Pyridine to aniline: An exceptional biologically driven rearrangement

During the course of our study on the innovative ligand for nicotinic acetylcholinergic receptors, LNAChR, and in order to assess activity and toxicity profiles of the drug’s metabolites, synthesis of the main metabolites was undertaken. This synthesis work was done in parallel by organic chemistry and by biotransformation of LNAChR. Filamentous fungus Aspergillus alliaceus (NRRL 315) neatly afforded three of the main metabolites, one of which arose from a very unexpected and very uncommon rearrangement.     

Multilocus patterns of genetic variation across Cryptosporidium species suggest balancing selection at the gp60 locus

Cryptosporidium is an apicomplexan protozoan that lives in most vertebrates, including humans. Its gp60 gene is functionally involved in its attachment to host cells, and its high level of genetic variation has made it the reference marker for sample typing in epidemiological studies. To understand the origin of such high diversity and to determine the extent to which this classification applies to the rest of the genome, we analysed the patterns of variation at gp60 and nine other nuclear loci in isolates of three Cryptosporidium species. Most loci showed low genetic polymorphism (π_S <1%) and similar levels of between‐species divergence. Contrastingly, gp60 exhibited very different characteristics: (i) it was nearly ten times more variable than the other loci; (ii) it displayed a significant excess of polymorphisms relative to between‐species differences in a maximum‐likelihood Hudson–Kreitman–Aguadé test; (iii) gp60 subtypes turned out to be much older than the species they were found in; and (iv) showed a significant excess of polymorphic variants shared across species from random expectations. These observations suggest that this locus evolves under balancing selection and specifically under negative frequency‐dependent selection (FDS). Interestingly, genetic variation at the other loci clusters very well within the groups of isolates defined by gp60 subtypes, which may provide new tools to understand the genome‐wide patterns of genetic variation of the parasite in the wild. These results suggest that gp60 plays an active and essential role in the life cycle of the parasite and that genetic variation at this locus might be essential for the parasite's long‐term success.     

Multispecies coexistence of trees in tropical forests: spatial signals of topographic niche differentiation increase with environmental heterogeneity

Neutral and niche theories give contrasting explanations for the maintenance of tropical tree species diversity. Both have some empirical support, but methods to disentangle their effects have not yet been developed. We applied a statistical measure of spatial structure to data from 14 large tropical forest plots to test a prediction of niche theory that is incompatible with neutral theory: that species in heterogeneous environments should separate out in space according to their niche preferences. We chose plots across a range of topographic heterogeneity, and tested whether pairwise spatial associations among species were more variable in more heterogeneous sites. We found strong support for this prediction, based on a strong positive relationship between variance in the spatial structure of species pairs and topographic heterogeneity across sites. We interpret this pattern as evidence of pervasive niche differentiation, which increases in importance with increasing environmental heterogeneity.     

The elimination of fox rabies from Europe: determinants of success and lessons for the future

Despite perceived challenges to controlling an infectious disease in wildlife, oral rabies vaccination (ORV) of foxes has proved a remarkably successful tool and a prime example of a sophisticated strategy to eliminate disease from wildlife reservoirs. During the past three decades, the implementation of ORV programmes in 24 countries has led to the elimination of fox-mediated rabies from vast areas of Western and Central Europe. In this study, we evaluated the efficiency of 22 European ORV programmes between 1978 and 2010. During this period an area of almost 1.9 million km² was targeted at least once with vaccine baits, with control taking between 5 and 26 years depending upon the country. We examined factors influencing effort required both to control and eliminate fox rabies as well as cost-related issues of these programmes. The proportion of land area ever affected by rabies and an index capturing the size and overlap of successive ORV campaigns were identified as factors having statistically significant effects on the number of campaigns required to both control and eliminate rabies. Repeat comprehensive campaigns that are wholly overlapping much more rapidly eliminate infection and are less costly in the long term. Disproportionally greater effort is required in the final phase of an ORV programme, with a median of 11 additional campaigns required to eliminate disease once incidence has been reduced by 90 per cent. If successive ORV campaigns span the entire affected area, rabies will be eliminated more rapidly than if campaigns are implemented in a less comprehensive manner, therefore reducing ORV expenditure in the longer term. These findings should help improve the planning and implementation of ORV programmes, and facilitate future decision-making by veterinary authorities and policy-makers.     

Predictive systems ecology

Human societies, and their well-being, depend to a significant extent on the state of the ecosystems that surround them. These ecosystems are changing rapidly usually in response to anthropogenic changes in the environment. To determine the likely impact of environmental change on ecosystems and the best ways to manage them, it would be desirable to be able to predict their future states. We present a proposal to develop the paradigm of predictive systems ecology, explicitly to understand and predict the properties and behaviour of ecological systems. We discuss the necessary and desirable features of predictive systems ecology models. There are places where predictive systems ecology is already being practised and we summarize a range of terrestrial and marine examples. Significant challenges remain but we suggest that ecology would benefit both as a scientific discipline and increase its impact in society if it were to embrace the need to become more predictive.     

Mammary tumor development is directly inhibited by lifelong n-3 polyunsaturated fatty acids

IntroductionDespite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis.Methodsfat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)-neu(ndl)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet.ResultsMice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (~30%) and multiplicity (~33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndl)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice.ConclusionUsing complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention.     

Effects of learning experience on behaviour of the generalist parasitoid Sclerodermus pupariae to novel hosts

Massicus raddei Blessig (Coleoptera: Cerambycidae), also referred to as the oak long‐horned beetle (OLB), is a non‐natural host for the generalist parasitoid Sclerodermus pupariae Yang et Yao (Hymenoptera: Bethylidae). To determine whether this generalist parasitoid might be a suitable agent for the control of OLB, the adaptive learning experience of adult female parasitoids to OLB larvae was investigated in the laboratory. A Y‐tube olfactometer bioassay was used to examine the effects of adaptive learning experience on the foraging ability of parasitoids for OLB larvae. The results indicated that parasitoids were significantly attracted by the volatiles of ash bark, Fraxinus velutina, with emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) larvae and larval frass, after exposure to ash bark mixed with EAB larval frass (learning condition A). In contrast, after exposure to oak bark, Quercus liaotungensis, mixed with OLB larval frass (learning condition C), parasitoids showed significant preference for the volatiles of oak bark with OLB larvae and larval frass. On the basis of the results of no‐choice tests, we found that parasitoids exposed to learning condition C had greater paralysis efficiency and higher OLB larvae parasitism rates than those exposed to learning condition A or no experience. Furthermore, parasitoids fed on OLB larvae in learning condition C had significantly greater paralysis efficiency and higher OLB larvae parasitism rates than other parasitoids tested. Parasitoids fed on EAB larvae in learning condition A had the lowest paralysis efficiency and OLB larvae parasitism rates among the parasitoids tested. These findings suggested that adaptive learning significantly enhanced the ability of a generalist parasitoid to utilize a novel host. This may provide a new approach to controlling non‐natural hosts using generalist parasitoids.     

Trends of karyotypical evolution in the pearl cichlid,Geophagus brasiliensis,from southern Brazil

Chromosomal rearrangements such as inversions can facilitate speciation even in the presence of gene flow. The present study aims to analyze the karyotypic variation in six populations of Geophagus brasiliensis from southern Brazil. All specimens showed 2n = 48 chromosomes, but three karyotypes were found to have one, two or three pairs of submetacentric chromosomes. Although G. brasiliensis did not exhibit variation in the diploid number, it presented a wide interpopulational variation mainly regarding the karyotype formula and specific chromosomal markers. Differences in the location of the major and minor rDNA loci were observed among the populations. Moreover, different patterns were observed in the distribution of the constitutive heterochromatin, presenting intra- and interpopulational variation. This supports the hypothesis that this taxon represents a complex species or that cryptic species are included in this group, indicating a possibleprocess of sympatric speciation. By potentially restricting gene flow between heterokaryotypes, the segregating chromosome rearrangements we describe for G. brasiliensis may play a role in diversification in this species complex.     

Equivalence between Euler angle conventions for the description of tensorial interactions in liquid NMR: application to different software programs

Long-range orientational restraints derived from alignment or rotational diffusion tensors have greatly contributed to the expansion of applications in biomolecular NMR. The orientation of the principal axis system of these tensors is usually described by the so-called Euler angles. However, no clear consensus has emerged concerning the convention of the associated orthogonal rotations. As a result, the different programs that derive or predict them have adopted different conventions, which make comparison between their results difficult. Moreover, the rotation schemes are seldom completely described. Here, we summarize the different conventions, determine which ones are adopted by commonly used software packages, and establish the formal equivalencies between the different calculated Euler angles.     

Barth syndrome: Cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation

Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the assembly of respiratory chain complexes, favoring full-yield operation. It also mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth syndrome patients, we showed that the production of abnormal cardiolipin led to mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes in electron transport chain stability, resulting in cellular defects. We found a destabilization of the supercomplex (respirasome) I + III₂ + IV_n but also decreased amounts of individual complexes I and IV and supercomplexes I + III and III + IV. No changes were observed in the amounts of individual complex III and complex II. We also found decreased levels of complex V. This complex is not part of the supercomplex suggesting that cardiolipin is required not only for the association/stabilization of the complexes into supercomplexes but also for the modulation of the amount of individual respiratory chain complexes. However, these alterations were compensated by an increase in mitochondrial mass, as demonstrated by electron microscopy and measurements of citrate synthase activity. We suggest that this compensatory increase in mitochondrial content prevents a decrease in mitochondrial respiration and ATP synthesis in the cells. We also show, by extensive flow cytometry analysis, that the type II apoptosis pathway was blocked at the mitochondrial level and that the mitochondria of patients with Barth syndrome cannot bind active caspase-8. Signal transduction is thus blocked before any mitochondrial event can occur. Remarkably, basal levels of superoxide anion production were slightly higher in patients' cells than in control cells as previously evidenced via an increased protein carbonylation in the taz1Δ mutant in the yeast. This may be deleterious to cells in the long term. The consequences of mitochondrial dysfunction and alterations to apoptosis signal transduction are considered in light of the potential for the development of future treatments.