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81.
Na+-NQR is a unique energy-transducing complex, widely distributed among marine and pathogenic bacteria. It converts the energy from the oxidation of NADH and the reduction of quinone into an electrochemical Na+-gradient that can provide energy for the cell. Na+-NQR is not homologous to any other respiratory protein but is closely related to the RNF complex. In this review we propose that sodium pumping in Na+-NQR is coupled to the redox reactions by a novel mechanism, which operates at multiple sites, is indirect and mediated by conformational changes of the protein. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). 相似文献
82.
Moreb JS Ucar D Han S Amory JK Goldstein AS Ostmark B Chang LJ 《Chemico-biological interactions》2012,195(1):52-60
There has been a new interest in using aldehyde dehydrogenase (ALDH) activity as one marker for stem cells since the Aldefluor flow cytometry-based assay has become available. Diethylaminobenzaldehyde (DEAB), used in the Aldeflour assay, has been considered a specific inhibitor for ALDH1A1 isoform. In this study, we explore the effects of human ALDH isoenzymes, ALDH1A2 and ALDH2, on drug resistance and proliferation, and the specificity of DEAB as an inhibitor. We also screened for the expression of 19 ALDH isoenzymes in K562 cells using TaqMan Low Density Array (TLDA). We used lentiviral vectors containing the full cDNA length of either ALDH2 or ALDH1A2 to over express the enzymes in K562 leukemia and H1299 lung cancer cell lines. Successful expression was measured by activity assay, Western blot, RT-PCR, and Aldefluor assay. Both cell lines, with either ALDH1A2 or ALDH2, exhibited higher cell proliferation rates, higher clonal efficiency, and increased drug resistance to 4-hydroperoxycyclophosphamide and doxorubicin. In order to study the specificity of known ALDH activity inhibitors, DEAB and disulfiram, we incubated each cell line with either inhibitor and measured the remaining ALDH enzymatic activity. Both inhibitors reduced ALDH activity of both isoenzymes by 65-90%. Furthermore, our TLDA results revealed that ALDH1, ALDH7, ALDH3 and ALDH8 are expressed in K562 cells. We conclude that DEAB is not a specific inhibitor for ALDH1A1 and that Aldefluor assay is not specific for ALDH1A1 activity. In addition, other ALDH isoenzymes seem to play a major role in the biology and drug resistance of various malignant cells. 相似文献
83.
Chong-Pérez B Kosky RG Reyes M Rojas L Ocaña B Tejeda M Pérez B Angenon G 《Journal of biotechnology》2012,159(4):265-273
Selectable marker genes are indispensable for efficient production of transgenic events, but are no longer needed after the selection process and may cause public concern and technological problems. Although several gene excision systems exist, few have been optimized for vegetatively propagated crops. Using a Cre-loxP auto-excision strategy, we obtained transgenic banana plants cv. Grande Naine (Musa AAA) devoid of the marker gene used for selection. We used T-DNA vectors with the cre recombinase gene under control of a heat shock promoter and selectable marker gene cassettes placed between two loxP sites in direct orientation, and a gene of interest inserted outside of the loxP sites. Heat shock promoters pGmHSP17.6-L and pHSP18.2, from soybean and Arabidopsis respectively, were tested. A transient heat shock treatment of primary transgenic embryos was sufficient for inducing cre and excising cre and the marker genes. Excision efficiency, as determined by PCR and Southern hybridization was 59.7 and 40.0% for the GmHSP17.6-L and HSP18.2 promoters, respectively. Spontaneous excision was not observed in 50 plants derived from untreated transgenic embryos. To our knowledge this is the first report describing an efficient marker gene removal system for banana. The method described is simple and might be generally applicable for the production of marker-free transgenic plants of many crop species. 相似文献
84.
85.
Díaz-Castro B Pintado CO García-Flores P López-Barneo J Piruat JI 《Molecular and cellular biology》2012,32(16):3347-3357
The SDHD gene (subunit D of succinate dehydrogenase) has been shown to be involved in the generation of paragangliomas and pheochromocytomas. Loss of heterozygosity of the normal allele is necessary for tumor transformation of the affected cells. As complete SdhD deletion is lethal, we have generated mouse models carrying a "floxed" SdhD allele and either an inducible (SDHD-ESR strain) or a catecholaminergic tissue-specific (TH-SDHD strain) CRE recombinase. Ablation of both SdhD alleles in adult SDHD-ESR mice did not result in generation of paragangliomas or pheochromocytomas. In contrast, carotid bodies from these animals showed smaller volume than controls. In accord with these observations, the TH-SDHD mice had decreased cell numbers in the adrenal medulla, carotid body, and superior cervical ganglion. They also manifested inhibited postnatal maturation of mesencephalic dopaminergic neurons and progressive cell loss during the first year of life. These alterations were particularly intense in the substantia nigra, the most affected neuronal population in Parkinson's disease. Unexpectedly, TH(+) neurons in the locus coeruleus and group A13, also lacking the SdhD gene, were unaltered. These data indicate that complete loss of SdhD is not sufficient to induce tumorigenesis in mice. They suggest that substantia nigra neurons are more susceptible to mitochondrial damage than other catecholaminergic cells, particularly during a critical postnatal maturation period. 相似文献
86.
Lines MA Huang L Schwartzentruber J Douglas SL Lynch DC Beaulieu C Guion-Almeida ML Zechi-Ceide RM Gener B Gillessen-Kaesbach G Nava C Baujat G Horn D Kini U Caliebe A Alanay Y Utine GE Lev D Kohlhase J Grix AW Lohmann DR Hehr U Böhm D;FORGE Canada Consortium Majewski J Bulman DE Wieczorek D Boycott KM 《American journal of human genetics》2012,90(2):369-377
Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. 相似文献
87.
Blanca Céspedes Iván Torres Belén Luna Beatriz Pérez José M. Moreno 《Plant Ecology》2012,213(3):383-393
Soil seed banks play a major role in the post-fire regeneration of Mediterranean shrublands. They vary throughout the year
in species composition, abundance, and readiness to germinate. After fire, germination occurs mainly during the following
fall to spring. Time of germination can determine recruitment success. It is unclear what factors control post-fire germination
and its timing. We tested the effects of season and fire on the readily germinable soil seed bank of a seeder-dominated shrubland.
Plots were burned early and late in the summer season (ES, LS). Soil samples were collected before and after fire, and germinated
in a chamber simulating successively autumn, winter, and spring conditions. Samples were kept moistened at all times. Fire
intensity was similar between ES and LS. Several species of Cistus and herbs, mostly annuals, were dominant. Most germination occurred during the simulated-autumn period, with little subsequent
germination during the following two periods. Germination speed (T
50) during simulated-autumn was similar for shrubs and herbs, and independent of season or fire. Germination was lower for two
shrubs (Rosmarinus officinalis, Cistus salvifolius) and higher for herbaceous dicots in LS than in ES soils. Fire reduced monocots and enhanced Cistus. Germination period significantly interacted with fire and season in some groups or species, altering the simulated-autumn
germination peak. We demonstrate that the seed bank can germinate swiftly under simulated-autumn conditions. Hence, water
availability is the main controlling factor of germination. Fire season differentially affected some species or groups, and
could affect the post-fire regeneration. 相似文献
88.
A Lamana A Balsa B Rueda AM Ortiz L Nuño ME Miranda-Carus MF Gonzalez-Escribano MA Lopez-Nevot D Pascual-Salcedo J Martin I González-Álvaro 《PloS one》2012,7(8):e43661
Background
The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.Methodology and Results
We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.Conclusions
Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability. 相似文献89.
Arango-Gonzalez B Schatz A Bolz S Eslava-Schmalbach J Willmann G Zhour A Zrenner E Fischer MD Gekeler F 《PloS one》2012,7(4):e35687