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151.
George TG Johnsamuel J Delfín DA Yakovich A Mukherjee M Phelps MA Dalton JT Sackett DL Kaiser M Brun R Werbovetz KA 《Bioorganic & medicinal chemistry》2006,14(16):5699-5710
N(1)-Phenyl-3,5-dinitro-N(4),N(4)-di-n-propylsulfanilamide (1) and N(1)-phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. Nine of the sulfonamides display in vitro IC(50) values under 500 nM against African trypanosomes, and the most active antikinetoplastid compounds also inhibit the in vitro assembly of purified leishmanial tubulin with potencies similar to that of 2. While several of the potent compounds are rapidly degraded by rat liver S9 fractions in vitro, N(1)-(3-hydroxy)phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (21) displays an IC(50) value of 260 nM against African trypanosomes in vitro and is more stable than 2 in the in vitro metabolism assay. 相似文献
152.
Recent experimental work involving Dictyostelium discoideum seems to contradict several theoretical models. Experiments suggest that localization of the release of the chemoattractant
cyclic adenosine monophosphate to the uropod of the cell is important for stream formation during aggregation. Yet several
mathematical models are able to reproduce streaming as the cells aggregate without taking into account localization of the
chemoattractant. A careful analysis of the experiments and the theory suggests the two major features of the system which
are important to stream formation are random cell motion and chemotaxis to regions of higher cell density. Random cell motion
acts to reduce streaming, whereas chemotaxis to regions of higher cell density reinforces streaming. With this understanding,
the experimental results can be explained in a manner consistent with the theoretical results. In all the experiments, alterations
in the two main factors of random motion and chemotaxis to regions of higher cell density, not the localization of the release
of the chemoattractant, can explain the results as they relate to streaming. Additionally, a comparison of results from a
mathematical model that simulates cells which localize the chemoattractant and cells which do not shows little difference
in the streaming patterns. 相似文献
153.
Doxorubicin immunoconjugates containing bivalent,lysosomally-cleavable dipeptide linkages 总被引:4,自引:0,他引:4
Dubowchik GM Radia S Mastalerz H Walker MA Firestone RA Dalton King H Hofstead SJ Willner D Lasch SJ Trail PA 《Bioorganic & medicinal chemistry letters》2002,12(11):1529-1532
Bivalent doxorubicin (DOX)-dipeptides (16a-c) were prepared and conjugated to the monoclonal antibody BR96. The dipeptides are cleaved by lysosomal proteases following internalization of the resulting immunoconjugates. Conjugate 18b demonstrated antigen-specific in vitro tumor cell killing activity (IC(50)=0.2 microM) that was equipotent to DOX with a near doubling of drug molecules/MAb. Size exclusion chromatography showed 18b to be a noncovalent dimer that was formed immediately upon conjugation. 相似文献
154.
Annamarie C. Dalton William A. Barton 《Protein science : a publication of the Protein Society》2014,23(5):517-525
Secreted mammalian proteins require the development of robust protein over‐expression systems for crystallographic and biophysical studies of protein function. Due to complex disulfide bonds and distinct glycosylation patterns preventing folding and expression in prokaryotic expression hosts, many secreted proteins necessitate production in more complex eukaryotic expression systems. Here, we elaborate on the methods used to obtain high yields of purified secreted proteins from transiently or stably transfected mammalian cell lines. Among the issues discussed are the selection of appropriate expression vectors, choice of signal sequences for protein secretion, availability of fusion tags for enhancing protein stability and purification, choice of cell line, and the large‐scale growth of cells in a variety of formats. 相似文献
155.
Brian E. Dalton Ellis R. Loew Thomas W. Cronin Karen L. Carleton 《Proceedings. Biological sciences / The Royal Society》2014,281(1797)
Vision frequently mediates critical behaviours, and photoreceptors must respond to the light available to accomplish these tasks. Most photoreceptors are thought to contain a single visual pigment, an opsin protein bound to a chromophore, which together determine spectral sensitivity. Mechanisms of spectral tuning include altering the opsin, changing the chromophore and incorporating pre-receptor filtering. A few exceptions to the use of a single visual pigment have been documented in which a single mature photoreceptor coexpresses opsins that form spectrally distinct visual pigments, and in these exceptions the functional significance of coexpression is unclear. Here we document for the first time photoreceptors coexpressing spectrally distinct opsin genes in a manner that tunes sensitivity to the light environment. Photoreceptors of the cichlid fish, Metriaclima zebra, mix different pairs of opsins in retinal regions that view distinct backgrounds. The mixing of visual pigments increases absorbance of the corresponding background, potentially aiding the detection of dark objects. Thus, opsin coexpression may be a novel mechanism of spectral tuning that could be useful for detecting prey, predators and mates. However, our calculations show that coexpression of some opsins can hinder colour discrimination, creating a trade-off between visual functions. 相似文献
156.
The Indian black berry (Syzygium cumini Skeels) has a great nutraceutical and medicinal properties. As in other fruit crops, the
fruit characteristics are important attributes for differentiation were also determined for different accessions of S. cumini. The fruit
weight, length, breadth, length: breadth ratio, pulp weight, pulp content, seed weight and pulp: seed ratio significantly varied in
different accessions. Molecular characterization was carried out using PCR based RAPD technique. Out of 80 RAPD primers, only
18 primers produced stable polymorphisms that were used to examine the phylogenetic relationship. A sum of 207 loci were
generated out of which 201 loci found polymorphic. The average genetic dissimilarity was 97 per cent among jamun accessions.
The phylogenetic relationship was also determined by principal coordinates analysis (PCoA) that explained 46.95 per cent
cumulative variance. The two-dimensional PCoA analysis showed grouping of the different accessions that were plotted into four
sub-plots, representing clustering of accessions. The UPGMA (r = 0.967) and NJ (r = 0.987) dendrogram constructed based on the
dissimilarity matrix revealed a good degree of fit with the cophenetic correlation value. The dendrogram grouped the accessions
into three main clusters according to their eco-geographical regions which given useful insight into their phylogenetic
relationships. 相似文献
157.
不同耕作措施对冬小麦-夏玉米复种连作系统土壤有机碳和水分利用效率的影响 总被引:2,自引:1,他引:1
在连续8年田间定位试验的基础上,分析了关中平原冬小麦 夏玉米复种连作系统2008—2009年连续两个生长季期间不同耕作措施(结合秸秆还田和不还田)对土壤有机碳和水分利用率的影响.结果表明: 相对于传统耕作,保护性耕作有利于土壤有机碳、水分利用效率和作物产量的提高,其中在“深松+秸秆还田”耕作模式下的增幅最高,土壤有机碳含量在0~30 cm土层增幅达到19.5%,水分利用效率和作物产量提高了16.9%和20.5%,而免耕模式则有效提高了0~10 cm土层有机碳含量.在该地区土壤和气候条件下,深松结合秸秆粉碎还田是最理想的耕作模式,最有利于土壤有机碳累积,并提高水分利用效率和作物产量. 相似文献
158.
159.
Fernanda Moura Vargas Dias Rogério Faustino Ribeiro Júnior Aurélia Araújo Fernandes Jonaina Fiorim Teresa Cristina Francischetto Travaglia Dalton Valentim Vassallo Ivanita Stefanon 《PloS one》2014,9(9)
Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones’ effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K+) channels and Na+K+-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K+ channels and Na+K+-ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100 µM) and the following K+ channels blockers: tetraethylammonium (TEA, 2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 µM) and charybdotoxin (ChTX, 0.1 µM). The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K+ channel (Kv) participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax in females than in males. The functional activity of the Na+K+-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUAincubation. OUA reduced K+-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na+K+-ATPase functional activity. L-NAME reduced K+-induced relaxation only in the female group, suggesting that nitric oxide (NO) participates more in their functional Na+K+-ATPase activity. These results suggest that the K+ channels involved in the gender-based vascular relaxation differences are the large conductance Ca2+-activated K+ channels (BKCa) in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males. 相似文献
160.
K Michałek M Laszczyńska AK Ciechanowicz A Herosimczyk I Rotter M Oganowska 《Biotechnic & histochemistry》2014,89(5):342-347
Aquaporin 2 (AQP2) is a small, integral tetrameric plasma membrane protein that is expressed in mammalian kidneys. The specific constitution of this protein and its selective permeability to water means that AQP2 plays an important role in hypertonic urine production. Immunolocalization of AQP2 has been studied in humans, monkeys, sheep, dogs, rabbits, rats, mice and adult cattle. We analyzed the expression of AQP2 in kidneys of 7-month-old Polish-Friesian var. black and white male calves. AQP2 was localized in the principal cells of collecting ducts in medullary rays penetrating the renal cortex and in the collecting ducts of renal medulla. AQP2 was expressed most strongly in the apical plasma membrane, but expression was observed also in the intracellular vesicles and basolateral plasma membrane. Our study provides new information concerning the immunolocalization of AQP2 in calf kidneys. 相似文献