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E. Hampton Sessions Michael Smolinski Bo Wang Bozena Frackowiak Sarwat Chowdhury Yan Yin Yen Ting Chen Claudia Ruiz Li Lin Jennifer Pocas Thomas Schröter Michael D. Cameron Philip LoGrasso Yangbo Feng Thomas D. Bannister 《Bioorganic & medicinal chemistry letters》2010,20(6):1939-1943
Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 <10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA). 相似文献
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Adrienn Guóth Dániel Benyó Jolán Csiszár Ágnes Gallé Ferenc Horváth László Cseuz László Erdei Irma Tari 《Acta Physiologiae Plantarum》2010,32(4):719-727
The effects of increasing osmotic stress induced by 100–400 mOsm (−0.976 MPa) polyethylene glycol (PEG 6000) were investigated
in a drought-tolerant (Triticum aestivum L. cv. Mv Emese) and drought-sensitive (cv. GK élet) wheat cultivar at the three-leaf stage. During osmotic stress, the decline
of the water potential (ψ
w) was more significant in the leaves, while the abscisic acid (ABA) levels of the roots increased earlier and remained higher
in the sensitive than in the tolerant variety. There was an increasing gradient of ABA content toward the youngest leaves
in the drought-sensitive GK élet, while more ABA accumulated in the fully developed, older leaves of the tolerant cultivar
Mv Emese. In accordance with the rapid and significant accumulation of ABA, the stomatal conductance decreased earlier in
the tolerant cultivar. The effect of water stress on the PSII photochemistry was pronounced only 1 week after the exposure
to PEG, as indicated by the earlier decrease of the net CO2 fixation, the effective quantum yield (ΦPSII) and the photochemical quenching (q
P) in light-adapted samples of the tolerant variety in 400 mOsm PEG 6000. The stress treatment caused more significant reductions
in these parameters toward the end of the experiment in the sensitive cultivar. In spite of small differences in the photosynthetic
characteristics, the net biomass production was not significantly altered by this osmotic stress. The accumulation of ABA
controlled the distribution of the biomass between the shoot and root systems under osmotic stress, and contributed to the
development of stronger and deeper roots in the drought-sensitive cultivar GK élet. However, the root elongation did not correlate
with the drought sensitivity of these cultivars on the basis of crop yield. 相似文献
85.
Rita Szabó Zoltán Bánóczi Gábor Mező Orsolya Láng László Kőhidai Ferenc Hudecz 《生物化学与生物物理学报:生物膜》2010,1798(12):2209-2216
We have developed a group of water-soluble drug conjugates in which daunomycin (Dau) is coupled to cationic, amphoteric or anionic branched polypeptides and a new conjugate containing a cationic polypeptide carrier modified with a cell penetrating octaarginine. We investigated in vitro physiological activity of these conjugates in several aspects: in vitro cytotoxicity and cytostatic effect, adhesion and cellular uptake were examined on murine (J774 and L1210) and human (MonoMac6 and HL-60) leukemia cell lines and on murine bone marrow derived macrophages. We found that these processes are dependent on the properties of the carrier, on experimental conditions like concentration and incubation time. We found that attachment of polypeptide and cell penetrating peptide to the bioactive agent, depending on the cell line, could significantly improve the antitumor activity of the drug. 相似文献
86.
Michal Dabrowski Norbert Dojer Malgorzata Zawadzka Jakub Mieczkowski Bozena Kaminska 《BMC systems biology》2010,4(1):86
Background
It is often desirable to separate effects of different regulators on gene expression, or to identify effects of the same regulator across several systems. Here, we focus on the rat brain following stroke or seizures, and demonstrate how the two tasks can be approached simultaneously. 相似文献87.
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Juszczuk IM Flexas J Szal B Dabrowska Z Ribas-Carbo M Rychter AM 《Physiologia plantarum》2007,131(4):527-541
The effects of changes in mitochondrial DNA in cucumber ( Cucumis sativus L.) mosaic mutant (MSC16) on respiration, photosynthesis and photorespiration were analyzed under non-stressed conditions. Decreased respiratory capacity of complex I in MSC16 mitochondria was indicated by lower respiration rates of intact mitochondria with malate and by rotenone-inhibited NADH or malate oxidation in the presence of alamethicin. Moreover, blue native PAGE indicated decreased intensity of protein bands of respiratory chain complex I in MSC16 leaves. Concerning the redox state, complex I impairment could be compensated to some extent by increased external NADH dehydrogenases (NDex NADH) and alternative oxidase (AOX) capacity, the latter presenting differential expression in the light and in the dark. Although MSC16 mitochondria have a higher AOX protein level and an increased capacity, the AOX activity measured in the dark conditions by oxygen discrimination technique is similar to that in wild-type (WT) plants. Photosynthesis induction by light followed different patterns in WT and MSC16, suggesting changes in feedback chloroplast ΔpH caused by different adenylate levels. At steady-state, net photosynthesis was only slightly impaired in MSC16 mutants, while photorespiration rate (PR) was significantly increased. This was the result of large decreases in both stomatal and mesophyll conductance to CO2 , which resulted in a lower CO2 concentration in the chloroplasts. The observed changes on CO2 diffusion caused by mitochondrial mutations open a whole new view of interaction between organelle metabolism and whole tissue physiology. The sum of all the described changes in photosynthetic and respiratory metabolism resulted in a lower ATP availability and a slower plant growth. 相似文献