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31.
Jan Haas Karen S. Frese Farbod Sedaghat-Hamedani Elham Kayvanpour Rewati Tappu Rouven Nietsch Oguz Firat Tugrul Michael Wisdom Carsten Dietrich Ali Amr Tanja Weis Torsten Niederdrnk Michael P. Murphy Thomas Krieg Marcus Drr Uwe Vlker Jens Fielitz Norbert Frey Stephan B. Felix Andreas Keller Hugo A. Katus Benjamin Meder 《International journal of molecular sciences》2021,22(4)
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10−6). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets. 相似文献
32.
Ann-Kathrin Eichelmann George C. Mayne Karen Chiam Steven L. Due Isabell Bastian Frederike Butz Tingting Wang Pamela J. Sykes Nicholas J. Clemons David S. Liu Michael Z. Michael Christos S. Karapetis Richard Hummel David I. Watson Damian J. Hussey 《International journal of molecular sciences》2021,22(11)
TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53. 相似文献
33.
Various examples of composite titania-based nanostructured materials exhibiting cooperative functionalities between different active components are presented. The fabrication of these integrated composite materials is based on one-pot supramolecular templating techniques combined with acidic sol-gel chemistry. The defined 3-D nanoscale organization and integration of various functional components results in advanced optoelectronic and photonic applications such as visible light sensitization of mesoporous titania photocatalysts with cadmium sulfide nanocrystals acting as sensitizing integral part of the mesopore wall structure, narrow bandwidth emission from rare earth ion activated nanocrystalline mesoporous titania films, and mirrorless lasing in dye-doped hybrid organic/inorganic mesostructured titania waveguides. 相似文献
34.
A bivoltine checkerspot butterfly,Poladryas minuta, is aPenstemon specialist, not known to utilize any other plant genus for oviposition and larval feeding. At several intermontane plains sites of central Colorado, the butterfly utilizesPenstemon virgatus as its sole host plant. Analysis of the host plant showed it to contain three cinnamyl-type catalpol esters (scutellarioside-II, globularin, globularicisin) and catalpol. The host plant contained an average of 10% dry weight iridoids, but some variation among individual plants and leaves within plants was noted. Field-collected butterflies contained 2.1–8.7% dry weight catalpol, but no other iridoids. Adults from larvae fedP. virgatus in the lab contained 4.2–9.0% dry weight catalpol and excreted large amounts of catalpol in the meconium. No catalpol was found in the larval frass. Larvae did not consume three alternate iridoid-containing host-plant species, and most eventually died rather than feed on the alternate plants. Larvae did consume small amounts of artificial diets containing the alternate species andP. virgatus, but most went into diapause and some died. Survival was good on artificial diet containing 10% dry weight of the iridoid esters fromP. virgatus. Only catalpol was found in pupae and adults, but it was absent from the larval frass. The cinnamic-type acids expected from larval hydrolysis of the esters were not found in larval frass, pupae, or adults. These results are contrasted with those found for another checkerspot,Euphydryas anicia, which consumes a different host-plant species but was present at one of the same sites withPoladryas minuta.Paper 15 in the series Chemistry of the Scrophulariaceae. Paper 14 Boros, C.M., Stermitz, F.R., and Harris, G.H. 1990.J. Nat. Prod. 5372–80. 相似文献
35.
为了加快法院信息化建设,为法院决策层提供决策信息支持,提出了一种基于数据仓库的法院信息决策支持系统的总体框架。在DSS系统设计过程中,采用了OLAP+DM+Web相结合的方式,重点介绍分析了多维数据模型的设计,数据仓库的构建,以及以可视化交互的决策支持,最后通过实例展示决策支持系统的设计分析过程。 相似文献
36.
37.
Poly(ethylene ether carbonate) polyols can be modified by chemical reactions with polyglycol modifiers under conditions of elevated temperatures and reduced pressures. The modifier becomes chemically incorporated into the modified polyol and is used to control properties such as moisture sensitivity, CO2 content, Tg, density, etc. in the resultant polyol. However, glycerol cannot be used as a modifier for poly(ethylene ether carbonate) polyols under the same conditions since it reacts with poly(ethylene ether carbonate) polyols by a transesterification reaction sequence to form glyceryl carbonate. As the temperature is increased, the glyceryl carbonate decomposes to yield glycidol and carbon dioxide. These reactions are conveniently followed by 13C-NMR. The preparation of glyceryl carbonate by this process has not been previously reported. 相似文献
38.
Erik L. Gaskin Militza Carrero-Colón Karen A. Hudson 《Journal of the American Oil Chemists' Society》2021,98(2):221-226
Stearic acid is one of five major fatty acids found in soybean oil. It is a fully saturated lipid and is known for neutral or positive effects on LDL cholesterol when consumed by humans. Unfortunately, stearic acid only accounts for about 4% of the total seed oil produced in commodity soybean. Previous work has shown that stearic acid can reach levels as high as 28% of the total oil fraction when the SACPD-C gene, encoding the delta-9-stearoyl-acyl carrier protein desaturase responsible for most of the stearic acid variation in soybean seed, is ablated in combination with other loci. In order to increase stearic acid content and create soybeans with improved utility based on fatty acid composition, we combined mutations in SACPD-C with other mutations in the fatty acid biosynthetic pathway. Soybean plants carrying mutant alleles of both SACPD-C and FAD2-1A produce seed with stearic acid levels from 14% to 21%, and with elevated levels of oleic acid. Soybeans carrying mutations in both SACPD-C and FAD3A or FAD3C have both statistically significantly elevated levels of stearic acid (from 15–21%) and statistically reduced linolenic acid levels. Neither mutant combination appears to affect other agronomic properties such as plant morphology or seed protein levels making this a potentially viable trait. 相似文献
39.
Ines Hofinger Jörg Möller Manfred Bobeth Karen Raab 《Journal of Thermal Spray Technology》2002,11(3):387-392
The adherence of plasma sprayed NiCrAlY bond coats can be improved by an appropriate substrate surface finish. The interface
fracture energy for crack propagation along the coating/substrate interface has been measured for different surface roughness
by means of a specially designed four-point bending test. An increase of the interface fracture energy of about 15% was observed
for a three times higher surface roughness. In addition, four-point bending tests with the coating on the side face of bending
specimens were performed to analyze the fracture and spalling behavior of the coatings both under large tensile and compressive
substrate deformations. 相似文献
40.