A Cretaceous carbonate delta drift in the Montagna della Maiella, Italy

The Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is compared to newly discovered contourite drifts in the Maldives. Like the drift deposits in the Maldives, the Orfento Formation fills a channel and builds a Miocene delta-shaped and mounded sedimentary body in the basin that is similar in size to the approximately 350 km 2 large coarse-grained bioclastic Miocene delta drifts in the Maldives. The composition of the bioclastic wedge of the Orfento Formation is also exclusively bioclastic debris sourced from the shallow-water areas and reworked clasts of the Orfento Formation itself. In the near mud-free succession, age-diagnostic fossils are sparse. The depositional textures vary from wackestone to float-rudstone and breccia/conglomerates, but rocks with grainstone and rudstone textures are the most common facies. In the channel, lensoid convex-upward breccias, cross-cutting channelized beds and thick grainstone lobes with abundant scours indicate alternating erosion and deposition from a high-energy current. In the basin, the mounded sedimentary body contains lobes with a divergent progradational geometry. The lobes are built by decametre thick composite megabeds consisting of sigmoidal clinoforms that typically have a channelized topset, a grainy foreset and a fine-grained bottomset with abundant irregular angular clasts. Up to 30 m thick channels filled with intraformational breccias and coarse grainstones pinch out downslope between the megabeds. In the distal portion of the wedge, stacked grainstone beds with foresets and reworked intraclasts document continuous sediment reworking and migration. The bioclastic wedge of the Orfento Formation has been variously interpreted as a succession of sea-level controlled slope deposits, a shoaling shoreface complex, or a carbonate tidal delta. Current-controlled delta drifts in the Maldives, however, offer a new interpretation because of their similarity in architecture and composition. These similarities include: (i) a feeder channel opening into the basin; (ii) an excavation moat at the exit of the channel; (iii) an overall mounded geometry with an apex that is in shallower water depth than the source channel; (iv) progradation of stacked lobes; (v) channels that pinch out in a basinward direction; and (vi) smaller channelized intervals that are arranged in a radial pattern. As a result, the Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is here interpreted as a carbonate delta drift

Morphology of the earliest reconstructable tetrapod Parmastega aelidae.

The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments1-15. The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles2,4,16-34. All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments5,10, and nearly 30 million years younger than the oldest known tetrapod footprints35. Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods

The soluble guanylyl cyclase inhibitor NS-2028 reduces vascular endothelial growth factor-induced angiogenesis and permeability

Nitric oxide (NO) is known to promote vascular endothelial growth factor (VEGF)-stimulated permeability and angiogenesis. However, effector molecules that operate downstream of NO in this pathway remain poorly characterized. Herein, we determined the effect of soluble guanylyl cyclase (sGC) inhibition on VEGF responses in vitro and in vivo. Treatment of endothelial cells (EC) with VEGF stimulated eNOS phosphorylation and cGMP accumulation; pretreatment with the sGC inhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS-2028) blunted cGMP levels without affecting VEGF-receptor phosphorylation. Incubation of cells with NS-2028 blocked the mitogenic effects of VEGF. In addition, cells in which sGC was inhibited exhibited no migration and sprouting in response to VEGF. To study the mechanisms through which NS-2028 inhibits EC migration, we determined the effects of alterations in cGMP levels on p38 MAPK. Initially, we observed that inhibition of sGC attenuated VEGF-stimulated activation of p38. In contrast, the addition of 8-Br-cGMP to EC stimulated p38 phosphorylation. The addition of cGMP elevating agents (BAY 41-2272, DETA NO and YC-1) enhanced EC migration. To test whether sGC also mediated the angiogenic effects of VEGF in vivo, we used the rabbit cornea assay. Animals receiving NS-2028 orally displayed a reduced angiogenic response to VEGF. As increased vascular permeability occurs prior to new blood vessel formation, we determined the effect of NS-2028 in vascular leakage. Using a modified Miles assay, we observed that NS-2028 attenuated VEGF-induced permeability. Overall, we provide evidence that sGC mediates the angiogenic and permeability-promoting activities of VEGF, indicating the significance of sGC as a downstream effector of VEGF-triggered responses