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141.
Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the γ-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal γ-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 (e.g. cg2106) is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins. 相似文献
142.
143.
Background
X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue. 相似文献144.
Structural genes of the mouse major urinary protein are on chromosome 4 总被引:10,自引:0,他引:10
The major urinary proteins (MUPs) of mouse are a family of at least three major proteins which are synthesized in the liver of all strains of mice. The relative levels of synthesis of these proteins with respect to each other in the presence of testosterone is regulated by the Mup-a locus located on chromosome 4. In an effort to determine the mechanism of this regulation in molecular terms, a cDNA clone containing most of the coding region of a MUP protein has been isolated and identified by partial DNA sequence analysis. Using a combination of hybridization analysis and somatic cell genetics, the structural gene family has been unambiguously mapped to mouse chromosome 4. These data suggest that Mup-a regulation operates in a cis fashion and that models proposing trans regulation of MUP protein synthesis are unlikely. 相似文献
145.
Dawson C. A.; Skebba S. C.; Linehan J. H.; Bronikowski T. A. 《Journal of applied physiology》1985,58(4):1061-1068
To evaluate the influence of embolus size on the absorption of 125I- deposited on the bronchoalveolar surface, we exposed isolated perfused rabbit lungs to an aerosol containing 125I- for 5 min. We monitored the blood radioactivity for the subsequent 2 h. Several groups of lungs were studied, including those in which blood flow was varied and those in which enough glass beads ranging in size from 58 to 548 micron were injected into the pulmonary artery to approximately double the vascular resistance. The results indicated that under control conditions approximately 94% of the 125I- deposited on the intrapulmonary bronchoalveolar surface was able to reach the pulmonary circulation during the 2-h perfusion period, and the bronchoalveolar surface was sufficiently perfused so that absorption was limited by the rate of diffusion into the blood rather than the rate of blood flow. In the absence of embolization, the initial absorption rate was approximately 10.4%/min regardless of the total flow rate. The 58-micron beads reduced the rate to approximately 7.5%/min, whereas the beads greater than or equal to 194 micron in diameter reduced the rate to approximately 4.5%/min. Thus the effect of the embolization on the absorption rate was directly related to the bead diameter, even though the number of beads injected was adjusted to produce about the same increase in vascular resistance. 相似文献
146.
Verena S Brauer Maayke Stomp Camillo Rosso Sebastiaan AM van Beusekom Barbara Emmerich Lucas J Stal Jef Huisman 《The ISME journal》2013,7(11):2105-2115
Marine nitrogen-fixing cyanobacteria are largely confined to the tropical and subtropical ocean. It has been argued that their global biogeographical distribution reflects the physiologically feasible temperature range at which they can perform nitrogen fixation. In this study we refine this line of argumentation for the globally important group of unicellular diazotrophic cyanobacteria, and pose the following two hypotheses: (i) nitrogen fixation is limited by nitrogenase activity at low temperature and by oxygen diffusion at high temperature, which is manifested by a shift from strong to weak temperature dependence of nitrogenase activity, and (ii) high respiration rates are required to maintain very low levels of oxygen for nitrogenase, which results in enhanced respiratory cost per molecule of fixed nitrogen at low temperature. We tested these hypotheses in laboratory experiments with the unicellular cyanobacterium Cyanothece sp. . In line with the first hypothesis, the specific growth rate increased strongly with temperature from 18 to 30 °C, but leveled off at higher temperature under nitrogen-fixing conditions. As predicted by the second hypothesis, the respiratory cost of nitrogen fixation and also the cellular C:N ratio rose sharply at temperatures below 21 °C. In addition, we found that low temperature caused a strong delay in the onset of the nocturnal nitrogenase activity, which shortened the remaining nighttime available for nitrogen fixation. Together, these results point at a lower temperature limit for unicellular nitrogen-fixing cyanobacteria, which offers an explanation for their (sub)tropical distribution and suggests expansion of their biogeographical range by global warming. BG043511相似文献
147.
Lotte Heimans Kirsten VC Wevers-de Boer KK Michel Koudijs Karen Visser Yvonne P Goekoop-Ruiterman Joop B Harbers Gerda M Steup-Beekman Leroy R Lard Bernard AM Grillet Tom WJ Huizinga Cornelia F Allaart 《Arthritis research & therapy》2013,15(5):R173
Introduction
The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment.Methods
In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models.Results
During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL.Conclusions
In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms.Trial registrations
ISRCTN11916566 and EudraCT2006-006186-16 相似文献148.
AM. Bergman G. Cristalli S. Vittori J. Wang S. Eriksson Gj Peters 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):897-898
Abstract Several 1-deazapurine nucleosides were tested for their biological activity; anti-HIV-1, cytotoxicity and inhibition of adenosine deaminase (ADA). A2780 human ovarian cancer cells and the deoxycytidine kinase (dCK) deficient variant AG6000, used to determine whether dCK plays a role in their activation, showed a similar sensitivity to the analogs. This is in line with substrate specificity tests, which revealed a very low affinity of dCK. 相似文献
149.
1.?Ecoimmunological theory predicts a link between life-history and immune-defence strategies such that fast-living organisms should rely more on constitutive innate defences compared to slow-living organisms. An untested assumption of this hypothesis is that the variation in immune defence associated with variation in life history has a genetic basis. 2.?Replicate populations of two life-history ecotypes of the garter snake Thamnophis elegans provide an ideal system in which to test this assumption. Free-ranging snakes of the fast-living ecotype, which reside in lakeshore habitats, show higher levels of three measures of constitutive innate immunity than those of the slow-living ecotype, which inhabit meadows around the lake. Although this pattern is consistent with the ecoimmunological pace-of-life hypothesis, environmental differences between the lakeshore and meadow habitats could also explain the observed differences in immune defence. 3.?We performed a common-environment experiment to distinguish between these alternatives. Snakes born and raised in common-environment conditions reflected the immune phenotype of their native habitats when sampled at 4 months of age (i.e. fast-living lakeshore snakes showed higher levels of natural antibodies, complement activity and bactericidal competence than slow-living meadow snakes), but no longer showed differences when 19 months old. 4.?This suggests that the differences in innate immunity observed between the two ecotypes have an important - and likely age-specific - environmental influence, with these immune components showing developmental plasticity. A genetic effect in early life may also be present, but further research is needed to confirm this possibility and therefore provide a more definitive test of the ecoimmunological pace-of-life hypothesis in this system. 相似文献
150.
Loes?AM?Leenen Ben?FM?WijnenEmail author Reina?JA?de Kinderen Marian?HJM?Majoie Caroline?M?van Heugten Silvia?MAA?Evers 《BMC neurology》2014,14(1):255