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81.
Maurizio Bevilacqua Ligia J. Dominguez Giorgio Gandolini Valeria Valdes Tarcisio Vago Velella Righini Massimo Barrella Mario Barbagallo 《The Journal of steroid biochemistry and molecular biology》2009,113(1-2):3-8
Absorptive hypercalciuria (AH) is associated with elevated levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). While no increase of 1,25(OH)2D after oral administration of 25-hydroxyvitamin D (25OHD) at high doses has been claimed in normal subjects, a substrate–product relationship has been reported in normal children, young people after UV irradiation, older persons, postmenopausal women, primary hyperparathyroidism, renal failure, osteomalacia, and sarcoidosis. No data of this relationship in AH is available. To investigate 25OHD-1,25(OH)2D substrate–product relationship in AH, 161 AH patients (mean age 60.9 ± 11.7 years) and 110 age- and sex-matched controls (mean age 61.5 ± 12.4 years) were studied. In 57 controls and 52 AH subjects 25OHD-1,25(OH)2D relationship in basal conditions and after 2-week oral 25OHD (25 μg/day) administration were evaluated. In basal conditions 25OHD and 1,25(OH)2D were correlated in both, controls and AH; 25OHD treatment was followed by an increase in serum 25OHD and 1,25(OH)2D in both groups. However, delta responses of 25OHD and 1,25(OH)2D to 25OHD were higher in AH suggesting an enhanced activity of 1α-hydroxylase. In conclusion, the higher response of 1,25(OH)2D after oral 25OHD in AH patients suggests a differential capacity between both groups in handling the increases in 1,25(OH)2D. 相似文献
82.
83.
Codon bias and base composition in major histocompatibility complex (MHC) sequences have been studied for both class I and
II loci in Homo sapiens and Pan troglodytes. There is low to moderate codon bias for the MHC of humans and chimpanzees. In the class I loci, the same level of moderate
codon bias is seen for HLA-B, HLA-C, Patr-A, Patr-B, and Patr-C, while at HLA-A the level of codon bias is lower. There is a correlation between codon usage bias and G+C content in the A and B loci in humans and chimps, but not at the C locus. To examine the effect of diversifying selection on codon bias, we subdivided class I alleles into antigen recognition
site (ARS) and non-ARS codons. ARS codons had lower bias than non-ARS codons. This may indicate that the constraint of codon
bias on nucleotide substitution may be selected against in ARS codons. At the class II loci, there are distinct differences
between alpha and beta chain genes with respect to codon usage, with the beta chain genes being much more biased. Species-specific
differences in base composition were seen in exon 2 at the DRB1 locus, with lower GC content in chimpanzees. Considering the complex evolutionary history of MHC genes, the study of codon
usage patterns provides us with a better understanding of both the evolutionary history of these genes and the evolution of
synonymous codon usage in genes under natural selection.
Received: 2 April 1998 / Revised: 2 September 1998 相似文献
84.
Geoghegan JC Valdes PA Orem NR Deleault NR Williamson RA Harris BT Supattapone S 《The Journal of biological chemistry》2007,282(50):36341-36353
The central pathogenic event of prion disease is the conformational conversion of a host protein, PrPC, into a pathogenic isoform, PrPSc. We previously showed that the protein misfolding cyclic amplification (PMCA) technique can be used to form infectious prion molecules de novo from purified native PrPC molecules in an autocatalytic process requiring accessory polyanions (Deleault, N. R., Harris, B. T., Rees, J. R., and Supattapone, S. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 9741-9746). Here we investigated the molecular mechanism by which polyanionic molecules facilitate infectious prion formation in vitro.Ina PMCA reaction lacking PrPSc template seed, synthetic polyA RNA molecules induce hamster HaPrPC to adopt a protease-sensitive, detergent-insoluble conformation reactive against antibodies specific for PrPSc. During PMCA, labeled nucleic acids form nuclease-resistant complexes with HaPrP molecules. Strikingly, purified HaPrPC molecules subjected to PMCA selectively incorporate an approximately 1-2.5-kb subset of [32P]polyA RNA molecules from a heterogeneous mixture ranging in size from approximately 0.1 to >6 kb. Neuropathological analysis of scrapie-infected hamsters using the fluorescent dye acridine orange revealed that RNA molecules co-localize with large extracellular HaPrP aggregates. These findings suggest that polyanionic molecules such as RNA may become selectively incorporated into stable complexes with PrP molecules during the formation of native hamster prions. 相似文献
85.
86.
Taylor LL Banwart SA Valdes PJ Leake JR Beerling DJ 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2012,367(1588):565-582
Global weathering of calcium and magnesium silicate rocks provides the long-term sink for atmospheric carbon dioxide (CO(2)) on a timescale of millions of years by causing precipitation of calcium carbonates on the seafloor. Catchment-scale field studies consistently indicate that vegetation increases silicate rock weathering, but incorporating the effects of trees and fungal symbionts into geochemical carbon cycle models has relied upon simple empirical scaling functions. Here, we describe the development and application of a process-based approach to deriving quantitative estimates of weathering by plant roots, associated symbiotic mycorrhizal fungi and climate. Our approach accounts for the influence of terrestrial primary productivity via nutrient uptake on soil chemistry and mineral weathering, driven by simulations using a dynamic global vegetation model coupled to an ocean-atmosphere general circulation model of the Earth's climate. The strategy is successfully validated against observations of weathering in watersheds around the world, indicating that it may have some utility when extrapolated into the past. When applied to a suite of six global simulations from 215 to 50 Ma, we find significantly larger effects over the past 220 Myr relative to the present day. Vegetation and mycorrhizal fungi enhanced climate-driven weathering by a factor of up to 2. Overall, we demonstrate a more realistic process-based treatment of plant fungal-geosphere interactions at the global scale, which constitutes a first step towards developing 'next-generation' geochemical models. 相似文献
87.
88.
GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor prognosis despite multi-modalities of treatment. Furthermore, recent failure of targeted therapy for these tumours highlights the need of appropriate rodent models for preclinical studies. In this review, we highlight the most commonly used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the pathological and genetic similarities to the human disease. We end with a comprehensive review of the CNS-1 rodent model. 相似文献
89.
Lynn F Cherkas Elizabeth C Oelsner Y T Mak Anna Valdes Tim D Spector 《Twin research》2004,7(6):649-658
In humans, in contrast to animals, the genetic influences on infidelity are unclear. We report here a large study of over 1600 unselected United Kingdom female twin pairs who confidentially reported previous episodes of infidelity and total lifetime number of sexual partners, as well as attitudes towards infidelity. Our findings demonstrate that infidelity and number of sexual partners are both under moderate genetic influence (41% and 38% heritable, respectively) and the genetic correlation between these two traits is strong (47%). Conversely, attitudes towards infidelity are driven by shared and unique environmental, but not genetic, influences. A genome-wide linkage scan identified three suggestive but nonsignificant linkage areas associated with infidelity and number of sexual partners on chromosomes 3, 7 and 20 with a maximum LOD score of 2.46. We were unsuccessful in associating infidelity or number of sexual partners with a locus implicated in other mammals' sexual behavior, the vasopressin receptor gene. Nonetheless, our findings on the heritability of sexual infidelity and number of sexual partners provide support for certain evolutionary theories of human sexual behavior, as well as justifying further genetic and molecular research in this domain. 相似文献
90.
Effects of receptor concentration, media pH and storage on nicotinic receptor-transmitted signal in a fiber-optic biosensor 总被引:3,自引:0,他引:3
The optical signal generated by a nicotinic acetylcholine receptor (nAChR)-based optical biosensor was dependent on the density of toxin binding sites (i.e. receptors) immobilized on the surface of the fiber. The maximum density of nAChR receptors absorbed on the optic fibers, measured using [125I]-alpha-bungarotoxin (the alpha-neurotoxin of the Bungarus snake venom) binding, was 6.2 pmol of receptor sites per fiber. Incubation time, that was required for maximal noncovalent immobilization of the receptor protein on the fiber, was less than 10 min. Immobilization of the nAChR protein on the quartz fiber was affected by pH of the medium, with pH 3.5 as the optimal. Stored in phosphate buffered saline (PBS) or in a dry nitrogen atmosphere, the nAChR optical sensor showed no loss of activity over the first 3 days, then showed a slow but gradual loss in activity (45% over the next 30 days). 相似文献