Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia

Abstract Background Angiopoietin-2 (Ang-2), a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis) is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth. Methods Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors. Results After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor-BB (PDGF-BB) mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis. Conclusions Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration

Vitronectin Increases Vascular Permeability by Promoting VE-Cadherin Internalization at Cell Junctions

Cross-talk between integrins and cadherins regulates cell function. We tested the hypothesis that vitronectin (VN), a multi-functional adhesion molecule present in the extracellular matrix and plasma, regulates vascular permeability via effects on VE-cadherin, a critical regulator of endothelial cell (EC) adhesion.Addition of multimeric VN (mult VN) significantly increased VE-cadherin internalization in human umbilical vein EC (HUVEC) monolayers. This effect was blocked by the anti-α(V)β(3) antibody, pharmacological inhibition and knockdown of Src kinase. In contrast to mult VN, monomeric VN did not trigger VE-cadherin internalization. In a modified Miles assay, VN deficiency impaired vascular endothelial growth factor-induced permeability. Furthermore, ischemia-induced enhancement of vascular permeability, expressed as the ratio of FITC-dextran leakage from the circulation into the ischemic and non-ischemic hindlimb muscle, was significantly greater in the WT mice than in the Vn(-/-) mice. Similarly, ischemia-mediated macrophage infiltration was significantly reduced in the Vn(-/-) mice vs. the WT controls. We evaluated changes in the multimerization of VN in ischemic tissue in a mouse hindlimb ischemia model. VN plays a previously unrecognized role in regulating endothelial permeability via conformational- and integrin-dependent effects on VE-cadherin trafficking.These results have important implications for the regulation of endothelial function and angiogenesis by VN under normal and pathological conditions

Genome Physical Mapping of Polyploids: A BIBAC Physical Map of Cultivated Tetraploid Cotton, Gossypium hirsutum L

Polyploids account for approximately 70% of flowering plants, including many field, horticulture and forage crops. Cottons are a world-leading fiber and important oilseed crop, and a model species for study of plant polyploidization, cellulose biosynthesis and cell wall biogenesis. This study has addressed the concerns of physical mapping of polyploids with BACs and/or BIBACs by constructing a physical map of the tetraploid cotton, Gossypium hirsutum L. The physical map consists of 3,450 BIBAC contigs with an N50 contig size of 863 kb, collectively spanning 2,244 Mb. We sorted the map contigs according to their origin of subgenome, showing that we assembled physical maps for the A- and D-subgenomes of the tetraploid cotton, separately. We also identified the BIBACs in the map minimal tilling path, which consists of 15,277 clones. Moreover, we have marked the physical map with nearly 10,000 BIBAC ends (BESs), making one BES in approximately 250 kb. This physical map provides a line of evidence and a strategy for physical mapping of polyploids, and a platform for advanced research of the tetraploid cotton genome, particularly fine mapping and cloning the cotton agronomic genes and QTLs, and sequencing and assembling the cotton genome using the modern next-generation sequencing technology

Large-Scale Outdoor SLAM Based on 2D Lidar

For autonomous driving, it is important to navigate in an unknown environment. In this paper, we propose a fully automated 2D simultaneous localization and mapping (SLAM) system based on lidar working in large-scale outdoor environments. To improve the accuracy and robustness of the scan matching module, an improved Correlative Scan Matching (CSM) algorithm is proposed. For efficient place recognition, we design an AdaBoost based loop closure detection algorithm which can efficiently reject false loop closures. For the SLAM back-end, we propose a light-weight graph optimization algorithm based on incremental smoothing and mapping (iSAM). The performance of our system is verified on various large-scale datasets including our real-world datasets and the KITTI odometry benchmark. Further comparisons to the state-of-the-art approaches indicate that our system is competitive with established techniques

Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA

Abstract Background Currently, resistance to tyrosine kinase inhibitors, such as gefitinib, has become a major obstacle in improving the clinical outcome of patients with metastatic and advanced-stage esophageal squamous cell carcinoma (ESCC). While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the roles of lncRNAs within extracellular vesicles (exosomes) are largely unknown. Therefore, we investigated the involvement and regulatory functions of potential lncRNAs enclosed in exosomes during formation of chemoresistance in human ESCC. Methods Gefitinib-resistant cell lines were established by continuously grafting TE1 and KYSE-450 cells into gefitinib-containing culture medium. LncRNA microarray assay followed by RT-qPCR were used to verify the differential expression of lncRNA Prostate Androgen-Regulated Transcript 1 (PART1) between gefitinib resistant and parental cell lines. RNA fluorescence in situ hybridization (FISH) was used to investigate whether extracellular PART1 could be incorporated into exosomes and transmitted to recipient cells. Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of lncRNA PART1 in ESCC cells. A signal transduction reporter array, bioinformatics analysis, western blotting, and immunofluorescence were carried out to verify the regulation of PART1 and its downstream Bcl-2 signaling pathway. Results lncRNA PART1 was upregulated in gefitinib-resistant cells when compared to parental ESCC cells. It was found that STAT1 can bind to the promoter region of lncRNA PART1, resulting in its activation. Knockdown of lncRNA PART1 potently promoted the gefitinib-induced cell death, while elevated PART1 promoted gefitinib resistance by competitively binding to miR-129 to facilitate Bcl-2 expression in ESCC cells. In addition, extracellular PART1 could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating gefitinib resistance. Clinically, high levels of serum lncRNA PART1 in exosome were associated with poor response to gefitinib treatment in ESCC patients. Conclusions LncRNA PART1 promotes gefitinib resistance by regulating miR-129/Bcl-2 pathway, and may serve as a therapeutic target for ESCC patients

<i>Vn^−/−</i> mice impaired vascular permeability.

<p>(A). Whole-mount FITC-dextran angiograms in the WT and the <i>Vn^−/−</i> mice at day 7 in a mouse hindlimb ischemia model. Dextran leakage was more marked in the wild-type mice (upper panels, arrows) than in the <i>Vn^−/−</i> mice in ischemic gastrocnemius muscles. Capillaries were visualized by red Cy3-conjugated PECAM-1 antibodies. (B). Fluorescent intensities of cross-sections of non-ischemic (R2) and ischemic muscles (R1) were measured, and the R1/R2 ratio was used to assess the level of extravasation of FITC-dextran. Permeability was reduced in the gastrocnemius muscles in the <i>Vn^−/−</i> mice compared to the WT mice (n = 6, <i>p</i><0.05). (C). Electron microscopy of capillaries in the ischemic gastrocnemius muscles showed a diffuse and irregular basement membrane without distinct boundaries in WT mice in contrast to those of the <i>Vn^−/−</i> mice (upper panel, scale in 2 µm; lower panel is higher magnification. (D). The miles assay was performed with 50 ng/mL of VEGF and saline in the right and left ears, respectively, in the WT and <i>Vn^−/−</i> mice. Evan's blue dye extravasation was quantified with a spectrophotometer. The results are expressed as the mean ± SEM. * p<0.05. (n = 6 for each strain).</p

Construction of a Stable Crystalline Polyimide Porous Organic Framework for C2H2/C2H4 and CO2/N-2 Separation

Utilization of porous materials for gas capture and separation is a hot research topic. Removal of acetylene (C2H2) from ethylene (C2H4) is important in the oil refining and petrochemical industries, since C2H2 impurities deactivate the catalysts and terminate the polymerization of C2H4. Carbon dioxide (CO2) emission from power plants contributes to global climate change and threatens the survival of life on this planet. Herein, 2D crystalline polyimide porous organic framework PAF-120, which was constructed by imidization of linear naphthalene-1,4,5,8-tetracarboxylic dianhydride and triangular 1,3,5-tris(4-aminophenyl)benzene, showed significant thermal and chemical stability. Low-pressure gas adsorption isotherms revealed that PAF-120 exhibits good selective adsorption of C2H2 over C2H4 and CO2 over N-2. At 298 K and 1 bar, its C2H2 and CO2 selectivities were predicted to be 4.1 and 68.7, respectively. More importantly, PAF-120 exhibits the highest selectivity for C2H2/C2H4 separation among porous organic frameworks. Thus PAF-120 could be a suitable candidate for selective separation of C2H2 over C2H4 and CO2 over N-2