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The timing of proton migration in membrane-reconstituted cytochrome c oxidase 总被引:1,自引:0,他引:1 下载免费PDF全文
Salomonsson L Faxén K Adelroth P Brzezinski P 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(49):17624-17629
In mitochondria and aerobic bacteria energy conservation involves electron transfer through a number of membrane-bound protein complexes to O2. The reduction of O2, accompanied by the uptake of substrate protons to form H2O, is catalyzed by cytochrome c oxidase (CcO). This reaction is coupled to proton translocation (pumping) across the membrane such that each electron transfer to the catalytic site is linked to the uptake of two protons from one side and the release of one proton to the other side of the membrane. To address the mechanism of vectorial proton translocation, in this study we have investigated the solvent deuterium isotope effect of proton-transfer rates in CcO oriented in small unilamellar vesicles. Although in H2O the uptake and release reactions occur with the same rates, in D2O the substrate and pumped protons are taken up first (tau(D) congruent with 200 micros, "peroxy" to "ferryl" transition) followed by a significantly slower proton release to the other side of the membrane (tau(D) congruent with 1 ms). Thus, the results define the order and timing of the proton transfers during a pumping cycle. Furthermore, the results indicate that during CcO turnover internal electron transfer to the catalytic site is controlled by the release of the pumped proton, which suggests a mechanism by which CcO orchestrates a tight coupling between electron transfer and proton translocation. 相似文献
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Dementia and depressive symptoms as predictors of home help utilization among the oldest old: population-based study in an urban area of Sweden 总被引:2,自引:0,他引:2
OBJECTIVE: The objective of this article is to investigate predictors of public home help utilization, particularly mental health problems such as dementia and depressive symptoms. METHODS: A population-based sample of community-dwelling people aged 81-100 was interviewed and assessed with medical examinations (N = 502). RESULTS: Dementia increased the odds of receiving public home help among people residing alone. Among coresiding people, it increased the odds of receiving home help, but only among those who had extra residential care. Depressive symptoms decreased the odds of receiving home help among people with lower levels of education who lived alone. Depressive symptoms among highly educated people who lived alone and among coresiding people of any educational level were not related to receipt of home help. DISCUSSION: Improvement of screening activities for public home help needs of community-dwelling elders might allow better targeting of limited social resources to the most needy. 相似文献
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Engman ML Malm G Engstrom L Petersson K Karltorp E Tear Fahnehjelm K Uhlen I Guthenberg C Lewensohn-Fuchs I 《Scandinavian journal of infectious diseases》2008,40(11-12):935-942
Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was assessed by otoacoustic emission (OAE) within a newborn screening programme. 12 infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One boy among the 12 infected infants had unilateral hearing loss, indicating that the risk of hearing loss is greatly increased (about 20 times) in CMV infected infants. No child developed ocular complications such as chorioretinopathy during 3 y of follow-up. Congenital CMV has an impact on child health but can easily be overlooked due to lack of signs in the neonatal period. Surveillance for congenital CMV is important in addition to programmes for prevention and treatment. 相似文献
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Grant S. Lipman David Pomeranz Patrick Burns Caleb Phillips Mary Cheffers Kristina Evans Carrie Jurkiewicz Nick Juul Peter Hackett 《The American journal of medicine》2018,131(2):200.e9-200.e16
Background
Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide.Methods
This double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire ≥3 and another symptom).Results
A total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups (P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4.Conclusion
Budesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent. 相似文献110.
Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans 总被引:3,自引:0,他引:3
Korstanje R Eriksson P Samnegård A Olsson PG Forsman-Semb K Sen S Churchill GA Rollins J Harris S Hamsten A Paigen B 《Atherosclerosis》2004,177(2):443-450
A previous study revealed that the difference in susceptibility to atherosclerotic lesions between inbred mouse strains SM/J and NZB/BlNJ was determined by one major locus (Ath8). In this study a (SM/J x NZB/BlNJ) F(1) x SM/J backcross localized Ath8 by quantitative trait locus mapping to chromosome 4 with a suggestive LOD score of 2.7. This quantitative trait locus (QTL) was confirmed using an (SM/J x NZB/BlNJ) intercross; Ath8 mapped to a 23cM region with a significant LOD score of 3.6. The genes for toll-like receptor 4 (T1r4), arachidonic acid epoxygenase (Cyp2j5), and angiopoietin-like protein 3 (Angptl3) map to this region. These candidate genes were analyzed for expression and sequence differences in the mouse and for associations with cardiovascular traits in human. Sequence analysis of Angptl3 shows a base pair substitution in SM, the susceptible strain, giving rise to an amino acid change in the fibrinogen homology domain of the protein. We found a significant association between ANGPTL3 and atherosclerotic lesions (P < 0.05) in human. These results suggest that Angptl3 is involved in atherosclerosis susceptibility in both mouse and human. 相似文献