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961.
Correlating EPR and X-ray structural analysis of arsenite-inhibited forms of aldehyde oxidoreductase
Anders Thapper D. R. Boer Carlos D. Brondino José J. G. Moura Maria J. Romão 《Journal of biological inorganic chemistry》2007,12(3):353-366
Two arsenite-inhibited forms of each of the aldehyde oxidoreductases from Desulfovibrio gigas and Desulfovibrio desulfuricans have been studied by X-ray crystallography and electron paramagnetic resonance (EPR) spectroscopy. The molybdenum site of
these enzymes shows a distorted square-pyramidal geometry in which two ligands, a hydroxyl/water molecule (the catalytic labile
site) and a sulfido ligand, have been shown to be essential for catalysis. Arsenite addition to active as-prepared enzyme
or to a reduced desulfo form yields two different species called A and B, respectively, which show different Mo(V) EPR signals.
Both EPR signals show strong hyperfine and quadrupolar couplings with an arsenic nucleus, which suggests that arsenic interacts
with molybdenum through an equatorial ligand. X-ray data of single crystals prepared from EPR-active samples show in both
inhibited forms that the arsenic atom interacts with the molybdenum ion through an oxygen atom at the catalytic labile site
and that the sulfido ligand is no longer present. EPR and X-ray data indicate that the main difference between both species
is an equatorial ligand to molybdenum which was determined to be an oxo ligand in species A and a hydroxyl/water ligand in
species B. The conclusion that the sulfido ligand is not essential to determine the EPR properties in both Mo–As complexes
is achieved through EPR measurements on a substantial number of randomly oriented chemically reduced crystals immediately
followed by X-ray studies on one of those crystals. EPR saturation studies show that the electron transfer pathway, which
is essential for catalysis, is not modified upon inhibition.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
962.
963.
Ontological analysis facilitates the interpretation of microarray data. Here we describe new ontological analysis methods which, unlike existing approaches, are threshold-free and statistically powerful. We perform extensive evaluations and introduce a new concept, detection spectra, to characterize methods. We show that different ontological analysis methods exhibit distinct detection spectra, and that it is critical to account for this diversity. Our results argue strongly against the continued use of existing methods, and provide directions towards an enhanced approach. 相似文献
964.
Background
The prediction of the secondary structure of proteins is one of the most studied problems in bioinformatics. Despite their success in many problems of biological sequence analysis, Hidden Markov Models (HMMs) have not been used much for this problem, as the complexity of the task makes manual design of HMMs difficult. Therefore, we have developed a method for evolving the structure of HMMs automatically, using Genetic Algorithms (GAs). 相似文献965.
Hawkey CJ Talley NJ Scheiman JM Jones RH Långström G Naesdal J Yeomans ND;NASA/SPACE author group 《Arthritis research & therapy》2007,9(1):R17
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal
(GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief
of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief
of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled
and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or
40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with
Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology,
gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The
primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months.
Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3
days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper
GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients
with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%)
(p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency
of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in
patients taking continuous NSAIDs, including selective COX-2 inhibitors. 相似文献
966.
Phosphoinositide-regulated retrograde transport of ricin: crosstalk between hVps34 and sorting nexins 总被引:3,自引:1,他引:2
Skånland SS Wälchli S Utskarpen A Wandinger-Ness A Sandvig K 《Traffic (Copenhagen, Denmark)》2007,8(3):297-309
The plant toxin ricin is transported from the plasma membrane via early endosomes and the Golgi apparatus to the endoplasmic reticulum. From this compartment, it enters the cytosol and inhibits protein synthesis. Lipid phosphorylation is an important regulator of vesicular transport, and in the present study we have investigated the role of the phosphatidylinositol (PI) 3-kinase hVps34 in retrograde transport of ricin. Our data demonstrate that transport of ricin from endosomes to the Golgi apparatus in human embryonic kidney cells (HEK 293) is dependent on PI(3)P. By using PI 3-kinase inhibitors, by sequestering the hVps34 product PI(3)P and by expressing mutants of hVps34 or small interfering RNA targeted against its messenger RNA, we show that hVps34 and its product PI(3)P are involved in transport of ricin from endosome to Golgi apparatus. Furthermore, we identify two effector proteins in the hVps34-dependent pathway, namely sorting nexin (SNX) 2 and SNX4. Knockdown of SNX2 or SNX4 inhibits ricin transport to the Golgi apparatus to the same extent as when hVps34 is perturbed. Furthermore, inhibition or knockdown of hVps34 redistributes these proteins. Interestingly, knocking down both SNX2 and SNX4 results in a better inhibition than knocking down only one of them, suggesting that they may act on separate pathways. 相似文献
967.
During the past century, Lake Tåkern and Lake Krankesjön, southern Sweden, have shifted repeatedly between a state of clear water and abundant submerged vegetation, and a state of turbid water and sparse vegetation. Long-term empirical data on such apparently alternative stable state dynamics are valuable as complements to modeling and experiments, although the causal mechanisms behind shifts are often difficult to identify in hindsight. Here, we summarize previous studies and discuss possible mechanisms behind the shifts. The most detailed information comes from monitoring of two recent shifts, one in each lake. In the 1980s, L. Krankesjön shifted to clear water following an expansion of sago pondweed, Potamogeton pectinatus. Water clarity increased when the pondweed was replaced by characeans. Zooplankton biomass in summer declined and the concentration of total phosphorus (TP) was reduced to half the previous level. The fish community changed over several years, including an increasing recruitment of piscivorous perch (Perca fluviatilis). An opposite directed shift to turbid water occurred in Lake Tåkern in 1995, when biomass of phytoplankton increased in spring, at the expense of submerged vegetation. Consistent with the findings in L. Krankesjön, phyto- and zooplankton biomass increased and the average concentration of TP doubled. After the shift to clear water in L. Krankesjön, TP concentration has increased during the latest decade, supporting the idea that accumulation of nutrients may lead to a long-term destabilization of the clear water state. In L. Tåkern, data on TP are inconclusive, but organic nitrogen concentrations oscillated during a 25-year period of clear water. These observations indicate that intrinsic processes cause gradual or periodic changes in system stability, although we cannot exclude the possibility that external forces are also involved. During such phases of destabilization of the clear water state, even small disturbances could possibly trigger a shift, which may explain why causes behind shifts are hard to identify even when they occur during periods of extensive monitoring. 相似文献
968.
969.
Mårten Kivi Sandra Rodin Ilya Kupershmidt Annelie Lundin Ylva Tindberg Marta Granström Lars Engstrand 《BMC microbiology》2007,7(1):54
Background
Helicobacter pylori infection is exceptionally prevalent and is considered to be acquired primarily early in life through person-to-person transmission within the family. H. pylori is a genetically diverse bacterial species, which may facilitate adaptation to new hosts and persistence for decades. The present study aimed to explore the genetic diversity of clonal isolates from a mother and her three children in order to shed light on H. pylori transmission and host adaptation. 相似文献970.