A gene expression signature for insulin resistance

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its aetiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a Gene Expression Signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made ‘insulin resistant&rsquo; by treatment with tumour necrosis factor-alpha (TNFα) and then reversed with aspirin and troglitazone (‘re-sensitized&rsquo;). The GES consisted of five genes whose expression levels best discriminated between the insulin resistant and insulin re-sensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3- L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed using aspirin and troglitazone. This screen identified both known and new insulin sensitizing compounds including non-steroidal anti inflammatory agents, β-adrenergic antagonists, beta-lactams and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels, P < 0.001). These findings show that GES technology can be used for both the discovery of insulin sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.r />

First probable Australian cases of human infection with Rickettsia felis (cat-flea typhus)

Human infection with Rickettsia felis has been reported in most parts of the world, and R. felis has recently been confirmed in cat fleas in Western Australia. The clinical presentations of R. typhi and R. felis are similar, and in the past, the incidence of R. felis infection may have been underestimated. We describe the first reported cases of probable human R. felis infection in Australia. Two adults and three children in Victoria contracted a rickettsial disease after exposure to fleas from kittens. Molecular testing of fleas demonstrated the presence of R. felis but not R. typhi.r />

Time-in-area represents foraging activity in a wide-ranging pelagic forager

Successful Marine Spatial Planning depends upon the identification of areas with high importance for particular species, ecosystems or processes. For seabirds, advancements in biologging devices have enabled us to identify these areas through the detailed study of at-sea behaviour. However, in many cases, only positional data are available and the presence of local biological productivity and hence seabird foraging behaviour is inferred from these data alone, under the untested assumption that foraging activity is more likely to occur in areas where seabirds spend more time. We fitted GPS devices and accelerometers to northern gannets Morus bassanus and categorised the behaviour of individuals outside the breeding colony as plunge diving, surface foraging, floating and flying. We then used the locations of foraging events to test the efficiency of 2 approaches: time-in-area and kernel density (KD) analyses, which are widely employed to detect highly-used areas and interpret foraging behaviour from positional data. For KD analyses, the smoothing parameter (h) was calculated using the ad hoc method (KDad hoc), and KDh=9.1, where h = 9.1 km, to designate core foraging areas from location data. A high proportion of foraging events occurred in core foraging areas designated using KDad hoc, KDh=9.1, and time-in-area. Our findings demonstrate that foraging activity occurs in areas where seabirds spend more time, and that both KD analysis and the time-in-area approach are equally efficient methods for this type of analysis. However, the time-in-area approach is advantageous in its simplicity, and in its ability to provide the shapes commonly used in planning. Therefore, the time-in-area approach can be used as a simple way of using seabirds to identify ecologically important locations from both tracking and survey data.

Nutritional regulation of long-chain PUFA biosynthetic genes in rainbow trout (Oncorhynchus mykiss)

Most studies on dietary vegetable oil in rainbow trout (Oncorhynchus mykiss) have been conducted on a background of dietary EPA (20 : 5n-3) and DHA (22 : 6n-3) contained in the fishmeal used as a protein source in aquaculture feed. If dietary EPA and DHA repress their endogenous synthesis from α-linolenic acid (ALA, 18 : 3n-3), then the potential of ALA-containing vegetable oils to maintain tissue EPA and DHA has been underestimated. We examined the effect of individual dietary n-3 PUFA on the expression of the biosynthetic genes required for metabolism of ALA to DHA in rainbow trout. A total of 720 juvenile rainbow trout were allocated to twenty-four experimental tanks and assigned one of eight diets. The effect of dietary ALA, EPA or DHA, in isolation or in combination, on hepatic expression of fatty acyl desaturase (FADS)2a(Δ6), FADS2b(Δ5), elongation of very long-chain fatty acid (ELOVL)5 and ELOVL2 was examined after 3 weeks of dietary intervention. The effect of these diets on liver and muscle phospholipid PUFA composition was also examined. The expression levels of FADS2a(Δ6), ELOVL5 and ELOVL2 were highest when diets were high in ALA, with no added EPA or DHA. Under these conditions ALA was readily converted to tissue DHA. Dietary DHA had the largest and most consistent effect in down-regulating the gene expression of all four genes. The ELOVL5 expression was the least responsive of the four genes to dietary n-3 PUFA changes. These findings should be considered when optimising aquaculture feeds containing vegetable oils and/or fish oil or fishmeal to achieve maximum DHA synthesis.

Australia's Prime Ministers : R. G. Menzies

In the run up to the Federal Election, The Overnights show is taking a look at some of Australia's former Prime Ministers. The second PM we discussed was Australia's longest serving Prime Minister Sir Robert Menzies.r />r />Often characterised as an extreme monarchist and British to the Bootstraps, Robert Menzies was responsible for many post-war socioeconomic developments and linked Australia more closely to South-East Asia and the USA to counter what was seen as the spread of Communism and the possible isolation of Australia.Michael Pavlich spoke to Geoff Robinson, a political historian and lecturer in Australian Studies and Politics at Deakin University.r />

Ecological processes : a key element in strategies for nature conservation

A common approach to nature conservation is to identify and protect natural 'assets&rsquo; such as ecosystems and threatened species. While such actions are essential, protection of assets will not be effective unless the ecological processes that sustain them are maintained. Here, we consider the role of ecological processes and the complementary perspective for conservation arising from an emphasis on process. Many kinds of ecological processes sustain biodiversity: including climatic processes, primary productivity, hydrological processes, formation of biophysical habitats, interactions between species, movements of organisms and natural disturbance regimes. Anthropogenic threats to conservation exert their influence by modifying or disrupting these processes. Such threats extend across tenures, they frequently occur offsite, they commonly induce non-linear responses, changes may be irreversible and the full consequences may not be experienced for lengthy periods. While many managers acknowledge these considerations in principle, there is much scope for greater recognition of ecological processes in nature conservation and greater emphasis on long time-frames and large spatial scales in conservation planning. Practical measures that promote ecological processes include: monitoring to determine the trajectory and rate of processes; incorporating surrogates for processes in conservation and restoration projects; specific interventions to manipulate and restore processes; and planning for the ecological future before options are foreclosed. The long-term conservation of biodiversity and the wellbeing of human society depend upon both the protection of natural assets and maintaining the integrity of the ecological processes that sustain them.

Genome - wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r</i>² > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10^-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

Improving biodiversity monitoring

Effective biodiversity monitoring is critical to evaluate, learn from, and ultimately improve conservation practice. Well conceived, designed and implemented monitoring of biodiversity should: (i) deliver information on trends in key aspects of biodiversity (e.g. population changes); (ii) provide early warning of problems that might otherwise be difficult or expensive to reverse; (iii) generate quantifiable evidence of conservation successes (e.g. species recovery following management) and conservation failures; (iv) highlight ways to make management more effective; and (v) provide information on return on conservation investment. The importance of effective biodiversity monitoring is widely recognized (e.g. Australian Biodiversity Strategy). Yet, while everyone thinks biodiversity monitoring is a good idea, this has not translated into a culture of sound biodiversity monitoring, or widespread use of monitoring data. We identify four barriers to more effective biodiversity monitoring in Australia. These are: (i) many conservation programmes have poorly articulated or vague objectives against which it is difficult to measure progress contributing to design and implementation problems; (ii) the case for long-term and sustained biodiversity monitoring is often poorly developed and/or articulated; (iii) there is often a lack of appropriate institutional support, co-ordination, and targeted funding for biodiversity monitoring; and (iv) there is often a lack of appropriate standards to guide monitoring activities and make data available from these programmes. To deal with these issues, we suggest that policy makers, resource managers and scientists better and more explicitly articulate the objectives of biodiversity monitoring and better demonstrate the case for greater investments in biodiversitymonitoring. There is an urgent need for improved institutional support for biodiversity monitoring in Australia, for improved monitoring standards, and for improved archiving of, and access to, monitoring data. We suggest that more strategic financial, institutional and intellectual investments in monitoring will lead to more efficient use of the resources available for biodiversity conservation and ultimately better conservation outcomes.r />