Roles of B Cell-Intrinsic TLR Signals in Systemic Lupus Erythematosus

Toll-like receptors (TLRs) are a large family of pattern recognition receptors. TLR signals are involved in the pathogenesis of systemic lupus erythematosus. Mouse and human B cells constitutively express most TLRs. Many B cell subpopulations are highly responsive to certain TLR ligation, including B-1 B cells, transitional B cells, marginal zone B cells, germinal center B cell and memory B cells. The B cell-intrinsic TLR signals play critical roles during lupus process. In this review, roles of B cell-intrinsic TLR2, 4, 7, 8 and 9 signals are discussed during lupus pathogenesis in both mouse model and patients. Moreover, mechanisms underlying TLR ligation-triggered B cell activation and signaling pathways are highlighted.published_or_final_versio

Research on stress sensitivity of fractured carbonate reservoirs based on CT technology

Fracture aperture change under stress has long been considered as one of primary causes of stress sensitivity of fractured gas reservoirs. However, little is known about the evolution of the morphology of fracture apertures on flow property in loading and unloading cycles. This paper reports a stress sensitivity experiment on carbonate core plugs in which Computed Tomography (CT) technology is applied to visualize and quantitatively evaluate morphological changes to the fracture aperture with respect to confining pressure. Fracture models were obtained at selected confining pressures on which pore-scale flow simulations were performed to estimate the equivalent absolute permeability. The results showed that with the increase of confining pressure from 0 to 0.6 MPa, the fracture aperture and equivalent permeability decreased at a greater gradient than their counterparts after 0.6 MPa. This meant that the rock sample is more stress-sensitive at low effective stress than at high effective stress. On the loading path, an exponential fitting was found to fit well between the effective confining pressure and the calculated permeability. On the unloading path, the relationship is found partially reversible, which can evidently be attributed to plastic deformation of the fracture as observed in CT images

Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis

Figure S1. The pathway flux (J) in the in vitro system when one enzyme concentration was increased. (A) The pathway flux when purified ThrA was added to the crude enzyme extract. (B) The pathway flux when purified Asd was added to the crude enzyme extract. (C) The pathway flux when purified ThrB was added to the crude enzyme extract. (D) The pathway flux when purified ThrC was added to the crude enzyme extract

Flow simulation of artificially induced microfractures using digital rock and lattice boltzmann methods

Microfractures have great significance in the study of reservoir development because they are an effective reserving space and main contributor to permeability in a large amount of reservoirs. Usually, microfractures are divided into natural microfractures and induced microfractures. Artificially induced rough microfractures are our research objects, the existence of which will affect the fluid-flow system (expand the production radius of production wells), and act as a flow path for the leakage of fluids injected to the wells, and even facilitate depletion in tight reservoirs. Therefore, the characteristic of the flow in artificially induced fractures is of great significance. The Lattice Boltzmann Method (LBM) was used to calculate the equivalent permeability of artificially induced three-dimensional (3D) fractures. The 3D box fractal dimensions and porosity of artificially induced fractures in Berea sandstone were calculated based on the fractal theory and image-segmentation method, respectively. The geometrical parameters (surface roughness, minimum fracture aperture, and mean fracture aperture), were also calculated on the base of digital cores of fractures. According to the results, the permeability lies between 0.071–3.759 (dimensionless LB units) in artificially induced fractures. The wide range of permeability indicates that artificially induced fractures have complex structures and connectivity. It was also found that 3D fractal dimensions of artificially induced fractures in Berea sandstone are between 2.247 and 2.367, which shows that the artificially induced fractures have the characteristics of self-similarity. Finally, the following relations were studied: (a) exponentially increasing permeability with increasing 3D box fractal dimension, (b) linearly increasing permeability with increasing square of mean fracture aperture, (c) indistinct relationship between permeability and surface roughness, and (d) linearly increasing 3D box fractal dimension with increasing porosity

Pore-scale remaining oil distribution under different pore volume water injection based on CT technology

A water-injection experiment was performed on a water-wet reservoir core plug that was filled with brine first and then displaced by synthetic oil. A X-ray Computed Tomography was used to take snapshots of the process of oil-water displacement at predefined time intervals to characterize the distribution of remaining oil. The quasi-real time images were used to understand the pore-scale phase displacement mechanisms and the distributional pattern of the remaining oil. Four forms of the distributional patterns, i.e. network, porous, isolated and film shape, were observed and analyzed with respect to the injected pore volumes (PV). The results show that with the increased level of water injection, the volume of the oil phase continuously decreases, and the morphology of the oil phase changes from initial continuous network-like to film shape forms. At 15 PV, the network- like remaining oil disappears and transforms into isolated and film-like forms. The statistics of the volume for each form of the remaining oil show that the isolated blobs increase with increasing water injection, by contrast, the average volume of the remaining oil decreases with increasing water injection. The rate of volumetric changes is fast before 5 PV but slow in the later period.Cited as: Liu, Z., Yang, Y., Yao, J., et al. Pore-scale remaining oil distribution under different pore volume water injection based on CT technology. Advances in Geo-Energy Research, 2017, 1(3): 171-181, doi: 10.26804/ager.2017.03.0

Effects of extreme drought on plant nutrient uptake and resorption in rhizomatous vs bunch grass dominated grasslands

Both the dominance and the mass ratio hypotheses predict that plant internal nutrient cycling in ecosystems is determined by the dominant species within plant communities. We tested this hypothesis under conditions of extreme drought by assessing plant nutrient (N, P and K) uptake and resorption in response to experimentally imposed precipitation reductions in two semiarid grasslands of northern China. These two communities shared similar environmental conditions, but had different dominant species-one was dominated by a rhizomatous grass (Leymus chinensis) and the other by a bunchgrass (Stipa grandis). Results showed that responses of N to drought differed between the two communities with drought decreasing green leaf N concentration and resorption in the community dominated by the rhizomatous grass, but not in the bunchgrass-dominated community. In contrast, negative effects of drought on green leaf P and K concentrations and their resorption efficiencies were consistent across the two communities. Additionally, in each community, the effects of extreme drought on soil N, P and K supply did not change synchronously with that on green leaf N, P and K concentrations, and senesced leaf N, P and K concentrations showed no response to extreme drought. Consistent with the dominance/mass ratio hypothesis, our findings suggest that differences in dominant species and their growth form (i.e., rhizomatous vs bunch grass) play an important nutrient-specific role in mediating plant internal nutrient cycling across communities within a single region

Truncating Mutation in the Autophagy Gene \u3cem\u3eUVRAG\u3c/em\u3e Confers Oncogenic Properties and Chemosensitivity in Colorectal Cancers

Autophagy-related factors are implicated in metabolic adaptation and cancer metastasis. However, the role of autophagy factors in cancer progression and their effect in treatment response remain largely elusive. Recent studies have shown that UVRAG, a key autophagic tumour suppressor, is mutated in common human cancers. Here we demonstrate that the cancer-related UVRAG frameshift (FS), which does not result in a null mutation, is expressed as a truncated UVRAGFS in colorectal cancer (CRC) with microsatellite instability (MSI), and promotes tumorigenesis. UVRAGFS abrogates the normal functions of UVRAG, including autophagy, in a dominant-negative manner. Furthermore, expression of UVRAGFS can trigger CRC metastatic spread through Rac1 activation and epithelial-to-mesenchymal transition, independently of autophagy. Interestingly, UVRAGFS expression renders cells more sensitive to standard chemotherapy regimen due to a DNA repair defect. These results identify UVRAG as a new MSI target gene and provide a mechanism for UVRAG participation in CRC pathogenesis and treatment response

MiR-4319 Suppress the Malignancy of Triple-Negative Breast Cancer by Regulating Self-Renewal and Tumorigenesis of Stem Cells

Background/Aims: High levels of cancer stem cells (CSCs) in patients with triple-negative breast cancer (TNBC) correlate with risk of poor clinical outcome and possibly contribute to chemoresistance and metastasis in patients with highly malignant TNBC. Aberrant microRNA expression is associated with the dysfunction of self-renewal and proliferation in cancer stem cells, while there is little information about the TNBC-specific microRNAs in regulating CSC ability. Methods: Solexa deep sequencing was performed to detect the expression levels of TNBC or non-TNBC stem cells (CSCs) microRNAs. Mammosphere formation assay, qRT-PCR and the xenograft model in nude mice were performed. Bioinformatic analysis and microarray were used to select the target gene, and luciferase reporter assays were used to confirm the binding sites. Results: Solexa sequencing data exhibited differential expression of 193 microRNAs between TNBC and non-TNBC stem cells. The gene ontology analysis and pathways analyses showed that genes were involved in the maintenance of stemness. MiR-4319 could suppress the self-renewal and formation of tumorspheres in TNBC CSCs through E2F2, and also inhibited tumor initiation and metastasis in vivo. Moreover, increased E2F2 could reverse the effect of miR-4319 on the self-renewal in TNBC CSCs. Conclusions: MiR-4319 suppresses the malignancy of TNBC by regulating self-renewal and tumorigenesis of stem cells and might be a remarkable prognostic factor or therapeutic target for patients with TNBC