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991.
Parul Goel Thorsten Jumpertz Anežka Tichá Isabella Ogorek David C. Mikles Martin Hubalek Claus U. Pietrzik Kvido Strisovsky Boris Schmidt Sascha Weggen 《Bioorganic & medicinal chemistry letters》2018,28(8):1417-1422
Rhomboids are intramembrane serine proteases with diverse physiological functions in organisms ranging from archaea to humans. Crystal structure analysis has provided a detailed understanding of the catalytic mechanism, and rhomboids have been implicated in various disease contexts. Unfortunately, the design of specific rhomboid inhibitors has lagged behind, and previously described small molecule inhibitors displayed insufficient potency and/or selectivity. Using a computer-aided approach, we focused on the discovery of novel scaffolds with reduced liabilities and the possibility for broad structural variations. Docking studies with the E. coli rhomboid GlpG indicated that 2-styryl substituted benzoxazinones might comprise novel rhomboid inhibitors. Protease in vitro assays confirmed activity of 2-styryl substituted benzoxazinones against GlpG but not against the soluble serine protease α-chymotrypsin. Furthermore, mass spectrometry analysis demonstrated covalent modification of the catalytic residue Ser201, corroborating the predicted mechanism of inhibition and the formation of an acyl enzyme intermediate. In conclusion, 2-styryl substituted benzoxazinones are a novel rhomboid inhibitor scaffold with ample opportunity for optimization. 相似文献
992.
HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia‐like animals 下载免费PDF全文
Josef Večeřa Eva Bártová Jana Krejčí Soňa Legartová Denisa Komůrková Jana Rudá‐Kučerová Tibor Štark Eva Dražanová Tomáš Kašpárek Alexandra Šulcová Frank J. Dekker Wiktor Szymanski Christian Seiser Georg Weitzer Raphael Mechoulam Vincenzo Micale Stanislav Kozubek 《Journal of cellular physiology》2018,233(1):530-548
Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1‐deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro‐differentiation was almost suppressed. Neuro‐differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia‐like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenia‐like brains that were treated with the cannabinoid receptor‐1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that co‐regulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro‐differentiation as well as the pathophysiology of a schizophrenia‐like phenotype. 相似文献
993.
Miao Liu Qiang Zhao Feng Qi Jiri Stiller Shican Tang Jiashun Miao Jan Vrána Kateřina Holušová Dengcai Liu Jaroslav Doležel John M. Manners Bin Han Chunji Liu 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2018,131(5):1125-1132
Key message
Sequence comparison between spelt and common wheat reveals that the former has huge potential in enriching the genetic variation of the latter.Abstract
Genetic variation is the foundation of crop improvement. By comparing genome sequences of a Triticum spelta accession and one of its derived hexaploid lines with the sequences of the international reference genotype Chinese Spring, we detected variants more than tenfold higher than those present among common wheat (T. aestivum L) genotypes. Furthermore, different from the typical ‘V-shaped’ pattern of variant distribution often observed along wheat chromosomes, the sequence variation detected in this study was more evenly distributed along the 3B chromosome. This was also the case between T. spelta and the wild emmer genome. Genetic analysis showed that T. spelta and common wheat formed discrete groups. These results showed that, although it is believed that the spelt and common wheat are evolutionarily closely related and belong to the same species, a significant sequence divergence exists between them. Thus, the values of T. spelta in enriching the genetic variation of common wheat can be huge.994.
Nicotine increases colon cancer cell migration and invasion through epithelial to mesenchymal transition (EMT): COX‐2 involvement 下载免费PDF全文
995.
Sour cherry cv. umadinka (Prunus cerasus L.) is the leading Yugoslav cultivar for production orchards. A method of micropropagation has been developed for the purpose of growing umadinka on its own roots and for rapid multiplication.Aseptic cultures were initiated from shoot explants 1–2 mm long on Murashige & Skoog medium with (in mgl-1) 6-benzylaminopurine (BAP): 1, indole-3-yl butyric acid (IBA): 1 and gibberellic acid (GA3): 0–1.The best medium for proliferation was MS with (in mgl-1): BAP 0.5, IBA 0.1, GA3 0.1, but media with (in mgl-1): BAP 0.5, NAA 0.1, GA3 0.1 and BAP 1, NAA 0.1 and GA3 0.1 were also shown to be good. A higher degree of proliferation obtained with some media did not necessarily result in a better quality of plantlets produced.For rooting the best combination of culture medium was achieved with pretreatment 10 days in MS 1/2 with 1 mgl-1 IBA, followed by transfer to a hormone-free medium after 5–10 days, resulting in 88% success.The rooted plants were planted in containers and acclimatized under mist, with over 90% of plants surviving transplantation. 相似文献
996.
Jožica Friedrich Aleksa Cimerman Anton Perdih 《Applied microbiology and biotechnology》1986,24(5):432-434
Summary The suitability of three ascomycetous fungi, Aspergillus niger, A. awamori and Trichoderma reesei, as well as two basidiomycetes, Pleurotus ostreatus and Phanerochaete chrysosporium, for bioconversion of apple distillery slop was compared. Trichoderma and Phanerochaete degraded raw fiberes by 20%, producing filter cakes with 17% to 22% raw protein contents. Aspergillus spp. were superior in filtration time and COD reduction and were of the same efficiency in protein synthesis as Trichoderma and Phanerochaete, but did not degrade fibres. Pleurotus ostreatus did not degrade lignin under fermentation conditions used and could not compete with other fungi due to its slower growth. 相似文献
997.
998.
K. Mikulík A. Jiráňová J. Maňas J. Spížek L. Anděra N. D. Savelyeva 《Archives of microbiology》1990,153(3):248-253
Ribosomes of the extreme thermophilic hydrogen-oxidizing bacterium Calderobacterium hydrogenophilum interact with a broad spectrum of polyamines. In the absence of polyamines and at 70°C close to the growth optimum (75°C), high salt washed ribosomes lost their activity in the poly(UG)-directed polypeptide synthesis. At 70°C the in vitro system synthesized the polypeptide in the presence of spermidine, spermine or natural polyamines (tri-pentaamines) isolated from ribosomal extracts but not in the presence of putrescine. The activity of ribosomes was affected by a number of antibiotics interfering with functions of typical eubacterial 70S, such as tetracyclines, lincomycin, chloramphenicol and erythromycin. However, the ribosomes were relatively resistant to streptomycin and insensitive to 80S inhibitors, such as ricin and cycloheximide. The 30S and 50S subunits have structural features typical of eubacterial ribosomes.The authors dedicated this paper to Professor Ivan Málek on the occasion of his 80th birthdy to remember his contribution to the Czechoslovak microbiology 相似文献
999.
Ivana Vančurová Aleš Vančura Jindřich Volc Jiří Neužzil Miroslav Flieger Gabriela Basařová Vladislav Běhal 《Archives of microbiology》1988,150(5):438-440
Alanine dehydrogenase was purified to near homogeneity from cell-free extract of Streptomyces aureofaciens, which produces tetracycline. The molecular weight of the enzyme determined by size-exclusion high-performance liquid chromatography was 395 000. The molecular weight determined by sodium dodecyl sulfate gel electrophoresis was 48 000, indicating that the enzyme consists of eight subunits with similar molecular weight. The isoelectric point of alanine dehydrogenase is 6.7. The pH optimum is 10.0 for oxidative deamination of L-alanine and 8.5 for reductive amination of pyruvate. K
M values were 5.0 mM for L-alanine and 0.11 mM for NAD+. K
M values for reductive amination were 0.56 mM for pyruvate, 0.029 mM for NADH and 6.67 mM for NH4Cl.Abbreviation AlaDH
alanine dehydrogenase 相似文献
1000.