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121.
Hoegberg P Schmidt CK Nau H Ross AC Zolfaghari R Fletcher N Trossvik C Nilsson CB Håkansson H 《Chemico-biological interactions》2003,145(1):1-16
Vitamin A (retinoids) has an essential role in development and throughout life of humans and animals. Consequently, effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid metabolism may be contributory to its toxicity. This study was performed to clarify the mechanism behind dioxin-induced retinyl ester formation in the rat kidney. In addition we investigated the possible role of CYP1A1 in dioxin-induced all-trans-retinoic acid (atRA) formation. Male Sprague-Dawley rats were exposed to a single oral dose of TCDD in a combined dose-response and time-course study, with doses ranging from 0.1 to 100 microg/kg bw and time points from 1 to 28 days. Levels of atRA and the expression of two potentially retinoic acid (RA)-controlled proteins critically involved in retinoid storage regulation, lecithin: retinol acyltransferase (LRAT) and cellular retinol binding protein I (CRBP I), were analyzed in liver and kidney. The expression and activity of cytochrome P4501A1 (assayed as ethoxyresorufin-O-deethylase activity) was assessed to gain insight into its potential role in RA synthesis. There was a significant increase in LRAT mRNA expression in the kidney, whereas no such increase could be observed in the liver, despite significantly increased atRA levels in both tissues. This suggests a tissue-specific regulation of LRAT by TCDD that may be dependent on other factors than atRA. Neither CRBP I mRNA nor protein levels were altered by TCDD. The time-course relationship between CYP1A1 activity and atRA levels in liver and kidney does not exclude a role of CYP1A1 in TCDD-induced RA synthesis. The observed altered regulation of the retinoid-metabolizing enzyme LRAT, together with the low doses and short time required by TCDD to change tissue RA levels, suggest that enzymes involved in retinoid metabolism are specific and/or direct targets of TCDD. 相似文献
122.
Heterodisulfide reductase (Hdr) from methanogenic Archaea catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic thiol coenzymes, coenzyme M (CoM-SH) and coenzyme B (CoB-SH). Upon reaction of the oxidized enzyme with CoM-SH a unique paramagnetic species is formed, which has been shown to be due to a novel type of [4Fe-4S](3+) cluster. In this work, it was addressed whether CoM-SH is directly attached to this [4Fe-4S] cluster using CoM-(33)SH as substrate and purified Hdr from Methanothermobacter marburgensis and Methanosarcina barkeri. With both enzymes treatment with CoM-(33)SH in the presence of duroquinone as an oxidant resulted in a significant broadening of the electron paramagnetic resonance spectrum as compared to CoM-SH as substrate. The signal broadening resulted from an unresolved anisotropic hyperfine coupling between the (33)S nucleus and the paramagnetic center. The results provide compelling evidence for a direct binding of CoM-SH to the [4Fe-4S] cluster in the active site of the enzyme. 相似文献
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A total of 8,859 DNA sequences encompassing ~1.9 million base pairs of the chimpanzee genome were sequenced and compared to corresponding human DNA sequences. Although the average sequence difference is low (1.24%), the extent of changes is markedly different among sites and types of substitutions. Whereas ~15% of all CpG sites have experienced changes between humans and chimpanzees, owing to a 23-fold excess of transitions and a 7-fold excess of transversions, substitutions at other sites vary in frequency, between 0.1% and 0.5%. If the nucleotide diversity in the common ancestral species of humans and chimpanzees is assumed to have been about fourfold higher than in contemporary humans, all possible comparisons between autosomes and X and Y chromosomes result in estimates of the ratio between male and female mutation rates of ~3. Thus, the relative time spent in the male and female germlines may be a major determinant of the overall accumulation of nucleotide substitutions. However, since the extent of divergence differs significantly among autosomes, additional unknown factors must also influence the accumulation of substitutions in the human genome. 相似文献
128.
The turn-inducing sequence Ala-Aib introduced into positions 31 and 32 of neuropeptide Y (NPY) and its analogues has been identified as the key structure for Y(5)-receptor selectivity. Analogues of NPY and PP/NPY chimera containing the motif Ala-Aib were prepared; these peptides turned out to be selective for the Y(5)-receptor. The affinity of the NPY-based peptides was in the range of 6-150 nM, while the affinity of three (Ala-Aib)-containing PP/NPY chimera was in the range of 0.2-0.9 nM. The circular dichroism spectra of the Aib analogues in aqueous solution were all characteristic of an alpha helix; however, they had different intensities of the two negative bands at 220 and 208 nm. Affinity and selectivity for the Y(5)-receptor were correlated with the ratio of the ellipticity at 220 nm versus the one at 208 nm (R), which indicates the presence of a pronounced helix (R > 1) versus a less stabile one (R < 1). When R was in the range 0.74-0.96, the affinity at the Y(5)-receptor was in the range >5 nM, while there was complete loss of affinity at the Y(4)-receptor. R > 1.15 was associated with very high affinity at the Y(5)-receptor and weak affinity at the Y(4)-receptor. These results suggest that the selectivity of the Ala(31)-Aib(32) motif for the Y(5)-receptor derives from a specific conformation that must be correlated with the bioactive conformation of NPY at this subtype. 相似文献
129.
Predation as a shaping force for the phenotypic and genotypic composition of planktonic bacteria 总被引:1,自引:0,他引:1
Predation is a major mortality factor of planktonic bacteria and an important shaping force for the phenotypic and taxonomic
structure of bacterial communities. In this paper we: (1) summarise current knowledge on bacterial phenotypic properties which
affect their vulnerability towards grazers, and (2) review experimental evidence demonstrating that this phenotypic heterogeneity
results in shifts of bacterial community composition during enhanced protist grazing pressure. Size-structured interactions
are especially important in planktonic systems and bacterial cell size influences the mortality rate and the type of grazer
to which bacteria are most susceptible. When protists are the major bacterivores, both very small and large bacterial cells
gain some size refuge. Recent studies have revealed that also various non-morphological traits such as motility, physicochemical
surface characters and toxicity affect bacterial vulnerability and protist feeding success. These properties are effective
at different stages during the feeding process of interception feeding flagellates (encounter, capture, ingestion, digestion).
Grazing-resistant bacteria in natural communities can account for a substantial portion of the total bacterial biomass at
least in more productive aquatic systems. In field and laboratory experiments it has been demonstrated that increased protozoan
grazing results in shifts in the phenotypic and genotypic composition of the bacterial assemblage. The importance of this
shaping force for the bacterial community structure depends, however, on the overall food web structure, especially on the
composition of the metazooplankton. Whereas the structuring impact of bacterial grazers is well documented, relatively little
is known about how grazing-mediated changes in bacterial communities influence microbially mediated processes and biogeochemically
important transformations.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
130.
Wiuf C 《Theoretical population biology》2002,62(4):357-363
In this article I derive an alternative algorithm to Hudson and Kaplan's (Genetics 111, 147-165) algorithm that gives a lower bound to the number of recombination events in a sample's history. It is shown that the number, T(M), found by the algorithm is the least number of topologies required to explain a set of DNA sequences sampled under the infinite-site assumption. Let Tao = (T(1),...,T(r)) be a list of topologies compatible with the sequences, i.e., T(k) is compatible with an interval, I(k), of sites in the alignment. A characterization of all lists having T(M) topologies is given and it is shown that T(M) relates to specific patterns in the alignment, here called chain series. Further, a number of theorems relating general lists of topologies to the number T(M) is presented. The results are discussed in relation to the true minimum number of recombination events required to explain an alignment. 相似文献