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121.
Yang SW Smotryski J McElroy WT Tan Z Ho G Tulshian D Greenlee WJ Guzzi M Zhang X Mullins D Xiao L Hruza A Chan TM Rindgen D Bleickardt C Hodgson R 《Bioorganic & medicinal chemistry letters》2012,22(1):235-239
A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model. 相似文献
122.
Thomas L Hodgson DA Wentzel A Nieselt K Ellingsen TE Moore J Morrissey ER Legaie R;STREAM Consortium Wohlleben W Rodríguez-García A Martín JF Burroughs NJ Wellington EM Smith MC 《Molecular & cellular proteomics : MCP》2012,11(2):M111.013797
Bacteria in the genus Streptomyces are soil-dwelling oligotrophs and important producers of secondary metabolites. Previously, we showed that global messenger RNA expression was subject to a series of metabolic and regulatory switches during the lifetime of a fermentor batch culture of Streptomyces coelicolor M145. Here we analyze the proteome from eight time points from the same fermentor culture and, because phosphate availability is an important regulator of secondary metabolite production, compare this to the proteome of a similar time course from an S. coelicolor mutant, INB201 (ΔphoP), defective in the control of phosphate utilization. The proteomes provide a detailed view of enzymes involved in central carbon and nitrogen metabolism. Trends in protein expression over the time courses were deduced from a protein abundance index, which also revealed the importance of stress pathway proteins in both cultures. As expected, the ΔphoP mutant was deficient in expression of PhoP-dependent genes, and several putatively compensatory metabolic and regulatory pathways for phosphate scavenging were detected. Notably there is a succession of switches that coordinately induce the production of enzymes for five different secondary metabolite biosynthesis pathways over the course of the batch cultures. 相似文献
123.
The Finapres finger cuff recording system provides continuous calculations of beat-to-beat variations in cardiac output (CO), total peripheral resistance, heart rate (HR), and blood pressure (BP). This system is unique in that it allows experimental subjects to immediately, continuously, and noninvasively visualize changes in CO at rest and during exercise. This study provides evidence that using the Finapres system improves undergraduate student engagement, understanding, and learning of how the cardiovascular system responds to exercise. Second-year science students undertaking a physiology practical class in 2009 (n = 243) and 2010 (n = 263) used the Finapres system to record CO, BP, and HR during graded exercise on a cycle ergometer. Student experiences with the Finapres was evaluated with a survey (a 5-point scale from strongly disagree to strongly agree). This indicated that students appreciated the immediacy of the recordings (88% of students agreed or strongly agreed, average for 2009 and 2010), gained an understanding of how to record physiological data (84%), enjoyed the practical (81%), and would recommend the Finapres to other students (81%). To determine if the practical enhanced student learning of cardiovascular physiology, identical tests were given to the students at the beginning (pretest) and end (posttest) of the class. There was a significant improvement from the pretest to the posttest (4% in 2009 and 20% in 2010). In summary, the ability of the Finapres to continuously display CO, BP, and HR during experimental protocols provides students with immediate feedback and improves their understanding of cardiovascular physiology. 相似文献
124.
Alexander Wentzel Per Bruheim Anders ?verby ?yvind M Jakobsen H?vard Sletta Walid A M Omara David A Hodgson Trond E Ellingsen 《BMC systems biology》2012,6(1):1-16
Background
Given the complex mechanisms underlying biochemical processes systems biology researchers tend to build ever increasing computational models. However, dealing with complex systems entails a variety of problems, e.g. difficult intuitive understanding, variety of time scales or non-identifiable parameters. Therefore, methods are needed that, at least semi-automatically, help to elucidate how the complexity of a model can be reduced such that important behavior is maintained and the predictive capacity of the model is increased. The results should be easily accessible and interpretable. In the best case such methods may also provide insight into fundamental biochemical mechanisms.Results
We have developed a strategy based on the Computational Singular Perturbation (CSP) method which can be used to perform a "biochemically-driven" model reduction of even large and complex kinetic ODE systems. We provide an implementation of the original CSP algorithm in COPASI (a COmplex PAthway SImulator) and applied the strategy to two example models of different degree of complexity - a simple one-enzyme system and a full-scale model of yeast glycolysis.Conclusion
The results show the usefulness of the method for model simplification purposes as well as for analyzing fundamental biochemical mechanisms. COPASI is freely available at http://www.copasi.org. 相似文献125.
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127.
Augustine AJ Kragh ME Sarangi R Fujii S Liboiron BD Stoj CS Kosman DJ Hodgson KO Hedman B Solomon EI 《Biochemistry》2008,47(7):2036-2045
The multicopper oxidases catalyze the 4e- reduction of O2 to H2O coupled to the 1e- oxidation of 4 equiv of substrate. This activity requires four Cu atoms, including T1, T2, and coupled binuclear T3 sites. The T2 and T3 sites form a trinuclear cluster (TNC) where O2 is reduced. The T1 is coupled to the TNC through a T1-Cys-His-T3 electron transfer (ET) pathway. In this study the two T3 Cu coordinating His residues which lie in this pathway in Fet3 have been mutated, H483Q, H483C, H485Q, and H485C, to study how perturbation at the TNC impacts the T1 Cu site. Spectroscopic methods, in particular resonance Raman (rR), show that the change from His to Gln to Cys increases the covalency of the T1 Cu-S Cys bond and decreases its redox potential. This study of T1-TNC interactions is then extended to Rhus vernicifera laccase where a number of well-defined species including the catalytically relevant native intermediate (NI) can be trapped for spectroscopic study. The T1 Cu-S covalency and potential do not change in these species relative to resting oxidized enzyme, but interestingly the differences in the structure of the TNC in these species do lead to changes in the T1 Cu rR spectrum. This helps to confirm that vibrations in the cysteine side chain of the T1 Cu site and the protein backbone couple to the Cu-S vibration. These changes in the side chain and backbone provide a possible mechanism for regulating intramolecular T1 to TNC ET in NI and partially reduced enzyme forms for efficient turnover. 相似文献
128.
119
Marine Algae of Pohnpei and Ant Atoll with Comparisons to Other Pacific Atolls and Island Groups
In 1978, the green turtle, Chelonia mydas , was listed as threatened in the United States under the Endangered Species Act. Any knowledge gained from an understanding of the diet and how it affects this species' ability to survive is crucial. Turf algae, the primary component of the diet of Chelonia mydas , and turtle fecal pellets were collected from Kaloko-Honokohau National Historical Park on the island of Hawaii at monthly intervals. The turf algae and fecal pellets were subjected to nutritional analyses for protein, carbohydrate, lipid, ash, and caloric content. The fecal pellets were higher in protein content than the turf algae, which may be related to fermentation carried out by bacteria in the turtle hindgut that increases the amount of protein available for absorption. From the nutritional data, assimilation efficiencies were calculated for the green turtle. 相似文献
129.
R K Daniel J Hodgson V S Lambros 《Plastic and reconstructive surgery》1990,85(6):859-66; discussion 867-8
The physical characteristics of the light reflexes of the nasal tip are defined in large part by the studio lighting configuration. By varying the lighting configuration, it is possible to alter the light reflexes as regards their number, distance apart, symmetry, and size. For the plastic surgeon, the quarter light system of the medical photographer has definite advantages over the key light system of the portrait photographer. The quarter light system consists of two lights of equal intensity with symmetrical angles of incidence placed at 45 degrees to the camera-subject axis. Measuring changes in the light reflexes as a method of determining the efficacy of surgical techniques is valid under very controlled conditions. 相似文献
130.