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51.
Src homology-3 (SH3) domains mediate important protein-protein interactions in a variety of normal and pathological cellular processes, thus providing an attractive target for the selective interference of SH3-dependent signaling events that govern these processes. Most SH3 domains recognize proline-rich peptides with low affinity and poor selectivity, and the goal to design potent and specific ligands for various SH3 domains remains elusive. Better understanding of the molecular basis for SH3 domain recognition is needed in order to design such ligands with potency and specificity. In this report, we seek to define a clear recognition preference of the specificity pocket of the Abl SH3 domain using targeted synthetic peptide libraries. High-resolution affinity panning coupled with mass spectrometric readout allows for quick identification of Trp as the preferred fourth residue in the decapeptide ligand APTWSPPPPP, which binds to Abl SH3 four times stronger than does the decapeptide containing Tyr or Phe in the fourth position. This finding is in contrast to several reports that Tyr is the only residue selected from phage displayed peptide libraries that interacts with the specificity pocket of Abl SH3. This simple, unbiased approach can fine-tune the affinity and selectivity of both natural and unnatural SH3 ligands whose consensus binding sequence has been pre-defined by combinatorial library methods. 相似文献
52.
Destoumieux-Garzón D Thomas X Santamaria M Goulard C Barthélémy M Boscher B Bessin Y Molle G Pons AM Letellier L Peduzzi J Rebuffat S 《Molecular microbiology》2003,49(4):1031-1041
The mechanism of action of microcin E492 (MccE492) was investigated for the first time in live bacteria. MccE492 was expressed and purified to homogeneity through an optimized large-scale procedure. Highly purified MccE492 showed potent antibacterial activity at minimal inhibitory concentrations in the range of 0.02-1.2 microM. The microcin bactericidal spectrum of activity was found to be restricted to Enterobacteriaceae and specifically directed against Escherichia and Salmonella species. Isogenic bacteria that possessed mutations in membrane proteins, particularly of the TonB-ExbB-ExbD complex, were assayed. The microcin bactericidal activity was shown to be TonB- and energy-dependent, supporting the hypothesis that the mechanism of action is receptor mediated. In addition, MccE492 depolarized and permeabilized the E. coli cytoplasmic membrane. The membrane depolarization was TonB dependent. From this study, we propose that MccE492 is recognized by iron-siderophore receptors, including FepA, which promote its import across the outer membrane via a TonB- and energy-dependent pathway. MccE492 then inserts into the inner membrane, whereupon the potential becomes destabilized by pore formation. Because cytoplasmic membrane permeabilization of MccE492 occurs beneath the threshold of the bactericidal concentration and does not result in cell lysis, the cytoplasmic membrane is not hypothesized to be the sole target of MccE492. 相似文献
53.
Campbell DJ Dixon B Kladis A Kemme M Santamaria JD 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,281(4):R1059-R1070
We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB. 相似文献
54.
Pere Casals Joan Romanyà Jordi Cortina Pierre Bottner Marie-Madeleine Coûteaux V. Ramon Vallejo 《Biogeochemistry》2000,48(3):261-281
We studied the seasonality of total soil CO2efflux and labeled C-CO2 released from 14Clabeled straw incubated in the H horizon of asemi-arid Mediterranean forest soil. Fieldmeasurements were carried out over 520 days in aseries of reconstructed soil profiles with and withouta gravel layer below the H horizon. We monitored soilclimate and related this to soil CO2 efflux.Seasonal variations in soil CO2 efflux in asemiarid Mediterranean forest were mainly related tochanges in soil temperature. In spite of drought, highrespiration rates were observed in mid summer. Highsoil CO2 efflux in hot and dry episodes wasattributed to increases in soil biological activity.The minimum soil CO2 efflux occurred in latesummer also under dry conditions, probably related toa decrease in soil biological activity in deephorizons. Biological activity in organic layers waslimited by water potential () in summer and bytemperature in winter. Rewetting a dry soil resultedin large increases in soil CO2 efflux only at hightemperatures. These large increases represented asignificant contribution to the decomposition oforganic matter in the uppermost horizons. Soilbiological activity in the uppermost horizons was moresensitive to changes in soil and hence tosummer rainstorms than the bulk soil microbialactivity. The presence of a layer of gravel improvedboth moisture and temperature conditions for thedecomposition of organic matter. As a result, soilCO2 efflux increased in soils containing rockfragments. These effects were especially large for theorganic layers. 相似文献
55.
Regulation of G Protein-Coupled Receptor Kinase 2 in Brains of Opiate-Treated Rats and Human Opiate Addicts 总被引:1,自引:1,他引:0
Andrés Ozaita Pablo V. Escribá Pere Ventayol Cristina Murga Federico Mayor Jr Jesús A. García-Sevilla 《Journal of neurochemistry》1998,70(3):1249-1257
Abstract: The effects of opiate drugs (heroin, morphine, and methadone) on the levels of G protein-coupled receptor kinase 2 (GRK2) were studied in rat and human brain frontal cortices. The density of brain GRK2 was measured by immunoblot assays in acute and chronic opiate-treated rats as well as in opiate-dependent rats after spontaneous or naloxone-precipitated withdrawal and in human opiate addicts who had died of an opiate overdose. In postmortem brains from human addicts, total GRK2 immunoreactivity was not changed significantly, but the level of the membrane-associated kinase was modestly but significantly increased (12%) compared with matched controls. In rats treated chronically with morphine or methadone modest increases of the enzyme levels (only significant after methadone) were observed. Acute treatments with morphine and methadone induced dose- and time-dependent increases (8–22%) in total GRK2 concentrations [higher increases were observed for the membrane-associated enzyme (46%)]. Spontaneous and naloxone-precipitated withdrawal after chronic morphine or methadone induced a marked up-regulation in the levels of total GRK2 in the rat frontal cortex (18–25%). These results suggest that GRK2 is involved in the short-term regulation of μ-opioid receptors in vivo and that the activity of this regulatory kinase in brain could have a relevant role in opiate tolerance, dependence, and withdrawal. 相似文献
56.
Uribe Xavier Torres Miguel Angel Capellades Montserrat Puigdomènech Pere Rigau Joan 《Plant molecular biology》1998,37(6):1069-1078
In the past few years many - and -tubulin genes of different organisms have been cloned and studied, and in most systems studied they constitute multigene families. In plants, most studies have been done in Arabidopsis thaliana and Zea mays. In this paper, the study of mRNA accumulation by in situ hybridization and the activity of three maize -tubulin gene promoters (tua1, tua2 and tua3) in transgenic tobacco plants are described. In maize, the expression of these three tubulin isotypes differ in the root and shoot apex and is associated with different groups of cells throughout the distinct stages of cell differentiation. In transgenic tobacco plants the promoters of the genes, fused to the uidA reporter gene (GUS), direct expression to the same tissues observed by in situ hybridization experiments. The tua1 promoter is mainly active in cortex-producing meristematic cells and in pollen, whereas tua3 is active in cells which are differentiating to form vascular bundles in the root and shoot apices. The accumulation of tua2 mRNA is detected by RNA blot in a similar form as tua1, but at a very much low level. In situ hybridization indicates that the tua2 mRNA specifically accumulates in the maize root epidermis. No GUS staining was detected in transgenic tobacco plants with the tua2 promoter. The difference in expression of the specific genes may be linked to processes where microtubules have different functions, suggesting that in plants, as in animals, there are differences in the function of the tubulin isotypes. 相似文献
57.
58.
Marc Guaita Umberto Melia Montserrat Vallverdú Pere Caminal Isabel Vilaseca Josep M. Montserrat Carles Gaig Manel Salamero Joan Santamaria 《PloS one》2015,10(4)
Aim
The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV) to detect sleep disordered breathing (SDB) patients with and without excessive daytime sleepiness (EDS) before sleep onset.Methods
Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests.Results
Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band) yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients.Conclusion
The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset. 相似文献59.
Inma Crespo Diana Toledo Núria Soldevila Iolanda Jordán Rubén Solano Jesús Castilla Joan A. Caylà Pere Godoy Carmen Mu?oz-Almagro ángela Domínguez Working Group on the Transmission of Pertussis in Households 《PloS one》2015,10(10)
Pertussis causes a large number of cases and hospitalizations in Catalonia and Navarra. We made a study of household cases of pertussis during 2012 and 2013 in order to identify risk factors for hospitalization in pertussis cases. Each primary case reported triggered the study of their contacts. Close contacts at home and people who were in contact for >2 hours during the transmission period of cases were included. The adjusted OR and 95% confidence intervals (CI) was calculated using logistic regression. A total of 1124 pertussis cases were detected, of which 14.9% were hospitalized. Inspiratory whoop (aOR: 1.64; CI: 1.02–2.65), apnoea (aOR: 2.47; CI: 1.51–4.03) and cyanosis (aOR: 15.51; CI: 1.87–128.09) were more common in hospitalized than in outpatient cases. Hospitalization occurred in 8.7% of correctly-vaccinated cases, 41.1% of non-vaccinated cases and 9.4% of partially-vaccinated cases. In conclusion, inspiratory whoop, apnoea and cyanosis were associated factors to hospitalization while vaccination reduced hospitalizations due to pertussis. 相似文献
60.
César Garriga Patricia García de Olalla Josep M. Miró Inma Oca?a Hernando Knobel Maria Jesús Barberá Victoria Humet Pere Domingo Josep M. Gatell Esteve Ribera Mercè Gurguí Andrés Marco Joan A. Caylà 《PloS one》2015,10(12)