Intra‐clinothem variability in sedimentary texture and process regime recorded down slope profiles

Shelf‐margin clinothem successions can archive process interactions at the shelf to slope transition, and their architecture provides constraints on the interplay of factors that control basin‐margin evolution. However, detailed textural analysis and facies distributions from shelf to slope transitions remain poorly documented. This study uses quantitative grain‐size and sorting data from coeval shelf and slope deposits of a single clinothem that crops out along a 5 km long, dip‐parallel transect of the Eocene Sobrarbe Deltaic Complex (Ainsa Basin, south‐central Pyrenees, Spain). Systematic sampling of sandstone beds tied to measured sections has captured vertical and basinward changes in sedimentary texture and facies distributions at an intra‐clinothem scale. Two types of hyperpycnal flow‐related slope deposits, both rich in mica and terrestrial organic matter, are differentiated according to grain size, sorting and bed geometry: (i) sustained hyperpycnal flow deposits, which are physically linked to coarse channelized sediments in the shelf setting and which deposit sand down the complete slope profile; (ii) episodic hyperpycnal flow deposits, which are disconnected from, and incise into, shelf sands and which are associated with sediment bypass of the proximal slope and coarse‐grained sand deposition on the medial and distal slope. Both types of hyperpycnites are interbedded with relatively homogenous, organic‐free and mica‐free, well‐sorted, very fine‐grained sandstones, which are interpreted to be remobilized from wave‐dominated shelf environments; these wave‐dominated deposits are found only on the proximal and medial slope. Coarse‐grained sediment bypass into the deeper‐water slope settings is therefore dominated by episodic hyperpycnal flows, whilst sustained hyperpycnal flows and turbidity currents remobilizing wave‐dominated shelf deposits are responsible for the full range of grain sizes in the proximal and medial slope, thus facilitating clinoform progradation. This novel dataset highlights previously undocumented intra‐clinothem variability related to updip changes in the shelf process‐regime, which is therefore a key factor controlling downdip architecture and resulting sedimentary texture

Cleavage of the urokinase receptor (uPAR) on oral cancer cells : regulation by transforming growth factor - beta 1 (TGF-beta 1) and potential effects on migration and invasion

Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - beta 1 (TGF-beta 1). The role of uPAR cleavage in cell proliferation and migration was analysed using real- time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-beta 1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF-beta 1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.Peer reviewe

Sedimentary response to the evolution of mobile substrates:Examples from offshore West Africa

Utilizing a regionally extensive 3D seismic volume from the deepwater region offshore West Africa, we present an interpretation of the variability of responses of slope channels to mobile substrate deformation on continental slopes. Within the study area, salt related deformation commenced in the Cretaceous and continues till present day. A series of NE-SW trending, structural dip parallel channel fairways, are initially positioned by elongate pre-Palaeogene salt-cored foldbelts and extensional faults. Typical dimensions of these elongate mini-basins are in the order of 50km length by 10km width. The ensuing interaction of submarine channels and salt structures through the Oligo-Miocene results in increasingly tortuous sediment pathways, blocking and confinement of submarine channel systems over length scales of 10's to 100 km and development of shadow zones devoid of sediment input.</p