Genetic differentiation between alpine and lowland populations of a butterfly is related to PGI enzyme genotype

Understanding the ecological process of population differentiation and identifying the molecular changes that contribute to adaptation is a central aspect of evolutionary biology. In this study we analyzed the geographic variation in allozyme allele frequencies (based on 15 enzyme systems representing 18 loci) across 18 populations of the butterfly Lycaena tityrus from different altitudes. Population genetic analyses showed that within population genetic diversity (e.g. mean number of alleles per loci: 1.8; expected heterozygosity: 12%) was within the typical value range for the Lepidoptera. The populations of L. tityrus investigated showed a remarkable genetic differentiation (F_ST: 0.065), being clearly divided into an alpine (high-altitude) and a non-alpine (low-altitude) cluster. This differentiation was almost entirely caused by variation at a single enzyme locus, PGI. Although the involvement of historical events cannot be ruled out, several lines of evidence suggest that the specific pattern of allozyme (and in this case particularly PGI) variation found is caused by thermal selection. For example, genetic variation was highly locus-specific rather than relatively uniform, as should be expected for effects of natural selection. Further, the PGI 2–2 genotype dominating in alpine (in contrast to low-altitude) populations is known to exhibit increased cold stress resistance and relatively long development times typical of alpine populations. Thus, PGI (or possibly a closely linked gene) is an obvious target for thermal selection in L. tityrus . This study exemplifies how allozyme analyses can be used to detect candidate loci likely to be under selection.     

Climate change, conservation and management: an assessment of the peer-reviewed scientific journal literature

Recent reviews of the conservation literature indicate that significant biases exist in the published literature regarding the regions, ecosystems and species that have been examined by researchers. Despite the global threat of climatic change, similar biases may be occurring within the sub-discipline of climate-change ecology. Here we hope to foster critical thought and discussion by considering the directions taken by conservation researchers when addressing climate change. To form a quantitative basis for our perspective, we assessed 248 papers from the climate change literature that considered the conservation management of biodiversity and ecosystems. We found that roughly half of the studies considered climate change in isolation from other threatening processes. We also found that the majority of surveyed scientific publications were conducted in the temperate forests of Europe and North America. Regions such as Latin America that are rich in biodiversity but may have low adaptive capacity to climate change were not well represented. We caution that such biases in research effort may be distracting our attention away from vulnerable regions, ecosystems and species. Specifically we suggest that the under-representation of research from regions low in adaptive capacity and rich in biodiversity requires international collaboration by those experienced in climate-change research, with researchers from less wealthy nations who are familiar with local issues, ecosystems and species. Furthermore, we caution that the propensity of ecologists to work in essentially unmodified ecosystems may fundamentally hamper our ability to make useful recommendations in a world that is experiencing significant global change.     

Aurora1 phosphorylation activity on histone H3 and its cross-talk with other post-translational histone modifications in Arabidopsis

The enzymological properties of AtAurora1, a kinase responsible for the cell cycle-dependent phosphorylation of histone H3 at S10, and its cross-talk with other post-translational histone modifications, were determined. In vitro phosphorylation of H3S10 by AtAurora1 is strongly increased by K9 acetylation, and decreased by K14 acetylation and T11 phosphorylation. However, S10 phosphorylation activity is unaltered by mono-, di- or trimethylation of K9. An interference of H3K9 dimethylation by SUVR4 occurs by a pre-existing phosphorylation at S10. Hence, cross-talk in plants exists between phosphorylation of H3S10 and methylation, acetylation or phosphorylation of neighbouring amino acid residues. AtAurora1 undergoes autophosphorylation in vivo regardless of the presence of substrate, and forms dimers in planta . Of the three ATP-competitive Aurora inhibitors tested, Hesperadin was most effective in reducing the in vivo kinase activity of AtAurora1. Hesperadin consistently inhibited histone H3S10 phosphorylation during mitosis in Arabidopsis cells, but did not affect other H3 post-translational modifications, suggesting a specific inhibition of AtAurora in vivo . Inactivation of AtAurora also caused lagging chromosomes in a number of anaphase cells, but, unlike the situation in mammalian cells, Hesperadin did not influence the microtubule dynamics in dividing cells.     

Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel,potent and selective GABAA α5 inverse agonist series

Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine was deemed the most promising GABA_A α5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation towards a central nervous system (CNS) acting medicine.     

From genes to ecosystems: a synthesis of the effects of plant genetic factors across levels of organization

Using two genetic approaches and seven different plant systems, we present findings from a meta-analysis examining the strength of the effects of plant genetic introgression and genotypic diversity across individual, community and ecosystem levels with the goal of synthesizing the patterns to date. We found that (i) the strength of plant genetic effects can be quite high; however, the overall strength of genetic effects on most response variables declined as the levels of organization increased. (ii) Plant genetic effects varied such that introgression had a greater impact on individual phenotypes than extended effects on arthropods or microbes/fungi. By contrast, the greatest effects of genotypic diversity were on arthropods. (iii) Plant genetic effects were greater on above-ground versus below-ground processes, but there was no difference between terrestrial and aquatic environments. (iv) The strength of the effects of intraspecific genotypic diversity tended to be weaker than interspecific genetic introgression. (v) Although genetic effects generally decline across levels of organization, in some cases they do not, suggesting that specific organisms and/or processes may respond more than others to underlying genetic variation. Because patterns in the overall impacts of introgression and genotypic diversity were generally consistent across diverse study systems and consistent with theoretical expectations, these results provide generality for understanding the extended consequences of plant genetic variation across levels of organization, with evolutionary implications.     

Effect of periplasmic nitrate reductase on diauxic lag of Paracoccus pantotrophus

Paracoccus pantotrophus expresses two nitrate reductases—membrane bound nitrate reductase (Nar) and periplasmic nitrate reductase (Nap). In growth experiments with two denitrifying species (Paracoccus pantotrophus and Alcaligenes eutrophus) that have both Nap and Nar and two species (Pseudomonas denitrificans and Pseudomonas fluorescens) with Nar only, it was found that diauxic lag is shorter for bacteria that express Nap. In P. pantotrophus, napEDABC encodes the periplasmic nitrate reductase. To analyze the effect of Nap on diauxic lag, the nap operon was deleted from P. pantotrophus. The growth experiments with nap^? mutant resulted in increased diauxic lag when switched from aerobic to anoxic respiration, suggesting Nap is responsible for shorter lags and helps in adaptation to anoxic metabolism after transition from aerobic conditions. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009     

Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers,structure–affinity relationships and in vitro metabolic stability

Several 3H-spiro[[2]benzofuran-1,4′-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF₃·OEt₂ catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure–affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar σ₁ affinity (K_i = 0.18 nM, 0.79 nM, 0.86 nM) and high selectivity against the σ₂ subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [¹⁸F]2a and [¹⁸F]2e two different radiosynthetic approaches were followed.