Cortactin Phosphorylated by ERK1/2 Localizes to Sites of Dynamic Actin Regulation and Is Required for Carcinoma Lamellipodia Persistence

Tumor cell motility and invasion is governed by dynamic regulation of the cortical actin cytoskeleton. The actin-binding protein cortactin is commonly upregulated in multiple cancer types and is associated with increased cell migration. Cortactin regulates actin nucleation through the actin related protein (Arp)2/3 complex and stabilizes the cortical actin cytoskeleton. Cortactin is regulated by multiple phosphorylation events, including phosphorylation of S405 and S418 by extracellular regulated kinases (ERK)1/2. ERK1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the Arp2/3 regulator neuronal Wiskott-Aldrich syndrome protein (N-WASp), promoting actin polymerization and enhancing tumor cell movement.In this report we have developed phosphorylation-specific antibodies against phosphorylated cortactin S405 and S418 to analyze the subcellular localization of this cortactin form in tumor cells and patient samples by microscopy. We evaluated the interplay between cortactin S405 and S418 phosphorylation with cortactin tyrosine phosphorylation in regulating cortactin conformational forms by Western blotting. Cortactin is simultaneously phosphorylated at S405/418 and Y421 in tumor cells, and through the use of point mutant constructs we determined that serine and tyrosine phosphorylation events lack any co-dependency. Expression of S405/418 phosphorylation-null constructs impaired carcinoma motility and adhesion, and also inhibited lamellipodia persistence monitored by live cell imaging.Cortactin phosphorylated at S405/418 is localized to sites of dynamic actin assembly in tumor cells. Concurrent phosphorylation of cortactin by ERK1/2 and tyrosine kinases enables cells with the ability to regulate actin dynamics through N-WASp and other effector proteins by synchronizing upstream regulatory pathways, confirming cortactin as an important integration point in actin-based signal transduction. Reduced lamellipodia persistence in cells with S405/418A expression identifies an essential motility-based process reliant on ERK1/2 signaling, providing additional understanding as to how this pathway impacts tumor cell migration

The Geomechanics of CO2 Storage in Deep Sedimentary Formations

This paper provides a review of the geomechanics and modeling of geomechanics associated with geologic carbon storage (GCS), focusing on storage in deep sedimentary formations, in particular saline aquifers. The paper first introduces the concept of storage in deep sedimentary formations, the geomechanical processes and issues related with such an operation, and the relevant geomechanical modeling tools. This is followed by a more detailed review of geomechanical aspects, including reservoir stress-strain and microseismicity, well integrity, caprock sealing performance, and the potential for fault reactivation and notable (felt) seismic events. Geomechanical observations at current GCS field deployments, mainly at the In Salah CO2 storage project in Algeria, are also integrated into the review. The In Salah project, with its injection into a relatively thin, low-permeability sandstone is an excellent analogue to the saline aquifers that might be used for large scale GCS in parts of Northwest Europe, the U.S. Midwest, and China. Some of the lessons learned at In Salah related to geomechanics are discussed, including how monitoring of geomechanical responses is used for detecting subsurface geomechanical changes and tracking fluid movements, and how such monitoring and geomechanical analyses have led to preventative changes in the injection parameters. Recently, the importance of geomechanics has become more widely recognized among GCS stakeholders, especially with respect to the potential for triggering notable (felt) seismic events and how such events could impact the long-term integrity of a CO{sub 2} repository (as well as how it could impact the public perception of GCS). As described in the paper, to date, no notable seismic event has been reported from any of the current CO{sub 2} storage projects, although some unfelt microseismic activities have been detected by geophones. However, potential future commercial GCS operations from large power plants will require injection at a much larger scale. For such largescale injections, a staged, learn-as-you-go approach is recommended, involving a gradual increase of injection rates combined with continuous monitoring of geomechanical changes, as well as siting beneath a multiple layered overburden for multiple flow barrier protection, should an unexpected deep fault reactivation occur

Nudges and cultural variance: a note on Selinger and Whyte

Selinger and Whyte argue that Thaler and Sunstein are insufficiently sensitive to cultural variance in Nudge. I construct a taxonomy of the various roles that cultural variance may play in nudges. First, biases that are exploited in nudging may interact with features that are culturally specific. Second, cultures may be more or less susceptible to certain biases. Third, cultures may resolve conflicting biases in different ways. And finally, nudge may be enlisted for different aims in different cultures

Geological record of fluid flow and seismogenesis along an erosive subducting plate boundary

Tectonic erosion of the overriding plate by the downgoing slab isbelieved to occur at half the Earth’s subduction zones. In situinvestigation of the geological processes at active erosive marginsis extremely difficult owing to the deep marine environment andthe net loss of forearc crust to deeper levels in the subduction zone.Until now, a fossil erosive subduction channel—the shear zonemarking the plate boundary—has not been recognized in thefield, so that seismic observations have provided the only information on plate boundary processes at erosive margins. Here we show that a fossil erosive margin is preserved in the Northern Apennines of Italy. It formed during the Tertiary transition from oceanic subduction to continental collision, and was preserved by the late deactivation and fossilization of the plate boundary. The outcropping erosive subduction channel is 500m thick. It is representative of the first 5km of depth, with its deeper portions reaching 150 C. The fossil zone records several surprises. Two decollements were simultaneously active at the top and base of the subduction channel. Both deeper basal erosion and near-surface frontal erosion occurred. At shallow depths extension was a key deformation component within this erosive convergent plate boundary, and slip occurred without an observable fluid pressure cycle. At depths greater than about 3km a fluid cycle is clearly shown by the development of veins and the alternation of fast (co-seismic) and slow (inter-seismic) slip. In the deepest portions of the outcropping subduction channel, extension is finally overprinted by compressional structures. In modern subduction zones the onset of seismic activity is believed to occur at 150 C, but in the fossil channel the onset occurred at cooler palaeo-temperatures

Abnormal behavior of silica doped with small amounts of aluminum

Silica is the most abundant mineral in the crust of the Earth. It has been demonstrated that the aluminum concentration in silica plays a key role in determining many properties of silica-based components. Although the alumina-silica system has been intensely studied, the effect of very small amounts of aluminum on the structure and properties of silica remains unclear. We report results of first principles calculations showing that small amounts of aluminum could be metastable when located in the center of Si-O rings without breaking the silica network. In contrast, higher aluminum contents will result in the destruction of the Si-O bonds, leading to the formation of triclusters and a 4-, 5-, and 6-fold Al-O coordination, as observed in previous studies. Based on the silica structure obtained through geometric optimization, the properties of silica doped with small amounts of aluminum were calculated. The results can account for many ‘abnormal’ phenomena experimentally observed. The results benefit most areas such as geosciences, microelectronics, glass industry, and ceramic materials