1,720,968 research outputs found
Dataset for: Conformational fingerprinting of tau variants and strains by Raman spectroscopy
No full textSupports article in RSC Advances - Conformational fingerprinting of tau variants and strains by Raman spectroscopy</span
Dataset in support of the Southampton doctoral thesis 'Developing a Drosophila–based model in which to study aspects of pathological Tau transfer and seeding'
No full textImages and Graphpad prism files (raw data, analysis and graphs) used in the creation of Developing a Drosophila–based model in which to study aspects of pathological Tau transfer and seeding. Organised by results chapter and figure </span
Raman spectroscopy: An emerging tool in neurodegenerative disease research and diagnosis
No full textThe pathogenesis underlining many neurodegenerative diseases remains incompletely understood. The lack of effective biomarkers and disease preventative medicine demands the development of new techniques to efficiently probe the mechanisms of disease and to detect early biomarkers predictive of disease onset. Raman spectroscopy is an established technique that allows the label-free fingerprinting and imaging of molecules based on their chemical constitution and structure. While analysis of isolated biological molecules has been widespread in the chemical community, applications of Raman spectroscopy to study clinically relevant biological species, disease pathogenesis, and diagnosis have been rapidly increasing since the past decade. The growing number of biomedical applications has shown the potential of Raman spectroscopy for detection of novel biomarkers that could enable the rapid and accurate screening of disease susceptibility and onset. Here we provide an overview of Raman spectroscopy and related techniques and their application to neurodegenerative diseases. We further discuss their potential utility in research, biomarker detection, and diagnosis. Challenges to routine use of Raman spectroscopy in the context of neuroscience research are also presented
Mid-infrared absorption spectroscopy of protein aggregates using germanium on silicon waveguides
No full textProteins in human samples can be used to detect the onset of a group of neurodegenerative diseases such as Alzheimer’s and Parkinson’s by studying their conformational (shape and structure) changes that can cause cognitive impairment. Proteins form aggregates from normal state (monomers) to disease state (amyloid deposition and fibril formation in central nervous system) that is associated with disease progression. These changes can be diagnosed and monitored using mid-infrared (MIR) absorption spectroscopy by studying line shapes and relative absorbance of amide bands. We have demonstrated MIR spectroscopy of proteins in three stages of aggregation: monomers, oligomers and fibrils of Bovine Serum Albumin (BSA) protein on a germanium on silicon (GOS) waveguide in the MIR wavelength region of 5.2 – 10 μm (1900 – 1000 cm-1). The protein samples were also characterised by atomic force microscopy to confirm their structure
Conformational evolution of molecular signatures during Amyloi-dogenic protein aggregation
No full textAggregation is a pathological hallmark of proteinopathies such as Alzheimer’s disease and results in the deposition of β-sheet-rich amyloidogenic protein aggregates. Such proteinopathies can be classified by the identity of one or more aggregated protein, with recent evidence also suggesting that distinct molecular conformers (strains) of the same protein can be observed in different diseases, as well is in sub-types of the same disease. Therefore, methods for the quantification of pathological changes in protein conformation are central to understanding and treating proteinopathies. In this work the evolution of Raman spectroscopic molecular signatures of three conformationally distinct proteins, Bovine Serum Albumin (α-helical-rich), β2-microglobulin (β-sheet-rich) and tau (natively disordered), was assessed during aggregation into oligomers and fibrils. The morphological evolution was tracked using Atomic Force Microscopy and corresponding conformational changes were assessed by their Raman signatures acquired in both wet and dried conditions. A deconvolution model was developed which allowed us to quantify the conformation of the non-regular protein tau, as well as for the oligomeric and fibrillar species of each of the proteins. Principle component analysis of the fingerprint region allowed further identification of the distinguishing spectral features and unsupervised distinction. While an increase in β-sheet is seen on aggregation, crucially, however, each protein also retains a significant proportion of its native monomeric structure after aggregation. Thus, spectral analysis of each aggregated species, oligomeric, as well as fibrillar, for each protein resulted in a unique and quantitative ‘conformational fingerprint’. This approach allowed us to provide the first differential detection of both oligomers and fibrils of the three different amyloidogenic proteins, including tau, whose aggregates have never before been interrogated using spontaneous Raman spectroscopy. Quantitative ‘conformational fingerprinting’ by Raman spectroscopy thus demonstrates its huge potential and utility in understanding proteinopathic disease mechanisms and for providing strain-specific early diagnostic markers and targets for disease-modifying therapies
A novel spectral barcoding and classification approach for complex biological samples using multiexcitation Raman spectroscopy (MX-Raman)
No full textWe report the development and application of a novel spectral barcoding approach that exploits our multiexcitation (MX) Raman spectroscopy-based methodology for improved label-free detection and classification of complex biological samples. To develop our improved MX-Raman methodology, we utilized post-mortem brain tissue from several neurodegenerative diseases (NDDs) that have considerable clinical overlap. For improving our methodology we used three sources of spectral information arising from distinct physical phenomena to assess which was most important for NDD classification. Spectral measurements utilized combinations of data from multiple, distinct excitation laser wavelengths and polarization states to differentially probe molecular vibrations and autofluorescence signals. We demonstrate that the more informative MX-Raman (532 nm–785 nm) spectra are classified with 96.7% accuracy on average, compared to conventional single-excitation Raman spectroscopy that resulted in 78.5% accuracy (532 nm) or 85.6% accuracy (785 nm) using linear discriminant analysis (LDA) on 5 NDD classes. By combining information from distinct laser polarizations we observed a nonsignificant increase in classification accuracy without the need of a second laser (785 nm–785 nm polarized), whereas combining Raman spectra with autofluorescence signals did not increase classification accuracy. Finally, by filtering out spectral features that were redundant for classification or not descriptive of disease class, we engineered spectral barcodes consisting of a minimal subset of highly disease-specific MX-Raman features that improved the unsupervised and cross-validated clustering of MX-Raman spectra. The results demonstrate that increasing spectral information content using our optical MX-Raman methodology enables enhanced identification and distinction of complex biological samples but only when that information is independent and descriptive of class. The future translation of such technology to biofluids could support diagnosis and stratification of patients living with dementia and potentially other clinical conditions such as cancer and infectious disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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