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Leslie Edwards Danielle Turner Cody Champion Megha Khandelwal Kailee Zingler Cassidy Stone Ruwini D. Rajapaksha Jing Yang Mahinda I. Ranasinghe Alexander Kornienko Liliya V. Frolova Snezna Rogelj 《Bioorganic & medicinal chemistry letters》2018,28(10):1879-1886
Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1?μM, the lead compound 1 completely (ca. 109?CFU/mL) eradicated such Gram-positive organisms as S. aureus (MRSA, MSSA), E. faecalis (VRE), S. pyogenes and S. mutans when irradiated with white light for 2?min. At the concentration of 5?μM and in the presence of polymyxin E at non-bactericidal 1.25?μg/mL concentration, 1 also showed a 7-log to 9-log reductions in bacterial counts of such Gram-negative organisms as multi-drug resistant (MDR) A. baumannii, MDR P. aeruginosa, E. coli and Klebsiella pneumoniae (CRE: KPC and NDM-1), also when irradiated with white light for 2?min. The structure-activity relationship studies revealed that unsubstituted at benzene rings 2,3-distyrylindole 2 was most potent and gave a 5-order of magnitude eradication of a MRSA strain at the concentration of 30?nM upon irradiation with white light. Initial mechanistic experiments revealed the disruption of bacterial cell membrane, but indicated that singlet oxygen production, which is commonly associated with photodynamic therapy, may not play a role in the bactericidal effects of the 2,3-distyrylindoles. 相似文献
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Recording of mitochondrial transmembrane potential and volume in cultured rat osteoclasts by confocal laser scanning microscopy 总被引:2,自引:0,他引:2
H. Fujii S. H. Cody U. Seydel J. M. Papadimitriou D. J. Wood M.-H. Zheng 《Journal of molecular histology》1997,29(8):571-581
Osteoclasts are multinuclear bone-resorbing cells which contain abundant mitochondria. Morphological studies have suggested
that a correlation may exist between mitochondrial concentration and bone resorption by osteoclasts. However, investigation
of mitochondrial transmembrane potential (Delta rho) and volume has been hampered by the difficulty in obtaining a sufficient
number of osteoclasts for assessing these characteristics by flow cytometric analysis. In this study, we have used confocal
laser scanning microscopy after loading the cells with Rhodamine 123 and 10-nonyl Acridine Orange to record mitochondrial
Delta rho and volume, respectively, in isolated rat osteoclasts cultured on bovine bone slices. Optimal staining conditions
were found to be 10 mu g ml-1 for 40 min for Rhodamine, and 1 mu S mD for 10 min for the 10-nonyl Acridine Orange derivative.
Two osteoclast populations, whose shape seemed to reflect bone resorption and migratory functions, were identified depending
on their shape and on the distribution of the two dye probes. ‘Round-shaped’ osteoclasts had significantly higher mitochondrial
Delta rho and volume in the apical regions than in the basolateral portions (p 0.00001). In contrast, mitochondrial Delta
rho and volume in ‘irregular- shaped’ osteoclasts were rather evenly distributed in both these regions (p > 0.05). Our results
indicate that there is an apical polarization of mitochondria in osteoclasts corresponding to the energy demands associated
with bone resorption.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
65.
Geiger Paige C.; Cody Mark J.; Macken Rebecca L.; Bayrd Megan E.; Fang Yun-Hua; Sieck Gary C. 《Journal of applied physiology》2001,90(1):380-388
It has beenfound that maximum specific force (Fmax; force percross-sectional area) of rat diaphragm muscle doubles from birth to 84 days (adult). We hypothesize that this developmental change inFmax reflects an increase in myosin heavy chain (MHC) content per half-sarcomere (an estimate of the number of cross bridgesin parallel) and/or a greater force per cross bridge in fibersexpressing fast MHC isoforms compared with slow and neonatal MHCisoforms (MHCslow and MHCneo, respectively).Single Triton 100-X-permeabilized fibers were activated at a pCa of4.0. MHC isoform expression was determined by SDS-PAGE. MHC content per half-sarcomere was determined by densitometric analysis and comparison to a standard curve of known MHC concentrations. MHC content per half-sarcomere progressively increased during early postnatal development. When normalized for MHC content per half-sarcomere, fibersexpressing MHCslow and coexpressing MHCneoproduced less force than fibers expressing fast MHC isoforms. Weconclude that lower force per cross bridge in fibers expressingMHCslow and MHCneo contributes to the lowerFmax seen in early postnatal development. 相似文献
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Genetic architecture,biochemical underpinnings and ecological impact of floral UV patterning 下载免费PDF全文
Marcus T. Brock Lauren K. Lucas Nickolas A. Anderson Matthew J. Rubin R. J. Cody Markelz Michael F. Covington Upendra K. Devisetty Clint Chapple Julin N. Maloof Cynthia Weinig 《Molecular ecology》2016,25(5):1122-1140
Floral attraction traits can significantly affect pollinator visitation patterns, but adaptive evolution of these traits may be constrained by correlations with other traits. In some cases, molecular pathways contributing to floral attraction are well characterized, offering the opportunity to explore loci potentially underlying variation among individuals. Here, we quantify the range of variation in floral UV patterning (i.e. UV ‘bulls‐eye nectar guides) among crop and wild accessions of Brassica rapa. We then use experimental crosses to examine the genetic architecture, candidate loci and biochemical underpinnings of this patterning as well as phenotypic manipulations to test the ecological impact. We find qualitative variation in UV patterning between wild (commonly lacking UV patterns) and crop (commonly exhibiting UV patterns) accessions. Similar to the majority of crops, recombinant inbred lines (RILs) derived from an oilseed crop × WI fast‐plant® cross exhibit UV patterns, the size of which varies extensively among genotypes. In RILs, we further observe strong statistical‐genetic and QTL correlations within petal morphological traits and within measurements of petal UV patterning; however, correlations between morphology and UV patterning are weak or nonsignificant, suggesting that UV patterning is regulated and may evolve independently of overall petal size. HPLC analyses reveal a high concentration of sinapoyl glucose in UV‐absorbing petal regions, which, in concert with physical locations of UV‐trait QTLs, suggest a regulatory and structural gene as candidates underlying observed quantitative variation. Finally, insects prefer flowers with UV bulls‐eye patterns over those that lack patterns, validating the importance of UV patterning in pollen‐limited populations of B. rapa. 相似文献
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Joseph Tillotson Magdalena Kedzior Larissa Guimarães Alison B. Ross Tara L. Peters Andrew J. Ambrose Cody J. Schmidlin Donna D. Zhang Letícia V. Costa-Lotufo Abimael D. Rodríguez Jonathan H. Schatz Eli Chapman 《Bioorganic & medicinal chemistry letters》2017,27(17):4082-4085
Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5′ m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies. To this end, we have used a simple ATPase biochemical screen to survey several hundred marine and terrestrial derived natural products. Herein, we report the discovery of two natural products from marine sources, elisabatin A (1) and allolaurinterol (2), which show low µM inhibition of eIF4A ATPase activity. Enzymological analyses revealed 1 and 2 to be ATP-competitive, and cellular evaluations showed reasonable cytotoxicity against A549 (lung cancer) and MDA-MA-468 (breast cancer) cell lines. However, only compound 2 showed potent inhibition of helicase activity congruent with its ATPase inhibitory activity. 相似文献