Specific Grb2-mediated interactions regulate clathrin-dependent endocytosis of the cMet-tyrosine kinase

Lysosomal degradation of the receptor-tyrosine kinase cMet requires receptor ubiquitination by the E3 ubiquitin ligase Cbl followed by clathrin-dependent internalization. A role for Cbl as an adaptor for cMet internalization has been previously reported. However, the requirement for Cbl ubiquitin ligase activity in this process and its mode of recruitment to cMet has yet to be determined. Cbl can directly bind cMet at phosphotyrosine 1003 or indirectly via Grb2 to phosphotyrosine 1356 in the multisubstrate binding domain of cMet. The direct binding of Cbl with cMet is critical for receptor degradation and not receptor internalization. Here we show a strict requirement for Grb2 and the ubiquitin ligase activity of Cbl for cMet endocytosis. Receptor internalization was impaired by small interfering RNA depletion of Grb2, overexpression of dominant negative Grb2 mutants, and point mutations in the cMet multisubstrate docking site that inhibits the direct association of Grb2 with cMet. The requirement for Grb2 was specific and did not involve the multiadaptor Gab1. cMet internalization was impaired in cells expressing an ubiquitin ligase-deficient Cbl mutant or conjugation-deficient ubiquitin but was unaffected in cells expressing a Cbl mutant that is unable to bind cMet directly. Expression of a Cbl-Grb2 chimera rescued impaired cMet endocytosis in cells depleted of endogenous Grb2. These results indicate that the ubiquitin ligase activity of Cbl is critical for clathrin-dependent cMet internalization and suggest a role for Grb2 as an intermediary linking Cbl ubiquitin ligase activity to this process

Modelling and Simulation of Heterogeneous and Anisotropic Formations using Advanced Fractal Reservoir Models

Energy and carbon-efficient exploitation, management, and remediation of subsurface aquifers, gas and oil resources, CO2-disposal sites, and energy storage reservoirs all require high quality modelling and simulation. The heterogeneity and anisotropy of such subsurface formations has always been a challenge to modellers, with the best current technology not being able to deal with variations at scales of less than about 30-50 m. Most formations exhibit heterogeneities and anisotropy which result in variations of the petrophysical properties controlling fluid flow down to millimetre scale and below. These variations are apparent in well-logs and core material, but cannot be characterised in the inter-well volume which makes up the great majority of the formation. This paper describes a new fractal approach to the modelling and simulation of heterogeneous and anisotropic aquifers and reservoirs. This approach includes data at all scales such that it can represent the heterogeneity of the reservoir correctly at each scale. Advanced Fractal Reservoir Models (AFRMs) in 3D can be produced using our code. These AFRMs can be used to model fluid flow in formations generically to understand the effects of an imposed degree of heterogeneity and anisotropy, or can be conditioned to match the characteristics of real aquifers and reservoirs. This paper will show how 3D AFRMs can be created such that they represent critical petrophysical parameters, as well as how fractal 3D porosity and permeability maps, synthetic poro-perm cross-plots, water saturation maps and relative permeability curves can all be calculated. It will also show how quantitative controlled variation of heterogeneity and anisotropy of generic models affects fluid flow. We also show how AFRMs can be conditioned to represent real reservoirs, and how they provide a much better simulated fluid flow than the current best technology. Results of generic modelling and simulation with AFRMs show how total hydrocarbon production, hydrocarbon production rate, water cut and the time to water breakthrough all depend strongly on heterogeneity, and also depend upon anisotropy. Modelling with different degrees and directions of anisotropy shows how critical hydrocarbon production data depends on the direction of the anisotropy, and how that changes over the lifetime of the reservoir. Advanced fractal reservoir models are of greatest utility if they can be conditioned to represent individual reservoirs. We have developed a method for matching AFRMs to aquifer and reservoir data across a wide range of scales that exceeds the range of scales currently used in such modelling. We show a hydrocarbon production case study which compares the hydrocarbon production characteristics of such an approach to a conventional krigging approach. The comparison shows that modelling of hydrocarbon production is appreciably improved when AFRMs are used, especially if heterogeneity and anisotropy are high. In this study AFRMs in moderate to high heterogeneity reservoirs always provided results within 5% of the reference case, while the conventional approach resulted in massive systematic underestimations of production rate by over 70%

Stratigraphic correlation and paleoenvironmental analysis of the hydrocarbon-bearing Early Miocene Euphrates and Jeribe formations in the Zagros folded-thrust belt

The Lower Miocene Euphrates and Jeribe formations are considered as the main targets of the Tertiary petroleum system in the western part of the Zagros Basin. The formations consist of carbonates with some evaporate intercalations of the Dhiban Formation. This study utilized data from a field investigation including newly described outcrop sections and newly discovered productive oil fields within the Kirkuk embayment zone of the Zagros fold and thrust belt such as Sarqala and Kurdamir wells. This work is the first to show a stratigraphic correlation and paleoenvironmental interpretation by investigating both well data and new outcrop data. Three depositional environments were identified, (1) an inner and outer ramp belts environment, (2) shoal environment, and (3) restricted lagoon environment. Within these 3 environments, 12 microfacies were identified, based on the distribution of fauna mainly benthonic foraminifera, rock textures, and sedimentary structures. The inferred shallow water depths and variable salinities in both the Euphrates Formation and Jeribe Formation carbonates are consistent with deposition on the inner ramp (restricted lagoon and shoal) environments. Those found in the Euphrates Formation constrained the depositional environment to the restricted lagoon and shoal environment, while the microfacies in the Jeribe Formation provided evidence for an inner ramp and middle to outer ramp belt environments. This study represents the first detailed research that focuses on the stratigraphic correlation and changes in carbonate facies with the main aim to provide a wider understanding of stratigraphy of these carbonate reservoirs throughout the northern part of Iraq

Ocean carbon from space: Current status and priorities for the next decade

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: Data for Fig. 1a were generated from a free Scopus (https://www.scopus.com/) search of the terms "Ocean carbon satellite" (using All fields) in March 2022. Data from Fig. 1b and 1c were generated from the workshop registration and are available within the figure (participation number, geographical representation and gender split).The ocean plays a central role in modulating the Earth’s carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and light. We also report on priorities for the specific pools and fluxes studied, and highlight issues and concerns that arose during discussions, such as the need to consider the environmental impact of satellites or space activities; the role satellites can play in monitoring ocean carbon dioxide removal approaches; economic valuation of the satellite based information; to consider how satellites can contribute to monitoring cycles of other important climatically-relevant compounds and elements; to promote diversity and inclusivity in ocean carbon research; to bring together communities working on different aspects of planetary carbon; maximising use of international bodies; to follow an open science approach; to explore new and innovative ways to remotely monitor ocean carbon; and to harness quantum computing. Overall, this paper provides a comprehensive scientific roadmap for the next decade on how satellite remote sensing could help monitor the ocean carbon cycle, and its links to the other domains, such as terrestrial and atmosphere.European Space AgencySimons FoundationUK National Centre for Earth Observation (NCEO)UKRIAtlantic Meridional Transect ProgrammeSwiss National Science Foundatio