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991.
Trushina E Nemutlu E Zhang S Christensen T Camp J Mesa J Siddiqui A Tamura Y Sesaki H Wengenack TM Dzeja PP Poduslo JF 《PloS one》2012,7(2):e32737
Background
The identification of early mechanisms underlying Alzheimer''s Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics.Methods and Findings
We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans.Conclusions
Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD. 相似文献992.
NN Mishra AS Bayer TT Tran Y Shamoo E Mileykovskaya W Dowhan Z Guan CA Arias 《PloS one》2012,7(8):e43958
Background
The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains.Methodology
Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: phospholipid content, fatty acid composition, membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs.Principal Findings
Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i) phosphatidic acid; and ii) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM.Conclusion
Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance. 相似文献993.
994.
Stella Zevgiti Juliana Gonzalez Zabala Ayub Darji Ursula Dietrich Eugenia Panou‐Pomonis Maria Sakarellos‐Daitsiotis 《Journal of peptide science》2012,18(1):52-58
The terminal parts of the influenza hemagglutinin (HA) receptors α2,6‐ and α2,3‐sialyllactoses were conjugated to an artificial carrier, named sequential oligopeptide carrier (SOC4), to formulate human and avian receptor mimics, respectively. SOC4, formed by the tripeptide unit Lys‐Aib‐Gly, adopts a rigid helicoids‐type conformation, which enables the conjugation of biomolecules to the Lys‐NεH2 groups. By doing so, it preserves their initial conformations and functionalities of the epitopes. We report that SOC4‐glyco‐conjugate bearing two copies of the α2,6‐sialyllactose is specifically recognized by the biotinylated Sambucus nigra (elderberry) bark lectin, which binds preferentially to sialic acid in an α2,6‐linkage. SOC4‐glyco‐conjugate bearing two copies of the α2,3‐sialyllactose was not recognized by the biotinylated Maackia amurensis lectin, despite its well‐known α2,3‐sialyl bond specificity. However, preliminary immune blot assays showed that H1N1 virus binds to both the SOC4‐glyco‐conjugates immobilized onto nitrocellulose membrane. It is concluded that Ac‐SOC4[(Ac)2,(3′SL‐Aoa)2]‐NH2 5 and Ac‐SOC4[(Ac)2,(6′SL‐Aoa)2]‐NH2 6 mimic the HA receptors. These findings could be useful for easy screening of binding and inhibition assays of virus–receptor interactions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
995.
Focà E Motta D Pollara C Brianese N Gotti D Albini L Quiros-Roldan E Torti C Manca N 《The new microbiologica》2012,35(2):227-231
Our objective was to explore whether positive human cytomegalovirus (HCMV) DNAemia at baseline impaired CD4+ T-cell increase after 1 year of HAART. A sub-study of a randomized clinical trial in selected patients with <200 cell/mm CD4+ at baseline was conducted. Six out of 30 patients had detectable HCMV DNAemia at baseline, all reaching HCMV suppression at week 52 after HAART (only 1 of them was treated with valgancyclovir). No significant differences were found between patients with detectable or undetectable HCMV DNAemia in terms of CD4+ T-cell increase and HIV RNA response to HAART. Although some data may favor HCVM pre-emptive therapy to decrease immune activation, our results do not indicate that this practice may increase CD4+ T-cell count after HAART. At the same time, HAART proved effective in reducing HCMV DNAemia without the need for a specific therapy. 相似文献
996.
Fesel C Barreto M Ferreira RC Costa N Venda LL Pereira C Carvalho C Morães-Fontes MF Ferreira CM Vasconcelos C Viana JF Santos E Martins B Demengeot J Vicente AM 《PloS one》2012,7(3):e33992
In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects. 相似文献
997.
DA Geisler C Päpke T Obata A Nunes-Nesi A Matthes K Schneitz E Maximova WL Araújo AR Fernie S Persson 《The Plant cell》2012,24(7):2792-2811
998.
Dumitrescu O Dauwalder O Boisset S Reverdy MÉ Tristan A Vandenesch F 《Médecine sciences : M/S》2010,26(11):943-949
Staphylococcus aureus has a strong adaptive capacity and thus acquired various types of resistance to antistaphylococcal agents. More than 90% of isolates produce a penicillinase. Oxacillin remains active against these strains, but hospital associated staphylococci and more recently community acquired staphylococci have developed crossed resistance between methicillin (MRSA), oxacillin and other beta-lactams by production of a penicillin binding protein (PBP) with low affinity for beta-lactams, PBP2a. The gene encoding PBP2a, mecA is carried by a chromosomal element which also contains other resistance genes to heavy metals and other antibiotics thus explaining the multiresistant profile of hospital associated MRSA. By contrast, community acquired MRSA (CA-MRSA) are only resistant to kanamycin, fusidic acid and tetracycline, in addition to methicillin. This profile is specific of the European CA-MRSA ST80 clone which also encodes for a very particular virulence factor, the Panton-Valentine leukocidin. Glycopeptides, vancomycin and teicoplanin, are alternatives to oxacillin in case of resistance or intolerance. Strains with decreased susceptibility to glycopeptides have been reported. Their detection is difficult but necessary because vancomycin MIC creep seems linked to poor outcome in patients. 相似文献
999.
This study was performed to assess the N2-fixing capability of the native actinorhizal species Ochetophila trinervis (sin. Discaria trinervis) and Discaria chacaye (Rhamnaceae) in Northwest Patagonia. We measured the N concentration and 15N natural abundance in leaves and nodules of O. trinervis and D. chacaye, in leaves of associated non-actinorhizal vegetation, and in the soils under each sampled plant. O. trinervis and D. chacaye had foliar N concentrations that were about twice that of non-actinorhizal shrubs growing at the same sites, even though soils varied four-fold in total N across the sites. Leaves of both actinorhizal plants had a similar δ15N at any site and were close to atmospheric values. The foliar δ15N of non-actinorhizal plants and soil δ15N were strongly correlated across the sites. Nodules were depleted in δ15N relative to the foliage of the respective actinorhizal species. In conjunction with the uniformly high foliage N concentration of these actinorhizal plants and the universal presence of vesicles observed in root nodules, these data strongly suggest that O. trinervis and D. chacaye obtain a significant amount of their N from N2 fixation. To calculate the proportion of N derived from atmosphere, theoretical B-values were estimated. In all cases where the δ15N of fixing and reference foliage were significantly different, O. trinervis and D. chacaye obtained almost all of their N from N2 fixation. These results are the first to demonstrate N2 fixation by O. trinervis and D. chacaye in the field and therefore suggest an important role for these actinorhizal plants in the N economy of ecosystems in northwest Patagonia as well as their potential use for restoration of degraded lands in this region. 相似文献
1000.
Frankia is a genus of soil actinomycetes famous for its ability to form N2-fixing root nodule symbioses with actinorhizal plants. Although Frankia strains display a high diversity in terms of ecological niches in soil, current knowledge about Frankia is dominated by its life as an endophyte in root nodules. Increased use of molecular methods has refined and expanded insights
into endophyte-host specificities and Frankia phylogeny. This review has focus on Frankia as a soil organism, including its part of microbial consortia, and how to study Frankia in soil. We highlight the use of nodulation tests and molecular methods to reveal population size and genetic diversity of
Frankia in soil and discuss how autoregulation of nodulation and interactions with other soil microorganisms may influence the results.
A comprehensive record of published interactions between Frankia and other soil microbes is summarized. 相似文献