfinavir resistance in Leishmania donovani axenic amastigotes

Drug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV‐1 co‐infections. We have delineated the mechanism of cell death induced by the HIV‐1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to further study Nelfinavir–Leishmania interactions, we selected Nelfinavir‐resistant axenic amastigotes in vitro and characterized them. RNA expression profiling analyses and comparative genomic hybridizations of closely related Leishmania species were used as a screening tool to compare Nelfinavir‐resistant and ‐sensitive parasites in order to identify candidate genes involved in drug resistance. Microarray analyses of Nelfinavir‐resistant and ‐sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters. Transporter assays using radiolabelled Nelfinavir suggest a greater drug accumulation in the resistant parasites and in a time‐dependent manner. Furthermore, high‐resolution electron microscopy and measurements of intracellular polyphosphate levels showed an increased number of cytoplasmic vesicular compartments known as acidocalcisomes in Nelfinavir‐resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in drug‐induced intracellular vesicles.     

Synthesis of tetrazole analogues of phosphonohydroxamic acids: An attempt to improve the inhibitory activity against the DXR

This work is focused on the design of new antimicrobial drugs and on the development of lipophilic inhibitors of the DXR, the second enzyme of the MEP pathway for the biosynthesis of isoprene units in most bacteria, by replacing the phosphonate group of fosmidomycin derivatives by a tetrazoyl moiety capable of multiple hydrogen bonding. The N- and C-substituted tetrazole analogues of phosphonohydroxamate inhibitors were synthesized and tested on the DXR of Escherichia coli. This work points out the hypothesis that the phosphonate/phosphate recognition site might be too rigid to accommodate other functional groups.     

Plant quality and local adaptation undermine relocation in a bog specialist butterfly

The butterfly Boloria aquilonaris is a specialist of oligotrophic ecosystems. Population viability analysis predicted the species to be stable in Belgium and to collapse in the Netherlands with reduced host plant quality expected to drive species decline in the latter. We tested this hypothesis by rearing B. aquilonaris caterpillars from Belgian and Dutch sites on host plants (the cranberry, Vaccinium oxycoccos). Dutch plant quality was lower than Belgian one conferring lower caterpillar growth rate and survival. Reintroduction and/or supplementation may be necessary to ensure the viability of the species in the Netherlands, but some traits may have been selected solely in Dutch caterpillars to cope with gradual changes in host plant quality. To test this hypothesis, the performance of Belgian and Dutch caterpillars fed with plants from both countries were compared. Dutch caterpillars performed well on both plant qualities, whereas Belgian caterpillars could not switch to lower quality plants. This can be considered as an environmentally induced plastic response of caterpillars and/or a local adaptation to plant quality, which precludes the use of Belgian individuals as a unique solution for strengthening Dutch populations. More generally, these results stress that the relevance of local adaptation in selecting source populations for relocation may be as important as restoring habitat quality.