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141.
Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase
Ulrich M Petre A Youhnovski N Prömm F Schirle M Schumm M Pero RS Doyle A Checkel J Kita H Thiyagarajan N Acharya KR Schmid-Grendelmeier P Simon HU Schwarz H Tsutsui M Shimokawa H Bellon G Lee JJ Przybylski M Döring G 《The Journal of biological chemistry》2008,283(42):28629-28640
Nitration of tyrosine residues has been observed during various acute and chronic inflammatory diseases. However, the mechanism of tyrosine nitration and the nature of the proteins that become tyrosine nitrated during inflammation remain unclear. Here we show that eosinophils but not other cell types including neutrophils contain nitrotyrosine-positive proteins in specific granules. Furthermore, we demonstrate that the human eosinophil toxins, eosinophil peroxidase (EPO), major basic protein, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), and the respective murine toxins, are post-translationally modified by nitration at tyrosine residues during cell maturation. High resolution affinity-mass spectrometry identified specific single nitration sites at Tyr349 in EPO and Tyr33 in both ECP and EDN. ECP and EDN crystal structures revealed and EPO structure modeling suggested that the nitrated tyrosine residues in the toxins are surface exposed. Studies in EPO(-/-), gp91phox(-/-), and NOS(-/-) mice revealed that tyrosine nitration of these toxins is mediated by EPO in the presence of hydrogen peroxide and minute amounts of NOx. Tyrosine nitration of eosinophil granule toxins occurs during maturation of eosinophils, independent of inflammation. These results provide evidence that post-translational tyrosine nitration is unique to eosinophils. 相似文献
142.
Song T Mika F Lindmark B Liu Z Schild S Bishop A Zhu J Camilli A Johansson J Vogel J Wai SN 《Molecular microbiology》2008,70(1):100-111
We discovered a new small non-coding RNA (sRNA) gene, vrrA of Vibrio cholerae O1 strain A1552. A vrrA mutant overproduces OmpA porin, and we demonstrate that the 140 nt VrrA RNA represses ompA translation by base-pairing with the 5' region of the mRNA. The RNA chaperone Hfq is not stringently required for VrrA action, but expression of the vrrA gene requires the membrane stress sigma factor, sigma(E), suggesting that VrrA acts on ompA in response to periplasmic protein folding stress. We also observed that OmpA levels inversely correlated with the number of outer membrane vesicles (OMVs), and that VrrA increased OMV production comparable to loss of OmpA. VrrA is the first sRNA known to control OMV formation. Moreover, a vrrA mutant showed a fivefold increased ability to colonize the intestines of infant mice as compared with the wild type. There was increased expression of the main colonization factor of V. cholerae, the toxin co-regulated pili, in the vrrA mutant as monitored by immunoblot detection of the TcpA protein. VrrA overproduction caused a distinct reduction in the TcpA protein level. Our findings suggest that VrrA contributes to bacterial fitness in certain stressful environments, and modulates infection of the host intestinal tract. 相似文献
143.
For both cells and tissues, shape is closely correlated with function presumably via geometry-dependent distribution of tension. In this study, we identify common shape determinants spanning cell and tissue scales. For cells whose sites of adhesion are restricted to small adhesive islands on a micropatterned substrate, shape resembles a sequence of inward-curved circular arcs. The same shape is observed for fibroblast-populated collagen gels that are pinned to a flat substrate. Quantitative image analysis reveals that, in both cases, arc radii increase with the spanning distance between the pinning points. Although the Laplace law for interfaces under tension predicts circular arcs, it cannot explain the observed dependence on the spanning distance. Computer simulations and theoretical modeling demonstrate that filamentous network mechanics and contractility give rise to a modified Laplace law that quantitatively explains our experimental findings on both cell and tissue scales. Our model in conjunction with actomyosin inhibition experiments further suggests that cell shape is regulated by two different control modes related to motor contractility and structural changes in the actin cytoskeleton. 相似文献
144.
The radius of gyration, Rg, of chicken erythrocyte nucleosome core particles, was found to be 4.56 (+/- 0.07) nm by small-angle X-ray scattering, independent of particle concentration and of NaCl concentration between 0.1 M and 0.6 M-NaCl. The large, positive, second virial coefficient, A2, from particle concentration dependence (but independent of NaCl concentration) in small-angle X-ray scattering may indicate non-electrostatic repulsive ordering over large distances. Density contrast variation in equilibrium sedimentation with a small probe (sucrose) and a larger probe (gamma-cyclodextrin) yields good results for core particle hydration in the first instance, and for an estimate of the total particle volume in the second instance. 相似文献
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147.
We often form intentions but have to postpone them until the appropriate situation for retrieval and execution has come, an ability also referred to as event-based prospective memory. After intention completion, our cognitive system has to deactivate no-more-relevant intention representations from memory to avoid interference with subsequent tasks. In everyday life, we frequently rely on these abilities also in stressful situations. Surprisingly, little is known about potential stress effects on these functions. Therefore, the present study aimed to examine the reliability of event-based prospective memory and of intention deactivation in conditions of acute psychosocial stress. To this aim, eighty-two participants underwent the Trier Social Stress Test, a standardized stress protocol, or a standardized control situation. Following this treatment, participants performed a computerized event-based prospective memory task with non-salient and focal prospective memory cues in order to assess prospective memory performance and deactivation of completed intentions. Although the stress group showed elevated levels of salivary cortisol as marker of a stress-related increase in hypothalamus-pituitary-adrenal axis activity throughout the cognitive testing period compared to the no-stress group, prospective memory performance and deactivation of completed intentions did not differ between groups. Findings indicate that cognitive control processes subserving intention retrieval and deactivation after completion may be mostly preserved even under conditions of acute stress. 相似文献
148.
Franziska Lauer Katharina Prost Renate Gerlach Stefan P?tzold Mareike Wolf Sarah Urmersbach Eva Lehndorff Eileen Eckmeier Wulf Amelung 《PloS one》2014,9(9)
Neolithic and Bronze Age topsoil relicts revealed enhanced extractable phosphorus (P) and plant available inorganic P fractions, thus raising the question whether there was targeted soil amelioration in prehistoric times. This study aimed (i) at assessing the overall nutrient status and the soil organic matter content of these arable topsoil relicts, and (ii) at tracing ancient soil fertilizing practices by respective stable isotope and biomarker analyses. Prehistoric arable topsoils were preserved in archaeological pit fillings, whereas adjacent subsoils served as controls. One Early Weichselian humic zone represented the soil status before the introduction of agriculture. Recent topsoils served as an additional reference. The applied multi-proxy approach comprised total P and micronutrient contents, stable N isotope ratios, amino acid, steroid, and black carbon analyses as well as soil color measurements. Total contents of P and selected micronutrients (I, Cu, Mn, Mo, Se, Zn) of the arable soil relicts were above the limits for which nutrient deficiencies could be assumed. All pit fillings exhibited elevated δ15N values close to those of recent topsoils (δ15N>6 to 7‰), giving first hints for prehistoric organic N-input. Ancient legume cultivation as a potential source for N input could not be verified by means of amino acid analysis. In contrast, bile acids as markers for faecal input exhibited larger concentrations in the pit fillings compared with the reference and control soils indicating faeces (i.e. manure) input to Neolithic arable topsoils. Also black carbon contents were elevated, amounting up to 38% of soil organic carbon, therewith explaining the dark soil color in the pit fillings and pointing to inputs of burned biomass. The combination of different geochemical analyses revealed a sufficient nutrient status of prehistoric arable soils, as well as signs of amelioration (inputs of organic material like charcoal and faeces-containing manure). 相似文献
149.
Franziska Wegerich Andrea Giachetti Marco Allegrozzi Fred Lisdat Paola Turano 《Journal of biological inorganic chemistry》2013,18(7):867-869
In his comments, W.H. Koppenol criticizes our article with respect to our conclusions and procedures. In this answer, we respond in detail to his objections, demonstrating that the approaches used are commonly accepted in the literature and that he makes a number of assumptions regarding our proposed mechanism that are not justified. Our study is thus a contribution to the ongoing investigation of the behavior of cytochrome c. 相似文献
150.
Flap endonuclease 1 (FEN1) is a member of the family of structure-specific endonucleases implicated in regulation of DNA damage response and DNA replication. So far, knowledge on the role of FEN1 during viral infections is limited. Previous publications indicated that poxviruses encode a conserved protein that acts in a manner similar to FEN1 to stimulate homologous recombination, double-strand break (DSB) repair and full-size genome formation. Only recently, cellular FEN1 has been identified as a key component for hepatitis B virus cccDNA formation. Here, we report on a novel functional interaction between Flap endonuclease 1 (FEN1) and the human cytomegalovirus (HCMV) immediate early protein 1 (IE1). Our results provide evidence that IE1 manipulates FEN1 in an unprecedented manner: we observed that direct IE1 binding does not only enhance FEN1 protein stability but also phosphorylation at serine 187. This correlates with nucleolar exclusion of FEN1 stimulating its DSB-generating gap endonuclease activity. Depletion of FEN1 and inhibition of its enzymatic activity during HCMV infection significantly reduced nascent viral DNA synthesis demonstrating a supportive role for efficient HCMV DNA replication. Furthermore, our results indicate that FEN1 is required for the formation of DSBs during HCMV infection suggesting that IE1 acts as viral activator of FEN1 in order to re-initiate stalled replication forks. In summary, we propose a novel mechanism of viral FEN1 activation to overcome replication fork barriers at difficult-to-replicate sites in viral genomes. 相似文献