Strategies for the retention of high genetic variability in European flat oyster (<Emphasis Type=Italic>Ostrea edulis</Emphasis>) restoration programmes

The native European flat oyster Ostrea edulis is listed in the OSPAR Convention for the Protection of the Marine Environment of the North-East Atlantic (species and habitat protection) and in the UK Biodiversity Action Plan. Once extremely abundant in the nineteenth century, European stocks of O. edulis have declined during the twentieth century to rare, small, localised populations due to overexploitation, habitat degradation and, most recently, the parasitic disease bonamiosis. Selective breeding programmes for resistance to bonamiosis have been initiated in France and Ireland. High genetic diversity and bonamiosis-resistance would be important features of any sustainable restoration programmes for O. edulis. Oysters were sampled across Europe from four hatchery sources, four pond-cultured sources and four wild, but managed fisheries and were genotyped at five microsatellite loci. Hatchery-produced populations from small numbers of broodstock showed a significant loss of genetic diversity relative to wild populations and pedigree reconstruction revealed that they were each composed of a single large full-sib family and several small full-sib families. This extremely low effective population size highlights the variance in reproductive success among the potential breeders. Pond-cultured oysters were intermediate in genetic diversity and effective population size between hatchery and wild populations. Controlled hatchery production allows the development of bonamiosis-resistant strains, but at the expense of genetic diversity. Large scale pond culture on the other hand can provide a good level of genetic diversity. A mixture of these two approaches is required to ensure a healthy and sustainable restoration programme for O. edulis in Europe.     

Maternal effects and the endocrine regulation of mandrill growth

Maternal effects can influence offspring growth and development, and thus fitness. However, the physiological factors mediating these effects in nonhuman primates are not well understood. We investigated the impact of maternal effects on variation in three important components of the endocrine regulation of growth in male and female mandrills (Mandrillus sphinx), from birth to 9 years of age. Using a mixed longitudinal set (N = 252) of plasma samples, we measured concentrations of insulin‐like growth factor‐I (IGF‐I), growth hormone binding protein (GHBP), and free testosterone (free T). We evaluated the relationship of ontogenetic patterns of changes in hormone concentration to patterns of growth in body mass and body length, and determined that these endocrine factors play a significant role in growth of both young (infant and juvenile) and adolescent male mandrills, but only in growth of young female mandrills. We also use mixed models analysis to determine the relative contribution of the effects of maternal rank, parity, and age on variation in hormone and binding protein concentrations. Our results suggest that all of these maternal effects account for significant variation in hormone and binding protein concentrations in all male age groups. Of the maternal effects measured, maternal rank was the most frequently identified significant maternal effect on variation in hormone and binding protein concentrations. We suggest that these endocrine factors provide mechanisms that contribute to the maternal effects on offspring growth previously noted in this population. Am. J. Primatol. 74:890‐900, 2012. © 2012 Wiley Periodicals, Inc.     

Bread matters: a national initiative to profile the genetic diversity of Australian wheat

The large and complex genome of wheat makes genetic and genomic analysis in this important species both expensive and resource intensive. The application of next-generation sequencing technologies is particularly resource intensive, with at least 17?Gbp of sequence data required to obtain minimal (1×) coverage of the genome. A similar volume of data would represent almost 40× coverage of the rice genome. Progress can be made through the establishment of consortia to produce shared genomic resources. Australian wheat genome researchers, working with Bioplatforms Australia, have collaborated in a national initiative to establish a genetic diversity dataset representing Australian wheat germplasm based on whole genome next-generation sequencing data. Here, we describe the establishment and validation of this resource which can provide a model for broader international initiatives for the analysis of large and complex genomes.     

Individual dispersal,landscape connectivity and ecological networks

Connectivity is classically considered an emergent property of landscapes encapsulating individuals' flows across space. However, its operational use requires a precise understanding of why and how organisms disperse. Such movements, and hence landscape connectivity, will obviously vary according to both organism properties and landscape features. We review whether landscape connectivity estimates could gain in both precision and generality by incorporating three fundamental outcomes of dispersal theory. Firstly, dispersal is a multi‐causal process; its restriction to an ‘escape reaction’ to environmental unsuitability is an oversimplification, as dispersing individuals can leave excellent quality habitat patches or stay in poor‐quality habitats according to the relative costs and benefits of dispersal and philopatry. Secondly, species, populations and individuals do not always react similarly to those cues that trigger dispersal, which sometimes results in contrasting dispersal strategies. Finally, dispersal is a major component of fitness and is thus under strong selective pressures, which could generate rapid adaptations of dispersal strategies. Such evolutionary responses will entail spatiotemporal variation in landscape connectivity. We thus strongly recommend the use of genetic tools to: (i) assess gene flow intensity and direction among populations in a given landscape; and (ii) accurately estimate landscape features impacting gene flow, and hence landscape connectivity. Such approaches will provide the basic data for planning corridors or stepping stones aiming at (re)connecting local populations of a given species in a given landscape. This strategy is clearly species‐ and landscape‐specific. But we suggest that the ecological network in a given landscape could be designed by stacking up such linkages designed for several species living in different ecosystems. This procedure relies on the use of umbrella species that are representative of other species living in the same ecosystem.     

Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR)

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects.     

Functional Expression of P-Glycoprotein in an Immortalised Cell Line of Rat Brain Endothelial Cells, RBE4

Abstract: The presence of P-glycoprotein in the cell plasma membrane limits the penetration of many cytotoxic substances into cells that express the gene product. There is considerable evidence also to indicate that P-glycoprotein is expressed as part of the normal blood-brain barrier in the luminal membranes of the cerebral capillary endothelial cells, where it presumably performs a protective function for the brain. This report describes the functional expression of P-glycoprotein in an immortalised cell line, RBE4, derived from rat cerebral capillary endothelial cells. The expression of P-glycoprotein is demonstrated by western immunoblotting and by immunogold and fluorescent staining with monoclonal antibodies. The cellular accumulation of [³H]colchicine and [³H]vinblastine is investigated and shown to be enhanced by the presence of azidothymidine, chlorpromazine, verapamil, cyclosporin A, and PSC 833 ([3'-keto-Bmt¹]-[Val²]-cyclosporin) at 50 or 100 µ M concentration. It is concluded that the RBE4 cell line is a valuable tool for investigating the mechanisms of P-glycoprotein activity both in the blood-brain barrier and in multidrug resistance in general.     

CpG Methylation Changes within the IL2RA Promoter in Type 1 Diabetes of Childhood Onset

None of the polymorphic variants of the IL2RA gene found associated with Type 1 Diabetes (T1D) was shown to have a functional effect. To test if the epigenetic variation could play a role at this locus, we studied the methylation of 6 CpGs located within the proximal promoter of IL2RA gene in 252 T1D patients compared with 286 age-matched controls. We found that DNA methylation at CpGs −373 and −456 was slightly but significantly higher in patients than in controls (40.4±4.6 vs 38.3±5.4, p = 1.4E4; 91.4±2.8 vs 89.5±5.3, p = 1.8E-6), while other CpG showed a strictly comparable methylation. Among 106 single nucleotide polymorphisms (SNPs) located in the neighboring 180kb region, we found that 28 SNPs were associated with DNA methylation at CpG −373. Sixteen of these SNPs were known to be associated with T1D. Our findings suggest that the effect of IL2RA risk alleles on T1D may be partially mediated through epigenetic changes.