Independent centromere formation in a capricious, gene-free domain of chromosome 13q21 in Old World monkeys and pigs

Background

Evolutionary centromere repositioning and human analphoid neocentromeres occurring in clinical cases are, very likely, two stages of the same phenomenon whose properties still remain substantially obscure. Chromosome 13 is the chromosome with the highest number of neocentromeres. We reconstructed the mammalian evolutionary history of this chromosome and characterized two human neocentromeres at 13q21, in search of information that could improve our understanding of the relationship between evolutionarily new centromeres, inactivated centromeres, and clinical neocentromeres.

Results

Chromosome 13 evolution was studied, using FISH experiments, across several diverse superordinal phylogenetic clades spanning >100 million years of evolution. The analysis revealed exceptional conservation among primates (hominoids, Old World monkeys, and New World monkeys), Carnivora (cat), Perissodactyla (horse), and Cetartiodactyla (pig). In contrast, the centromeres in both Old World monkeys and pig have apparently repositioned independently to a central location (13q21). We compared these results to the positions of two human 13q21 neocentromeres using chromatin immunoprecipitation and genomic microarrays.

Conclusion

We show that a gene-desert region at 13q21 of approximately 3.9 Mb in size possesses an inherent potential to form evolutionarily new centromeres over, at least, approximately 95 million years of mammalian evolution. The striking absence of genes may represent an important property, making the region tolerant to the extensive pericentromeric reshuffling during subsequent evolution. Comparison of the pericentromeric organization of chromosome 13 in four Old World monkey species revealed many differences in sequence organization. The region contains clusters of duplicons showing peculiar features.     

Gene therapy: can neural stem cells deliver?

Neural stem cells are a self-renewing population that generates the neurons and glia of the developing brain. They can be isolated, proliferated, genetically manipulated and differentiated in vitro and reintroduced into a developing, adult or pathologically altered CNS. Neural stem cells have been considered for use in cell replacement therapies in various neurodegenerative diseases, and an unexpected and potentially valuable characteristic of these cells has recently been revealed--they are highly migratory and seem to be attracted to areas of brain pathology such as ischaemic and neoplastic lesions. Here, we speculate on the ways in which neural stem cells might be exploited as delivery vehicles for gene therapy in the CNS.     

Neural signatures of economic preferences for risk and ambiguity

People often prefer the known over the unknown, sometimes sacrificing potential rewards for the sake of surety. Overcoming impulsive preferences for certainty in order to exploit uncertain but potentially lucrative options may require specialized neural mechanisms. Here, we demonstrate by functional magnetic resonance imaging (fMRI) that individuals' preferences for risk (uncertainty with known probabilities) and ambiguity (uncertainty with unknown probabilities) predict brain activation associated with decision making. Activation within the lateral prefrontal cortex was predicted by ambiguity preference and was also negatively correlated with an independent clinical measure of behavioral impulsiveness, suggesting that this region implements contextual analysis and inhibits impulsive responses. In contrast, activation of the posterior parietal cortex was predicted by risk preference. Together, this novel double dissociation indicates that decision making under ambiguity does not represent a special, more complex case of risky decision making; instead, these two forms of uncertainty are supported by distinct mechanisms.     

Critical role of STAT3 in leptin's metabolic actions

Leptin has pleiotropic effects on glucose homeostasis and feeding behavior. Here, we validate the use of a cell-permeable phosphopeptide that blocks STAT3 activation in vivo. The combination of this biochemical approach with stereotaxic surgical techniques allowed us to pinpoint the contribution of hypothalamic STAT3 to the acute effects of leptin on food intake and glucose homeostasis. Leptin's ability to acutely reduce food intake critically depends on intact STAT3 signaling. Likewise, hypothalamic signaling of leptin through STAT3 is required for the acute effects of leptin on liver glucose fluxes. Lifelong obliteration of STAT3 signaling via the leptin receptor in mice (s/s mice) results in severe hepatic insulin resistance that is comparable to that observed in db/db mice, devoid of leptin receptor signaling. Our results demonstrate that the activation of the hypothalamic STAT3 pathway is an absolute requirement for the effects of leptin on food intake and hepatic glucose metabolism.     

Determination of celecoxib in human plasma and breast milk by high-performance liquid chromatographic assay

A rapid and simple HPLC assay was developed for the determination of celecoxib in human plasma and breast milk. After proteins were precipitated with acetonitrile, celecoxib was resolved on a C18 column and detected by UV detection at 254 nm. Standard curves were linear over the concentration range 10-2000 microg/L (r(2)>0.99). Bias was 相似文献   

Rapid adaptation of insect herbivores to an invasive plant

Introduced plant success often is attributed to release from natural enemies in their new ranges. However, herbivores may accumulate over time and reduce invasiveness but evidence for this process to date is weak. We report here that enemy release is indeed limited to the early stages of introduction of the Chinese tallow tree (Sapium sebiferum). In bioassays and gardens along a geographical gradient of time since tallow tree introduction, herbivory was highest and tree performance was poorest where tallow tree has been present longer (i.e. introduced earlier). Additionally, Asian ecotypes (grown from seeds collected in Asia) had lower survival than North American ecotypes (seeds collected in North America), which is consistent with genetic responses to low herbivory in the introduced range (EICA Hypothesis). Release from insect herbivores appears to contribute to early success of the tallow tree, but accumulation of insect herbivores has apparently reduced this benefit over time.     

Influence of hydrogeographic history and hybridization on the distribution of genetic variation in the pupfishes Cyprinodon atrorus and C. bifasciatus

The evolutionary importance of hybridization in animals has been subject of much debate. In this study, we examined the influence of hydrogeographic history and hybridization on the present distribution of nuclear and mitochondrial DNA variation in two pupfish species, Cyprinodon atrorus and Cyprinodon bifasciatus. Results presented here indicate that there has been limited introgression of nuclear genes; however, mtDNA introgression has been substantial, with complete replacement of the C. bifasciatus mitochondrial genome by that of C. atrorus. Subsequent to this replacement, there has been diversification of mitochondrial haplotypes along major geographic regions in the basin. Evidence was also found that mitochondrial replacement follows a predictable, cyclical pattern in this system, with isolation and diversification followed by re-contact and replacement of C. bifasciatus mitochondrial haplotypes by those of C. atrorus. This pattern is best explained by a combination of a numeric bias towards C. atrorus and mating site selection rather than selection for C. atrorus mitochondrial genome. These results demonstrate the important role hybridization can play in evolution.     

Prey-mediated effects of transgenic canola on a beneficial, non-target, carabid beetle

Transgenic plants producing insecticidal proteins from Bacillus thuringiensis (Bt) can control some major insect pests and reduce reliance on sprayed insecticides. However, large scale adoption of this technology has raised concerns about potential negative effects, including evolution of pest resistance to Bt toxins, transgene flow from Bt crops to other plants, and harm to non-target beneficial organisms. Furthermore, concern has also been expressed over the effects this technology may have on biodiversity in general. Ecologically relevant risk assessment is therefore required (Risk = Hazard × Exposure). Transgenic plants that produce Bt toxins to kill insect pests could harm beneficial predators. This might occur directly by transmission of toxin via prey, or indirectly by toxin-induced reduction in prey quality (Hazard). To test these hypotheses, we determined the effects of Bt-producing canola on a predatory ground beetle (Pterostichus madidus) fed larvae of diamondback moth (Plutella xylostella) that were either susceptible or resistant to the Bt toxin. Survival, weight gain, and adult reproductive fitness did not differ between beetles fed prey reared on Bt-producing plants and those fed prey from control plants. Furthermore, while Bt-resistant prey was shown to deliver high levels of toxin to the beetle when they were consumed, no significant impact upon the beetle was observed. Subsequent investigation showed that in choice tests (Exposure), starved and partially satiated female beetles avoided Bt-fed susceptible prey, but not Bt-fed resistant prey. However, in the rare cases when starved females initially selected Bt-fed susceptible prey, they rapidly rejected them after beginning to feed. This prey type was shown to provide sufficient nutrition to support reproduction in the bioassay suggesting that Bt-fed susceptible prey is acceptable in the absence of alternative prey, however adults possess a discrimination ability based on prey quality. These results suggest that the direct effects of Bt-producing canola on predator life history was minimal, and that predators’ behavioural preferences may mitigate negative indirect effects of reduced quality of prey caused by consumption of Bt-producing plants. The results presented here therefore suggest that cultivation of Bt canola may lead to conservation of non-target predatory and scavenging organisms beneficial in pest control, such as carabids, and may therefore provide more sustainable agricultural systems than current practices. In addition, minimal impacts on beneficial carabids in agro-ecosystems suggest that Bt canola crops are likely to be compatible with integrated pest management (IPM) systems.     

Feeding activity of scallops and mussels measured simultaneously in the field: Repeated measures sampling and implications for modelling

Many studies on the biology of bivalves have focused on identifying the importance of various environmental factors in regulating feeding behaviour in order to predict ingestion and growth responses in a variety of habitats. When taking into consideration the diversity of studies undertaken and the variety of methodologies employed, it is perhaps not surprising that there have been inconsistencies in both interspecific and intraspecific comparisons. In order to compare and contrast the way in which feeding activities of a mussel species (Mytilus edulis) and a scallop species (Placopecten magellanicus) respond to environmental factors and seston characteristics, we exposed both species simultaneously to a fluctuating assemblage of natural particles found in their local environment. Similar sizes of mussels (40-73 mm) and scallops (40-88 mm) were held in flow through chambers at two different sites in Atlantic Canada on four separate occasions, during which environmental conditions, including seston characteristics, were monitored and individual clearance rates were measured. Because the same individuals were measured over time, repeated-measures statistical procedures were used to analyze the data. Results indicate that weight standardized clearance rates of mussels were significantly higher than those of scallops only at the highest concentration tested (12.8 mg l^− 1), which translates into almost 3 times more material being filtered. Scallops appeared to respond to fluctuations in environment parameters and suspended food particles more consistently than mussels. These data suggest that the feeding behaviour of these two species is mediated differently by the same environmental parameters. Our study also demonstrates the importance of selecting appropriate statistical tests (e.g., repeated measures) for the analyses of data obtained from repeated sampling of the same individuals over time, and the need to consider species-specific feeding responses when developing models that predict the influence of bivalve feeding on ecosystem function.