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81.
Sanchez RM Erhard K Hardwicke MA Lin H McSurdy-Freed J Plant R Raha K Rominger CM Schaber MD Spengler MD Moore ML Yu H Luengo JI Tedesco R Rivero RA 《Bioorganic & medicinal chemistry letters》2012,22(9):3198-3202
A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (~ 0.100 μM IC(50)) growth inhibition in a PTEN deficient cancer cell line. 相似文献
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The first successful isolation of discharged ejectisomes from pigmented cryptophytes is reported. Discharged ejectisomes from
a Chroomonas and two Cryptomonas species were characterized by transmission electron microscopy using negative staining and freeze-etching. Tubular-shaped
fragments of variable lengths and diameters were obtained which showed a paracrystalline lattice. Particle periodicities of
4.1 nm along the longitudinal axis and 3.1 nm in the transverse direction were measured in negative-stained fragments. The
dimensions measured from freeze-etched ejectisome fragments were about 0.5–1 nm larger. Sodium dodecyl sulfate polyacrylamide
gel electrophoresis revealed a protein banding pattern, dominated by polypeptides of 40–44, 23–25 and 16–18 kDa. The results
are discussed in the context of what is currently known about extrusomes of protists. 相似文献
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Kähne T Kolodziej A Smalla KH Eisenschmidt E Haus UU Weismantel R Kropf S Wetzel W Ohl FW Tischmeyer W Naumann M Gundelfinger ED 《Proteomics》2012,12(15-16):2433-2444
Changes in synaptic efficacy underlying learning and memory processes are assumed to be associated with alterations of the protein composition of synapses. Here, we performed a quantitative proteomic screen to monitor changes in the synaptic proteome of four brain areas (auditory cortex, frontal cortex, hippocampus striatum) during auditory learning. Mice were trained in a shuttle box GO/NO-GO paradigm to discriminate between rising and falling frequency modulated tones to avoid mild electric foot shock. Control-treated mice received corresponding numbers of either the tones or the foot shocks. Six hours and 24 h later, the composition of a fraction enriched in synaptic cytomatrix-associated proteins was compared to that obtained from na?ve mice by quantitative mass spectrometry. In the synaptic protein fraction obtained from trained mice, the average percentage (±SEM) of downregulated proteins (59.9 ± 0.5%) exceeded that of upregulated proteins (23.5 ± 0.8%) in the brain regions studied. This effect was significantly smaller in foot shock (42.7 ± 0.6% down, 40.7 ± 1.0% up) and tone controls (43.9 ± 1.0% down, 39.7 ± 0.9% up). These data suggest that learning processes initially induce removal and/or degradation of proteins from presynaptic and postsynaptic cytoskeletal matrices before these structures can acquire a new, postlearning organisation. In silico analysis points to a general role of insulin-like signalling in this process. 相似文献
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C C Carroll J M Dickinson J M Haus G A Lee C J Hollon P Aagaard S P Magnusson T A Trappe 《Journal of applied physiology》2008,105(6):1907-1915
Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study. 相似文献
87.
Tamara Hoffmann Alexandra Schütz Margot Brosius Andrea Vlker Uwe Vlker Erhard Bremer 《Journal of bacteriology》2002,184(3):718-727
Proteome analysis of Bacillus subtilis cells grown at low and high salinity revealed the induction of 16 protein spots and the repression of 2 protein spots, respectively. Most of these protein spots were identified by mass spectrometry. Four of the 16 high-salinity-induced proteins corresponded to DhbA, DhbB, DhbC, and DhbE, enzymes that are involved in the synthesis of 2,3-dihydroxybenzoate (DHB) and its modification and esterification to the iron siderophore bacillibactin. These proteins are encoded by the dhbACEBF operon, which is negatively controlled by the central iron regulatory protein Fur and is derepressed upon iron limitation. We found that iron limitation and high salinity derepressed dhb expression to a similar extent and that both led to the accumulation of comparable amounts of DHB in the culture supernatant. DHB production increased linearly with the degree of salinity of the growth medium but could still be reduced by an excess of iron. Such an excess of iron also partially reversed the growth defect exhibited by salt-stressed B. subtilis cultures. Taken together, these findings strongly suggest that B. subtilis cells grown at high salinity experience iron limitation. In support of this notion, we found that the expression of several genes and operons encoding putative iron uptake systems was increased upon salt stress. The unexpected finding that high-salinity stress has an iron limitation component might be of special ecophysiological importance for the growth of B. subtilis in natural settings, in which bioavailable iron is usually scarce. 相似文献
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