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61.
62.
Griebenow N Buchmueller A Kolkhof P Schamberger J Bischoff H 《Bioorganic & medicinal chemistry letters》2011,21(12):3648-3653
Novel squalene synthase inhibitors are disclosed. The design, synthesis, SAR and pharmacological profile of the compounds are discussed. 相似文献
63.
The coating of a C18-reversed-phase high performance liquid chromatography support (octadecylsilyl-Hypersil) with a tetraalkylammonium salt (methyltrioctylammonium chloride) produces a chromatographic matrix with both ionic and hydrophobic character. Using this material oligonucleotides and tRNAs can be separated with high resolution. The observed resolution is in part due to the apparent lack of diffusion processes occurring during chromatography with this matrix. Some tRNAs can be obtained in high purity from a bulk tRNA mixture after a single chromatographic step. In general it is more efficient to use the matrix as the last step of a purification procedure for a particular tRNA. A two-step procedure is described which allows, in some cases, the isolation of small quantities of specific tRNA isoacceptors. 相似文献
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65.
A recent study of beta-hemolytic Escherichia coli isolated from diarrheic swine found that 53% were resistant to chloramphenicol, a drug that has been prohibited from use in food animals in the US since the mid-1980s. To identify the factors governing the persistence of chloramphenicol resistance in the absence of specific selection pressure, the location of the chloramphenicol resistance gene cmlA and its linkage to other resistance determinants were investigated. Southern blot analysis of plasmid DNA from 46 swine E. coli isolates indicated that cmlA was present on large plasmids greater than 100 kbp. Fifty-two percent of the isolates were able to transfer chloramphenicol resistance to an E. coli recipient at conjugation frequencies ranging from 10(-3) to 10(-8) per recipient. Antimicrobial susceptibility tests on transconjugant strains demonstrated that resistance to sulfamethoxazole, tetracycline, and kanamycin frequently transferred along with chloramphenicol resistance. The transconjugant strains possessed at least two distinct class 1 integrons that linked cmlA to both aminoglycoside resistance genes aadA1 and aadA2 and either to sul1 or to sul3 sulphonamide resistance genes. These results suggest that in the absence of specific chloramphenicol selection pressure, the cmlA gene is maintained by virtue of gene linkage to genes encoding resistance to antimicrobials that are currently approved for use in food animals. 相似文献
66.
AIMS: The dynamics of bioaerosol generation in specific occupational environments where mail is manually unpacked and sorted was investigated. METHODS AND RESULTS: Total number of airborne particles was determined in four different size classes (0.3-0.5, 0.5-1, 1-5 and >5 microm) by laser particle counting. Time dependent formation of bioaerosols was monitored by culturing methods and by specific staining followed by flow cytometry. Besides handling of regular mail, specially prepared letters ('spiked letters') were added to the mailbags to deliberately release powdered materials from letters and to simulate high impact loads. These letters contained various dry powdered biological and nonbiological materials such as milk powder, mushrooms, herbs and cat litter. Regarding the four size classes, particulate aerosol composition before mail handling was determined as 83.2 +/- 1.0, 15.2 +/- 0.7, 1.7 +/- 0.4 and 0.04 +/- 0.02%, respectively, whereas the composition changed during sorting to 66.8 +/- 7.9, 22.3 +/- 3.6, 10.4 +/- 4.0 and 0.57 +/- 0.27%, respectively. Mail processing resulted in an increase in culturable airborne bacteria and fungi. Maximum concentrations of bacteria reached 450 CFU m(-3), whereas 270 CFU of fungi were detected. CONCLUSIONS: Indoor particle concentrations steadily increased during mail handling mostly associated with particles of diameters >1 microm. However, it was not possible to distinguish spiked letters from nonspiked by simple particle counting and CFU determinations. SIGNIFICANCE AND IMPACT OF STUDY: The dynamics of bioaerosol generation have to be addressed when monitoring specific occupational environments (such as mail sorting facilities) regarding the occurrence of biological particles. 相似文献
67.
In a recent study on the degradation of N,N-dibutylurea (DBU), a breakdown product of benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate], the active ingredient in Benlate® fungicides, degradation half-lives of 1.4–46.5days were observed across several soils incubated at various combinations of soil moisture potential (–0.03 and –0.1MPa) and temperature (23, 33, and 44°C) for a single DBU application of 0.08 and 0.8 g g–1 (Lee et al. 2004). However, Benlate® can be applied as often as every 7days resulting in the repeated application of DBU likely to be present in the Benlate® over a growing season. In this study, the effect of seven repeated DBU applications on mineralization rate was investigated in two soils, which encompass the range in rates previously observed. For the slower degrading soil, repeated DBU application increased mineralization from 0.029 to 0.99day–1 at the 0.08 g g–1 rate, and 0.037 to 0.89day–1 at the 0.8 g g–1 rate. For the faster degrading soil, effects on mineralization of repeated DBU applications were small to negligible. For the latter soil, the effect on mineralization of applied DBU concentrations from 0.0008 to 80 g g–1 was also investigated. Mineralization rates decreased from 0.43 to 0.019day–1 with increasing DBU concentrations. However, the amount of DBU mineralized by day 70 was similar across concentrations and averaged 83% of applied. Microbial respiration was not affected by increasing DBU concentrations. These findings support the supposition that DBU is readily degraded by soil microorganisms, thus unlikely to accumulate in agricultural soils. 相似文献
68.
Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death 下载免费PDF全文
Chatterjee I Becker P Grundmeier M Bischoff M Somerville GA Peters G Sinha B Harraghy N Proctor RA Herrmann M 《Journal of bacteriology》2005,187(13):4488-4496
The ability of Staphylococcus aureus to adapt to various conditions of stress is the result of a complex regulatory response. Previously, it has been demonstrated that Clp homologues are important for a variety of stress conditions, and our laboratory has shown that a clpC homologue was highly expressed in the S. aureus strain DSM20231 during biofilm formation relative to expression in planktonic cells. Persistence and long-term survival are a hallmark of biofilm-associated staphylococcal infections, as cure frequently fails even in the presence of bactericidal antimicrobials. To determine the role of clpC in this context, we performed metabolic, gene expression, and long-term growth and survival analyses of DSM20231 as well as an isogenic clpC allelic-replacement mutant, a sigB mutant, and a clpC sigB double mutant. As expected, the clpC mutant showed increased sensitivity to oxidative and heat stresses. Unanticipated, however, was the reduced expression of the tricarboxylic acid (TCA) cycle gene citB (encoding aconitase), resulting in the loss of aconitase activity and preventing the catabolization of acetate during the stationary phase. clpC inactivation abolished post-stationary-phase recovery but also resulted in significantly enhanced stationary-phase survival compared to that of the wild-type strain. These data demonstrate the critical role of the ClpC ATPase in regulating the TCA cycle and implicate ClpC as being important for recovery from the stationary phase and also for entering the death phase. Understanding the stationary- and post-stationary-phase recovery in S. aureus may have important clinical implications, as little is known about the mechanisms of long-term persistence of chronic S. aureus infections associated with formation of biofilms. 相似文献
69.
Misof B Niehuis O Bischoff I Rickert A Erpenbeck D Staniczek A 《Journal of experimental zoology. Part B. Molecular and developmental evolution》2006,306(1):70-88
RNA molecules and in particular the nuclear SSU RNA play an important role in molecular systematics. With the advent of increasingly parameterized substitution models in systematic research, the incorporation of secondary-structure information became a realistic option compensating interdependence of character variation. As a prerequisite, consensus structures of eukaryotic SSU RNA molecules have become available through extensive comparative analyses and crystallographic studies. Despite extensive research in hexapod phylogenetics, consensus SSU RNA secondary structures focusing on hexapods have not yet been explored. In this study, we compiled a representative hexapod SSU data set of 261 sequences and inferred a specific consensus SSU secondary-structure model. Our search for conserved structural motives relied on a combined approach of thermodynamic and covariation analyses. The hexapod consensus-structure model deviates from the canonical eukaryotic model in a number of helices. Additionally, in several helices the hexapod sequences did not support a single consensus structure. We provide consensus structures of these sections of single less-inclusive taxa, thus facilitating the adaptation of the consensus hexapod model to less-inclusive phylogenetic questions. The secondary-structure catalog will foster the application of RNA structure models in phylogenetic analyses using the SSU rRNA molecule, and it will improve the realism of substitution models and the reliability of reconstructions based on rRNA sequences. 相似文献
70.
Bischoff JE 《Journal of biomechanics》2006,39(7):1361-2; author reply1362