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901.
Spasojevic I Kos I Benov LT Rajic Z Fels D Dedeugd C Ye X Vujaskovic Z Reboucas JS Leong KW Dewhirst MW Batinic-Haberle I 《Free radical research》2011,45(2):188-200
In the cell Mn porphyrins (MnPs) likely couple with cellular reductants which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to three orders of magnitude depending upon the length of alkylpyridyl chains and type of isomer. The effects result from the interplay of solvation, lipophilicit and stericity. Impact of ascorbate on accumulation of MnPs was measured in E. coli and in Balb/C mouse tumours and muscle; for the latter measurements, the LC/ESI-MS/MS method was developed. Accumulation was significantly enhanced when MnPs were co-administered with ascorbate in both prokaryotic and eukaryotic systems. Further, MnTnHex-2-PyP(5+) accumulates 5-fold more in the tumour than in a muscle. Such data increase our understanding of MnPs cellular and sub-cellular accumulation and remarkable in vivo effects. The work is in progress to understand how coupling of MnPs with ascorbate affects their mechanism of action, in particular with respect to cancer therapy. 相似文献
902.
Bartocci E Singh R von Stein FB Amedome A Caceres AJ Castillo J Closser E Deards G Goltsev A Ines RS Isbilir C Marc JK Moore D Pardi D Sadhu S Sanchez S Sharma P Singh A Rogers J Wolinetz A Grosso-Applewhite T Zhao K Filipski AB Gilmour RF Grosu R Glimm J Smolka SA Cherry EM Clarke EM Griffeth N Fenton FH 《Advances in physiology education》2011,35(4):427-437
As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York(1) collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions using an in silico model. The primary goal of the workshop was to cultivate student interest in computational modeling and analysis of complex systems by introducing them through lectures and laboratory activities to current research in cardiac modeling and by engaging them in a hands-on research experience. The success of the workshop lay in the exposure of the students to active researchers and experts in their fields, the use of hands-on activities to communicate important concepts, active engagement of the students in research, and explanations of the significance of results as the students generated them. The workshop content addressed how spiral waves of electrical activity are initiated in the heart and how different parameter values affect the dynamics of these reentrant waves. Spiral waves are clinically associated with tachycardia, when the waves remain stable, and with fibrillation, when the waves exhibit breakup. All in silico experiments were conducted by simulating a mathematical model of cardiac cells on graphics processing units instead of the standard central processing units of desktop computers. This approach decreased the run time for each simulation to almost real time, thereby allowing the students to quickly analyze and characterize the simulated arrhythmias. Results from these simulations, as well as some of the background and methodology taught during the workshop, is presented in this article along with the programming code and the explanations of simulation results in an effort to allow other teachers and students to perform their own demonstrations, simulations, and studies. 相似文献
903.
Some of the most prevalent human degenerative diseases appear as a result of the misfolding and aggregation of proteins. Compelling evidence suggest that misfolded protein aggregates play an important role in cell dysfunction and tissue damage, leading to the disease. Prion protein (Prion diseases), amyloid-beta (Alzheimer's disease), alpha-synuclein (Parkinson's disease), Huntingtin (Huntington's disease), serum amyloid A (AA amyloidosis) and islet amyloid polypeptide (type 2 diabetes) are some of the proteins that trigger disease when they get misfolded. The recent understanding of the crucial role of misfolded proteins as well as the structural requirements and mechanism of protein misfolding have raised the possibility that these diseases may be transmissible by self-propagation of the protein misfolding process in a similar way as the infamous prions transmit prion diseases. Future research in this field should aim to clarify this possibility and translate the knowledge of the basic disease mechanisms into development of novel strategies for early diagnosis and efficient treatment. 相似文献
904.
Vincenza Crupi Graziano Guella Domenico Majolino Ines Mancini Barbara Rossi Rosanna Stancanelli Valentina Venuti Paolo Verrocchio Gabriele Viliani 《Food biophysics》2011,6(2):267-273
The effects of chiral discrimination in inclusion complexes formed by native β-cyclodextrin and its substituted form (namely
methyl-β-cyclodextrin) with racemate or pure enantiomers of the non-steroidal anti-inflammatory drug ibuprofen have been investigated
in water. Stability constants and complexation efficiency have been determined for these host–guest systems with a 1:1 molar
ratio from phase solubility profiles, showing that in aqueous solution, methylated cyclodextrin is a better complex agent
than native cyclodextrin, with more enhanced effects for the (R)-enantiomer. These results have been validated using NMR technique. In particular, 1H NMR spectra in D2O show a splitting of the signals for the methyl group and the aromatic protons close to the asymmetric centre of the racemate
ibuprofen included in cyclodextrin cavity. 相似文献
905.
Substrate competition can be found in many types of biological processes, ranging from gene expression to signal transduction and metabolic pathways. Although several experimental and in silico studies have shown the impact of substrate competition on these processes, it is still often neglected, especially in modelling approaches. Using toy models that exemplify different metabolic pathway scenarios, we show that substrate competition can influence the dynamics and the steady state concentrations of a metabolic pathway. We have additionally derived rate laws for substrate competition in reversible reactions and summarise existing rate laws for substrate competition in irreversible reactions. 相似文献
906.
Ines Fürtbauer Michael Heistermann Oliver Schülke Julia Ostner 《American journal of physical anthropology》2013,151(2):311-315
An extensive body of research exists on androgen secretion in males. Although androgens are also known to drive patterns of female reproductive physiology and behavior, little attention has been paid to these “male” hormones in females. Here, we examined female fecal androgen excretion in strictly seasonally breeding wild Assamese macaques (Macaca assamensis) and tested the hypothesis that changes in premating season fecal androgens vary with female readiness to resume ovarian cycling and thus to conceive. Across 2 years, 155 fecal samples were collected from seven reproductively quiescent (i.e., acyclic) females during the premating season months, August and September. Samples were analyzed for immunoreactive epiandrosterone (iEA), a major fecal metabolite of testosterone in macaques. Changes in iEA concentrations during the premating season were significantly negatively associated with (1) the presence of dependent offspring, i.e., lactating females showed a smaller change, and (2) with the timing of conceptions in the mating seasons, i.e., females that conceived early exhibited the greatest changes. These results provide strong evidence for a relationship between changes in androgens during the premating season and female readiness to conceive. Am J Phys Anthropol 151:311–315, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
907.
908.
909.
Sabrina Polzin Claudia Huber Eva Eylert Ines Elsenhans Wolfgang Eisenreich Herbert Schmidt 《Applied and environmental microbiology》2013,79(12):3703-3715
In this study, the intracellular proteome of Escherichia coli O157:H7 strain EDL933 was analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) spectrometry after growth in simulated ileal environment media (SIEM) and simulated colonic environment media (SCEM) under aerobic and microaerobic conditions. Differentially expressed intracellular proteins were identified and allocated to functional protein groups. Moreover, metabolic fluxes were analyzed by isotopologue profiling with [U-13C6]glucose as a tracer. The results of this study show that EDL933 responds with differential expression of a complex network of proteins and metabolic pathways, reflecting the high metabolic adaptability of the strain. Growth in SIEM and SCEM is obviously facilitated by the upregulation of nucleotide biosynthesis pathway proteins and could be impaired by exposition to 50 µM 6-mercaptopurine under aerobic conditions. Notably, various stress and virulence factors, including Shiga toxin, were expressed without having contact with a human host. 相似文献
910.
Simone Di Micco Maria Giovanna Chini Stefania Terracciano Ines Bruno Raffaele Riccio Giuseppe Bifulco 《Bioorganic & medicinal chemistry》2013,21(13):3795-3807
Histone Deacetylases are considered promising targets for cancer epigenetic therapy, and small molecules able to modulate their biological function have recently gained an increasing interest as potential anticancer agents. In spite of their potential application in cancer therapy, most HDAC inhibitors unselectively bind the several HDAC isoforms, giving rise to different side-effects. In this context, we have traced out the structural elements responsible of selective binding for the therapeutically relevant different HDAC isoforms. The structural analysis has been carried out by molecular modeling, docking in the binding pockets of HDAC1–4 and HDAC6–8, 36 inhibitors presenting a well defined selectivity for the different isoforms. As quick proof of evidence, we have designed, synthesized and experimentally tested three selective ligands. The experimental data suggest that the obtained structural guidelines can be useful tools for the rational design of new potent inhibitors against selected HDAC isoforms. 相似文献