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61.
Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl(3), in the amide I and NH/OH-stretching regions, and their corresponding magnesium complexes in CD(3)CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of Cdbond;O and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6-31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl(3) solution; CsH, however, assumes both an intramolecularly hydrogen-bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH-stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen-bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal-free and magnesium-complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions. 相似文献
62.
Ruggiero D Dalmasso C Nutile T Sorice R Dionisi L Aversano M Bröet P Leutenegger AL Bourgain C Ciullo M 《PloS one》2011,6(2):e16982
Vascular Endothelial Growth Factor (VEGF) is the main player in angiogenesis. Because of its crucial role in this process, the study of the genetic factors controlling VEGF variability may be of particular interest for many angiogenesis-associated diseases. Although some polymorphisms in the VEGF gene have been associated with a susceptibility to several disorders, no genome-wide search on VEGF serum levels has been reported so far. We carried out a genome-wide linkage analysis in three isolated populations and we detected a strong linkage between VEGF serum levels and the 6p21.1 VEGF region in all samples. A new locus on chromosome 3p26.3 significantly linked to VEGF serum levels was also detected in a combined population sample. A sequencing of the gene followed by an association study identified three common single nucleotide polymorphisms (SNPs) influencing VEGF serum levels in one population (Campora), two already reported in the literature (rs3025039, rs25648) and one new signal (rs3025020). A fourth SNP (rs41282644) was found to affect VEGF serum levels in another population (Cardile). All the identified SNPs contribute to the related population linkages (35% of the linkage explained in Campora and 15% in Cardile). Interestingly, none of the SNPs influencing VEGF serum levels in one population was found to be associated in the two other populations. These results allow us to exclude the hypothesis that the common variants located in the exons, intron-exon junctions, promoter and regulative regions of the VEGF gene may have a causal effect on the VEGF variation. The data support the alternative hypothesis of a multiple rare variant model, possibly consisting in distinct variants in different populations, influencing VEGF serum levels. 相似文献
63.
Mutations at residues 282, 286, and 293 of phage lambda integrase exert pathway-specific effects on synapsis and catalysis in recombination 下载免费PDF全文
Bankhead TM Etzel BJ Wolven F Bordenave S Boldt JL Larsen TA Segall AM 《Journal of bacteriology》2003,185(8):2653-2666
Bacteriophage lambda integrase (Int) catalyzes site-specific recombination between pairs of attachment (att) sites. The att sites contain weak Int-binding sites called core-type sites that are separated by a 7-bp overlap region, where cleavage and strand exchange occur. We have characterized a number of mutant Int proteins with substitutions at positions S282 (S282A, S282F, and S282T), S286 (S286A, S286L, and S286T), and R293 (R293E, R293K, and R293Q). We investigated the core- and arm-binding properties and cooperativity of the mutant proteins, their ability to catalyze cleavage, and their ability to form and resolve Holliday junctions. Our kinetic analyses have identified synapsis as the rate-limiting step in excisive recombination. The IntS282 and IntS286 mutants show defects in synapsis in the bent-L and excisive pathways, respectively, while the IntR293 mutants exhibit synapsis defects in both the excision and bent-L pathways. The results of our study support earlier findings that the catalytic domain also serves a role in binding to core-type sites, that the core contacts made by this domain are important for both synapsis and catalysis, and that Int contacts core-type sites differently among the four recombination pathways. We speculate that these residues are important for the proper positioning of the catalytic residues involved in the recombination reaction and that their positions differ in the distinct nucleoprotein architectures formed during each pathway. Finally, we found that not all catalytic events in excision follow synapsis: the attL site probably undergoes several rounds of cleavage and ligation before it synapses and exchanges DNA with attR. 相似文献
64.
Differential toxicity of TAR DNA‐binding protein 43 isoforms depends on their submitochondrial localization in neuronal cells 下载免费PDF全文
Illari Salvatori Alberto Ferri Silvia Scaricamazza Ilaria Giovannelli Alessia Serrano Simona Rossi Nadia D'Ambrosi Mauro Cozzolino Andrea Di Giulio Sandra Moreno Cristiana Valle Maria Teresa Carrì 《Journal of neurochemistry》2018,146(5):585-597
65.
Comparative proteomic analysis of Xanthomonas citri ssp. citri periplasmic proteins reveals changes in cellular envelope metabolism during in vitro pathogenicity induction 下载免费PDF全文
Juliana Artier Flávia da Silva Zandonadi Flávia Maria de Souza Carvalho Bianca Alves Pauletti Adriana Franco Paes Leme Carolina Moretto Carnielli Heloisa Sobreiro Selistre‐de‐Araujo Maria Célia Bertolini Jesus Aparecido Ferro José Belasque Júnior Julio Cezar Franco de Oliveira Maria Teresa Marques Novo‐Mansur 《Molecular Plant Pathology》2018,19(1):143-157
Citrus canker is a plant disease caused by Gram‐negative bacteria from the genus Xanthomonas. The most virulent species is Xanthomonas citri ssp. citri (XAC), which attacks a wide range of citrus hosts. Differential proteomic analysis of the periplasm‐enriched fraction was performed for XAC cells grown in pathogenicity‐inducing (XAM‐M) and pathogenicity‐non‐inducing (nutrient broth) media using two‐dimensional electrophoresis combined with liquid chromatography‐tandem mass spectrometry. Amongst the 40 proteins identified, transglycosylase was detected in a highly abundant spot in XAC cells grown under inducing condition. Additional up‐regulated proteins related to cellular envelope metabolism included glucose‐1‐phosphate thymidylyltransferase, dTDP‐4‐dehydrorhamnose‐3,5‐epimerase and peptidyl‐prolyl cis–trans‐isomerase. Phosphoglucomutase and superoxide dismutase proteins, known to be involved in pathogenicity in other Xanthomonas species or organisms, were also detected. Western blot and quantitative real‐time polymerase chain reaction analyses for transglycosylase and superoxide dismutase confirmed that these proteins were up‐regulated under inducing condition, consistent with the proteomic results. Multiple spots for the 60‐kDa chaperonin and glyceraldehyde‐3‐phosphate dehydrogenase were identified, suggesting the presence of post‐translational modifications. We propose that substantial alterations in cellular envelope metabolism occur during the XAC infectious process, which are related to several aspects, from defence against reactive oxygen species to exopolysaccharide synthesis. Our results provide new candidates for virulence‐related proteins, whose abundance correlates with the induction of pathogenicity and virulence genes, such as hrpD6, hrpG, hrpB7, hpa1 and hrpX. The results present new potential targets against XAC to be investigated in further functional studies. 相似文献
66.
Cement plants account for significant emissions of CO2 and other pollutants into the atmosphere. As a means for its mitigation, we tested the effect of a cement industry-based flue gas simulation (FGS — 18% CO2, 9% O2, 300 ppm NO2, 140 ppm SO2) on the green alga, Chlorella sorokiniana. Culture pH, cell density, cell viability and productivity, specific growth rates, photosynthetic performance, and biochemical composition were monitored. The treatments consisted of different FGS volumes (0.1, 0.3, 0.8, 1.5, 6, and 48 L day?1) that were applied in a series of laboratory-scale semi-continuous batch cultures under controlled conditions. Controls were exposed to 18% CO2 enriched air. Cell density showed that C. sorokiniana was able to grow in all treatments, but compared to the controls, low pH (~ 5.0) caused by 48 L FGS day?1 led to 27% decrease in specific growth rate. Increasing FGS exposure decreased maximum and operational quantum yields obtained by pulse amplitude modulated fluorometry, while photochemical quenching remained constant (~ 0.93). The α and rETR max parameters calculated from rapid light curves decreased with increasing FGS exposure. Total proteins and carbohydrates (per cell basis) increased after 6 and 48 L FGS day?1, which can be advantageous for biotechnological applications, but cell productivity (cells L?1 day?1) decreased. Despite the effects in physiology, C. sorokiniana could withstand a pH range of 6.0–5.0 imposed by 48 L FGS day?1. Overall, C. sorokiniana can be considered a robust species in flue gas bioremediation. 相似文献
67.
Echevarría-Machado I Martínez-Estévez M Muñoz-Sánchez JA Loyola-Vargas VM Hernández-Sotomayor SM De Los Santos-Briones C 《Molecular biotechnology》2007,35(3):297-309
We have previously reported that Catharanthus roseus transformed roots contain at least two phosphatidylinositol 4,5-bisphosphate-phospholipase C (PLC) activities, one soluble
and the other membrane associated. Detergent, divalent cations, and neomycin differentially regulate these activities and
pure protein is required for a greater understanding of the function and regulation of this enzyme. In this article we report
a partia purification of membrane-associated PLC. We found that there are at least two forms of membrane-associated PLC in
transformed roots of C. roseus. These forms were separated on the basis of their affinity for heparin. One form shows an affinity for heparin and elutes
at approx 600 mM KCl. This form has a molecular mass of 67 kDa by size exclusion chromatography and Western blot analysis, whereas the other
form does not bind to heparin and has a molecular mass of 57 kDa. Possible differential regulation of these forms during transformed
root growth is discussed. 相似文献
68.
Marino-Merlo Francesca Papaianni Emanuela Maugeri Teresa L. Zammuto Vincenzo Spanò Antonio Nicolaus Barbara Poli Annarita Di Donato Paola Mosca Claudia Mastino Antonio Gugliandolo Concetta 《Applied microbiology and biotechnology》2017,101(20):7487-7496
Applied Microbiology and Biotechnology - Herpes simplex virus type 1 (HSV-1) is responsible of common and widespread viral infections in humans through the world, and of rare, but extremely severe,... 相似文献
69.
Fabrizi F Mincione F Somma T Scozzafava G Galassi F Masini E Impagnatiello F Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2012,27(1):138-147
The clinically used sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma. 相似文献
70.
A fundamental step in neuronal development is the acquisition of a polarized form, with distinct axons and dendrites. Although the ability to develop a polarized form appears to be largely an intrinsic property of neurons, it can be influenced by environmental cues. For example, in cell cultures substrate and diffusible factors can enhance and orient axonal development. In this study we examine the effects of growth on each of two cell adhesion molecules (CAMs), NgCAM and N-cadherin, on the development of polarity by cultured hippocampal neurons. We find that although the same pattern of development occurs on control substrates and the CAMs, the CAMs greatly accelerate the rate and extent of development of axons—axons form sooner and grow longer on the CAMs than on the control substrate. In contrast, the CAMs have opposite effects on dendritic development—N-cadherin enhances, but NgCAM reduces dendritic growth compared to control. These results provide further evidence that the development of polarity is largely determined by a cell-autonomous program, but that environmental cues can independently regulate axonal and dendritic growth. 相似文献