Recent trends in UK insects that inhabit early successional stages of ecosystems

Improved recording of less popular groups, combined with new statistical approaches that compensate for datasets that were hitherto too patchy for quantitative analysis, now make it possible to compare recent trends in the status of UK invertebrates other than butterflies. Using BRC datasets, we analysed changes in status between 1992 and 2012 for those invertebrates whose young stages exploit early seral stages within woodland, lowland heath and semi-natural grassland ecosystems, a habitat type that had declined during the 3 decades previous to 1990 alongside a disproportionally high number of Red Data Book species that were dependent on it. Two clear patterns emerged from a meta-analysis involving 299 classifiable species belonging to ten invertebrate taxa: (i) during the past 2 decades, most early seral species that are living near their northern climatic limits in the UK have increased relative to the more widespread members of these guilds whose distributions were not governed by a need for a warm micro-climate; and (ii) independent of climatic constraints, species that are restricted to the early stages of woodland regeneration have fared considerably less well than those breeding in the early seral stages of grasslands or, especially, heathland. The first trend is consistent with predicted benefits for northern edge-of-range species as a result of climate warming in recent decades. The second is consistent with our new assessment of the availability of early successional stages in these three ecosystems since c. 1990. Whereas the proportion and continuity of early seral patches has greatly increased within most semi-natural grasslands and lowland heaths, thanks respectively to agri-environmental schemes and conservation management, the representation of fresh clearings has continued to dwindle within UK woodlands, whose floors are increasingly shaded and ill-suited for this important guild of invertebrates

Loss of the Tumor Suppressor Pten Promotes Proliferation of Drosophila melanogaster Cells In Vitro and Gives Rise to Continuous Cell Lines

In vivo analysis of Drosophila melanogaster has enhanced our understanding of many biological processes, notably the mechanisms of heredity and development. While in vivo analysis of mutants has been a strength of the field, analyzing fly cells in culture is valuable for cell biological, biochemical and whole genome approaches in which large numbers of homogeneous cells are required. An efficient genetic method to derive Drosophila cell lines using expression of an oncogenic form of Ras (RasV12) has been developed. Mutations in tumor suppressors, which are known to cause cell hyperproliferation in vivo, could provide another method for generating Drosophila cell lines. Here we screened Drosophila tumor suppressor mutations to test if they promoted cell proliferation in vitro. We generated primary cultures and determined when patches of proliferating cells first emerged. These cells emerged on average at 37 days in wild-type cultures. Using this assay we found that a Pten mutation had a strong effect. Patches of proliferating cells appeared on average at 11 days and the cultures became confluent in about 3 weeks, which is similar to the timeframe for cultures expressing RasV12. Three Pten mutant cell lines were generated and these have now been cultured for between 250 and 630 cell doublings suggesting the life of the mutant cells is likely to be indefinite. We conclude that the use of Pten mutants is a powerful means to derive new Drosophila cell lines

Canalization of Gene Expression and Domain Shifts in the Drosophila Blastoderm by Dynamical Attractors

The variation in the expression patterns of the gap genes in the blastoderm of the fruit fly Drosophila melanogaster reduces over time as a result of cross regulation between these genes, a fact that we have demonstrated in an accompanying article in PLoS Biology (see Manu et al., doi:10.1371/journal.pbio.1000049). This biologically essential process is an example of the phenomenon known as canalization. It has been suggested that the developmental trajectory of a wild-type organism is inherently stable, and that canalization is a manifestation of this property. Although the role of gap genes in the canalization process was established by correctly predicting the response of the system to particular perturbations, the stability of the developmental trajectory remains to be investigated. For many years, it has been speculated that stability against perturbations during development can be described by dynamical systems having attracting sets that drive reductions of volume in phase space. In this paper, we show that both the reduction in variability of gap gene expression as well as shifts in the position of posterior gap gene domains are the result of the actions of attractors in the gap gene dynamical system. Two biologically distinct dynamical regions exist in the early embryo, separated by a bifurcation at 53% egg length. In the anterior region, reduction in variation occurs because of stability induced by point attractors, while in the posterior, the stability of the developmental trajectory arises from a one-dimensional attracting manifold. This manifold also controls a previously characterized anterior shift of posterior region gap domains. Our analysis shows that the complex phenomena of canalization and pattern formation in the Drosophila blastoderm can be understood in terms of the qualitative features of the dynamical system. The result confirms the idea that attractors are important for developmental stability and shows a richer variety of dynamical attractors in developmental systems than has been previously recognized

Molecular basis of USP7 inhibition by selective small-molecule inhibitors

Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise 'undruggable' targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers. Here we report that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and within human cells. Co-crystal structures reveal that both compounds target a dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases. Consistent with USP7 target engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53, and results in the transcription of p53 target genes, induction of the tumour suppressor p21, and inhibition of tumour growth in mice

Assessing reintroduction schemes by comparing genetic diversity of reintroduced and source populations: a case study of the globally threatened large blue butterfly (Maculinea arion)

An important factor in reintroductions is the amount of genetic diversity captured in the introduced individuals. Introduced populations are initially small, and thus vulnerable to genetic drift and stochastic events. The level of genetic diversity maintained is important for the long-term persistence of populations and their evolutionary potential to react to, for example, climate changes. The national extinction of many butterfly species has been pronounced in many European countries. The globally Vulnerable large blue butterfly (Maculinea arion) went extinct in the UK in 1979 and was later reintroduced from Öland in Sweden. We investigated the genetic diversity of reintroduced large blues nineteen generations after translocation on five sites in the UK, and seven sites on Öland, including the source population. We found similar levels of genetic diversity in the reintroduced and source populations, but the UK and Swedish populations were genetically differentiated; we also found significant genetic differentiation among reintroduced UK populations only a few kilometres apart. The reintroduced populations had several private alleles not found in the source population in 2011, and thus may already represent a unique subset of genetic diversity of the north-western populations of M. arion. Our results show that the IUCN and other protocols followed in the 1990s for translocating and maintaining the maximum available genetic diversity during reintroductions were largely adequate for this species, and hence will be valuable for informing the growing use of reintroductions as a strategy for the conservation of endangered species of insect

Mimetic host shifts in an endangered social parasite of ants

An emerging problem in conservation is whether listed morpho-species with broad distributions, yet specialized lifestyles, consist of more than one cryptic species or functionally distinct forms that have different ecological requirements. We describe extreme regional divergence within an iconic endangered butterfly, whose socially parasitic young stages use non-visual, non-tactile cues to infiltrate and supplant the brood in ant societies. Although indistinguishable morphologically or when using current mitochondrial and nuclear sequence-, or microsatellite data, Maculinea rebeli from Spain and southeast Poland exploit different Myrmica ant species and experience 100 per cent mortality with each other’s hosts. This reflects major differences in the hydrocarbons synthesized from each region by the larvae, which so closely mimic the recognition profiles of their respective hosts that nurse ants afford each parasite a social status above that of their own kin larvae. The two host ants occupy separate niches within grassland; thus, conservation management must differ in each region. Similar cryptic differentiation may be common, yet equally hard to detect, among the approximately 10 000 unstudied morpho-species of social parasite that are estimated to exist, many of which are Red Data Book listed

Adipocyte iron regulates adiponectin and insulin sensitivity

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores