1,960 research outputs found

    A Genomic Point Mutation in the Extracellular Domain of the Thyrotropin Receptor in Patients with Graves’ Ophthalmopathy

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    Orbital and pretibial fibroblasts are targets of autoimmune attack in Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD). The fibroblast autoantigen involved in these peripheral manifestations of Graves' disease and the reason for the association of GO and PTD with hyperthyroidism are unknown. RNA encoding the full-length extracellular domain of the TSH receptor has been demonstrated in orbital and dermal fibroblasts from patients with GO and normal subjects, suggesting a possible antigenic link between fibroblasts and thyrocytes. RNA was isolated from cultured orbital, pretibial, and abdominal fibroblasts obtained from patients with severe GO (n = 22) and normal subjects (n = 5). RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction, using primers spanning overlapping regions of the entire extracellular domain of the TSH receptor. Nucleotide sequence analysis showed an A for C substitution in the first position of codon 52 in 2 of the patients, both of whom had GO, PTD, and acropachy. Genomic DNA isolated from the 2 affected patients, and not from an additional 12 normal subjects, revealed the codon 52 mutation by direct sequencing and AciI restriction enzyme digestions. In conclusion, we have demonstrated the presence of a genomic point mutation, leading to a threonine for proline amino acid shift in the predicted peptide, in the extracellular domain of the TSH receptor in two patients with severe GO, PTD, acropachy, and high thyroid-stimulating immunoglobulin levels. RNA encoding this mutant product was demonstrated in the fibroblasts of these patients. We suggest that the TSH receptor may be an important fibroblast autoantigen in GO and PTD, and that this mutant form of the receptor may have unique immunogenic properties

    Inelastic fingerprints of hydrogen contamination in atomic gold wire systems

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    We present series of first-principles calculations for both pure and hydrogen contaminated gold wire systems in order to investigate how such impurities can be detected. We show how a single H atom or a single H2 molecule in an atomic gold wire will affect forces and Au-Au atom distances under elongation. We further determine the corresponding evolution of the low-bias conductance as well as the inelastic contributions from vibrations. Our results indicate that the conductance of gold wires is only slightly reduced from the conductance quantum G0=2e^2/h by the presence of a single hydrogen impurity, hence making it difficult to use the conductance itself to distinguish between various configurations. On the other hand, our calculations of the inelastic signals predict significant differences between pure and hydrogen contaminated wires, and, importantly, between atomic and molecular forms of the impurity. A detailed characterization of gold wires with a hydrogen impurity should therefore be possible from the strain dependence of the inelastic signals in the conductance.Comment: 5 pages, 3 figures, Contribution to ICN+T2006, Basel, Switzerland, July-August 200

    Gene expression becomes heterogeneous with age

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    Biotic interactions and biogeochemical processes in the soil environment

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    Soils play a key role in the terrestrial carbon (C) cycle by storing and emitting large quantities of C. The impact of abiotic conditions (mainly soil temperature and moisture) on soil C turnover is well documented, but unravelling the influence of these drivers across temporal and spatial scales remains an important challenge. Biotic factors, such as microbial abundance and diversity, macro-faunal food webs and below-ground plant (i.e. root) biomass and diversity, play an important role in controlling soil C storage and emission, but remain under-investigated. To better understand the soil processes underlying terrestrial C cycling, the interactions between plants (autotrophs) and soil organisms (heterotrophs) need to be addressed more explicitly and integrated with short- and long-term effects of abiotic drivers. This special issue presents recent advances in field, laboratory, and modelling studies on soil C dynamics, with a particular emphasis on those aiming to resolve abiotic and biotic influences. The manuscripts highlight three areas of investigation that we suggest are central to current and future progress in ecosystem C dynamic research: (1) novel interpretations of abiotic controls on soil CO2 efflux, (2) legacy effects of abiotic drivers of soil C dynamics, and (3) the interaction between plant C dynamics and soil biological processes
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