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1.
Two experiments involving laying hens and mature roosters were carried out to determine the effect of pH on the ultrafilterable fraction of Mg((Mg)u) present in the digesta along the gastrointestinal tract. Concurrently, the approximate molecular weight of the (Mg)u was determined. The average pH's for laying hens were: crop 4.88, proventriculus 5.27, ventriculus 4.77, duodenum 5.57, jejunum 6.15, ileum 7.82, and colon 6.65. Similar pH values were obtained for mature roosters. The (Mg)u fraction decreased significantly in the ileum where the pH was greater than 7.00. However, treating the ileal digesta with an acid pH buffer released about 70% of the nonfilterable Mg. The molecular weight of the (Mg)u was found to be less than 700, suggesting that the Mg was present in digesta as an inorganic salt or as an organic complex of low molecular weight. 相似文献
2.
Marlene Buchebner Thomas Pfeifer Nora Rathke Prakash G. Chandak Achim Lass Renate Schreiber Adelheid Kratzer Robert Zimmermann Wolfgang Sattler Harald Koefeler Eleonore Fr?hlich Gerhard M. Kostner Ruth Birner-Gruenberger Kyle P. Chiang Guenter Haemmerle Rudolf Zechner Sanja Levak-Frank Benjamin Cravatt Dagmar Kratky 《Journal of lipid research》2010,51(10):2896-2908
Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormone-sensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363−/− and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL−/− mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363−/− but unchanged in HSL−/− mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL−/− macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages. 相似文献
3.
Melanoma is the leading cause of skin cancer-related deaths, which is due in large part to its aggressive behavior, resistance to therapy, and ability to metastasize to multiple organs such as the lymph nodes, lung, and brain. Melanoma progresses in a stepwise manner from the benign nevus, to radial spreading through the dermis, to a vertical invasive phase, and finally to metastasis. The carbohydrate-binding family of galectins has a strong influence on each phase of melanoma progression through their effects on immune surveillance, angiogenesis, cell migration, tumor cell adhesion, and the cellular response to chemotherapy. Galectins share significant homology in their carbohydrate recognition domain (CRD), which mediates binding to an array of N-glycosylated proteins located on the surface of tumor cells, endothelial cells, T-cells, and to similarly glycosylated extracellular matrix proteins. Galectins are also present within tumor cells where they perform anti-apoptotic functions and enhance intracellular signaling that results in deregulated expression of genes involved in tumor progression. The most extensively studied galectins, galectin-1 and galectin-3, have been shown to have profound effects on melanoma growth and metastasis by influencing many of these biological processes. 相似文献
4.
Crystal structure of a transcription regulator (TM1602) from Thermotoga maritima at 2.3 A resolution
Weekes D Miller MD Krishna SS McMullan D McPhillips TM Acosta C Canaves JM Elsliger MA Floyd R Grzechnik SK Jaroszewski L Klock HE Koesema E Kovarik JS Kreusch A Morse AT Quijano K Spraggon G van den Bedem H Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,67(1):247-252
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Kenneth D. James Guenter von Kiedrowski Andrew D. Ellington 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1821-1836
Abstract An efficient method for synthesizing 5′-Boc-5′-amino-2′, 5′- dideoxynucleoside phosphoramidites and conditions for their incorporation in solid-phase oligonucleotide synthesis are presented. 相似文献
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Nina M. Pollak Martina Schweiger Doris Jaeger Dagmar Kolb Manju Kumari Renate Schreiber Stephanie Kolleritsch Philipp Markolin Gernot F. Grabner Christoph Heier Kathrin A. Zierler Thomas Rülicke Robert Zimmermann Achim Lass Rudolf Zechner Guenter Haemmerle 《Journal of lipid research》2013,54(4):1092-1102
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs. 相似文献
9.
Chandramohan Chitraju Martin Tr?tzmüller Jürgen Hartler Heimo Wolinski Gerhard G. Thallinger Guenter Haemmerle Rudolf Zechner Robert Zimmermann Harald C. K?feler Friedrich Spener 《Journal of lipid research》2013,54(8):2185-2194
We showed earlier that nutritional stress like starvation or high-fat diet resulted in phenotypic changes in the lipidomes of hepatocyte lipid droplets (LDs), representative for the pathophysiological status of the mouse model. Here we extend our former study by adding genetic stress due to knockout (KO) of adipocyte triglyceride lipase (ATGL), the rate limiting enzyme in LD lipolysis. An intervention trial for 6 weeks with male wild-type (WT) and ATGL-KO mice was carried out; both genotypes were fed lab chow or were exposed to short-time starvation. Isolated LDs were analyzed by LC-MS/MS. Triacylglycerol, diacylglycerol, and phosphatidylcholine lipidomes, in that order, provided the best phenotypic signatures characteristic for respective stresses applied to the animals. This was evidenced at lipid species level by principal component analysis, calculation of average values for chain-lengths and numbers of double bonds, and by visualization in heat maps. Structural backgrounds for analyses and metabolic relationships were elaborated at lipid molecular species level. Relating our lipidomic data to nonalcoholic fatty liver diseases of nutritional and genetic etiologies with or without accompanying insulin resistance, phenotypic distinction in hepatocyte LDs dependent on insulin status emerged. Taken together, lipidomes of hepatocyte LDs are sensitive responders to nutritional and genetic stress. 相似文献
10.
Lucia Vernerova Frantisek Spoutil Miroslav Vlcek Katarina Krskova Adela Penesova Milada Meskova Andrea Marko Katarina Raslova Branislav Vohnout Jozef Rovensky Zdenko Killinger Ivana Jochmanova Ivica Lazurova Guenter Steiner Josef Smolen Richard Imrich 《PloS one》2016,11(4)
IntroductionThe aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA).MethodsA total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA.ResultsHLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.ConclusionsThe association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA. 相似文献