Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.      

Leaf epidermis morphological differentiation between Tamarix africana Poir. and Tamarix gallica L. (Tamaricaceae) with ecological remarks

Abstract

Recent work, based on morphological and cytotaxonomical information, claimed the independence of Plantago brutia Ten., a narrow endemic of South Italy, with respect to Plantago media L. Here, we present a further evaluation of the systematic relationships occurring between these two taxa as revealed by molecular studies. We sampled P. brutia in most of the known populations and P. media in several European stands, from Sweden to the Iberian Peninsula and Balkans. We then investigated the relationships among the sampled populations by using as molecular markers the internal transcribed spacer regions ITS1 and ITS2. Furthermore, we considered cpDNA to gain further insight into the relationships among P. brutia/P. media populations. Based on nrDNA data, P. brutia appeared to be nested within the P. media complex, but as a well distinct subunit. This is congruent with a subspecific rank for this taxon within P. media. The cpDNA revealed the occurrence of several haplotypes in the studied material. Most of the assessed haplotypes were exclusive for single populations and thus phylogenetically uninformative. Nonetheless, we have found some haplotypes that are shared by different cytotypes or populations throughout the species range, suggesting possible explanations for the phylogenetic relationships occurring between P. brutia and the autopolyploid complex P. media.     

Ghrelin induces apoptosis in colon adenocarcinoma cells via proteasome inhibition and autophagy induction

Ghrelin is a metabolism-regulating hormone recently investigated for its role in cancer survival and progression. Controversially, ghrelin may act as either anti-apoptotic or pro-apoptotic factor in different cancer cells, suggesting that the effects are cell type dependent. Limited data are currently available on the effects exerted by ghrelin on intracellular proteolytic pathways in cancer. Both the lysosomal and the proteasomal systems are fundamental in cellular proliferation and apoptosis regulation. With the aim of exploring if the proteasome and autophagy may be possible targets of ghrelin in cancer, we exposed human colorectal adenocarcinoma cells to ghrelin. Preliminary in vitro fluorimetric assays evidenced for the first time a direct inhibition of 20S proteasomes by ghrelin, particularly evident for the trypsin-like activity. Moreover, 1 μM ghrelin induced apoptosis in colorectal adenocarcinoma cells by inhibiting the ubiquitin–proteasome system and by activating autophagy, with p53 having an “interactive” role.     

The Relationship between Anxiety and the Social Judgements of Approachability And Trustworthiness

The aim of the current study was to examine the relationship between individual differences in anxiety and the social judgements of trustworthiness and approachability. We assessed levels of state and trait anxiety in eighty-two participants who rated the trustworthiness and approachability of a series of unexpressive faces. Higher levels of trait anxiety (controlling for age, sex and state anxiety) were associated with the judgement of faces as less trustworthy. In contrast, there was no significant association between trait anxiety and judgements of approachability. These findings indicate that trait anxiety is a significant predictor of trustworthiness evaluations and illustrate the importance of considering the role of individual differences in the evaluation of trustworthiness. We propose that trait anxiety may be an important variable to control for in future studies assessing the cognitive and neural mechanisms underlying trustworthiness. This is likely to be particularly important for studies involving clinical populations who often experience atypical levels of anxiety.     

Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II

Abstract

Acknowledging the importance of studies toward the development of measures against terrorism and bioterrorism, this study aims to contribute to the design of new prototypes of potential drugs against smallpox. Based on a former study, nine synthetic feasible prototypes of selective inhibitors for thymidylate kinase from Variola virus (VarTMPK) were designed and submitted to molecular docking, molecular dynamics simulations and binding energy calculations. The compounds are simplifications of two more complex scaffolds, with a guanine connected to an amide or alcohol through a spacer containing ether and/or amide groups, formerly suggested as promising for the design of selective inhibitors of VarTMPK. Our study showed that, despite the structural simplifications, the compounds presented effective energy values in interactions with VarTMPK and HssTMPK and that the guanine could be replaced by a simpler imidazole ring linked to a –NH₂ group, without compromising the affinity for VarTMPK. It was also observed that a positive charge in the imidazole ring is important for the selectivity toward VarTMPK and that an amide group in the spacer does not contribute to selectivity. Finally, prototype 3 was pointed as the most promising to be synthesized and experimentally evaluated.

Communicated by Ramaswamy H. Sarma