MhcVizPipe: A Quality Control Software for Rapid Assessment of Small- to Large-Scale Immunopeptidome Datasets

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Design of fluorinated 5-HT4R antagonists: Influence of the basicity and lipophilicity toward the 5-HT4R binding affinities

Analogues of potent 5-HT₄R antagonists possessing a fluorinated N-alkyl chain have been synthesized in order to investigate the effect of the resulting change in basicity and lipophilicity on the affinity and selectivity profile. We demonstrate that for this series, the affinity is decreased with decreased basicity of the piperidine’s nitrogen atom. In contrast, the resulting increase in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3-Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind to the 5-HT₄R while maintaining their pharmacological profile and selectivity toward other 5-HT receptors.     

Identification, developmental expression and tissue distribution of deaminoneuraminate hydrolase (KDNase) activity in rainbow trout

A deaminoneuraminosyl-glycohydrolase (KDNase), which catalysesthe hydrolysis of      

Functional and evolutionary trade-offs co-occur between two consolidated memory phases in Drosophila melanogaster

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In Drosophila, two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic.     

Determinants and costs of natal dispersal in a lekking species

Avoidance of competition and inbreeding have been invoked as the major ultimate causes of natal dispersal, but proximate factors such as sex, body condition or birth date can also be important. Natal dispersal is expected to be of particular importance to understanding the ecological and evolutionary implications of dispersal strategies, since 1) numerous evidences suggest that individual differences in dispersal strategies are expressed early in life (i.e. at the onset of dispersal movement), 2) ultimate and proximate factors are more likely to act during this stage and 3) this stage is associated with the highest mortality rates in most vertebrates. We analysed the natal dispersal (hereafter, dispersal) behaviour in 100 marked individuals of a lekking species, the North African houbara bustards Chlamydotis undulata undulata, during four years. We investigated the effects of proximate factors on dispersal pattern and distance, as well as the mortality cost associated with movement using multievent models, allowing uncertainty in sex assignment and mixture of live recaptures and dead recoveries. Overall, males exhibited longer dispersal distances than females, contrary to the common pattern in birds. Moreover, males in poorer body condition moved further than those in better condition, whereas distance was independent of body condition in females. Finally, survival rates during dispersal were lower for females than for males and were negatively correlated with the distances covered with a similar distance‐survival slope in the two sexes. Collectively, our results suggest that 1) there is substantial dispersal cost in both sexes, 2) dispersal is strongly male‐biased, 3) this bias is unlikely to be explained by differential movement costs of each sex, and 4) dispersal differences found across different categories of individuals are in broad agreement with both the inbreeding avoidance and intraspecific competition mechanisms for dispersal.     

Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal Antibodies

Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (NAbs) against primary HIV-2 strains (T. I. de Silva, et al., J. Virol. 86:930–946, 2012; R. Kong, et al., J. Virol. 86:947–960, 2012; G. Ozkaya Sahin, et al., J. Virol. 86:961–971, 2012). Here, we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (MAbs), 14 of which were newly generated from 9 chronically infected subjects. All 15 MAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2_7312A and HIV-2_ST. Ten of 15 MAbs neutralized a third heterologous primary virus strain, HIV-2_UC1. The median 50% inhibitory concentrations (IC₅₀s) for these MAbs were surprisingly low, ranging from 0.007 to 0.028 μg/ml. Competitive Env binding studies revealed three MAb competition groups: CG-I, CG-II, and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions, and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3), the epitope of CG-II antibodies to a conformational region centered on the carboxy terminus of V4, and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency, and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive NAbs. The availability of 15 human MAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity, and immunogenicity.