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71.
Kuduk SD DiPardo RM Chang RK Di Marco CN Murphy KL Ransom RW Reiss DR Tang C Prueksaritanont T Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2007,17(13):3608-3612
SAR study of the biphenyl region of cyclopropanecarboxamide derived bradykinin B(1) antagonists was examined. Incorporation of a pyridine in place of the proximal phenyl ring and chlorination of the distal phenyl ring proved to be well tolerated and provided compounds with improved pharmacokinetic profiles, CNS penetration, and enhanced receptor occupancy. 相似文献
72.
Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale. 相似文献
73.
Nitric oxide (NO) is an important vasorelaxant produced along with L-citrulline from L-arginine in a reaction catalyzed by endothelial nitric oxide synthase (eNOS). Previous studies suggested that the recycling of L-citrulline to L-arginine is essential for NO production in endothelial cells. However, there is no direct evidence demonstrating the degree to which the recycling of L-citrulline to L-arginine is coupled to NO production. We hypothesized that the amount of NO formed would be significantly higher than the amount of L-citrulline formed due to the efficiency of L-citrulline recycling via the citrulline-NO cycle. To test this hypothesis, endothelial cells were incubated with [14C]-L-arginine and stimulated by various agents to produce NO. The extent of NO and [14C]-L-citrulline formation were simultaneously determined. NO production exceeded apparent L-citrulline formation of the order of 8 to 1, under both basal and stimulated conditions. As further support, alpha-methyl-DL-aspartate, an inhibitor of argininosuccinate synthase (AS), a component of the citrulline-NO cycle, inhibited NO production in a dose-dependent manner. The results of this study provide evidence for the essential and efficient coupling of L-citrulline recycling, via the citrulline-NO cycle, to endothelial NO production. 相似文献
74.
Soil Organic Phosphorus Transformations During Pedogenesis 总被引:2,自引:0,他引:2
Benjamin L. Turner Leo M. Condron Sarah J. Richardson Duane A. Peltzer Victoria J. Allison 《Ecosystems》2007,10(7):1166-1181
Abstract
Long-term changes in soil phosphorus influence ecosystem development and lead to a decline in the productivity of forests
in undisturbed landscapes. Much of the soil phosphorus occurs in a series of organic compounds that differ in their availability
to organisms, but changes in the relative abundance of these compounds during pedogenesis remain unknown. We used alkaline
extraction and solution phosphorus-31 nuclear magnetic resonance spectroscopy to assess the chemical nature of soil organic
phosphorus along a 120,000-year post-glacial chronosequence at Franz Josef, New Zealand. Inositol phosphates, DNA, phospholipids,
and phosphonates accumulated rapidly during the first 500 years of soil development characterized by nitrogen limitation of
biological productivity, but then declined slowly to low concentrations in older soils characterized by intense phosphorus
limitation. However, the relative contribution of the various compounds to the total organic phosphorus varied along the sequence
in dramatic and surprising ways. The proportion of inositol hexakisphosphate, conventionally considered to be relatively recalcitrant
in the environment, declined markedly in older soils, apparently due to a corresponding decline in amorphous metal oxides,
which weather to crystalline forms during pedogenesis. In contrast, the proportion of DNA, considered relatively bioavailable
in soil, increased continually throughout the sequence, due apparently to incorporation within organic structures that provide
protection from biological attack. The changes in soil organic phosphorus coincided with marked shifts in plant and microbial
communities, suggesting that differences in the forms and bioavailability of soil organic phosphorus have ecological significance.
Overall, the results strengthen our understanding of phosphorus transformations during pedogenesis and provide important insight
into factors regulating the composition of soil organic phosphorus. 相似文献
75.
High cell density cultivation of Pseudomonas putida KT2440 using glucose without the need for oxygen enriched air supply 下载免费PDF全文
76.
Algar WR Prasuhn DE Stewart MH Jennings TL Blanco-Canosa JB Dawson PE Medintz IL 《Bioconjugate chemistry》2011,22(5):825-858
Interest in developing diverse nanoparticle (NP)-biological composite materials continues to grow almost unabated. This is motivated primarily by the desire to simultaneously exploit the properties of both NP and biological components in new hybrid devices or materials that can be applied in areas ranging from energy harvesting and nanoscale electronics to biomedical diagnostics. The utility and effectiveness of these composites will be predicated on the ability to assemble these structures with control over NP/biomolecule ratio, biomolecular orientation, biomolecular activity, and the separation distance within the NP-bioconjugate architecture. This degree of control will be especially critical in creating theranostic NP-bioconjugates that, as a single vector, are capable of multiple functions in vivo, including targeting, image contrast, biosensing, and drug delivery. In this review, a perspective is given on current and developing chemistries that can provide improved control in the preparation of NP-bioconjugates. The nanoscale properties intrinsic to several prominent NP materials are briefly described to highlight the motivation behind their use. NP materials of interest include quantum dots, carbon nanotubes, viral capsids, liposomes, and NPs composed of gold, lanthanides, silica, polymers, or magnetic materials. This review includes a critical discussion on the design considerations for NP-bioconjugates and the unique challenges associated with chemistry at the biological-nanoscale interface-the liabilities of traditional bioconjugation chemistries being particularly prominent therein. Select bioorthogonal chemistries that can address these challenges are reviewed in detail, and include chemoselective ligations (e.g., hydrazone and Staudinger ligation), cycloaddition reactions in click chemistry (e.g., azide-alkyne cyclyoaddition, tetrazine ligation), metal-affinity coordination (e.g., polyhistidine), enzyme driven modifications (e.g., HaloTag, biotin ligase), and other site-specific chemistries. The benefits and liabilities of particular chemistries are discussed by highlighting relevant NP-bioconjugation examples from the literature. Potential chemistries that have not yet been applied to NPs are also discussed, and an outlook on future developments in this field is given. 相似文献
77.
Suen G Weimer PJ Stevenson DM Aylward FO Boyum J Deneke J Drinkwater C Ivanova NN Mikhailova N Chertkov O Goodwin LA Currie CR Mead D Brumm PJ 《PloS one》2011,6(4):e18814
Fibrobacter succinogenes is an important member of the rumen microbial community that converts plant biomass into nutrients usable by its host. This bacterium, which is also one of only two cultivated species in its phylum, is an efficient and prolific degrader of cellulose. Specifically, it has a particularly high activity against crystalline cellulose that requires close physical contact with this substrate. However, unlike other known cellulolytic microbes, it does not degrade cellulose using a cellulosome or by producing high extracellular titers of cellulase enzymes. To better understand the biology of F. succinogenes, we sequenced the genome of the type strain S85 to completion. A total of 3,085 open reading frames were predicted from its 3.84 Mbp genome. Analysis of sequences predicted to encode for carbohydrate-degrading enzymes revealed an unusually high number of genes that were classified into 49 different families of glycoside hydrolases, carbohydrate binding modules (CBMs), carbohydrate esterases, and polysaccharide lyases. Of the 31 identified cellulases, none contain CBMs in families 1, 2, and 3, typically associated with crystalline cellulose degradation. Polysaccharide hydrolysis and utilization assays showed that F. succinogenes was able to hydrolyze a number of polysaccharides, but could only utilize the hydrolytic products of cellulose. This suggests that F. succinogenes uses its array of hemicellulose-degrading enzymes to remove hemicelluloses to gain access to cellulose. This is reflected in its genome, as F. succinogenes lacks many of the genes necessary to transport and metabolize the hydrolytic products of non-cellulose polysaccharides. The F. succinogenes genome reveals a bacterium that specializes in cellulose as its sole energy source, and provides insight into a novel strategy for cellulose degradation. 相似文献
78.
Bird song is a widely used model in the study of animal communication and sexual selection, and several song features have been shown to reflect the quality of the singer. Recent studies have demonstrated that song amplitude may be an honest signal of current condition in males and that females prefer high amplitude songs. In addition, birds raise the amplitude of their songs to communicate in noisy environments. Although it is generally assumed that louder song should be more costly to produce, there has been little empirical evidence to support this assumption. We tested the assumption by measuring oxygen consumption and respiratory patterns in adult male zebra finches (Taeniopygia guttata) singing at different amplitudes in different background noise conditions. As background noise levels increased, birds significantly increased the sound pressure level of their songs. We found that louder songs required significantly greater subsyringeal air sac pressure than quieter songs. Though increased pressure is probably achieved by increasing respiratory muscle activity, these increases did not correlate with measurable increases in oxygen consumption. In addition, we found that oxygen consumption increased in higher background noise, independent of singing behaviour. This observation supports previous research in mammals showing that high levels of environmental noise can induce physiological stress responses. While our study did not find that increasing vocal amplitude increased metabolic costs, further research is needed to determine whether there are other non-metabolic costs of singing louder or costs associated with chronic noise exposure. 相似文献
79.
80.
Brim H Kumar K Nazarian J Hathout Y Jafarian A Lee E Green W Smoot D Park J Nouraie M Ashktorab H 《PloS one》2011,6(6):e20216