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91.
Davis GE Koh W Stratman AN 《Birth defects research. Part C, Embryo today : reviews》2007,81(4):270-285
Recent data have revealed new mechanisms that underlie endothelial cell (EC) lumen formation during vascular morphogenic events in development, wound repair, and other disease states. It is apparent that EC interactions with extracellular matrices (ECMs) establish signaling cascades downstream of integrin ligation leading to activation of the Rho GTPases, Cdc42 and Rac1, which are required for lumen formation. In large part, this process is driven by intracellular vacuole formation and coalescence, which rapidly leads to the creation of fluid-filled matrix-free spaces that are then interconnected via EC-EC interactions to create multicellular tube structures. EC vacuoles markedly accumulate in a polarized fashion directly adjacent to the centrosome in a region that strongly accumulates Cdc42 protein as indicated by green fluorescent protein (GFP)-Cdc42 during the lumen formation process. Downstream of Cdc42-mediated signaling, key molecules that have been identified to be required for EC lumen formation include Pak2, Pak4, Par3, Par6, and the protein kinase C (PKC) isoforms zeta and epsilon. Together, these molecules coordinately regulate the critical EC lumen formation process in three-dimensional (3D) collagen matrices. These events also require cell surface proteolysis mediated through membrane type 1 matrix metalloproteinase (MT1-MMP), which is necessary to create vascular guidance tunnels within the 3D matrix environment. These tunnels represent physical spaces within the ECM that are necessary to regulate vascular morphogenic events, including the establishment of interconnected vascular tube networks as well as the recruitment of pericytes to initiate vascular tube maturation (via basement membrane matrix assembly) and stabilization. Current research continues to analyze how specific molecules integrate signaling information in concert to catalyze EC lumen formation, pericyte recruitment, and stabilization processes to control vascular morphogenesis in 3D extracellular matrices. 相似文献
92.
Isabel Guerrero Montero Kirsty L. Richards Chillel Jawara Douglas F. Browning Amber R. Peswani Mickael Labrit Matthew Allen Cedric Aubry Emma Davé David P. Humphreys Stephen J. W. Busby Colin Robinson 《Biotechnology and bioengineering》2019,116(12):3282-3291
Escherichia coli is a heavily used platform for the production of biotherapeutic and other high-value proteins, and a favored strategy is to export the protein of interest to the periplasm to simplify downstream processing and facilitate disulfide bond formation. The Sec pathway is the standard means of transporting the target protein but it is unable to transport complex or rapidly folding proteins because the Sec system can only transport proteins in an unfolded state. The Tat system also operates to transport proteins to the periplasm, and it has significant potential as an alternative means of recombinant protein production because it transports fully folded proteins. Here, we have tested the Tat system's full potential for the production of biotherapeutics for the first time using fed-batch fermentation. We expressed human growth hormone (hGH) with a Tat signal peptide in E. coli W3110 “TatExpress” strains that contain elevated levels of the Tat apparatus. This construct contained four amino acids from TorA at the hGH N-terminus as well as the initiation methionine from hGH, which is removed in vivo. We show that the protein is efficiently exported to the periplasm during extended fed-batch fermentation, to the extent that it is by far the most abundant protein in the periplasm. The protein was shown to be homogeneous, disulfide bonded, and active. The bioassay showed that the yields of purified periplasmic hGH are 5.4 g/L culture whereas an enzyme-linked immunosorbent assay gave a figure of 2.39 g/L. Separate analysis of a TorA signal peptide linked to hGH construct lacking any additional amino acids likewise showed efficient export to the periplasm, although yields were approximately two-fold lower. 相似文献
93.
Siddiqui Rehan Ahmed Simjee Shabana Usman Kabir Nurul Ateeq Muhammad Shah M. Raza Hussain Syed Saad 《Molecular and cellular biochemistry》2019,450(1-2):43-52
Molecular and Cellular Biochemistry - The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury... 相似文献
94.
Mohd Faizan Siddiqui Mohd Shahnawaz Khan Fohad Mabood Husain 《Journal of biomolecular structure & dynamics》2019,37(9):2230-2241
Carbendazim is a benzimidazole fungicide used to control the fungal invasion. However, its exposure might lead to potential health problems. The present study evaluates the interaction of carbendazim (CAR) with human serum albumin (HSA) which is an important drug carrier protein and plays a very crucial role in the transportation of small molecules. A number of biophysical techniques were employed to investigate the binding of CAR with HSA. The increased UV-absorption of HSA on titrating with CAR suggests the formation of HSA–CAR complex and it could be due to the exposure of aromatic residues. The fluorescence study confirmed that CAR quenches the fluorescence of HSA and showed the static mode of quenching. CAR (50 µM) quenches around 56.14% of the HSA fluorescence. The quenching constant, binding constant, number of binding site and free energy change was calculated by fluorescence quenching experiment. Competitive displacement assay showed Sudlow’s site I as the primary binding site of CAR on HSA. The synchronous fluorescence study revealed the perturbation in the microenvironment around tyrosine and tryptophan residues upon binding of CAR to HSA. The circular dichroism results suggested that the binding of CAR to HSA altered its secondary structure. Molecular docking experiment demonstrated the binding of CAR to Sudlow’s site I of HSA. Docking studies suggested that the hydrogen bonding, van der Waals and pi-alkyl are playing role in the interaction of CAR with HSA. The study confirmed the conformational changes within HSA upon binding of CAR. 相似文献
95.
96.
Faizan Q. Siddiqui Farnaz Malik F. R. Y. Fazli 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1995,666(2)
A rapid, sensitive and specific high-performance liquid chromatographic method was developed for the determination of serum levels of retinol in humans. A direct serum injection technique after deproteinisation was used to avoid lengthy pretreatment steps which can result in degradation of retinol during analysis. The column used was CLC-ODS, the mobile phase was acetonitrile-water and detection wavelength was 328 nm. Deterioration in column performance was not observed even after injection of 300 samples. The lower detection limit was 10 μg/l. On analyzing a serum pool six times, a C.V of 0.7% was obtained. The method is quantitative, reproducible, rapid and highly accurate for routine analysis. 相似文献
97.
Analysis of the relative amount and distribution pattern of phloem sclerenchyma in some 29 tropical trees of India was carried out with systematic considerations. Both the features exhibited considerable diversity among the species analyzed. The extent of area occupied by sclerenchyma in transections of the bark of these species varied from zero to 35% and 3 to 49% in the conducting and non-conducting phloem zones respectively, the overall amount constituting about 3 to 45% of the secondary phloem as a whole. The sclerenchyma cells differentiated either as isolated elements or in the form of bands or fascicles of diverse shape and size showing various distribution patterns. 相似文献
98.
Conformational searches on three closely related pp60(c-src) protein tyrosine kinase inhibitors of varying potencies were performed to determine a structural basis for their activity. The first was a linear peptide (PDNEYAFFQf), the second its 10-membered cyclic analogue, and the third a cyclic analogue with a para carboxyphenylalanine in place of one the F residues. A common backbone conformation with an antiparallel beta-sheet-like geometry capped by similar beta-turns was found for all three peptides, which may be a binding conformation and gives a candidate pharmacophore for further testing. The interaction between some polar side chains and between some of the aromatic rings may be important for maintaining the correct conformation. The differences in potencies of these inhibitors may be attributed to certain thermodynamic and chemical reasons. 相似文献
99.
100.