Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer

Recently, we identified recurrent gene fusions involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers. Whereas TMPRSS2-ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 5' fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA-PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 5' fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer.     

The human footprint in the carbon cycle of temperate and boreal forests

Temperate and boreal forests in the Northern Hemisphere cover an area of about 2 x 10(7) square kilometres and act as a substantial carbon sink (0.6-0.7 petagrams of carbon per year). Although forest expansion following agricultural abandonment is certainly responsible for an important fraction of this carbon sink activity, the additional effects on the carbon balance of established forests of increased atmospheric carbon dioxide, increasing temperatures, changes in management practices and nitrogen deposition are difficult to disentangle, despite an extensive network of measurement stations. The relevance of this measurement effort has also been questioned, because spot measurements fail to take into account the role of disturbances, either natural (fire, pests, windstorms) or anthropogenic (forest harvesting). Here we show that the temporal dynamics following stand-replacing disturbances do indeed account for a very large fraction of the overall variability in forest carbon sequestration. After the confounding effects of disturbance have been factored out, however, forest net carbon sequestration is found to be overwhelmingly driven by nitrogen deposition, largely the result of anthropogenic activities. The effect is always positive over the range of nitrogen deposition covered by currently available data sets, casting doubts on the risk of widespread ecosystem nitrogen saturation under natural conditions. The results demonstrate that mankind is ultimately controlling the carbon balance of temperate and boreal forests, either directly (through forest management) or indirectly (through nitrogen deposition).     

Evidence for an ancient martian ocean in the topography of deformed shorelines

A suite of observations suggests that the northern plains of Mars, which cover nearly one third of the planet's surface, may once have contained an ocean. Perhaps the most provocative evidence for an ancient ocean is a set of surface features that ring the plains for thousands of kilometres and that have been interpreted as a series of palaeoshorelines of different age. It has been shown, however, that topographic profiles along the putative shorelines contain long-wavelength trends with amplitudes of up to several kilometres, and these trends have been taken as an argument against the martian shoreline (and ocean) hypothesis. Here we show that the long-wavelength topography of the shorelines is consistent with deformation caused by true polar wander--a change in the orientation of a planet with respect to its rotation pole--and that the inferred pole path has the geometry expected for a true polar wander event that postdates the formation of the massive Tharsis volcanic rise.     

Low Atlantic hurricane activity in the 1970s and 1980s compared to the past 270 years

Hurricane activity in the North Atlantic Ocean has increased significantly since 1995 (refs 1, 2). This trend has been attributed to both anthropogenically induced climate change and natural variability, but the primary cause remains uncertain. Changes in the frequency and intensity of hurricanes in the past can provide insights into the factors that influence hurricane activity, but reliable observations of hurricane activity in the North Atlantic only cover the past few decades. Here we construct a record of the frequency of major Atlantic hurricanes over the past 270 years using proxy records of vertical wind shear and sea surface temperature (the main controls on the formation of major hurricanes in this region) from corals and a marine sediment core. The record indicates that the average frequency of major hurricanes decreased gradually from the 1760s until the early 1990s, reaching anomalously low values during the 1970s and 1980s. Furthermore, the phase of enhanced hurricane activity since 1995 is not unusual compared to other periods of high hurricane activity in the record and thus appears to represent a recovery to normal hurricane activity, rather than a direct response to increasing sea surface temperature. Comparison of the record with a reconstruction of vertical wind shear indicates that variability in this parameter primarily controlled the frequency of major hurricanes in the Atlantic over the past 270 years, suggesting that changes in the magnitude of vertical wind shear will have a significant influence on future hurricane activity.     

An arid-adapted middle Pleistocene vertebrate fauna from south-central Australia

How well the ecology, zoogeography and evolution of modern biotas is understood depends substantially on knowledge of the Pleistocene. Australia has one of the most distinctive, but least understood, Pleistocene faunas. Records from the western half of the continent are especially rare. Here we report on a diverse and exceptionally well preserved middle Pleistocene vertebrate assemblage from caves beneath the arid, treeless Nullarbor plain of south-central Australia. Many taxa are represented by whole skeletons, which together serve as a template for identifying fragmentary, hitherto indeterminate, remains collected previously from Pleistocene sites across southern Australia. A remarkable eight of the 23 Nullarbor kangaroos are new, including two tree-kangaroos. The diverse herbivore assemblage implies substantially greater floristic diversity than that of the modern shrub steppe, but all other faunal and stable-isotope data indicate that the climate was very similar to today. Because the 21 Nullarbor species that did not survive the Pleistocene were well adapted to dry conditions, climate change (specifically, increased aridity) is unlikely to have been significant in their extinction.