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.     

Sequence- and target-independent angiogenesis suppression by siRNA via TLR3

Clinical trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular degeneration, are premised on gene silencing by means of intracellular RNA interference (RNAi). We show instead that CNV inhibition is a siRNA-class effect: 21-nucleotide or longer siRNAs targeting non-mammalian genes, non-expressed genes, non-genomic sequences, pro- and anti-angiogenic genes, and RNAi-incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off-target RNAi or interferon-alpha/beta activation. Non-targeted (against non-mammalian genes) and targeted (against Vegfa or Vegfr1) siRNA suppressed CNV via cell-surface toll-like receptor 3 (TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin-12. Non-targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA-induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2:1 TLR3-RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA-induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects.