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991.
L S Harman D K Carver J Schreiber R P Mason 《The Journal of biological chemistry》1986,261(4):1642-1648
The oxidation of glutathione by horseradish peroxidase forms a thiyl free radical as demonstrated with the spin trapping ESR technique. Reactions of this thiyl free radical result in oxygen consumption, which is inhibited by the radical trap 5,5-dimethyl-1-pyrroline-N-oxide. In contrast to L-cysteine oxidation, glutathione oxidation is highly hydrogen peroxide-dependent. The oxidation of glutathione by glutathione peroxidase forms glutathione disulfide without forming a thiyl radical intermediate, except in the presence of the thiyl radical-generating horseradish peroxidase. 相似文献
992.
E Lesniewska P J Flamion C Cachia J P Schreiber J P Goudonnet 《Biochemical and biophysical research communications》1991,178(3):1280-1287
The scanning tunnelling microscope has been used to image 16S ribosomal RNA molecules in water electrophoretically deposited on graphite surface. Two kinds of images have been obtained: images showing aggregates of 16S ribosomal RNA molecules similar to those obtained from DNA solutions and others showing individual 16S ribosomal RNA molecules. An interesting characteristic of these images, recorded in constant current mode, is that the 16S ribosomal RNA molecules appear to be located below the graphite surface. The morphology and several structural parameters of the molecules were consistent with the data obtained from electron microscopy. 相似文献
993.
994.
1. The reverse reactions induced by coupled ATP hydrolysis were studied in spinach chloroplasts by measurements of the ATP-induced increase in chlorophyll fluorescence reflecting reverse electron flow, and of the ATP-induced decrease in 9-aminoacridine fluorescence, representing formation of the transthylakoidal proton gradient (ΔpH). ATP-driven reverse electron flow was kinetically analysed into three phases, of which only the second and third one were paralleled by corresponding phases in ΔpH formation. The rapid first phase and formation of a ΔpH occur also in the absence of the electron transfer mediator phenazine methosulfate.2. The rate and extent of the reverse reactions were measured at temperatures in the range from 0 to 30°C. The rate of formation of ΔpH and of reverse electron flow were faster at high temperatures, but the maximal extent of ΔpH and chlorophyll fluorescence increase were observed at the lowest temperature. Considering rate and extent of the ATP-stimulated reactions, a temperature optimum around 15°C was found. Light activation of the ATPase occurred throughout the range studied. At 0°C and in the presence of inorganic phosphate the activated state for ATPase was maintained for more then 10 min.3. The ATP-induced rise in chlorophyll fluorescence yield was found to be of similar magnitude as the rise induced by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), when both were measured with an extremely weak measuring beam. It is concluded, that both effects, although derived via distinctly different pathways, are limited by the same electron donating or electron accepting pool. 相似文献
995.
The fungus Phoma medicaginis var. pinodella (L.K. Jones) Boerema has been shown to split off the O(3)-acetyl group of gibberellic acid acetates without affecting O(13)-acetyl 19,10-lactone, and methyl ester groups. Fungal deacetylation of O(3,13)-diacetylgibberellic acid (VII) yielded O(13)-acetylgibberellic acid (V), which has not previously been prepared. 相似文献
996.
Amrita Basu Nicole E. Bodycombe Jaime H. Cheah Edmund V. Price Ke Liu Giannina I. Schaefer Richard Y. Ebright Michelle L. Stewart Daisuke Ito Stephanie Wang Abigail L. Bracha Ted Liefeld Mathias Wawer Joshua C. Gilbert Andrew J. Wilson Nicolas Stransky Gregory V. Kryukov Vlado Dancik Jordi Barretina Levi A. Garraway C. Suk-Yee Hon Benito Munoz Joshua A. Bittker Brent R. Stockwell Dineo Khabele Andrew M. Stern Paul A. Clemons Alykhan F. Shamji Stuart L. Schreiber 《Cell》2013
997.
Satish Keshav Tomá? Vaňásek Yaron Niv Robert Petryka Stephanie Howaldt Mauro Bafutto István Rácz David Hetzel Ole Haagen Nielsen Séverine Vermeire Walter Reinisch Per Karlén Stefan Schreiber Thomas J. Schall Pirow Bekker the Prospective Randomized Oral-Therapy Evaluation in Crohn’s Disease Trial- Study Group 《PloS one》2013,8(3)
CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn’s disease. Crohn’s Disease Activity Index (CDAI) scores were 250–450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn’s medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn’s disease.
Trial Registration
ClinicalTrials.gov . NCT00306215相似文献998.
Andrew R. Germain Leigh C. Carmody Partha P. Nag Barbara Morgan Lynn VerPlank Cristina Fernandez Etienne Donckele Yuxiong Feng Jose R. Perez Sivaraman Dandapani Michelle Palmer Eric S. Lander Piyush B. Gupta Stuart L. Schreiber Benito Munoz 《Bioorganic & medicinal chemistry letters》2013,23(6):1834-1838
A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure–activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations. 相似文献
999.
M. Gruber M. Rawolle J. Wagner D. Magerl U. Hörmann J. Perlich S. V. Roth A. Opitz F. Schreiber P. Müller‐Buschbaum W. Brütting 《Liver Transplantation》2013,3(8):1075-1083
The performance of organic photovoltaic cells (OPVCs) shows a critical dependence on morphology and structure of the active layers. In small molecule donor/acceptor (D/A) cells fabrication parameters, like substrate temperature and evaporation rate, play a significant role for crystallization and roughening of the film. In particular, the fraction of mixed material at the interface between donor and acceptor is highly relevant for device performance. While an ideal planar heterojunction (PHJ) exhibits the smallest possible interface area resulting in suppressed recombination losses, mixed layers suffer strongly from recombination but show higher exciton dissociation efficiencies. In this study we investigate PHJ and planar‐mixed heterojunction (PM‐HJ) solar cells based on diindenoperylene (DIP) as donor and C60 as acceptor, fabricated under different growth conditions. Grazing incidence small angle X‐ray scattering (GISAXS), X‐ray reflectometry (XRR) and atomic force microscopy (AFM) are used to obtain detailed information about in‐ and out‐of‐plane structures and topography. In that way we find that surface and bulk domain distances are correlated in size for PHJs, while PM‐HJs show no correlation at all. The resulting solar cell characteristics are strongly affected by the morphology, as reorganizations in structure correlate with changes in the solar cell performance. 相似文献
1000.
Shao L Wang F Malcolm SC Ma J Hewitt MC Campbell UC Bush LR Spicer NA Engel SR Saraswat LD Hardy LW Koch P Schreiber R Spear KL Varney MA 《Bioorganic & medicinal chemistry》2011,19(1):663-676
The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype. 相似文献