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61.
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
62.
Anna Kutschenko Selma Staege Karen Grütz Hannes Glaß Norman Kalmbach Thomas Gschwendtberger Lisa M. Henkel Johanne Heine Anne Grünewald Andreas Hermann Philip Seibler Florian Wegner 《International journal of molecular sciences》2021,22(7)
Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia. 相似文献
63.
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
64.
The melt rheological analysis of high‐density polyethylene reinforced with vapor‐grown carbon nanofibers (VGCNFs) was performed on an oscillatory rheometer. The influence of frequency, temperature, and nanofiber concentration (up to 30 wt %) on the rheological properties of composites was investigated. Specifically, the viscosity increase is accompanied by an increase in the elastic melt properties, represented by the storage modulus G′, which is much higher than the increase in the loss modulus G″. The composites and pure PE exhibit a typical shear thinning behavior as complex viscosity decreases rapidly with the increase of shearing frequency. The shear thinning behavior is much more pronounced for the composites with high fiber concentration. The rheological threshold value for this system was found to be around 10 wt % of VGCNF. The damping factor was reduced significantly by the inclusion of nanofibers into the matrix. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 155–162, 2004 相似文献
65.
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
66.
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
67.
Michael?J.?HaasEmail author Paul?J.?Michalski Stan?Runyon Alberto?Nunez Karen?M.?Scott 《Journal of the American Oil Chemists' Society》2003,80(1):97-102
Simple alkyl FA esters have numerous uses, including serving as biodiesel, a fuel for compression ignition (diesel) engines.
The use of acid-catalyzed esterification for the synthesis of FAME from acid oil, a by-product of edible vegetable oil refining
that is produced from soapstock, was investigated. Soybean acid oil contained 59.3 wt% FFA, 28.0 wt% TAG, 4.4 wt% DAG, and
less than 1% MAG. Maximum esterification occurred at 65°C and 26 h reaction at a molar ratio of total FA/methanol/sulfuric
acid of 1∶15∶1.5. Residual unreacted species under these conditions, as a fraction of their content in unesterified acid oil,
were FFA, 6.6%; TAG, 5.8%; and DAG, 2.6%. This corresponds to estimated concentrations of FFA, 3.2%; TAG, 1.3%; and DAG, 0.2%,
on a mass basis, in the ester product. In an alternative approach, the acylglycerol species in soapstock were saponified prior
to acidulation. High-acid (HA) acid oil made from this saponified soapstock had an FFA content of 96.2 wt% and no detectable
TAG, DAG, or MAG. Optimal esterification conditions for HA acid oil at 65°C were a mole ratio of FFA/methanol/acid of 1∶1.8∶0.17,
and 14 h incubation. FAME recovery under these conditions was 89% of theoretical, and the residual unesterified FFA content
was approximately 20 mg/g. This was reduced to 3.5 mg/g, below the maximum FFA level allowed for biodiesel, by washing with
NaCl, NaHCO3, and Ca(OH)2 solutions. Alternatively, by subjecting the unwashed ester layer to a second esterification, the FFA level was reduced to
less than 2 mg/g. The acid value of this material exceeded the maximum allowed for biodiesel, but was reduced to an acceptable
value by a brief wash with 0.5 N NaOH. 相似文献
68.
Novel biocatalysts: Recent developments 总被引:1,自引:0,他引:1
The limited number of suitably well characterized biocatalysts continues to limit progress in the application of biological routes in the synthesis of compounds for novel pharmaceuticals, materials, or performance chemicals. In this situation, the discovery of novel biocatalysts or novel functionalities or substrates on existing ones is an important task. This work describes a range of novel biocatalysts obtained recently through one of three techniques: environmental sampling or screening, protein engineering on existing enzymes, or extension of the catalytic profile of existing catalysts. 相似文献
69.
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
70.
Microcellular foams in polypropylene containing rubber particles were produced in an injection molding process. The foams are generated because of the thermodynamic instability and are controlled by formation process. The effect of processing parameters on microcellular foaming was investigated in the injection molding process. Injection speed and pressure are less important factors but packing pressure plays an important role in controlling the foam density. A critical packing pressure, about 5 × 106 Pa, was found to generate microcellular foams in our polypropylene material system. Rubber particles inside the polypropylene seem to stabilize the microcellular foams. 相似文献