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81.
Ganapathi R. Revankar Roland K. Robins 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):709-724
Abstract A general and stereospecific method has been developed for the direct preparation of βD-ribofuranosyl, βD-arabinofuranosyl and 2-deoxy-βD-erythro-pentofuranosyl derivatives of a number of nitrogen heterocycles. The azoles thus far employed include appropriately substituted pyrrole, pyrazole, imidazole, 1,2,4-triazole, indole, imidazo[4,5-c]pyridine, pyrrolo[2,3-d]pyrimidine, pyrro10[3,2-c]pyridine, pyrrolo[4,2-c]pyrimidine, purine, pyrazolo[3,4-b]pyridine and pyrazolo-[3,4-d]pyrimidine. This simple high-yield methodology provided a facile route to the large-scale preparation of biologically significant nucleo-sides, such as 2′-deoxyribavirin, 2-chloro-2′-deoxyadenosine, tuber-cidin, Z'-deoxytubercidin, =sangivarnycin, 2′-deoxytoyocamycin, cade-guomycin, 2′-deoxycadeguomycin, G-cadeguomycin, kanagawamicin, 2′-deoxy-3-deazaguanosine, sG, brunfelsarnidine ribonucleoside and 2′-deoxyribofuranosyl derivative of the antibiotic SF-2140. This procedure appears to be considerably superior to the previously reported glycosylation methods. 相似文献
82.
Kandasamy Ramasamy Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(3):385-392
Abstract A synthesis of 2,4-dideazaribavirin ( 2 ), brunfelsamidine ribonucleoside ( 8c ) and certain related derivatives are described for the first time using the stereospecific sodium salt glycosylation procedure. Glycosylation of the sodium salt of pyrrole-3-carbonitrile ( 4 ) with 1-chloro-2, 3-O-t-isopropylidene-5-O-t-butyldimethylsilyl-α-D-ribofuranose ( 5 ) gave exclusively the corresponding blocked nucleoside ( 6 ) with β-anomeric configuration, which on deprotection provided 1-β-D-ribofuranosylpyrrole-3-carbonitrile ( 7 ). Functional group tranformation of 7 gave 2 , 8c and related 3-substituted pyrrole ribonucleosides. These compounds are devoid of any significant antiviral/antitumor activity invitro. 相似文献
83.
Ganesh D. Kini William J. Hennen Roland K. Robins 《Nucleosides, nucleotides & nucleic acids》2013,32(3):581-587
Abstract A new, facile synthesis of 7-methyl-8-oxoguanosine is reported. 2-Chloro-7-methylpurine-6, 8-dione (5) was silylated with hexamethyldi-silazane and the silylated intermediate, 6, glycosylated with 1-0-acetyl-2, 3, 5-tri-0-benzoyl-D-ribofuranose to yield 2-chloro-7-methyl-9-(2′, 3′,-5′-tri-0-benzoyl-β-D-ribofuranosyl) purin-6, 8-dione (8). Deprotection of 8 with sodium hydroxide in aqueous methanol gave 2-chloro-7-methyl-9-(β-D-ribofuranosyl) purine-6,8-dione (9), which was aminated with liquid ammonia or methanolic ammonia to yield 7-methyl-8-oxoguanosine (3). 相似文献
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86.
Roland M Klar Raquel Duarte Therese Dix‐Peek Caroline Dickens Carlo Ferretti Ugo Ripamonti 《Journal of cellular and molecular medicine》2013,17(11):1444-1457
Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca++ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca++ activating stem cell differentiation and the induction of bone formation. 相似文献
87.
Alexander Thiel Nils Tippkötter Kirstin Suck Ulrich Sohling Friedrich Ruf Roland Ulber 《Engineering in Life Science》2013,13(3):239-246
Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta‐zeolite‐based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta‐zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources. 相似文献
88.
Franz Oberwinkler Kai Riess Robert Bauer Roland Kirschner Sigisfredo Garnica 《Mycological Progress》2013,12(4):763-776
A taxonomic re-evaluation of the Ceratobasidium-Rhizoctonia group suggests that Ceratobasidium contains only the type species C. calosporum, which deviates in micromorphological and ultrastructural characters from all other species so far included in that genus. Rhizoctonia species are compared with the type species of Ceratobasidium, Cejpomyces, Oncobasidium, Tofispora, Waitea, and Ypsilonidium. The micromorphology, ultrastructure, cellular interaction with the host, and molecular phylogeny of a Rhizoctonia species parasitic on needles and young shoots of Picea abies have been studied. The parasite has been known for a long time, but misinterpreted, and not named so far. Rhizoctonia butinii is described and compared with related species of the genus. 相似文献
89.
Michael Haase Anja Haase-Fielitz Michael Plass Hermann Kuppe Roland Hetzer Claire Hannon Patrick T. Murray Michael J. Bailey Rinaldo Bellomo Sean M. Bagshaw 《PLoS medicine》2013,10(4)
Background
Preliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery.Methods and Findings
In a multicenter, double-blinded (patients, clinical and research personnel), randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg) or sodium chloride (5.1 mmol/kg). The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%]) presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p = 0.009). Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001). More patients receiving bicarbonate (83/174 [47.7%]) developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04–2.45]; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90–2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (11/174 [6.3%] versus 3/176 [1.7%], OR 3.89 [1.07–14.2], p = 0.031).Conclusions
Urinary alkalinization using sodium bicarbonate infusion was not found to reduce the incidence of acute kidney injury or attenuate tubular damage following open heart surgery; however, it was associated with a possible increase in mortality. On the basis of these findings we do not recommend the prophylactic use of sodium bicarbonate infusion to reduce the risk of acute kidney injury. Discontinuation of growing implementation of this therapy in this setting seems to be justified.Trial registration
ClinicalTrials.gov Please see later in the article for the Editors'' Summary NCT00672334相似文献90.
Roland Kardos Elisa Nevalainen Miklós Nyitrai Gábor Hild 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(10):2010-2019
The main goal of the work was to uncover the dynamical changes in actin induced by the binding of cofilin and profilin. The change in the structure and flexibility of the small domain and its function in the thermodynamic stability of the actin monomer were examined with fluorescence spectroscopy and differential scanning calorimetry (DSC). The structure around the C-terminus of actin is slightly affected by the presence of cofilin and profilin. Temperature dependent fluorescence resonance energy transfer measurements indicated that both actin binding proteins decreased the flexibility of the protein matrix between the subdomains 1 and 2. Time resolved anisotropy decay measurements supported the idea that cofilin and profilin changed similarly the dynamics around the fluorescently labeled Cys-374 and Lys-61 residues in subdomains 1 and 2, respectively. DSC experiments indicated that the thermodynamic stability of actin increased by cofilin and decreased in the presence of profilin. Based on the information obtained it is possible to conclude that while the small domain of actin acts uniformly in the presence of cofilin and profilin the overall stability of actin changes differently in the presence of the studied actin binding proteins. The results support the idea that the small domain of actin behaves as a rigid unit during the opening and closing of the nucleotide binding pocket in the presence of profilin and cofilin as well. The structural arrangement of the nucleotide binding cleft mainly influences the global stability of actin while the dynamics of the different segments can change autonomously. 相似文献