Differential expression of interferon responsive genes in rodent models of transmissible spongiform encephalopathy disease

Background

Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.

Results

Adeno-associated viral (AAV) vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits.

Conclusion

The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in vivo, and demonstrate that whilst expression of Aβ42 alone is sufficient to initiate Aβ deposition, both Aβ40 and Aβ42 may contribute to cognitive deficits.     

Breaking taboos in the tropics: incest promotes colonization by wood-boring beetles

• 1 Inbreeding and parthenogenesis are especially frequent in colonizing species of plants and animals, and inbreeding in wood‐boring species in the weevil families Scolytinae and Platypodidae is especially common on small islands. In order to study the relationship between colonization success, island attributes and mating system in these beetles, we analysed the relative proportions of inbreeders and outbreeders for 45 Pacific and Old World tropical islands plus two adjacent mainland sites, and scored islands for size, distance from nearest source population, and maximum altitude.
• 2 The numbers of wood‐borer species decreased with decreasing island size, as expected; the degree of isolation and maximum island altitude had negligible effects on total species numbers.
• 3 Numbers of outbreeding species decreased more rapidly with island size than did those of inbreeders. Comparing species with similar ecology (e.g. ambrosia beetles) showed that this difference was best explained by differential success in colonization, rather than by differences in resource utilization or sampling biases. This conclusion was further supported by analyses of data from small islands, which suggested that outbreeding species have a higher degree of endemism and that inbreeding species are generally more widespread.
• 4 Recently established small populations necessarily go through a period of severe inbreeding, which should affect inbreeding species much less than outbreeding ones. In addition, non‐genetic ecological and behavioural (‘Allee’) effects are also expected to reduce the success of outbreeding colonists much more than that of inbreeders: compared with inbreeders, outbreeders are expected to have slower growth rates, have greater difficulties with mate‐location and be vulnerable to random extinction over a longer period.

     

Molecules and morphology: evidence for cryptic hybridization in African Hyalomma (Acari: Ixodidae)

The role of natural hybridization and introgression as part of the evolutionary process is of increasing interest to zoologists, particularly as more examples of gene exchange among species are identified. We present mitochondrial and nuclear sequence data for Hyalomma dromedarii, Hyalomma truncatum, and Hyalomma marginatum rufipes (Acari: Ixodidae) collected from one-humped camels in Ethiopia. These species are well differentiated morphologically and genetically; sequence data from the mitochondrial DNA (mtDNA) cytochrome oxidase I gene indicates 10-14% divergence between the species. However, incongruence between morphology and the mtDNA phylogeny was observed, with multiple individuals of H. dromedarii and H. truncatum present on the same mtDNA lineage as H. marginatum rufipes. Thus, individuals with morphology of H. dromedarii and H. truncatum are indistinguishable from H. marginatum rufipes on the basis of mtDNA. Multiple copies of ITS-2 were subsequently cloned and sequenced for a subset of individuals from the mtDNA phylogeny, representing both 'normal' and 'putative hybrid' individuals. Very low sequence divergence (0.3%) was observed within 'normal' individuals of both H. dromedarii and H. truncatum relative to the 'putative hybrid' individuals (6 and 2.7%, respectively). The pattern of intra-individual variation in ITS-2 within 'putative hybrid' individuals, particularly in H. dromedarii, strongly suggests that gene flow has occurred among these Hyalomma species, but no indication of this is given by the morphology of the individuals.     

Efficacy of hyaluronic acid binding assay in selecting motile spermatozoa with normal morphology at high magnification

Background  

The present study aimed to evaluate the efficacy of the hyaluronic acid (HA) binding assay in the selection of motile spermatozoa with normal morphology at high magnification (8400x).     

On the track of the Red Queen: bark beetles, their nematodes, local climate and geographic parthenogenesis

Geographic parthenogenesis has been explained as resulting from parasite pressure (Red Queen hypothesis): several studies have found high degrees of sexuals where the prevalence of parasites is high. However, it is important to address whether prevalence of parasites mirrors risk of infection. We explored geographic parthenogenesis of Ips acuminatus bark beetles and their nematodes. Local climate is crucial for nematode stages outside the host, in spring and summer, and prevalence should thus be associated with those temperatures if prevalence reliably reflects exposure risk across populations. This was the case; however, high prevalence of a virulent nematode species was not associated with many sexuals, whereas highly sexual populations were characterized by high infection risk of benign nematodes. Low virulence of the latter makes Red Queen dynamics unlikely. Geographical patterns of parthenogenesis were instead associated with winter temperature and variance in temperature.     

The costs of sex: facing real-world complexities

Understanding the maintenance of sexual reproduction constitutes a difficult problem for evolutionary biologists because of the immediate costs that sex seems to incur. Typically, general benefits to sex and recombination are investigated that might outweigh these costs. However, several factors can strongly influence the complex balance between costs and benefits of sex; these include constraints on the evolution of asexuality, ecological differentiation, and certain lif-history traits. We review these factors and their empirical support for the first time in a unified framework and find that they can reduce the costs of sex, circumvent them, or make them inapplicable. These factors can even tip the scales to a net benefit for sex. The reviewed factors affect species and species groups differently, and we conclude consequently that understanding the maintenance of sex could turn out to be more species-specific than commonly assumed. Interestingly, our study suggests that, in some species, no general benefits to sex and recombination might be needed to understand the maintenance of sex, as in our case study of dandelions.     

Improbable but true: the invasive inbreeding ambrosia beetle Xylosandrus morigerus has generalist genotypes

The wide distribution and dominance of invasive inbreeding species in many forest ecosystems seems paradoxical in face of their limited genetic variation. Successful establishment of invasive species in new areas is nevertheless facilitated by clonal reproduction: parthenogenesis, regular self-fertilization, and regular inbreeding. The success of clonal lineages in variable environments has been explained by two models, the frozen niche variation (FNV) model and the general-purpose genotype (GPG) model. We tested these models on a widely distributed forest pest that has been recently established in Costa Rica-the sibling-mating ambrosia beetle Xylosandrus morigerus. Two deeply diverged mitochondrial haplotypes coexist at multiple sites in Costa Rica. We find that these two haplotypes do not differ in their associations with ecological factors. Overall the two haplotypes showed complete overlap in their resource utilization; both genotypes have broad niches, supporting the GPG model. Thus, probable or not, our findings suggest that X. morigerus is a true ecological generalist. Clonal aspects of reproduction coupled with broad niches are doubtless important factors in the successful colonization of new habitats in distant regions.     

Inbreeding variability and population structure in the invasive haplodiploid palm‐seed borer (Coccotrypes dactyliperda)

We investigated the mating system and population genetic structure of the invasive haplodiploid palm‐seed borer Coccotrypes dactyliperda in California. We focused on whether these primarily inbreeding beetles have a ‘mixed‐breeding’ system that includes occasional outbreeding, and whether local inbreeding coefficients (F_IS) varied with dominant environmental factors. We also analysed the genetic structure of C. dactyliperda populations across local and regional scales. Based on the analysis of genetic variation at seven microsatellite loci in 1034 individual beetles from 59 populations, we found both high rates of inbreeding and plentiful evidence of mixed‐breeding. F_IS ranged from ?0.56 to 0.90, the highest variability reported within any animal species. There was a negative correlation between F_IS and latitude, suggesting that some latitude‐associated factor affecting mating decisions influenced inbreeding rates. Multiple regressions suggested that precipitation, but not temperature, may be an important correlate. Finally, we found highly significant genetic differentiation among sites, even over short geographic distances (< 1000 m).