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991.
The interpretation of the electron ionization mass spectra of straight-chain and methyl-branched saturated and unsaturated wax esters (WEs) is discussed in this study based on the spectra of 154 standards. The most important fragments indicative of the structure of the acid and alcohol chains are identified and summarized for WEs with various number of double bonds in the chains. Briefly, most WEs provide acylium ions allowing structural characterization of the acid part, whereas the alcohol part gives corresponding alkyl radical cations. The elemental composition of selected important fragments is established from a high-resolution accurate mass analysis. The ion abundances are discussed with respect to the length and unsaturation of the aliphatic chains. The interpretation of the spectra of branched or unsaturated WEs requires the recognition of small but important peaks that are difficult to discern among the other fragments. We demonstrate that such fragments are easily detected in differential mass spectra. This approach requires spectra of WE standards (e.g., straight-chain analogs in the case of branched WEs) recorded under the same experimental conditions. The WEs mass spectral database provided in the supplemental data can be used as a reference for the analysis of the GC/EI-MS data. 相似文献
992.
Avia Rosenhouse-Dantsker Sergei Noskov Huazhi Han Scott K. Adney Qiong-Yao Tang Aldo A. Rodríguez-Menchaca Gregory B. Kowalsky Vasileios I. Petrou Catherine V. Osborn Diomedes E. Logothetis Irena Levitan 《The Journal of biological chemistry》2012,287(48):40266-40278
Inwardly rectifying potassium (Kir) channels play an important role in setting the resting membrane potential and modulating membrane excitability. An emerging feature of several Kir channels is that they are regulated by cholesterol. However, the mechanism by which cholesterol affects channel function is unclear. Here we show that mutations of two distant Kir2.1 cytosolic residues, Leu-222 and Asn-251, form a two-way molecular switch that controls channel modulation by cholesterol and affects critical hydrogen bonding. Notably, these two residues are linked by a residue chain that continues from Asn-251 to connect adjacent subunits. Furthermore, our data indicate that the same switch also regulates the sensitivity of the channels to phosphatidylinositol 4,5-bisphosphate, a phosphoinositide that is required for activation of Kir channels. Thus, although cholesterol and phosphatidylinositol 4,5-bisphosphate do not interact with the same region of Kir2.1, these different modulators induce a common gating pathway of the channel. 相似文献
993.
Elevated levels of oxLDL in the bloodstream and increased vasculature stiffness are both associated with cardiovascular disease in patients. However, it is not known how oxLDL and subendothelial matrix stiffness together regulate an immune response. Here, we used an in vitro model of the vascular endothelium to explore the combined effects of oxLDL and subendothelial matrix stiffening on neutrophil transmigration. We prepared fibronectin-coated polyacrylamide gels of varying stiffness and plated human umbilical vein endothelial cells (ECs) onto the gels. We observed that oxLDL treatment of the endothelium promoted neutrophil transmigration (from <1% to 26% on soft 0.87kPa substrates), with stiffer substrates further promoting transmigration (54% on 5kPa and 41% on 280kPa). OxLDL exposure enhanced intercellular adhesion molecule-1 (ICAM-1) expression on the endothelium, which was likely responsible for the oxLDL-induced transmigration. Importantly, inhibition of MLCK-mediated EC contraction reduced transmigration to ~9% on all substrates and eliminated the effects of subendothelial matrix stiffness. In addition, large holes, thousands of square microns in size, formed in monolayers on stiff substrates following transmigration, indicating that oxLDL treatment and subsequent neutrophil transmigration caused serious damage to the endothelium. Our results reveal that an interplay between ICAM-1 and MLCK-dependent contractile forces mediates neutrophil transmigration through oxLDL-treated endothelium. Thus, microvasculature stiffness, which likely varies depending on tissue location and health, is an important regulator of the transmigration step of the immune response in the presence of oxLDL. 相似文献
994.
Ingrid Falnoga Andreja Zelenik Pevec Zdenka ?lejkovec Magda Tu?ek ?nidari? Irena Zajc Simona Jurkovi? Mlakar Janja Marc 《Biological trace element research》2012,149(3):331-339
Arsenic trioxide (As2O3; ATO, TRISENOX?) is used to treat patients with refractory or relapsed acute promyelocytic leukaemia while its application for treatment of solid cancers like glioblastoma is still under evaluation. In the present study, we investigated the interaction of arsenic trioxide with metallothionein (MT) isoforms as a possible (protective response) resistance of glioblastoma cells to arsenic-induced cytotoxicity. Special attention was focused on MT3, the isoform expressed mainly in the brain. MT3 has low metal inducibility, fast metal binding/releasing properties and outstanding neuronal inhibitory activity. The human astrocytoma (glioblastoma) cell line U87 MG was treated with 0.6, 2 and 6?C7???M arsenic (equivalent to 0.3, 1 and 3?C3.5???M As2O3) for 12, 24 or 48?h and gene expression for different MT isoforms, namely MT2A, MT1A, MT1F, MT1X, MT1E and MT3, was measured by real time qPCR using SYBR Green I and Taqman? gene expression assays. TfR, 18S rRNA, GAPDH and AB were tested as reference genes, and the last two evaluated to be appropriate in conditions of low (GAPDH) and high (AB) arsenic exposure. The gene expression of MT3 gene was additionally tested and confirmed by restriction enzyme analysis with PvuII. In the given conditions the mRNAs of six MT isoforms were identified in human glioblastoma cell line U87 MG. Depending on arsenic exposure conditions, an increase or decrease of MT gene expression was observed for each isoform, with the highest increase for isoforms MT1X, MT1F and MT2A mRNA (up to 13-fold) and more persistent decreases for MT1A, MT1E and MT3 mRNA. Despite the common assumption of the noninducibility of MT3, the evident MT3 mRNA increase was observed during high As exposure (up to 4-fold). In conclusion, our results clearly demonstrate the influence of As on MT isoform gene expression. The MT1X, MT1F and MT2A increase could represent brain tumour acquired resistance to As cytotoxicity while the MT3 increase is more enigmatic, with its possible involvement in arsenic-related induction of type II cell death. 相似文献
995.
Dębowski D Łukajtis R Łęgowska A Karna N Pikuła M Wysocka M Maliszewska I Sieńczyk M Lesner A Rolka K 《Peptides》2012,35(2):276-284
A series of linear and cyclic fragments and analogs of two peptides (OGTI and HV-BBI) isolated from skin secretions of frogs were synthesized by the solid-phase method. Their inhibitory activity against several serine proteinases: bovine β-trypsin, bovine α-chymotypsin, human leukocyte elastase and cathepsin G from human neutrophils, was investigated together with evaluation of their antimicrobial activities against Gram-negative bacteria (Escherichia coli) and Gram-positive species isolated from patients (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus sp., Streptococcus sp.). The cytotoxicity of the selected peptides toward an immortal human skin fibroblast cell line was also determined. Three peptides: HV-BBI, its truncated fragment HV-BBI(3-18) and its analog [Phe(8)]HV-BBI can be considered as bifunctional compounds with inhibitory as well as antibacterial properties. OGTI, although it did not display trypsin inhibitory activity as previously reported in the literature, exerted antimicrobial activity toward S. epidermidis. In addition, under our experimental conditions, this peptide did not show cytotoxicity. 相似文献
996.
997.
Isles Peter D. F. Creed Irena F. Jonsson Anders Bergström Ann-Kristin 《Ecosystems》2021,24(8):1837-1852
Ecosystems - Northern lakes are experiencing widespread increases in dissolved organic carbon (DOC) that are likely to lead to changes in pelagic phytoplankton biomass. Pelagic phytoplankton... 相似文献
998.
The multifunctional‐autoprocessing repeats‐in‐toxin (MARTX) toxins are bacterial protein toxins that serve as delivery platforms for cytotoxic effector domains. The domain of unknown function in position 5 (DUF5) effector domain is present in at least six different species' MARTX toxins and as a hypothetical protein in Photorhabdus spp. Its presence increases the potency of the Vibrio vulnificus MARTX toxin in mouse virulence studies, indicating DUF5 directly contributes to pathogenesis. In this work, DUF5 is shown to be cytotoxic when transiently expressed in HeLa cells. DUF5 localized to the plasma membrane dependent upon its C1 domain and the cells become rounded dependent upon its C2 domain. Both full‐length DUF5 and the C2 domain caused growth inhibition when expressed in Saccharomyces cerevisiae. A structural model of DUF5 was generated based on the structure of Pasteurella multocida toxin facilitating localization of the cytotoxic activity to a 186 amino acid subdomain termed C2A. Within this subdomain, an alanine scanning mutagenesis revealed aspartate‐3721 and arginine‐3841 as residues critical for cytotoxicity. These residues were also essential for HeLa cell intoxication when purified DUF5 fused to anthrax toxin lethal factor was delivered cytosolically. Thermal shift experiments indicated that these conserved residues are important to maintain protein structure, rather than for catalysis. The Aeromonas hydrophila MARTX toxin DUF5Ah domain was also cytotoxic, while the weakly conserved C1–C2 domains from P. multocida toxin were not. Overall, this study is the first demonstration that DUF5 as found in MARTX toxins has cytotoxic activity that depends on conserved residues in the C2A subdomain. Proteins 2014; 82:2643–2656. © 2014 Wiley Periodicals, Inc. 相似文献
999.