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61.
Commercially available sodium heparinate has been sequentially treated with methanolic 0.06M hydrogen chloride and nitrous acid. The nondegraded material was separated by gel filtration from the nonsulfated and monosulfated disaccharides produced. The latter ones, obtained in 10% yield, have been used as a substrate for the direct measurement of the enzyme L-iduronic acid 2-sulfate sulfatase present in human plasma and fibroblast homogenates. Studies of the kinetics and pH optimum of the enzyme, by use of plasma of a patient with mucolipidosis II, indicated an apparent Km of 2.5mM and a pH optimum of 4.6-4.8. The levels of activity in normal plasma and plasma of a patient with Hunter's disease were found to be 20.4 ± 1.22 units (μmol sulfate/24 h/g protein) and 3.25 ± 0.35 units, respectively. In homogenates of cultured skin fibroblasts, the levels were 137.6 ± 10.7 units for normal controls and 6.4 ± 5.1 for patients with Hunter's disease. The plasma of two obligated heterozygotes gave intermediate levels of activity, whereas the plasma of two possible heterozygotes gave either intermediate levels or entirely normal levels of activity. 相似文献
62.
Romeu Cardoso Guimarães 《Origins of life and evolution of the biosphere》2011,41(4):357-371
An investigation of the biosynthesis pathways producing glycine and serine was necessary to clarify an apparent inconsistency
between the self-referential model (SRM) for the formation of the genetic code and the model of coevolution of encodings and
of amino acid biosynthesis routes. According to the SRM proposal, glycine was the first amino acid encoded, followed by serine.
The coevolution model does not state precisely which the first encodings were, only presenting a list of about ten early assignments
including the derivation of glycine from serine—this being derived from the glycolysis intermediate glycerate, which reverses
the order proposed by the self-referential model. Our search identified the glycine-serine pathway of syntheses based on one-carbon
sources, involving activities of the glycine decarboxylase complex and its associated serine hydroxymethyltransferase, which
is consistent with the order proposed by the self-referential model and supports its rationale for the origin of the genetic
code: protein synthesis was developed inside an early metabolic system, serving the function of a sink of amino acids; the
first peptides were glycine-rich and fit for the function of building the early ribonucleoproteins; glycine consumption in
proteins drove the fixation of the glycine-serine pathway. 相似文献
63.
Jakub Hofman Radim Ku?era Daniela Cihalova Jiri Klimes Martina Ceckova Frantisek Staud 《PloS one》2013,8(10)
Purine cyclin-dependent kinase inhibitors have been recognized as promising candidates for the treatment of various cancers; nevertheless, data regarding interaction of these substances with drug efflux transporters is still lacking. Recently, we have demonstrated inhibition of breast cancer resistance protein (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able to synergistically potentiate the antiproliferative effect of mitoxantrone, an ABCG2 substrate. In this follow up study, we investigated whether olomoucine II and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine II will be affected by both ABCB1 and ABCG2 transport proteins, which might potentially result in limited accumulation of the compound in tumor tissues or lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically favoring this drug in the potential treatment of efflux transporter-based multidrug resistant tumors. In addition, we observed intensive sulfatation of olomoucine II in MDCKII cell lines with subsequent active efflux of the metabolite out of the cells. Therefore, care should be taken when performing pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates are used; the generated sulfated conjugate may largely contaminate pharmacokinetic analysis and result in misleading interpretation. With regard to chemical structures of olomoucine II and purvalanol A, our data emphasize that even drugs with remarkable structure similarity may show different pharmacokinetic behavior such as interactions with ABC transporters or biotransformation enzymes. 相似文献
64.
Daniela Zappi 《Curtis's Botanical Magazine》1993,10(4):166-170
65.
Elmar Porten Beate Seliger Verena A. Schneider Stefan W?ll Daniela Stangel Rene Ramseger Stephan Kr?ger 《The Journal of biological chemistry》2010,285(5):3114-3125
Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system. 相似文献
66.
A possible method of finding the best concentration of a chemical mutagen or a shortterm action is demonstrated by the results
obtained withChlamydomonas geitleri. Mostly two cases occur. We must either use the shortest time of the mutagen action with a sufficiently high effect or utilize
the whole limited time for this action using a suitable concentration with a similar effect. It is possible to choose such
a structure of the doae of the chemical mutagen which in the mutation spectrum ensures either the optimal frequencies of all
components or of only some of them chosen beforehand. 相似文献
67.
Ferruccio Berti Claudio Omini Daniela Longiave 《Prostaglandins & other lipid mediators》1977,14(2):241-249
The horse-chestnut saponin Aescin, an anti-exudative compound, induces contraction of isolated portal vein of rat and rabbit. This effect appears to be mediated by Prostaglandins of Fα type.The ability of Aescin to stimulate generation and release of Prostaglandins has been demonstrated in isolated lung of the rat. Mass-fragmentographic analysis of the lung effluent indicate that when Aescin is perfused through this organ the release of PGF2α is increased. The capability of Aescin to generate Prostaglandins is discussed in connection with its anti-exudative activity. 相似文献
68.
Patricia Kabitzke Diana Morales Dansha He Kimberly Cox Jane Sutphen Lucinda Thiede Emily Sabath Taleen Hanania Barbara Biemans Daniela Brunner 《Genes, Brain & Behavior》2020,19(7)
Phenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter‐ and intra‐laboratory replicability, particularly in behavioral domains such as social and cognitive function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies of five genetic mouse model systems of ASD. To assess the intra‐laboratory robustness of previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three‐yearlong effort using informatics techniques to assess commonalities and differences. Our results showed high intra‐laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle but pivotal differences in testing conditions, housing enrichment, or background strains and less so on the variability of the behavioral phenotypes. The overall informatics analysis suggests that in our behavioral assays we can separate the set of tested mouse model system into two main classes that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept. 相似文献
69.
Simon Borna Ales Drobek Jarmila Kralova Daniela Glatzova Iva Splichalova Matej Fabisik Jana Pokorna Tereza Skopcova Pavla Angelisova Veronika Kanderova Julia Starkova Petr Stanek Orest V. Matveichuk Nataliia Pavliuchenko Katarzyna Kwiatkowska Majd B. Protty Michael G. Tomlinson Meritxell Alberich‐Jorda Vladimir Korinek Tomas Brdicka 《Journal of cellular and molecular medicine》2020,24(2):1980-1992
WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis. 相似文献
70.