Shale Reservoir 3D Structural Modeling Using Horizontal Well Data: Main Issues and an Improved Method

Shale oil and gas fields usually contain many horizontal wells. The key of 3D structural modeling for shale reservoirs is to effectively utilize all structure-associated data (e.g., formation tops) in these horizontal wells. The inclination angle of horizontal wells is usually large, especially in the lateral section. As a result, formation tops in a horizontal well are located at the distinct lateral positions, while formation tops in a vertical well are usually stacked in the same or similar lateral position. It becomes very challenging to estimate shale layer thickness and structural map of multiple formation surfaces using formation tops in horizontal wells. Meanwhile, the large inclination angle of horizontal wells indicates a complicated spatial relation with shale formation surfaces. The 3D structural modeling using horizontal well data is much more difficult than that using vertical well data. To overcome these new challenges in 3D structural modeling using horizontal well data, we developed a method for 3D structural modeling using horizontal well data. The main process included 1) adding pseudo vertical wells at formation tops to convert the uncoupled formation tops to coupled formation tops as in vertical wells, 2) estimating shale thickness by balancing the shale thickness and dip angle change of a key surface, and 3) detecting horizontal well segments landing in the wrong formations and adding pseudo vertical wells to fix them. We used our improved method to successfully construct two structural models of Longmaxi–Wufeng shale reservoirs at a well pad scale and a shale oil/gas field scale. Our research demonstrated that 3D structural modeling could be improved by maximizing the utilization of horizontal well data, thus optimizing the quality of the structural model of shale reservoirs.

RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion

Cdc42-GTP is required for apical domain formation in epithelial cells, where it recruits and activates the Par-6–aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically is unclear. We used sequence analysis and 3D structural modeling to determine which Drosophila GTPase-activating proteins (GAPs) are likely to interact with Cdc42 and identified RhoGAP19D as the only high-probability Cdc42GAP required for polarity in the follicular epithelium. RhoGAP19D is recruited by α-catenin to lateral E-cadherin adhesion complexes, resulting in exclusion of active Cdc42 from the lateral domain. rhogap19d mutants therefore lead to lateral Cdc42 activity, which expands the apical domain through increased Par-6/aPKC activity and stimulates lateral contractility through the myosin light chain kinase, Genghis khan (MRCK). This causes buckling of the epithelium and invasion into the adjacent tissue, a phenotype resembling that of precancerous breast lesions. Thus, RhoGAP19D couples lateral cadherin adhesion to the apical localization of active Cdc42, thereby suppressing epithelial invasion.

Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia

Background Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. Methods To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. Results Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. Conclusions The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.

A MATE Transporter is Involved in Pathogenicity and IAA Homeostasis in the Hyperplastic Plant Pathogen Pseudomonas savastanoi pv. nerii

During the last years, many evidences have been accumulating about the phytohormone indole-3-acetic acid (IAA) as a multifaceted compound in the microbial world, with IAA playing a role as a bacterial intra and intercellular signaling molecule or as an effector during pathogenic or beneficial plant–bacteria interactions. However, pretty much nothing is known on the mechanisms that bacteria use to modulate IAA homeostasis, in particular on IAA active transport systems. Here, by an approach combining in silico three-dimensional (3D) structural modeling and docking, mutagenesis, quantitative gene expression analysis, and HPLC FLD auxin quantitative detection, for the first time a bacterial multidrug and toxic compound extrusion (MATE) transporter was demonstrated to be involved in the efflux of IAA, as well as of its conjugate IAA–Lysine, in the plant pathogenic hyperplastic bacterium Pseudomonas savastanoi pv. nerii strain Psn23. Furthermore, according to the role proved to be played by Psn23 MatE in the development of plant disease, and to the presence of Psn23 MatE homologs in all the genomospecies of the P. syringae complex, this membrane transporter could likely represent a promising target for the design of novel and selective anti-infective molecules for plant disease control.

Extended Cleavage Specificities of Rabbit and Guinea Pig Mast Cell Chymases: Two Highly Specific Leu-Ases

Serine proteases constitute the major protein content of mast cell (MC) secretory granules. These proteases can generally be subdivided into chymases and tryptases based on their primary cleavage specificity. Here, we presented the extended cleavage specificities of a rabbit β-chymase and a guinea pig α-chymase. Analyses by phage display screening and a panel of recombinant substrates showed a marked similarity in catalytic activity between the enzymes, both being strict Leu-ases (cleaving on the carboxyl side of Leu). Amino acid sequence alignment of a panel of mammalian chymotryptic MC proteases and 3D structural modeling identified an unusual residue in the rabbit enzyme at position 216 (Thr instead of more common Gly), which is most likely critical for the Leu-ase specificity. Almost all mammals studied, except rabbit and guinea pig, express classical chymotryptic enzymes with similarly extended specificities, indicating an important role of chymase in MC biology. The rabbit and guinea pig are the only two mammalian species currently known to lack a classical MC chymase. Key questions are now how this major difference affects their MC function, and if genes of other loci can rescue the loss of a chymotryptic activity in MCs of these two species.

Micro-machined silicon accelerometer with piezoresistive SCR implementation for glucolysis

Micro-Electro-Mechanical Systems (MEMS) noted as micro generation have grown to advance greater than in previous decades. This venture reports approximately the silicon-based piezoresistive (PZR) microcantilever for glucose sensing. Elevated sensitivity, highest operation collection, extensive frequency reaction, excessive resolution, proper linearity are the majority preferred residences of the sensor. The displacement strain at specific limits, sensitivity and deformation is analyzed by means of finite element method for two exclusive structures. 3D structural modeling of three layers in micromechanical sensors may be achieved at ANSYS 14.5. In bio-medical request, adsorption of glucose on a functionalized exterior of the micro-fabricated cantilever will gather an exterior strain and therefore meander the cantilever beam. The cantilever meandering enhances the sensitivity of the microcantilevers sensor. Instead of capacitive accelerometer which produces changes in the seismic mass, the best method is PZR accelerometer that takes advantage of change in resistance and produces electrical output signal. The argument of the resolution problem in the study of a system for PZR detection technique with requirement of devices like Low pressure chemical vapor deposition (LPCVD) etc. is easily done by introducing stress concentrated region (SCR) which is considered as slot in the structure so that it enhances sensitivity of the device further higher. This technique is used for a sample, to detect and monitor glucose level and it produces simulation wrapping up in the microcantilever beam such as twist, pressure, injure and displacement.