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排序方式: 共有397条查询结果,搜索用时 31 毫秒
51.
Klaus Urbahns Michael H?rter Markus Albers Delf Schmidt Beatrix Stelte-Ludwig Ulf Brüggemeier Andrea Vaupel Christoph Gerdes 《Bioorganic & medicinal chemistry letters》2002,12(2):205-208
Vitronectin receptor (alpha(V)beta(3)) antagonism has been implicated as a mechanism for the treatment of restenosis following balloon angioplasty. In this work we present results from screening of a focused combinatorial library based on a biphenyl moiety. Our SAR studies led to the identification of compounds with subnanomolar activity, selectivity towards the related GPIIbIIIa receptor and functional activity on human smooth muscle cell migration. 相似文献
52.
The RelE and RelB proteins constitute the RNA interferase (toxin) and its cognate inhibitor (antitoxin) components of the Escherichia coli relBE toxin-antitoxin system. Despite the well-described functionality and physiological activity of this system in E. coli, no structural study was performed on the folding and stability of the protein pair in solution. Here we structurally and thermodynamically characterize the RelBE system components from E. coli in solution, both separately and in their complexed state. The RelB antitoxin, an alpha-helical protein according to circular dichroism and infrared spectroscopy, forms oligomers in solution, exhibits high thermostability with a TM of 58.5 degrees C, has a considerable heat resistance, and has high unfolding reversibility. In contrast, the RelE toxin includes a large portion of antiparallel beta-sheets, displays lower thermostability with a TM of 52.5 degrees C, and exhibits exceptional sensitivity to heat. Complex formation, accompanied by a structural transition, leads to a 12 degrees C increase in the TM and substantial heat resistance. Moreover, in vivo interaction and protein footprint experiments indicate that the C-terminal part of RelB is responsible for RelB-RelE interaction, being protease sensitive in its free state, while it becomes protected from proteolysis when complexed with RelE. Overall, our findings support the notion that RelB lacks a well-organized hydrophobic core in solution whereas RelE is a well-folded protein. Furthermore, our results support that RelB protein from E. coli is similar to ParD and CcdA antitoxins in both fold and thermodynamic properties. The differential folding state of the proteins is discussed in the context of their physiological activities. 相似文献
53.
Mechanism of DNA segregation in prokaryotes: ParM partitioning protein of plasmid R1 co-localizes with its replicon during the cell cycle.
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The parA locus of plasmid R1 encodes a prokaryotic centromere-like system that mediates genetic stabilization of plasmids by an unknown mechanism. The locus codes for two proteins, ParM and ParR, and a centromere-like DNA region (parC) to which the ParR protein binds. We showed recently that ParR mediates specific pairing of parC-containing DNA molecules in vitro. To obtain further insight into the mechanism of plasmid stabilization, we examined the intracellular localization of the components of the parA system. We found that ParM forms discrete foci that localize to specific cellular regions in a simple, yet dynamic pattern. In newborn cells, ParM foci were present close to both cell poles. Concomitant with cell growth, new foci formed at mid-cell. A point mutation that abolished the ATPase activity of ParM simultaneously prevented cellular localization and plasmid partitioning. A parA-containing plasmid localized to similar sites, i.e. close to the poles and at mid-cell, thus indicating that the plasmid co-localizes with ParM. Double labelling of single cells showed that plasmid DNA and ParM indeed co-localize. Thus, our data indicate that parA is a true partitioning system that mediates pairing of plasmids at mid-cell and subsequently moves them to the cell poles before cell division. 相似文献
54.
Excess mortality in persons with severe mental disorders: a multilevel intervention framework and priorities for clinical practice,policy and research agendas
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Nancy H. Liu Gail L. Daumit Tarun Dua Ralph Aquila Fiona Charlson Pim Cuijpers Benjamin Druss Kenn Dudek Melvyn Freeman Chiyo Fujii Wolfgang Gaebel Ulrich Hegerl Itzhak Levav Thomas Munk Laursen Hong Ma Mario Maj Maria Elena Medina‐Mora Merete Nordentoft Dorairaj Prabhakaran Karen Pratt Martin Prince Thara Rangaswamy David Shiers Ezra Susser Graham Thornicroft Kristian Wahlbeck Abe Fekadu Wassie Harvey Whiteford Shekhar Saxena 《World psychiatry》2017,16(1):30-40
Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base are scarce. Furthermore, the majority of available interventions focus on a single or an otherwise limited number of risk factors. Here we present a multilevel model highlighting risk factors for excess mortality in persons with SMD at the individual, health system and socio‐environmental levels. Informed by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual‐focused, health system‐focused, and community level and policy‐focused interventions. Incorporating lessons learned from the multilevel model of risk and the comprehensive intervention framework, we identify priorities for clinical practice, policy and research agendas. 相似文献
55.
The long-term benthic disturbance experiment (BENDEX) was started on the eastern Weddell Sea shelf off Austasen (Antarctica)
during ‘Polarstern’ cruise ANT XXI/2 in December 2003 to simulate the impact of grounding icebergs on the seabed and follow
the steps and timescales of recovery of disturbed benthos and demersal fish communities. Here, we report the basic approach
and first results for this experimental field study. By means of 11 densely-placed hauls with a modified bottom trawl, a seabed
area of approximately 100 × 1000 m was artificially scoured to inflict a similar damage to the benthic habitats as a grounding
iceberg. Before the disturbance event and 11 days after it, the seafloor communities were sampled (invertebrate assemblages
by multibox corers, the fish fauna by trawl hauls) and comparatively analyzed. Sediment texture and chemistry was not significantly
altered by the heavy disturbance inflicted by repeated trawling, whereas the fauna was negatively affected. Invertebrate benthic
biomass was drastically reduced by a factor of 10, while mean abundances were only slightly reduced. Demersal fish biomass
and abundance were slightly but not significantly smaller after the disturbance. Effects of disturbance became more evident
in the composition of the fish fauna, with Trematomus pennelli and T. hansoni being dominant at disturbed sites, whereas Chionodraco myersi was the dominant species in trawl catches from undisturbed stations. 相似文献
56.
Kenn Gerdes 《The EMBO journal》2009,28(3):171-172
57.
58.
59.
Synthesis, dopamine and serotonin transporter binding affinities of novel analogues of meperidine 总被引:1,自引:0,他引:1
Lomenzo SA Izenwasser S Gerdes RM Katz JL Kopajtic T Trudell ML 《Bioorganic & medicinal chemistry letters》1999,9(23):3273-3276
A series of meperidine analogues was synthesized and the binding affinities for the dopamine and serotonin transporters were determined. The substituents on the phenyl ring greatly influenced the potency and selectivity of these compounds for the transporter binding sites. In general, meperidine (3) and its analogues were more selective for serotonin transporter binding sites and the esters 9 were more potent than the corresponding nitriles 8. The 3,4-dichloro derivative 9e was the most potent ligand of the series for dopamine transporter binding sites while the 2-naphthyl derivative 9g exhibited the most potent binding affinity and was highly selective for serotonin transporter binding sites. 相似文献
60.
Foubert K Cuyckens F Matheeussen A Vlietinck A Apers S Maes L Pieters L 《Phytochemistry》2011,72(11-12):1414-1423
Bioassay-guided isolation was performed on the leaves of Apodytes dimidiata E. Mey. Ex Arn. (Icacinaceae), based on previously demonstrated activity against Leishmania. Six saponins never isolated from nature before were elucidated with LC-MS/MS, GC-MS and 1D and 2D NMR. The compounds apodytine A-F are responsible at least in part for the antiprotozoal activity, but also possess haemolytic activity and display antiangiogenic activity in the rat aorta ring assay, an effect which may be due to a non-selective toxicity. 相似文献