N-(1,2-diphenylethyl)piperazines: a new class of dual serotonin/noradrenaline reuptake inhibitor

The synthesis and structure-activity relationships of a novel series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake is described. Two compounds possessed comparable in vitro profiles to the dual reuptake inhibitor duloxetine.     

Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors

We report the structure-activity relationships of further analogues in a series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake, that is, with additional substitution of the phenyl rings, or their replacement by heterocycles. The enantiomers of compounds 1 and 2 were also profiled, and possessed drug-like physicochemical properties. In particular, compound (-)-2 lacked potent inhibitory activity against any of the important cytochromes P(450) and high selectivity over a wide range of receptors, which is unusual for a compound that inhibits human amine transporters.     

The captivating coral--the origins of early evolutionary imagery

In the 'Origin of Species', Darwin sums up his ideas about the evolutionary process in a single diagram. Tracing the 'evolution' of this diagram reveals a host of sources that may have inspired Darwin's imagination.     

Comparative analysis of the within-population genetic structure in wild cherry (Prunus avium L.) at the self-incompatibility locus and nuclear microsatellites

Gametophytic self-incompatibility (SI) systems in plants exhibit high polymorphism at the SI controlling S-locus because individuals with rare alleles have a higher probability to successfully pollinate other plants than individuals with more frequent alleles. This process, referred to as frequency-dependent selection, is expected to shape number, frequency distribution, and spatial distribution of self-incompatibility alleles in natural populations. We investigated the genetic diversity and the spatial genetic structure within a Prunus avium population at two contrasting gene loci: nuclear microsatellites and the S-locus. The S-locus revealed a higher diversity (15 alleles) than the eight microsatellites (4-12 alleles). Although the frequency distribution of S-alleles differed significantly from the expected equal distribution, the S-locus showed a higher evenness than the microsatellites (Shannon's evenness index for the S-locus: E = 0.91; for the microsatellites: E = 0.48-0.83). Also, highly significant deviations from neutrality were found for the S-locus whereas only minor deviations were found for two of eight microsatellites. A comparison of the frequency distribution of S-alleles in three age-cohorts revealed no significant differences, suggesting that different levels of selection acting on the S-locus or on S-linked sites might also affect the distribution and dynamics of S-alleles. Autocorrelation analysis revealed a weak but significant spatial genetic structure for the multilocus average of the microsatellites and for the S-locus, but could not ascertain differences in the extent of spatial genetic structure between these locus types. An indirect estimate of gene dispersal, which was obtained to explain this spatial genetic pattern, indicated high levels of gene dispersal within our population (sigma(g) = 106 m). This high gene dispersal, which may be partly due to the self-incompatibility system itself, aids the effective gene flow of the microsatellites, thereby decreasing the contrast between the neutral microsatellites and the S-locus.     

Ferrocenyl-substituted allenylidene complexes of chromium, molybdenum and tungsten: Synthesis, structure and reactivity

Bis(ferrocenyl)-substituted allenylidene complexes, [(CO)₅MCCCFc₂] (1a-c, Fc = (C₅H₄)Fe(C₅H₅), M = Cr (a), Mo (b), W (c)) were obtained by sequential reaction of Fc₂CO with Me₃Si-CCH, KF/MeOH, n-BuLi, and [(CO)₅M(THF)]. For the synthesis of related mono(ferrocenyl)allenylidene chromium complexes, [(CO)₅CrCCC(Fc)R] (R = Ph, NMe₂), three different routes were developed: (a) reaction of the deprotonated propargylic alcohol HCCC(Fc)(Ph)OH with [(CO)₅Cr(THF)] followed by desoxygenation with Cl₂CO, (b) Lewis acid induced alcohol elimination from alkenyl(alkoxy)carbene complexes, [(CO)₅CrC(OR)CHC(NMe₂)Fc], and (c) replacement of OMe in [(CO)₅CrCCC(OMe)NMe₂] by Fc. Complex 1a was also formed when the mono(ferrocenyl)allenylidene complex [(CO)₅CrCCC(Fc)NMe₂] was treated first with Li[Fc] and the resulting adduct then with SiO₂. The replacement route (c) was also applied to the synthesis of an allenylidene complex (7a) with a CC spacer in between the ferrocenyl unit and C_γ of the allenylidene ligand, [(CO)₅CrCCC(NMe₂)-CCFc]. The related complex containing a CHCH spacer (9a) was prepared by condensation of [(CO)₅CrCCC(Me)NMe₂] with formylferrocene in the presence of NEt₃. The bis(ferrocenyl)-substituted allenylidene complexes 1a-c added HNMe₂ across the C_α-C_β bond to give alkenyl(dimethylamino)carbene complexes and reacted with diethylaminopropyne by regioselective insertion of the CC bond into the C_β-C_γ bond to afford alkenyl(diethylamino)allenylidene complexes, [(CO)₅MCCC(NEt₂)CMeCFc₂]. The structures of 5a, 7a, and 9a were established by X-ray diffraction studies.     

The evolution of floral scent: the influence of olfactory learning by insect pollinators on the honest signalling of floral rewards

1.  The evolution of flowering plants has undoubtedly been influenced by a pollinator's ability to learn to associate floral signals with food. Here, we address the question of 'why' flowers produce scent by examining the ways in which olfactory learning by insect pollinators could influence how floral scent emission evolves in plant populations.
2.  Being provided with a floral scent signal allows pollinators to learn to be specific in their foraging habits, which could, in turn, produce a selective advantage for plants if sexual reproduction is limited by the income of compatible gametes. Learning studies with honeybees predict that pollinator-mediated selection for floral scent production should favour signals which are distinctive and exhibit low variation within species because these signals are learned faster. Social bees quickly learn to associate scent with the presence of nectar, and their ability to do this is generally faster and more reliable than their ability to learn visual cues.
3.  Pollinators rely on floral scent as a means of distinguishing honestly signalling flowers from deceptive ones. Furthermore, a pollinator's sensitivity to differences in nectar rewards can bias the way that it responds to floral scent. This mechanism may select for flowers that provide olfactory signals as an honest indicator of the presence of nectar or which select against the production of a detectable scent signal when no nectar is present.
4.  We expect that an important yet commonly overlooked function of floral scent is an improvement in short-term pollinator specificity which provides an advantage to both pollinator and plant over the use of a visual signal alone. This, in turn, impacts the evolution of plant mating systems via its influence on the species-specific patterns of floral visitation by pollinators.     

Hyperoxia-induced neurodegeneration as a tool to identify neuroprotective genes in Drosophila melanogaster

Oxidative stress has been reported to be a common underlying mechanism in the pathogenesis of many neurodegenerative disorders such as Alzheimer, Huntington, Creutzfeld–Jakob, and Parkinson disease. Despite the increasing number of articles showing a correlation between oxidative damage and neurodegeneration little is known about the genetic elements that confer protection against the deleterious effects of an oxidative imbalance in neurons. We show that oxygen-induced damage is a direct cause of brain degeneration in Drosophila and establish an experimental setup measuring dopaminergic neuron survival to model oxidative stress-induced neurodegeneration in flies. The overexpression of superoxide dismutase but not catalase was able to protect dopaminergic neurons against oxidative imbalance under hyperoxia treatment. In an effort to identify new genes involved in the process of oxidative stress-induced neurodegeneration, we have carried out a genome-wide expression analysis to identify genes whose expression is upregulated in fly heads under hyperoxia. Among them, a number of mitochondrial and cytoplasmic chaperones could be identified and were shown to protect dopaminergic neurons when overexpressed, thus validating our approach to identifying new genes involved in the neuronal defense mechanism against oxidative stress.     

The Arabidopsis thaliana Sucrose Transporter Gene AtSUC4 is Expressed in Meloidogyne incognita-induced Root Galls

The plant parasitic nematode Meloidogyne incognita is as an obligate parasite entirely dependent on the plants solute supply. Therefore, the nematodes induce the formation of several giant cells which are embedded into root galls. At present only little information is available about the solute transfer mechanisms of the plants to supply the induced galls and giant cells and consequently the nematodes. In the present work we could show by phloem-loading experiments that giant cells in the roots of Arabidopsis thaliana are not symplasmically connected to the phloem elements, thus differing considerably form the comparable plant–nematode interaction of Arabidopsis and Heterodera schachtii . Consequently the gene expression of the sucrose transporter AtSUC4 ( AtSUT4 ) was studied during nematode development, and its functionality was shown using RNAi gene silencing lines.     

Attitudes towards forest,biomass and certification – A case study approach to integrate public opinion in Japan

The purpose of this study was to contribute to filling the knowledge gap in public opinion and knowledge about forest and its certification in Japan, as well as to identify key elements and the possible role of public opinion within integrated bottom-up policies, bridging the sectors of forest, environment and energy. For the study 1930 questionnaires were disseminated in a small town in early 2007. Results from the statistical analysis indicated that forest was perceived as an ecosystem with a protective function against e.g. soil erosion or flooding, rather than a place that might serve for wood production and providing jobs. Forest certification and bioenergy from forest were identified as key elements for future integrated bottom-up policies that need to concentrate on facilitating the linkage between forestry and renewable energy as well as on promoting environmentally sound management and forest certification.