249 research outputs found

    Protein fibrillogenesis model tracked by its intrinsic time-resolved emission spectra

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    The excited-state kinetics of the fluorescence of tyrosine in a de novo protein fibrillogenesis model was investigated as a potential tool for monitoring protein fibre formation and complexation with glucose (glycation). In stark contrast to insulin the time-resolved emission spectra (TRES) recorded over the period of 700 hours in buffered solutions of the model with and without glucose revealed no apparent changes in Tyr fluorescence responses. This indicates the stability of the model and provides a measurement-supported basis for its use as a reference material in fluorescence studies of protein aggregation

    Insulin aggregation tracked by its intrinsic TRES

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    Time-resolved emission spectra (TRES) have been used to detect conformational changes of intrinsic tyrosines within bovine insulin at a physiological pH. The approach offers the ability to detect the initial stages of insulin aggregation at the molecular level. The data analysis has revealed the existence of at least three fluorescent species undergoing dielectric relaxation and significant spectral changes due to insulin aggregation. The results indicate the suitability of the intrinsic TRES approach for insulin studies and for monitoring its stability during storage and aggregation in insulin delivery devices

    The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates.

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    The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty nine healthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. The expression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performed using a non-parametric test (Mann-Whitney U-Test). The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4 expressions were significantly higher in peripheral blood of healthy adults (

    Tyrosine photophysics during the early stages of β-amyloid aggregation leading to Alzheimer's

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    We have monitored the formation of toxic β-amyloid oligomers leading to Alzheimer's disease by detecting changes in the fluorescence decay of intrinsic tyrosine. A new approach based on the non-Debye model of fluorescence kinetics resolves the complexity of the underlying photophysics. The gradual disappearance of nonmonotonic fluorescence decay rates, at the early stages of aggregation as larger, tighter-packed oligomers are formed, is interpreted in terms of tyrosine-peptide dielectric relaxation influencing the decay. The results demonstrate the potential for a new type of fluorescence lifetime sensing based on dual excited-state/dielectric relaxation, with application across a broad range of biological molecules. The results also reconcile previously conflicting models of protein intrinsic fluorescence decay based on rotamers or dielectric relaxation by illustrating conditions under which both are manifest

    On the use of core-shell type semiconductor nanocrystals as sensors

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    Here we describe progress towards our objective of non contact transition metal ion sensing. Semiconductor nanocrystals show complex photophysical properties and require a very careful setup of the measurement parameters. Under these conditions they allow for very high resolution sensing of ions

    Bayesian Model Selection and Emulation for Protein Fluorescence

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    Fluorescence decay of amino acids in protein is a complex process for which multiple models have been proposed. Likelihood function evaluation for certain models can be computationally expensive, and as such surrogate models may be introduced to speed up inference. In this paper, Gaussian processes are implemented in likelihood estimation of a range of models defined by convolutions of an initial excitation input and a decay function using both synthetic and real world data. Parameter inference and model selection using the surrogate models are performed and compared against the exact results. Model selection when incorporating surrogate models into the inference process is shown to be consistent

    Impact of the flavonoid quercetin on beta-amyloid aggregation revealed by intrinsic fluorescence

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    We report the effects of quercetin, a flavonoid present in human diet, on early stage beta-amyloid (Aβ) aggregation – a seminal event in Alzheimer’s disease. Molecular level changes in Aβ arrangements are monitored by time-resolved emission spectral (TRES) measurements of the fluorescence of Aβ’s single tyrosine intrinsic fluorophore (Tyr). The results suggest that quercetin binds beta-amyloid oligomers at early stages of their aggregation, which leads to the formation of modified oligomers and hinders the creation of beta-sheet structures, potentially preventing the onset of Alzheimer’s disease
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