The Four Canonical TPR Subunits of Human APC/C Form Related Homo-Dimeric Structures and Stack in Parallel to Form a TPR Suprahelix

AbstractThe anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for >80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23Nterm). Cdc23Nterm is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23Nterm structure, we generated a model of full-length Cdc23. The resultant “V”-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes

Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state.

Funder: Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre); doi: https://doi.org/10.13039/501100007202Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790DOCK (dedicator of cytokinesis) proteins are multidomain guanine nucleotide exchange factors (GEFs) for RHO GTPases that regulate intracellular actin dynamics. DOCK proteins share catalytic (DOCKDHR2) and membrane-associated (DOCKDHR1) domains. The structurally-related DOCK1 and DOCK2 GEFs are specific for RAC, and require ELMO (engulfment and cell motility) proteins for function. The N-terminal RAS-binding domain (RBD) of ELMO (ELMORBD) interacts with RHOG to modulate DOCK1/2 activity. Here, we determine the cryo-EM structures of DOCK2-ELMO1 alone, and as a ternary complex with RAC1, together with the crystal structure of a RHOG-ELMO2RBD complex. The binary DOCK2-ELMO1 complex adopts a closed, auto-inhibited conformation. Relief of auto-inhibition to an active, open state, due to a conformational change of the ELMO1 subunit, exposes binding sites for RAC1 on DOCK2DHR2, and RHOG and BAI GPCRs on ELMO1. Our structure explains how up-stream effectors, including DOCK2 and ELMO1 phosphorylation, destabilise the auto-inhibited state to promote an active GEF

Essays in Financial Economics

This dissertation explores the applications of information economics in finance. How does an entrepreneur raise capital from investors with heterogeneous priors? The first chapter shows that when a secondary market exists, a price bubble arises and provides an incentive for the entrepreneur to manipulate investors’ beliefs through strategic communication. Under mild conditions, the amount of information disclosed decreases in disagreement. Without a secondary market, the price bubble vanishes, and the entrepreneur discloses more information. This chapter also discusses applications to emerging capital-raising methods, in particular initial coin offerings, and the regulatory implications for policymakers. In general, a regulator’s commitment power is necessary for implementing the optimal transparency policy in the financial system. The literature points out that lack of commitment power leads to excess opacity if investors additionally observe a sufficiently precise signal. Instead, the second chapter shows that an equilibrium featuring excess transparency always exists and survives natural refinements under certain conditions. Moreover, the optimal transparency policy and if the regulator needs commitment power to implement it are sensitive to the exogenous information structure

Paleoenvironment and Organic Matter Accumulation Mechanism of Marine–Continental Transitional Shales: Outcrop Characterizations of the Carboniferous–Permian Strata, Ordos Basin, North China

In the Carboniferous–Permian period, several organic-rich black shales were deposited in a marine–continental transitional environment in the Linfen area on the eastern margin of the Ordos Basin. Integrated sedimentological and organic geochemical analyses are performed on an outcrop in order to clarify the relationship between paleoenvironment and organic matter accumulation. The results of this study show that the marine–continental transitional strata of the Upper Carboniferous Benxi Formation to Lower Permian Taiyuan and Shanxi Formation exposed in the Linfen area are composed of sandstone, shale, coal, and limestone. Total organic carbon (TOC) contents of the studied samples were mainly distributed in the range of 0.59%–35.4%, with an average of 7.32%. From Benxi Formation to Shanxi formation, the humidity gradually increased, and the climate gradually changed from hot and humid to warm and humid during Carboniferous to Permian. The deposition of the Shanxi Formation ended with the climate returning to hot and humid, having an oxic-suboxic conditions and a high paleoproductivity. Paleoredox conditions and paleoproductivity are the two vital factors controlling the formation of organic matter in black shales. The transitional environment characterized by oxic-suboxic, relatively high deposition rate, and various source of organic matter, although different from the marine environment, provides a good material basis for the deposition of organic-rich shales

Quantitative characterization of sandstone amalgamation and its impact on reservoir connectivity

Taking turbidite lobe deposits as an example, the types and formation mechanisms of sandstone amalgamation were discussed, the indications of sandstone amalgamations to sedimentary environment and stacking pattern of sand bodies were investigated, and “amalgamation ratio” was employed to quantitatively describe the degree of sandstone amalgamation. Sandstone amalgamation is a common sedimentological phenomenon in sand/mud dominated clastic deposits, which generally consists of two processes: erosion of inter-sand mudstone barriers and amalgamation of sandstone beds which were previously separated by the mudstone barriers. Statistics analysis suggests that amalgamation ratio varies greatly in different hierarchical levels. Based on these analyses, three sets of conceptual 3D lobe models with identical NTG (net to gross ratio) and bed sizes but different hierarchies and different amalgamation ratio using an object-based modeling approach. Static connectivity analysis of these models suggests that the more the hierarchical levels involved, the worse connectivity the model has; for models with identical hierarchical settings, the higher the amalgamation ratio, the better the connectivity. Key words: sandstone amalgamation, turbidity lobes, sandstone connectivity, reservoir modelin

Hierarchical parameterization and compression-based object modelling of high net: gross but poorly amalgamated deep-water lobe deposits

Deepwater lobe deposits are arranged hierarchically and can be characterized by high net:gross ratios but poor sand connectivity due to thin but laterally extensive shale layers. This heterogeneity makes them difficult to represent in standard full-field object-based models, since the sands in an object-based model are not stacked compensationally and become connected at a low net:gross ratio. The compression algorithm allows generation of low connectivity object-based models at high net:gross ratios, by including the net: gross and amalgamation ratios as independent input parameters. Object-based modelling constrained by the compression algorithm has been included in a recursive workflow, permitting generation of realistic models of hierarchical lobe deposits. Representative dimensional and stacking parameters collected at four different hierarchical levels have been used to constrain a 250 m thick, 14 km2 model that includes hierarchical elements ranging from 20 cm thick sand beds to 30+ m thick lobe complexes. Sand beds and the fine-grained units are represented explicitly in the model, and the characteristic facies associations often used to parameterize lobe deposits are emergent from the modelling process. The model is subsequently resampled without loss of accuracy for flow simulation, and results show clearly the influence of the hierarchical heterogeneity on drainage and sweep efficiency during a water-flood simulation.University College DublinPIPCO RSG Ltd.FIFT II joint industry projectChina Scholarship CouncilUpdate citation details during checkdate report - A

Sequence Stratigraphy, Sedimentology, and Reservoir Characteristics of the Middle Cretaceous Mishrif Formation, South Iraq

The Cenomanian–Early Turonian Mishrif Formation is a great contributor to oil production in Iraq. Integrating petrographic, mineralogical, and wireline logging data from 52 wells, this study provides an improved understanding of the sequence stratigraphy, depositional evolution, and reservoir characteristics of the Mishrif Formation in the Mesopotamian Basin, south Iraq. Five types of facies associations are classified: lagoon, shoal, rudist bioherm, shallow marine, and deep marine. Such a classification allows convenient differentiation and interpretation of wireline logs. A sequence stratigraphic framework including five third-order sequences (Mhf 1 to Mhf 5) for the Mishrif Formation is established mainly using wireline logging data of close-distance wells, with the aid of cores and thin sections. Two end-member depositional evolution stages are recognized, from clinoform-like progradational shoal complexes in Mhf 1 within a shallow marine environment, to tidal channels in Mhf 2–3 within a lagoon environment. For Mhf 4–5, abrupt changes in facies associations from north to south indicate the development of an intra-shelf basin where organic-rich mudstones directly overlie the shallow marine grainstone shoals and lagoonal wackestones. Reservoir characteristics and compartmentalization are directly controlled by the sequence stratigraphic framework. Sequence boundaries are featured by wackestones and mudstones overprinted by cementation; they are regionally correlatable and work as regional barriers. Shoal complexes in Mhf 1 and tidal channels in Mhf 2–3 are the main reservoir units. Mudstones and wackestones are intra-reservoir baffles and become more frequently developed towards the south, reflecting the increasing water depth towards south. The characterization of the tidal channels, clinoform-like shoals, and intrashelf basinal deposits in the current study could benefit later development of the Mishrif Formation

A Big Data Method Based on Random BP Neural Network and Its Application for Analyzing Influencing Factors on Productivity of Shale Gas Wells

In recent years, big data and artificial intelligence technology have developed rapidly and are now widely used in fields of geophysics, well logging, and well test analysis in the exploration and development of oil and gas. The development of shale gas requires a large number of production wells, so big data and artificial intelligence technology have inherent advantages for evaluating the productivity of gas wells and analyzing the influencing factors for a whole development block. To this end, this paper combines the BP neural network algorithm with random probability analysis to establish a big data method for analyzing the influencing factors on the productivity of shale gas wells, using artificial intelligence and in-depth extraction of relevant information to reduce the unstable results from single-factor statistical analysis and the BP neural network. We have modeled and analyzed our model with a large amount of data. Under standard well conditions, the influences of geological and engineering factors on the productivity of a gas well can be converted to the same scale for comparison. This can more intuitively and quantitatively reflect the influences of different factors on gas well productivity. Taking 100 production wells in the Changning shale gas block as a case, random BP neural network analysis shows that maximum EUR can be obtained when a horizontal shale gas well has a fracture coefficient of 1.6, Type I reservoir of 18 m thick, optimal horizontal section of 1600 m long, and 20 fractured sections

The geochemical and pore characteristics of a typical marine–continental​ transitional gas shale: A case study of the Permian Shanxi Formation on the eastern margin of the Ordos Basin

The marine–continental transitional Permian Shanxi Formation, which is located on the eastern margin of the Ordos Basin, is expected to be another set of economic gas shale for exploration and development in China. In this study, geochemical methods, low-pressure gas adsorption, high-pressure mercury intrusion, and field emission scanning electron microscopy (FE-SEM) imaging were performed to investigate the pore structure characteristics of the second member of the Permian Shanxi gas shale. The results show that the average TOC content of the shale is 5.90%, the average thermal maturity is 2.22% Ro, and these organic-rich shales are enriched in clay minerals. Mesopores are the predominant pore type in these shales, and have slit-like shapes. FE-SEM analysis reveals that the interparticle pores associated with clay minerals are more developed than organic-hosted pores, while a few SEM-invisible micropores may be related to the aromatic structures of kerogen in the shale. Pore development in the studied samples is influenced by the TOC and clay mineral contents. The development of organic-hosted pores in the shale shows obvious differences when compared to representative marine gas shales worldwide, which are ascribed to the differences in kerogen types. Nevertheless, the development of micropores and mesopores in the samples is comparable to that of marine shales, which indicates the presence of qualified space for gas storage in the studied shale. This study will provide crucial theoretical guidance for determining of sweet spots and for the further exploration and development of the transitional shale gas