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1.
Isabel A. Cáceres Mariana Arcaya Eugene Declercq Candice M. Belanoff Vanitha Janakiraman Bruce Cohen Jeffrey Ecker Lauren A. Smith S. V. Subramanian 《PloS one》2013,8(3)
Objective
We examined the extent to which differences in hospital-level cesarean delivery rates in Massachusetts were attributable to hospital-level, rather than maternal, characteristics.Methods
Birth certificate and maternal in-patient hospital discharge records for 2004–06 in Massachusetts were linked. The study population was nulliparous, term, singleton, and vertex births (NTSV) (n = 80,371) in 49 hospitals. Covariates included mother''s age, race/ethnicity, education, infant birth weight, gestational age, labor induction (yes/no), hospital shift at time of birth, and preexisting health conditions. We estimated multilevel logistic regression models to assess the likelihood of a cesarean deliveryResults
Overall, among women with NTSV births, 26.5% births were cesarean, with a range of 14% to 38.3% across hospitals. In unadjusted models, the between-hospital variance was 0.103 (SE 0.022); adjusting for demographic, socioeconomic and preexisting medical conditions did not reduce any hospital-level variation 0.108 (SE 0.023).Conclusion
Even after adjusting for both socio-demographic and clinical factors, the chance of a cesarean delivery for NTSV pregnancies varied according to hospital, suggesting the importance of hospital practices and culture in determining a hospital''s cesarean rate. 相似文献2.
To examine the biochemical mechanism by which hsp90 exerts its essential positive function on certain signal transduction proteins, we characterized the effects of molybdate and geldanamycin on hsp90 function and structure. Molybdate inhibited hsp90-mediated p56lck biogenesis and luciferase renaturation while enforcing salt-stable interactions with these substrates. Molybdate also reduced the amount of free hsp90 present in cell lysates, inhibited hsp90's ability to bind geldanamycin, and induced resistance to proteolysis at a specific region within the C-terminal domain of hsp90. In contrast, the hsp90 inhibitor geldanamycin prevented hsp90 from assuming natural or molybdate-induced conformations that allow salt-stable interactions with substrates. When these compounds were applied sequentially, the order of addition determined the effects observed, indicating that these agents had opposing effects on hsp90. We conclude that a specific region within the C-terminal domain of hsp90 (near residue 600) determines the mode by which hsp90 interacts with substrates and that the ability of hsp90 to cycle between alternative modes of interaction is obligatory for hsp90 function. 相似文献
3.
The ability of two high-affinity Hsc70-binding peptides [FYQLALT (peptide-Phi) and NIVRKKK (peptide-K)] to differentially inhibit Hsc70-dependent processes in rabbit reticulocyte lysate (RRL) was examined. Both peptide-Phi and peptide-K inhibited chaperone-dependent renaturation of luciferase in RRL. Peptide-Phi, but not peptide-K, blocked Hsp90/Hsc70-dependent transformation of the heme-regulated eIF2 alpha kinase (HRI) into an active, heme-regulatable kinase. In contrast, peptide-K, but not peptide-Phi, inhibited Hsc70-mediated suppression of the activation of mature-transformed HRI. Furthermore, HDJ2 (Human DnaJ homologue 2), but not HDJ1, potentiated the ability of Hsc70 to suppress the activation of HRI in RRL. Mechanistically, peptide-K inhibited, while peptide-Phi enhanced, HDJ2-induced stimulation of Hsc70 ATPase activity in vitro. The data presented support the hypotheses that peptide-Phi acts to inhibit Hsc70 function by binding to the hydrophobic peptide-binding cleft of Hsc70, while peptide-K acts through binding to a site that modulates the interaction of Hsc70 with DnaJ homologues. Overall, the data indicate that peptide-Phi and peptide-K have differential effects on Hsc70 functions under quasi-physiological conditions in RRL, and suggest that therapeutically valuable peptide mimetics can be designed to inhibit specific functions of Hsc70. 相似文献
4.
Selectivity of Ferric Enterobactin Binding and Cooperativity of Transport in Gram-Negative Bacteria 总被引:6,自引:5,他引:1
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Padmamalini Thulasiraman Salete M. C. Newton Jide Xu Kenneth N. Raymond Christine Mai Angela Hall Marjorie A. Montague Phillip E. Klebba 《Journal of bacteriology》1998,180(24):6689-6696
The ligand-gated outer membrane porin FepA serves Escherichia coli as the receptor for the siderophore ferric enterobactin. We characterized the ability of seven analogs of enterobactin to supply iron via FepA by quantitatively measuring the binding and transport of their 59Fe complexes. The experiments refuted the idea that chirality of the iron complex affects its recognition by FepA and demonstrated the necessity of an unsubstituted catecholate coordination center for binding to the outer membrane protein. Among the compounds we tested, only ferric enantioenterobactin, the synthetic, left-handed isomer of natural enterobactin, and ferric TRENCAM, which substitutes a tertiary amine for the macrocyclic lactone ring of ferric enterobactin but maintains an unsubstituted catecholate iron complex, were recognized by FepA (Kd ≈ 20 nM). Ferric complexes of other analogs (TRENCAM-3,2-HOPO; TREN-Me-3,2-HOPO; MeMEEtTAM; MeME-Me-3,2-HOPO; K3MECAMS; agrobactin A) with alterations to the chelating groups and different net charge on the iron center neither adsorbed to nor transported through FepA. We also compared the binding and uptake of ferric enterobactin by homologs of FepA from Bordetella bronchisepticus, Pseudomonas aeruginosa, and Salmonella typhimurium in the native organisms and as plasmid-mediated clones expressed in E. coli. All the transport proteins bound ferric enterobactin with high affinity (Kd ≤ 100 nM) and transported it at comparable rates (≥50 pmol/min/109 cells) in their own particular membrane environments. However, the FepA and IroN proteins of S. typhimurium failed to efficiently function in E. coli. For E. coli, S. typhimurium, and P. aeruginosa, the rate of ferric enterobactin uptake was a sigmoidal function of its concentration, indicating a cooperative transport reaction involving multiple interacting binding sites on FepA. 相似文献
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Bannen RM Suresh V Phillips GN Wright SJ Mitchell JC 《Bioinformatics (Oxford, England)》2008,24(20):2339-2343
MOTIVATION: For many biotechnological purposes, it is desirable to redesign proteins to be more structurally and functionally stable at higher temperatures. For example, chemical reactions are intrinsically faster at higher temperatures, so using enzymes that are stable at higher temperatures would lead to more efficient industrial processes. We describe an innovative and computationally efficient method called Improved Configurational Entropy (ICE), which can be used to redesign a protein to be more thermally stable (i.e. stable at high temperatures). This can be accomplished by systematically modifying the amino acid sequence via local structural entropy (LSE) minimization. The minimization problem is modeled as a shortest path problem in an acyclic graph with nonnegative weights and is solved efficiently using Dijkstra's method. 相似文献
8.
Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in the human proteome. As many of these possess multiple PDZ domains, the potential combinations of associations with proteins that possess PBMs (PDZ-binding motifs) are vast. However, PDZ domain recognition is a highly specific process, and much less promiscuous than originally thought. Furthermore, a large number of PDZ domain-containing proteins have been linked directly to the control of processes whose loss, or inappropriate activation, contribute to the development of human malignancies. These regulate processes as diverse as cytoskeletal organization, cell polarity, cell proliferation and many signal transduction pathways. In the present review, we discuss how PBM-PDZ recognition and imbalances therein can perturb cellular homoeostasis and ultimately contribute to malignant progression. 相似文献
9.
Selvarajan Vanitha Upashi Goswami Nidhi Chaubey Siddhartha S. Ghosh Pallab Sanpui 《Biotechnology letters》2016,38(2):243-249
Objectives
Granulocyte macrophage colony stimulating factor (GMCSF), an important therapeutic cytokine, was immobilized onto silica nanoparticles. Maintenance of structural integrity and biological performance in immobilized cytokine was assessed to augment its applicability in possible biomedical implications.Results
Following its cloning and expression in E. coli, the recombinant human GMCSF (hGMCSF) was purified as a GST-tagged protein corresponding to a 42 kDa band on SDS-PAGE. The purified cytokine was immobilized onto biocompatible silica nanoparticles (~129.4 nm) by adsorption and the binding was confirmed by dynamic light scattering and infrared spectroscopy. Maximum binding of hGMCSF was at 6.4 µg mg?1 silica nanoparticles. Efficient release of the cytokine from the nanoparticles with its structural integrity intact was deduced from circular dichroism spectroscopy. hGMCSF-immobilized silica nanoparticles efficiently increased the proliferation of RAW 264.7 macrophage cells with 50 % increase in proliferation at 600 ng hGMCSF µg?1 silica nanoparticles.Conclusions
Silica nanoparticles successfully immobilized hGMCSF maintaining its structural integrity. The release of the immobilized cytokine from silica nanoparticles resulted in the increased proliferation of macrophages indicating the potential of the system in future applications.10.