Research Explorer | The University of Manchester
FTIR imaging of the molecular burden around Aβ deposits in an early-stage 3-Tg-APP-PSP1-TAU mouse model of Alzheimer’s diseaseArtur Dawid Surowka1, Michael Pilling2,3, Alex Henderson2,3, Hervey Boutin4, Lidan Christie4, Magdalena Szczerbowska-Boruchowska1, Peter Gardner2,31AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow, Poland2Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, UK3School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester, UK4Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UKAbstractAlzheimer's disease is one of the major causes of dementia in the elderly. The disease is caused by the misfolding of water soluble alpha-helical proteins, which leads to the accumulation of β-sheets in the form of amyloid plaques, which can subsequently affect surrounding tissue areas by oxidative stress neurotoxicity. The aim of the present study was to design a novel methodology to analyze the extent to the neuronal burden around protein-rich Aβ plaques suspected to affect molecular components by oxidative stress induced by inflammatory states. To do so, sagittal brain tissue sections from triple transgenic APPxPSP1xTAU mice were used to carry high magnification FTIR-FPA bench-top chemical imaging. The study used the combination of chemometric procedures involving spectral curve fitting and image processing to study the molecular changes occurring around the plaques. The study shows the performance of the approach by demonstrating its usefulness to co-localize molecular changes to different areas around the plaques. The results, although very preliminary, point to the strong interplay between the distance from the plaque and co-accumulation of molecular components indicative of inflammatory states. IntroductionOf all the human central nervous system diseases, Alzheimer's disease (AD) has deservedly received great attention as this age-associated disease causes the progressive decline in both cognitive and bodily functions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrn2420", "ISBN" : "1471-0048 (Electronic)", "ISSN" : "1471-003X", "PMID" : "18568014", "abstract" : "Insoluble protein aggregates have been linked to Alzheimer's disease (AD) and frontotemporal dementia (FTD). Recent work in transgenic mice has shed light on the role of these aggregates by identifying soluble oligomeric species that may interfere with essential cellular mechanisms at an early disease stage. This review summarizes what we have learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms. Proteomic and transcriptomic analyses of tissue from these animal models have identified new molecules with crucial roles in disease. Moreover, transgenic animals have been instrumental in defining drug targets and designing novel therapeutic strategies. With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach.", "author" : [ { "dropping-particle" : "", "family" : "G\u00f6tz", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ittner", "given" : "Lars M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Neuroscience", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "532-544", "title" : "Animal models of Alzheimer's disease and frontotemporal dementia.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>1</sup>", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "<sup>1</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1. AD is the most prevalent dementia in the elderly affecting around 24 million globally which is likely to quadruple before 2050 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bcp.2013.12.024", "ISBN" : "1873-2968 (Electronic)\\r0006-2952 (Linking)", "ISSN" : "18732968", "PMID" : "24398425", "abstract" : "The global prevalence of dementia is as high as 24 million, and has been predicted to quadruple by the year 2050. In the US alone, Alzheimer disease (AD) - the most frequent cause of dementia characterized by a progressive decline in cognitive function in particular the memory domain - causes estimated health-care costs of $ 172 billion per year. Key neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques - often surrounded by dystrophic neurites - and intracellular neurofibrillary tangles. These pathological changes are frequently accompanied by reactive microgliosis and loss of neurons, white matter and synapses. The etiological mechanisms underlying these neuropathological changes remain unclear, but are probably caused by both environmental and genetic factors. In this review article, we provide an overview of the epidemiology of AD, review the biomarkers that may be used for risk assessment and in diagnosis, and give suggestions for future research. ?? 2014 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Reitz", "given" : "Christiane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayeux", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochemical Pharmacology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "640-651", "title" : "Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers", "type" : "article", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>2</sup>", "plainTextFormattedCitation" : "2", "previouslyFormattedCitation" : "<sup>2</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2. The pathological features of AD appear within the hippocampus and frontal cortex, whilst it is thought that the disease affects the former at the onset ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0001-6322", "PMID" : "1759558", "abstract" : "Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.", "author" : [ { "dropping-particle" : "", "family" : "Braak", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braak", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta neuropathologica", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "239-59", "title" : "Neuropathological stageing of Alzheimer-related changes.", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nrn3887", "ISBN" : "1471-0048 (Electronic)\\r1471-003X (Linking)", "ISSN" : "1471-0048", "PMID" : "25588378", "abstract" : "The progression of many neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell-cell transmission of characteristic disease-related proteins, leading to the sequential dissemination of pathological protein aggregates. Recent evidence strongly suggests that the anatomical connections made by neurons - in addition to the intrinsic characteristics of neurons, such as morphology and gene expression profile - determine whether they are vulnerable to degeneration in these disorders. Notably, this common pathogenic principle opens up opportunities for pursuing novel targets for therapeutic interventions for these neurodegenerative disorders. We review recent evidence that supports the notion of neuron-neuron protein propagation, with a focus on neuropathological and positron emission tomography imaging studies in humans.", "author" : [ { "dropping-particle" : "", "family" : "Brettschneider", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Del", "family" : "Tredici", "given" : "Kelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Virginia M-Y Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trojanowski", "given" : "John Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Neuroscience", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "109-20", "title" : "Spreading of pathology in neurodegenerative diseases: a focus on human studies.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>3,4</sup>", "plainTextFormattedCitation" : "3,4", "previouslyFormattedCitation" : "<sup>3,4</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }3,4. The main hallmark lesions of the AD pathology are the extracellular plaques of β-amyloid (Aβ) assumed to develop before the emergence of the symptoms ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrn3887", "ISBN" : "1471-0048 (Electronic)\\r1471-003X (Linking)", "ISSN" : "1471-0048", "PMID" : "25588378", "abstract" : "The progression of many neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell-cell transmission of characteristic disease-related proteins, leading to the sequential dissemination of pathological protein aggregates. Recent evidence strongly suggests that the anatomical connections made by neurons - in addition to the intrinsic characteristics of neurons, such as morphology and gene expression profile - determine whether they are vulnerable to degeneration in these disorders. Notably, this common pathogenic principle opens up opportunities for pursuing novel targets for therapeutic interventions for these neurodegenerative disorders. We review recent evidence that supports the notion of neuron-neuron protein propagation, with a focus on neuropathological and positron emission tomography imaging studies in humans.", "author" : [ { "dropping-particle" : "", "family" : "Brettschneider", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Del", "family" : "Tredici", "given" : "Kelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Virginia M-Y Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trojanowski", "given" : "John Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Neuroscience", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "109-20", "title" : "Spreading of pathology in neurodegenerative diseases: a focus on human studies.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>4</sup>", "plainTextFormattedCitation" : "4", "previouslyFormattedCitation" : "<sup>4</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4. They are made of a 40-42 amino -acid long polypeptide called Aβ that derives from β- and γ-secretase-mediated sequential cleavage of the amyloid-precursor-protein (APP). Two major Aβ proteins, Aβ1-42 and Aβ1-40, are thought to differentially contribute to the pathology. A number of studies have reported Aβ1-42 more pathogenic as it is more prone to fibrilization, but much less is known about the reason for this ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/emboj.2010.211", "ISBN" : "0261-4189", "ISSN" : "0261-4189", "PMID" : "20818335", "abstract" : "The amyloid peptides A\u03b2(40) and A\u03b2(42) of Alzheimer's disease are thought to contribute differentially to the disease process. Although A\u03b2(42) seems more pathogenic than A\u03b2(40), the reason for this is not well understood. We show here that small alterations in the A\u03b2(42):A\u03b2(40) ratio dramatically affect the biophysical and biological properties of the A\u03b2 mixtures reflected in their aggregation kinetics, the morphology of the resulting amyloid fibrils and synaptic function tested in vitro and in vivo. A minor increase in the A\u03b2(42):A\u03b2(40) ratio stabilizes toxic oligomeric species with intermediate conformations. The initial toxic impact of these A\u03b2 species is synaptic in nature, but this can spread into the cells leading to neuronal cell death. The fact that the relative ratio of A\u03b2 peptides is more crucial than the absolute amounts of peptides for the induction of neurotoxic conformations has important implications for anti-amyloid therapy. Our work also suggests the dynamic nature of the equilibrium between toxic and non-toxic intermediates.", "author" : [ { "dropping-particle" : "", "family" : "Kuperstein", "given" : "Inna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broersen", "given" : "Kerensa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benilova", "given" : "Iryna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozenski", "given" : "Jef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonckheere", "given" : "Wim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Debulpaep", "given" : "Maja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandersteen", "given" : "Annelies", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Segers-Nolten", "given" : "Ine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werf", "given" : "Kees", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subramaniam", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braeken", "given" : "Dries", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callewaert", "given" : "Geert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartic", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Hooge", "given" : "Rudi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martins", "given" : "Ivo Cristiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rousseau", "given" : "Frederic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schymkowitz", "given" : "Joost", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strooper", "given" : "Bart", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" } ], "container-title" : "The EMBO journal", "id" : "ITEM-1", "issue" : "19", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "3408-3420", "title" : "Neurotoxicity of Alzheimer's disease A\u03b2 peptides is induced by small changes in the A\u03b242 to A\u03b240 ratio.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>5</sup>", "plainTextFormattedCitation" : "5", "previouslyFormattedCitation" : "<sup>5</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5. However, the study by Kim and Hecht proposed its ability for aggregation is due to two additional hydrophobic amino-acids at its C-terminal end ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1074/jbc.M505763200", "ISSN" : "0021-9258", "author" : [ { "dropping-particle" : "", "family" : "Kim", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hecht", "given" : "M. H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Biological Chemistry", "id" : "ITEM-1", "issue" : "41", "issued" : { "date-parts" : [ [ "2005", "10", "14" ] ] }, "page" : "35069-35076", "title" : "Sequence Determinants of Enhanced Amyloidogenicity of Alzheimer A 42 Peptide Relative to A 40", "type" : "article-journal", "volume" : "280" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>6</sup>", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "<sup>6</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6. Evidence suggests that upon its aggregation into Aβ plaque, an innate immune response is triggered on the site involving mostly microglial cells. Importantly, the detection of pathological triggers by microglial cells is stimulated by a variety of cell-surface receptors that recognize different danger-associated molecular patterns (DAMPs) including those present in Aβ fibrils or pathogen-associated molecular patterns (PAMPs) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1474-4422(15)70016-5", "ISBN" : "1474-4465 (Electronic)\\r1474-4422 (Linking)", "ISSN" : "14744465", "PMID" : "25792098", "abstract" : "Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.", "author" : [ { "dropping-particle" : "", "family" : "Heneka", "given" : "Michael T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carson", "given" : "Monica J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "El", "family" : "Khoury", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landreth", "given" : "Gary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brosseron", "given" : "Frederic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feinstein", "given" : "Douglas L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Andreas H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyss-Coray", "given" : "Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitorica", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ransohoff", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrup", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frautschy", "given" : "Sally A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finsen", "given" : "Bente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Guy C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verkhratsky", "given" : "Alexei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamanaka", "given" : "Koji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koistinaho", "given" : "Jari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Latz", "given" : "Eicke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halle", "given" : "Annett", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petzold", "given" : "Gabor C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Town", "given" : "Terrence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Dave", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shinohara", "given" : "Mari L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "V. Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "Clive", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bazan", "given" : "Nicolas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brooks", "given" : "David J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunot", "given" : "St??phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joseph", "given" : "Bertrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deigendesch", "given" : "Nikolaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garaschuk", "given" : "Olga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boddeke", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinarello", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Breitner", "given" : "John C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Greg M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golenbock", "given" : "Douglas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kummer", "given" : "Markus P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet Neurology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "388-405", "title" : "Neuroinflammation in Alzheimer's disease", "type" : "article", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>7</sup>", "plainTextFormattedCitation" : "7", "previouslyFormattedCitation" : "<sup>7</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7. Previous studies have reported a causative role for Aβ plaques in the production of reactive oxygen species (ROS) that have a very high potential to damage all cellular components ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0197-4580(01)00340-2", "ISBN" : "0197-4580 (Print)\\n0197-4580 (Linking)", "ISSN" : "01974580", "PMID" : "12392766", "abstract" : "Amyloid ??-peptide [A??(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. A??(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, A?? induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). These alkenals covalently bind to synaptosomal protein cysteine, histidine, and lysine residues by Michael addition to change protein conformation and function. HNE or acrolein binding to proteins introduces a carbonyl to the protein, making the protein oxidatively modified as a consequence of lipid peroxidation. Immunoprecipitation of proteins from AD and control brain, obtained no longer than 4h PMI, showed selective proteins are oxidatively modified in the AD brain. Creatine kinase (CK) and ??-actin have increased carbonyl groups, and Glt-1, a glutamate transporter, has increased binding of HNE in AD. A??(1-42) addition to synaptosomes also results in HNE binding to Glt-1, thereby coupling increased A??(1-42) in AD brain to increased lipid peroxidation and its sequelae and possibly explaining the mechanism of glutatmate transport inhibition known in AD brain. A?? also inhibits CK. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. The epsilon-4 allele of the lipid carrier protein apolipoprotein E (APOE) allele is a risk factor for AD. Synaptosomes from APOE knock-out mice are more vulnerable to A??-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. Further, synaptosomes from allele-specific APOE knock-in mice have tiered vulnerability to A??(1-42)-induced oxidative stress, with APOE4 more vulnerable to A??(1-42) than are those from APOE2 or APOE3 mice. These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by A??(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE\u2026", "author" : [ { "dropping-particle" : "", "family" : "Allan Butterfield", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castegna", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauderback", "given" : "Christopher M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drake", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurobiology of Aging", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "655-664", "title" : "Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death", "type" : "article", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>8</sup>", "plainTextFormattedCitation" : "8", "previouslyFormattedCitation" : "<sup>8</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }8. Recently, it was also found that 4-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, is present in high levels in the brains affected by Aβ pathology, which also supports a putative relationship of oxidative stress neurotoxicity caused by ROS over-production and brain amyloid burden ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.nbd.2015.06.013", "ISSN" : "09699961", "author" : [ { "dropping-particle" : "", "family" : "Arimon", "given" : "Muriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeda", "given" : "Shuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Post", "given" : "Kathryn L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Svirsky", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hyman", "given" : "Bradley T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berezovska", "given" : "Oksana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurobiology of Disease", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "12" ] ] }, "page" : "109-119", "title" : "Oxidative stress and lipid peroxidation are upstream of amyloid pathology", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>9</sup>", "plainTextFormattedCitation" : "9", "previouslyFormattedCitation" : "<sup>9</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }9.To address the problem of the genesis and spread out of the AD disease, there has been an increasing interest in the analytical methods to extract the subtle biochemical information on Aβ pathology. One of the greatest challenges was to find a technique that is capable of analyzing a myriad of molecules at a (sub)cellular spatial resolution in-situ with special emphasis on proteins particularly prone to various effects of oxidative stress ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroimage.2011.11.033", "ISBN" : "1053-8119", "ISSN" : "10538119", "PMID" : "22119649", "abstract" : "In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. ?? 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Caine", "given" : "Sally", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heraud", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobin", "given" : "Mark J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNaughton", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernard", "given" : "Claude C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "3624-3640", "title" : "The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue", "type" : "article", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>10</sup>", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "<sup>10</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10. Fourier Transform Infrared Spectroscopy (FTIR) has been shown as an excellent method to probe the chemical and structural composition of brain samples at the desired resolution ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nprot.2014.110", "ISBN" : "1750-2799 (Electronic)\\r1750-2799 (Linking)", "ISSN" : "1750-2799", "PMID" : "24992094", "abstract" : "IR spectroscopy is an excellent method for biological analyses. It enables the nonperturbative, label-free extraction of biochemical information and images toward diagnosis and the assessment of cell functionality. Although not strictly microscopy in the conventional sense, it allows the construction of images of tissue or cell architecture by the passing of spectral data through a variety of computational algorithms. Because such images are constructed from fingerprint spectra, the notion is that they can be an objective reflection of the underlying health status of the analyzed sample. One of the major difficulties in the field has been determining a consensus on spectral pre-processing and data analysis. This manuscript brings together as coauthors some of the leaders in this field to allow the standardization of methods and procedures for adapting a multistage approach to a methodology that can be applied to a variety of cell biological questions or used within a clinical setting for disease screening or diagnosis. We describe a protocol for collecting IR spectra and images from biological samples (e.g., fixed cytology and tissue sections, live cells or biofluids) that assesses the instrumental options available, appropriate sample preparation, different sampling modes as well as important advances in spectral data acquisition. After acquisition, data processing consists of a sequence of steps including quality control, spectral pre-processing, feature extraction and classification of the supervised or unsupervised type. A typical experiment can be completed and analyzed within hours. Example results are presented on the use of IR spectra combined with multivariate data processing.", "author" : [ { "dropping-particle" : "", "family" : "Baker", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trevisan", "given" : "J\u00falio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butler", "given" : "Holly J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorling", "given" : "Konrad M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fielden", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fogarty", "given" : "Simon W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullwood", "given" : "Nigel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heys", "given" : "Kelly a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Caryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lasch", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin-Hirsch", "given" : "Pierre L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obinaju", "given" : "Blessing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sockalingum", "given" : "Ganesh D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sul\u00e9-Suso", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strong", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Bayden R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Francis L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature protocols", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1771-91", "title" : "Using Fourier transform IR spectroscopy to analyze biological materials.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>11</sup>", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "<sup>11</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11. This label-free spectroscopic method does not require any complicated sample preparation protocols, hence thin (~10 ?m) neural tissue sections (predominantly subjected to freeze drying, desiccation) can be analyzed in air with satisfactory signal-to-noise ratio ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroimage.2011.11.033", "ISBN" : "1053-8119", "ISSN" : "10538119", "PMID" : "22119649", "abstract" : "In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. ?? 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Caine", "given" : "Sally", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heraud", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobin", "given" : "Mark J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNaughton", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernard", "given" : "Claude C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "3624-3640", "title" : "The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue", "type" : "article", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>10</sup>", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "<sup>10</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10. The first serious attempts to analyze AD pathology using FTIR spectroscopy coupled with a synchrotron source (SR) revealed the Congo red-positive human-derived Aβ plaques to exhibit slightly elevated levels of β-sheets and reduced contents of random coils and alpha-helices. However, the FTIR analyses made use of single-point-raster-scanning mode and operating at relatively low spatial resolution of 12 ?m (defined by the size of the aperture). In addition, the authors did not conduct any more sophisticated chemometric analyses in an attempt to separate different secondary structure components ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0006-3002", "PMID" : "8399370", "abstract" : "Fourier transform infrared spectroscopy has been used for the characterisation of white matter, grey matter and multiple sclerosis plaques from human central nervous system tissue. We demonstrate significant differences in the infrared spectra of the three types of tissue, which show that an infrared spectroscopic discrimination of multiple sclerosis plaques from healthy brain tissue is possible in principle. The spectral changes reveal pronounced lipid loss in plaques, consistent with the demyelinating nature of the disease. The chronic plaques studied here can also be distinguished from other non-myelinated areas of the brain, based on differences in water content.", "author" : [ { "dropping-particle" : "", "family" : "Choo", "given" : "L P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halliday", "given" : "W C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mantsch", "given" : "H H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimica et Biophysica Acta", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "333-337", "title" : "Infrared spectroscopic characterisation of multiple sclerosis plaques in the human central nervous system.", "type" : "article-journal", "volume" : "1182" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>12</sup>", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "<sup>12</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }12. The study by Miller et al. presented detailed examination of human-derived Aβ plaques using both single-point FTIR to image molecular components and X-Ray fluorescence microprobe imaging (both using 5-10 ?m synchrotron beam) to assess for the content of chemical trace elements. In agreement with the previous research, it was demonstrated the Aβ deposits were enriched in β-sheets and accumulated transition metals: Fe, Cu, Zn ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jsb.2005.09.004", "ISBN" : "1047-8477", "ISSN" : "10478477", "PMID" : "16325427", "abstract" : "Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (A??). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 ??m was achieved. FTIRM results showed that the amyloid plaques have elevated ??-sheet content, as demonstrated by a strong amide I absorbance at 1625 cm-1. Using SXRF microprobe, we find that AD tissue also contains \"hot spots\" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The \"hot spots\" of accumulated Zn and Cu were co-localized with ??-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated ??-sheet content in A?? plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD. ?? 2005 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Telivala", "given" : "Tejas P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Randy J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanzirotti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miklossy", "given" : "Judit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Structural Biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "30-37", "title" : "Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with ??-amyloid deposits in Alzheimer's disease", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>13</sup>", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "<sup>13</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. Importantly, Cu2+, Fe3+ are thought to be implicated in ROS production and further lipid and protein oxidation in AD-affected brains, while Zn2+ was found to even attenuate the toxicity of Aβ in cell cultures ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bbamem.2007.02.002", "ISBN" : "0006-3002 (Print)\\r0006-3002 (Linking)", "ISSN" : "00052736", "PMID" : "17433250", "abstract" : "There is a growing body of evidence to support a role for oxidative stress in Alzheimer's disease (AD), with increased levels of lipid peroxidation, DNA and protein oxidation products (HNE, 8-HO-guanidine and protein carbonyls respectively) in AD brains. The brain is a highly oxidative organ consuming 20% of the body's oxygen despite accounting for only 2% of the total body weight. With normal ageing the brain accumulates metals ions such iron (Fe), zinc (Zn) and copper (Cu). Consequently the brain is abundant in antioxidants to control and prevent the detrimental formation of reactive oxygen species (ROS) generated via Fenton chemistry involving redox active metal ion reduction and activation of molecular oxygen. In AD there is an over accumulation of the Amyloid \u03b2 peptide (A\u03b2), this is the result of either an elevated generation from amyloid precursor protein (APP) or inefficient clearance of A\u03b2 from the brain. A\u03b2 can efficiently generate reactive oxygen species in the presence of the transition metals copper and iron in vitro. Under oxidative conditions A\u03b2 will form stable dityrosine cross-linked dimers which are generated from free radical attack on the tyrosine residue at position 10. There are elevated levels of urea and SDS resistant stable linked A\u03b2 oligomers as well as dityrosine cross-linked peptides and proteins in AD brain. Since soluble A\u03b2 levels correlate best with the degree of degeneration [C.A. McLean, R.A. Cherny, F.W. Fraser, S.J. Fuller, M.J. Smith, K. Beyreuther, A.I. Bush, C.L. Masters, Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease, Ann. Neurol. 46 (1999) 860\u2013866] we suggest that the toxic A\u03b2 species corresponds to a soluble dityrosine cross-linked oligomer. Current therapeutic strategies using metal chelators such as clioquinol and desferrioxamine have had some success in altering the progression of AD symptoms. Similarly, natural antioxidants curcumin and ginkgo extract have modest but positive effects in slowing AD development. Therefore, drugs that target the oxidative pathways in AD could have genuine therapeutic efficacy.", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Danielle G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappai", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnham", "given" : "Kevin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimica et Biophysica Acta (BBA) - Biomembranes", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "1976-1990", "title" : "The redox chemistry of the Alzheimer's disease amyloid \u03b2 peptide", "type" : "article-journal", "volume" : "1768" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>14</sup>", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "<sup>14</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14. The work by Rak et al. involving similar spatial resolution revealed the plaques found in the hippocampal, cortical and caudal tissue of 21-month-old TgCRND8 mice of two distinct types: dense core and diffuse core Aβ plaques. The former, congo-positive, were recognized based on the elevated content of β sheets, whilst the latter were not detectable using FTIR spectroscopy but visible only upon immunohistochemical staining against anti-Aβ antibody 4G8 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/bip.20820", "ISBN" : "0006-3525 (Print)\\r0006-3525 (Linking)", "ISSN" : "00063525", "PMID" : "17680701", "abstract" : "Plaques composed of the A\u03b2 peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of A\u03b2, showing all the classical properties of amyloid including \u03b2-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an early age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a \u03b2-sheet conformation. The amide I maximum of plaque cores was at 1623 cm\u22121, and unlike for in vitro A\u03b2 fibrils, the high-frequency (1680\u20131690 cm\u22121) component attributed to antiparallel \u03b2-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.", "author" : [ { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bigio", "given" : "Marc R.", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mai", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westaway", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biopolymers", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "207-217", "title" : "Dense-core and diffuse A?? plaques in TgCRND8 mice studied with synchrotron FTIR microspectroscopy", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>15</sup>", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "<sup>15</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15. Recent developments in the state-of-art of the instrumentation have led to successful applications of Focal Plane Array (FPA) FTIR detectors to measure thousands of spectra simultaneously ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nprot.2014.110", "ISBN" : "1750-2799 (Electronic)\\r1750-2799 (Linking)", "ISSN" : "1750-2799", "PMID" : "24992094", "abstract" : "IR spectroscopy is an excellent method for biological analyses. It enables the nonperturbative, label-free extraction of biochemical information and images toward diagnosis and the assessment of cell functionality. Although not strictly microscopy in the conventional sense, it allows the construction of images of tissue or cell architecture by the passing of spectral data through a variety of computational algorithms. Because such images are constructed from fingerprint spectra, the notion is that they can be an objective reflection of the underlying health status of the analyzed sample. One of the major difficulties in the field has been determining a consensus on spectral pre-processing and data analysis. This manuscript brings together as coauthors some of the leaders in this field to allow the standardization of methods and procedures for adapting a multistage approach to a methodology that can be applied to a variety of cell biological questions or used within a clinical setting for disease screening or diagnosis. We describe a protocol for collecting IR spectra and images from biological samples (e.g., fixed cytology and tissue sections, live cells or biofluids) that assesses the instrumental options available, appropriate sample preparation, different sampling modes as well as important advances in spectral data acquisition. After acquisition, data processing consists of a sequence of steps including quality control, spectral pre-processing, feature extraction and classification of the supervised or unsupervised type. A typical experiment can be completed and analyzed within hours. Example results are presented on the use of IR spectra combined with multivariate data processing.", "author" : [ { "dropping-particle" : "", "family" : "Baker", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trevisan", "given" : "J\u00falio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butler", "given" : "Holly J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorling", "given" : "Konrad M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fielden", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fogarty", "given" : "Simon W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullwood", "given" : "Nigel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heys", "given" : "Kelly a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Caryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lasch", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin-Hirsch", "given" : "Pierre L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obinaju", "given" : "Blessing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sockalingum", "given" : "Ganesh D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sul\u00e9-Suso", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strong", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Bayden R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Francis L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature protocols", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1771-91", "title" : "Using Fourier transform IR spectroscopy to analyze biological materials.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1366/12-06801", "ISSN" : "00037028", "author" : [ { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Applied Spectroscopy", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "page" : "1091-1120", "title" : "Infrared Spectroscopic Imaging: The Next Generation", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>11,16</sup>", "plainTextFormattedCitation" : "11,16", "previouslyFormattedCitation" : "<sup>11,16</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11,16. One of these studies with synchrotron FTIR-FPA imaging by means of the 64×64 pixel array detector (at the effective geometric pixel size of 5.5 x 5.5 ?m2) presented an elevated lipid envelope surrounding dense core plaques in the TgCRND8 animal model of AD. The authors proposed the envelope is due to lipid-rich glial cells infiltrating the Aβ deposits. It was also confirmed the spatial resolution of the method is sufficient to distinguish between the plaque areas and glial cells infiltrating/engulfing the surrounding neuropil ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroimage.2011.11.069", "ISBN" : "1053-8119", "ISSN" : "10538119", "PMID" : "22197789", "abstract" : "The critical questions into the cause of neural degeneration, in Alzheimer disease and other neurodegenerative disorders, are closely related to the question of why certain neurons survive. Answers require detailed understanding of biochemical changes in single cells. Fourier transform infrared microspectroscopy is an excellent tool for biomolecular imaging in situ, but resolution is limited. The mid-infrared beamline IRENI (InfraRed ENvironmental Imaging) at the Synchrotron Radiation Center, University of Wisconsin-Madison, enables label-free subcellular imaging and biochemical analysis of neurons with an increase of two orders of magnitude in pixel spacing over current systems. With IRENI's capabilities, it is now possible to study changes in individual neurons in situ, and to characterize their surroundings, using only the biochemical signatures of naturally-occurring components in unstained, unfixed tissue. We present examples of analyses of brain from two transgenic mouse models of Alzheimer disease (TgCRND8 and 3xTg) that exhibit different features of pathogenesis. Data processing on spectral features for nuclei reveals individual hippocampal neurons, and neurons located in the proximity of amyloid plaque in TgCRND8 mouse. Elevated lipids are detected surrounding and, for the first time, within the dense core of amyloid plaques, offering support for inflammatory and aggregation roles. Analysis of saturated and unsaturated fatty acid ester content in retina allows characterization of neuronal layers. IRENI images also reveal spatially-resolved data with unprecedented clarity and distinct spectral variation, from sub-regions including photoreceptors, neuronal cell bodies and synapses in sections of mouse retina. Biochemical composition of retinal layers can be used to study changes related to disease processes and dietary modification. ?? 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Kastyak-Ibrahim", "given" : "M. Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nasse", "given" : "M. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bigio", "given" : "M. R.", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "B. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "K. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "376-383", "title" : "Biochemical label-free tissue imaging with subcellular-resolution synchrotron FTIR with focal plane array detector", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>17</sup>", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "<sup>17</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17. Liao et al. using SR-FTIR-FPA imaging of dense core plaques confirmed the presence of lipid envelope around the Aβ plaques found both in the animal model and autopsy brain tissue sections from humans affected by advanced AD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c3an00295k", "ISBN" : "1204237409", "ISSN" : "1364-5528", "PMID" : "23586070", "abstract" : "While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and A\u03b2 peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 \u00d7 0.54 \u00b5m(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3\u00d7Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Catherine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Jillian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unger", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "Benedict C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "3991-7", "title" : "Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>18</sup>", "plainTextFormattedCitation" : "18", "previouslyFormattedCitation" : "<sup>18</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }18. Another recent study by Benseny-Cases et al. on the human tissue sections from the AD patients set out with the aim of assessing the regional extent of lipid peroxidation around the fibrillar Aβ deposits. By using single-point SR-FTIR spectroscopy (aperture’s size of 8 ?m x 8 ?m), the authors concluded the co-localization of oxidized lipids in the immediate surroundings of the plaques. Importantly, it was also reported that the Aβ plaques found in the AD-affected brains display significantly higher level of lipid oxidation than those identified in the non-AD aged individuals ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/ac502667b", "ISBN" : "1520-6882 (Electronic)\\r0003-2700 (Linking)", "PMID" : "25415602", "abstract" : "Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.", "author" : [ { "dropping-particle" : "", "family" : "Benseny-Cases", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klementieva", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotte", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrer", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cladera", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anal Chem", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "12047-12054", "title" : "Microspectroscopy (muFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>19</sup>", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "<sup>19</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19. Further upgrades to FTIR-FPA optics enabled high magnification synchrotron chemical imaging at 0.54 ?m effective pixel size using multiple synchrotron beams, though the data had to be oversampled ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nmeth.1585", "ISBN" : "1548-7105 (Electronic) 1548-7091 (Linking)", "ISSN" : "1548-7105", "PMID" : "21423192", "abstract" : "Conventional Fourier-transform infrared (FTIR) microspectroscopic systems are limited by an inevitable trade-off between spatial resolution, acquisition time, signal-to-noise ratio (SNR) and sample coverage. We present an FTIR imaging approach that substantially extends current capabilities by combining multiple synchrotron beams with wide-field detection. This advance allows truly diffraction-limited high-resolution imaging over the entire mid-infrared spectrum with high chemical sensitivity and fast acquisition speed while maintaining high-quality SNR.", "author" : [ { "dropping-particle" : "", "family" : "Nasse", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Eric C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reininger", "given" : "Ruben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kajdacsy-Balla", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macias", "given" : "Virgilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature methods", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "413-6", "title" : "High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>20</sup>", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "<sup>20</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20. In turn, the correct theory-based rigorous figure of 1.1 ?m by a bench-top IR source was more recently reported by Reddy et al., and the system is currently used in the latest commercial instruments ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1366/11-06568", "ISSN" : "00037028", "author" : [ { "dropping-particle" : "", "family" : "Reddy", "given" : "Rohith K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Schulmerich", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carney", "given" : "P. Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Applied Spectroscopy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1", "1" ] ] }, "page" : "93-105", "title" : "High-Definition Infrared Spectroscopic Imaging", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>21</sup>", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "<sup>21</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21. Using the FTIR instrument equipped with these optics, Findlay et al. confirmed the previous remarks on lipid envelope around the plaques and demonstrated possibility to perform high-magnification FTIR-FPA experiments on Aβ pathology without the use of SR radiation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c4an01982b", "ISSN" : "1364-5528", "PMID" : "25600495", "abstract" : "A recent upgrade to the optics configuration of a thermal source FTIR microscope equipped with a focal plane array detector has enabled rapid acquisition of high magnification spectrochemical images, in transmission, with an effective geometric pixel size of \u223c1 \u00d7 1 \u03bcm(2) at the sample plane. Examples, including standard imaging targets for scale and accuracy, as well as biomedical tissues and microorganisms, have been imaged with the new system and contrasted with data acquired at normal magnification and with a high magnification multi-beam synchrotron instrument. With this optics upgrade, one can now conduct rapid biodiagnostic ex vivo tissue imaging in-house, with images collected over larger areas, in less time (minutes) and with comparable quality and resolution to the best synchrotron source FTIR imaging capabilities.", "author" : [ { "dropping-particle" : "", "family" : "Findlay", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiens", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedlmair", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mundy", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kansiz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2493-503", "title" : "Rapid biodiagnostic ex vivo imaging at 1 \u03bcm pixel resolution with thermal source FTIR FPA.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>22</sup>", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "<sup>22</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22. Taken together, one may propose that upon the infiltration of glial cells, Aβ plaques are capable of producing excessive amounts of free radicals which damage proteins and lipids around. An extension of the above-mentioned studies, employed here, is to attempt curve-fitting of amide I to elucidate the protein secondary structure contents for more cogent and quantitative assessment of the results. An important question that remains unanswered therefore is what is the regional extent of oxidative damage to proteins/lipids within and in close proximity of Aβ plaques.The general objective of this study was design a methodology for the analysis of Aβ plaques and their surrounding tissue areas. We combined chemical mapping, simple chemometrics and image processing to analyze several adjacent areas around Aβ plaques to correlate the changes in the abundance of various molecular components and colocalize them to various tissue areas adjacent to the depoits. We used the triple transgenic (3xTg) APPxPS1xTAU animal model Alzheimer’s disease to study the molecular processes present at the onset of the pathology. The (3xTg) model of AD harbors APPSwe, PS1M146V and tauP301L transgenes and therefore develops all neuropathological correlates of the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0896-6273(03)00434-3", "ISBN" : "0896-6273 (Print)", "ISSN" : "08966273", "PMID" : "12895417", "abstract" : "The neuropathological correlates of Alzheimer's disease (AD) include amyloid-?? (A??) plaques and neurofibrillary tangles. To study the interaction between A?? and tau and their effect on synaptic function, we derived a triple-transgenic model (3xTg-AD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Rather than crossing independent lines, we microinjected two transgenes into single-cell embryos from homozygous PS1M146V knockin mice, generating mice with the same genetic background. 3xTg-AD mice progressively develop plaques and tangles. Synaptic dysfunction, including LTP deficits, manifests in an age-related manner, but before plaque and tangle pathology. Deficits in long-term synaptic plasticity correlate with the accumulation of intraneuronal A??. These studies suggest a novel pathogenic role for intraneuronal A?? with regards to synaptic plasticity. The recapitulation of salient features of AD in these mice clarifies the relationships between A??, synaptic dysfunction, and tangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.", "author" : [ { "dropping-particle" : "", "family" : "Oddo", "given" : "Salvatore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caccamo", "given" : "Antonella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shepherd", "given" : "Jason D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murphy", "given" : "M. Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golde", "given" : "Todd E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayed", "given" : "Rakez", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metherate", "given" : "Raju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Mark P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akbari", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "LaFerla", "given" : "Frank M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuron", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "409-421", "title" : "Triple-transgenic model of Alzheimer's Disease with plaques and tangles: Intracellular A?? and synaptic dysfunction", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>23</sup>", "plainTextFormattedCitation" : "23", "previouslyFormattedCitation" : "<sup>23</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }23.Materials and methodsSample preparationTriple mutant (3xTg) mice were housed under regular light/dark conditions and had ad libitium access for food and water. The animals were culled at the age of 15 months to have some early stage histopathological features of AD developed. Once sacrificed, three brains (n=3) were rapidly frozen in -80 oC, carefully cut into 10 ?m thin sagittal tissue sections using a cryomicrotome, put on IR transmissive CaF2 substrate and kept frozen at -80 oC around 4 days to enable the water to sublime out of the samples. From each brain specimen, two adjacent tissue sections were taken. All sections were stored in darkness until the FTIR experiments. Just before the experiment, a sample was taken from the freezer and desiccated (to remove the excess of water aggregating at the top of a sample). All procedures were carried out in accordance with the Animals (Scientific Procedures) Act 1986, the specific project license was approved by the UK Home Office. FTIR experimentsThe FTIR-FPA transmission maps were recorded using an Agilent Cary 670-IR spectrometer coupled with a Cary 620-IR imaging microscope using 128 × 128 FPA detector in high-magnification mode to enable the effective pixel size of 1.1 ?m × 1.1 ?m. Although this pixel size is not the same as the spatial resolution it has been shown that smaller pixel size significantly increases the fidelity of the images obtained ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nmeth.1585", "ISBN" : "1548-7105 (Electronic) 1548-7091 (Linking)", "ISSN" : "1548-7105", "PMID" : "21423192", "abstract" : "Conventional Fourier-transform infrared (FTIR) microspectroscopic systems are limited by an inevitable trade-off between spatial resolution, acquisition time, signal-to-noise ratio (SNR) and sample coverage. We present an FTIR imaging approach that substantially extends current capabilities by combining multiple synchrotron beams with wide-field detection. This advance allows truly diffraction-limited high-resolution imaging over the entire mid-infrared spectrum with high chemical sensitivity and fast acquisition speed while maintaining high-quality SNR.", "author" : [ { "dropping-particle" : "", "family" : "Nasse", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Eric C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reininger", "given" : "Ruben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kajdacsy-Balla", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macias", "given" : "Virgilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature methods", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "413-6", "title" : "High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>20</sup>", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "<sup>20</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20 and it has also been shown that if the spectral output of features are different it is possible to obtain images with a resolution exceeding the expected diffraction limit ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1364/OE.21.012822", "ISSN" : "1094-4087", "author" : [ { "dropping-particle" : "", "family" : "Dijk", "given" : "Thomas", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayerich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carney", "given" : "P. Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Optics Express", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "5", "20" ] ] }, "page" : "12822", "title" : "Rapid spectral-domain localization", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>24</sup>", "plainTextFormattedCitation" : "24", "previouslyFormattedCitation" : "<sup>24</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }24. The spectra were collected in air in 4000-950 cm-1 spectral range at a spectral resolution of 5 cm-1 with a zero filling factor 1 to lead to data spacing of 2.5 cm-1. Just before the background measurements, the 20 minutes purging of the setup was applied to avoid any uncompensated contributions arising from CO2 and water vapor in the FTIR spectra. We used 512 and 256 scans co-added for background and for sample acquisitions, respectively. For the interferograms, the Blackmann-Harris 4-point apodisation function was used.For orientation purposes Fig 1a shows a large area optical microscope image of the hippocampus and cortex (the main area where plaques can be found). A plaque in the cortex is identified in the insert Fig 1b. Figs 1c and 1d shows the FTIR image of the same region representing the amide I band intensity and the CH stretching region intensity respectively. Figs 1e and f show the FTIR images of the plaque in Fig 1b at 5.5 μm and 1.1 μm pixel resolution respectively.Data pre-processingFig 2a shows the FTIR spectra acquired within the Aβ plaques. The spectra revealed strong Mie scattering distortions, as their baselines were of oscillatory nature. The absorbance at 2500 cm-1 was used as an indicator of this effect within the Aβ deposits. To alleviate the contribution of this phenomenon, the spectra were subjected to the RMies-EMSC scattering correction involving 7 iterationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/b921056c", "ISBN" : "1364-5528 (Electronic)\\r0003-2654 (Linking)", "ISSN" : "0003-2654", "PMID" : "20098758", "abstract" : "Infrared spectra of single biological cells often exhibit the 'dispersion artefact' observed as a sharp decrease in intensity on the high wavenumber side of absorption bands, in particular the Amide I band at approximately 1655 cm(-1), causing a downward shift of the true peak position. The presence of this effect makes any biochemical interpretation of the spectra unreliable. Recent theory has shed light on the origins of the 'dispersion artefact' which has been attributed to resonant Mie scattering (RMieS). In this paper a preliminary algorithm for correcting RMieS is presented and evaluated using simulated data. Results show that the 'dispersion artefact' appears to be removed; however, the correction is not perfect. An iterative approach was subsequently implemented whereby the reference spectrum is improved after each iteration, resulting in a more accurate correction. Consequently the corrected spectra become increasingly more representative of the pure absorbance spectra. Using this correction method reliable peak positions can be obtained.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byrne", "given" : "Hugh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gazi", "given" : "Ehsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "268-277", "title" : "Resonant Mie scattering (RMieS) correction of infrared spectra from highly scattering biological samples.", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>25</sup>", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "<sup>25</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }25ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jbio.201000036", "ISBN" : "1864-0648 (Electronic)\\r1864-063X (Linking)", "ISSN" : "1864063X", "PMID" : "20414907", "abstract" : "In the field of biomedical infrared spectroscopy it is often desirable to obtain spectra at the cellular level. Samples consisting of isolated single biological cells are particularly unsuited to such analysis since cells are strong scatterers of infrared radiation. Thus measured spectra consist of an absorption component often highly distorted by scattering effects. It is now known that the predominant contribution to the scattering is Resonant Mie Scattering (RMieS) and recently we have shown that this can be corrected for, using an iterative algorithm based on Extended Multiplicative Signal Correction (EMSC) and a Mie approximation formula. Here we present an iterative algorithm that applies full Mie scattering theory. In order to avoid noise accumulation in the iterative algorithm a curve-fitting step is implemented on the new reference spectrum. The new algorithm increases the computational time when run on an equivalent processor. Therefore parallel processing by a Graphics Processing Unit (GPU) was employed to reduce computation time. The optimised RMieS-EMSC algorithm is applied to an IR spectroscopy data set of cultured single isolated prostate cancer (PC-3) cells, where it is shown that spectral distortions from RMieS are removed.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lockyer", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Biophotonics", "id" : "ITEM-1", "issue" : "8-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "609-620", "title" : "RMieS-EMSC correction for infrared spectra of biological cells: Extension using full Mie theory and GPU computing", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>26</sup>", "plainTextFormattedCitation" : "26", "previouslyFormattedCitation" : "<sup>26</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c2an16088a", "ISSN" : "1364-5528", "PMID" : "22318917", "abstract" : "Transmission and transflection infrared microscopy of biological cells and tissue suffer from significant baseline distortions due to scattering effects, predominantly resonant Mie scattering (RMieS). This scattering can also distort peak shapes and apparent peak positions making interpretation difficult and often unreliable. A correction algorithm, the resonant Mie scattering extended multiplicative signal correction (RMieS-EMSC), has been developed that can be used to remove these distortions. The correction algorithm has two key user defined parameters that influence the accuracy of the correction. The first is the number of iterations used to obtain the best outcome. The second is the choice of the initial reference spectrum required for the fitting procedure. The choice of these parameters influences computational time. This is not a major concern when correcting individual spectra or small data sets of a few hundred spectra but becomes much more significant when correcting spectra from infrared images obtained using large focal plane array detectors which may contain tens of thousands of spectra. In this paper we show that, classification of images from tissue can be achieved easily with a few (<10) iterations but a reliable interpretation of the biochemical differences between classes could require more iterations. Regarding the choice of reference spectrum, it is apparent that the more similar it is to the pure absorption spectrum of the sample, the fewer iterations required to obtain an accurate corrected spectrum. Importantly however, we show that using three different non-ideal reference spectra, the same unique correction solution can be obtained.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "Ashwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Caryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boyle", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shanks", "given" : "Jonathan H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1370-7", "title" : "FTIR microscopy of biological cells and tissue: data analysis using resonant Mie scattering (RMieS) EMSC algorithm.", "type" : "article-journal", "volume" : "137" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>27</sup>", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "<sup>27</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27. High-throughput computations of thousands of FTIR spectra simultaneously were assisted with the CONDOR pool at the University of Manchester, compromised of thousands of nodes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/cpe.938", "ISSN" : "1532-0626", "author" : [ { "dropping-particle" : "", "family" : "Thain", "given" : "Douglas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tannenbaum", "given" : "Todd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Livny", "given" : "Miron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Concurrency and Computation: Practice and Experience", "id" : "ITEM-1", "issue" : "2-4", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "323-356", "title" : "Distributed computing in practice: the Condor experience", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>28</sup>", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "<sup>28</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28. Further data-processing steps were implemented using Python 2.7 with scipy and numpy modules ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1109/MCSE.2011.37", "ISBN" : "1521-9615 VO - 13", "ISSN" : "15219615", "abstract" : "In the Python world, NumPy arrays are the standard representation for numerical data and enable efficient implementation of numerical computations in a high-level language. As this effort shows, NumPy performance can be improved through three techniques: vectorizing calculations, avoiding copying data in memory, and minimizing operation counts.", "author" : [ { "dropping-particle" : "", "family" : "Walt", "given" : "St\u00e9fan", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colbert", "given" : "S. Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varoquaux", "given" : "Ga\u00ebl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Computing in Science and Engineering", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "22-30", "title" : "The NumPy array: A structure for efficient numerical computation", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>29</sup>", "plainTextFormattedCitation" : "29", "previouslyFormattedCitation" : "<sup>29</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29. Once corrected, the spectra were quality tested based on the height of the band at 1655 cm-1 with minimal permissible height of this band set to 0.05. The FTIR spectra were subsequently truncated to desired range between 1750-950 cm-1 (fingerprint) as well as 3050-2750 cm-1 (lipid) and baseline corrected (a simple linear baseline). Curve-fittingFor this study, to identify the Aβ plaques, and to extract the subtle spectroscopic information on the protein secondary structure contents, we used a simplified curve-fitting approach of amide I with the mixed Gaussian-Lorentzian peak model, involving an iterative Levenburg-Marquardt algorithm to minimize the R2 function (see eq 1-3) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1137/0111030", "ISSN" : "00401706", "abstract" : "Introduction. M\\ost algorithms for the least-squares estimation of non- linear parameters have centered about either of two approaches. On the one hand, the model may be expanded as a Taylor series and corrections to the several parameters calculated at each iteration on the assumption of local linearity. On the other hand, various modifications of the method of steepest-descent have been used. Both methods not infrequently run aground, the Taylor series method because of divergence of the successive iterates, the steepest-descent (or gradient) methods because of agonizingly slow convergence after the first few iterations. In this paper a maximtum neighborhood method is developed which, in effect, performs an optimum interpolation between the Taylor series method and the gradient method, the interpolation being based upon the maximum neighborhood in which the truncated Taylor series gives an adequate representation of the nonlinear model. The results are extended to the problem of solving a set of nonlinear algebraic equations", "author" : [ { "dropping-particle" : "", "family" : "Marquardt", "given" : "Donald W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Society for Industrial and Applied Mathematics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1963" ] ] }, "page" : "431-441", "title" : "An Algorithm for Least Squares Estimation of Nonlinear Parameters", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "citeulike-article-id:10796881", "ISSN" : "<null>", "abstract" : "Levenberg-Marquardt. One dimensional search for optimal value of damping\\nfactor to be added to the diagonal.", "author" : [ { "dropping-particle" : "", "family" : "Levenberg", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Quarterly of Applied Mathematics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1944" ] ] }, "page" : "196-168", "title" : "A method for the solution of certain non-linear problems in least squares", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>30,31</sup>", "plainTextFormattedCitation" : "30,31", "previouslyFormattedCitation" : "<sup>30,31</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30,31.R2=1-SSESST and 0≤R2≤1 (1)SSE=i=1nYi-Yi2 (2)SST=i=1nYi-Yi2 (3)Where: Yi- the i-th fitted value of the dependent value Yi.Only four peaks attributed to major components were taken into account, as proposed in ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.sbi.2010.07.007", "ISBN" : "0959-440X", "ISSN" : "0959440X", "PMID" : "20739176", "abstract" : "Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X-ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in bridging the gap towards 'functional biology' is discussed based upon recent achievements, with a critical assessment of the contributions to biological and biomedical research. ?? 2010.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Structural Biology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "649-656", "title" : "From structure to cellular mechanism with infrared microspectroscopy", "type" : "article", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>32</sup>", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "<sup>32</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32. For the purpose of further computations, the spectra were additionally cut to 1600-1700 cm-1 range, baseline corrected (a simple linear baseline), cubically interpolated (to increase the number of data points in the spectra) and finally 0-1 normalized. The data were neither additionally noise reduced or smoothed. The positions of the most intense bands, determined according to the second order derivative spectra of interpolated amide I spectra, revealed they should be present around 1665, 1654, 1645 and 1636 cm-1 (cf. Fig 3a), which in good agreement with Miller et al. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.sbi.2010.07.007", "ISBN" : "0959-440X", "ISSN" : "0959440X", "PMID" : "20739176", "abstract" : "Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X-ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in bridging the gap towards 'functional biology' is discussed based upon recent achievements, with a critical assessment of the contributions to biological and biomedical research. ?? 2010.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Structural Biology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "649-656", "title" : "From structure to cellular mechanism with infrared microspectroscopy", "type" : "article", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>32</sup>", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "<sup>32</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32. To increase the reliability of the computational procedures, we optimized the fitting model by analyzing the effect of selected parameters, including either the peaks’ half-widths (FWHM) or Lorentzian’s function fraction (Lf), on the R2 functions upon analysis of 100 spectra selected from the area indicated in Fig 2c. The effect of the FWHM parameter was assessed following analysis of the peaks fixed in their nominal positions. The positions were constrained within reasonably small range (± 2 cm-1). The second experiment to assess the effect of Lorentzian’s fraction was run with the positions and FWHM’s to vary within their optimal range. Building upon these experiments, we propose the equally-mixed Lorentzian-Gaussian (50%:50%, cf. Fig 5a-c) fitting model with the peaks’ half-widths to range between 14-16 cm-1 to produce the most accurate fits, since the results were found to minimize the R2 function of the devised model (cf. Fig 3c and 3b, respectively). All curve fitting procedures including data preprocessing and curve fitting were implemented in Python 2.7 with scipy, numpy ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1109/MCSE.2011.37", "ISBN" : "1521-9615 VO - 13", "ISSN" : "15219615", "abstract" : "In the Python world, NumPy arrays are the standard representation for numerical data and enable efficient implementation of numerical computations in a high-level language. As this effort shows, NumPy performance can be improved through three techniques: vectorizing calculations, avoiding copying data in memory, and minimizing operation counts.", "author" : [ { "dropping-particle" : "", "family" : "Walt", "given" : "St\u00e9fan", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colbert", "given" : "S. Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varoquaux", "given" : "Ga\u00ebl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Computing in Science and Engineering", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "22-30", "title" : "The NumPy array: A structure for efficient numerical computation", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>29</sup>", "plainTextFormattedCitation" : "29", "previouslyFormattedCitation" : "<sup>29</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29, matplotlib ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1109/MCSE.2007.55", "ISBN" : "1521-9615 VO - 9", "ISSN" : "15219615", "PMID" : "1000044628", "abstract" : "Matplotlib is a 2D graphics package used for Python for application development, interactive scripting,and publication-quality image generation across user interfaces and operating systems", "author" : [ { "dropping-particle" : "", "family" : "Hunter", "given" : "John D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Computing in Science and Engineering", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "99-104", "title" : "Matplotlib: A 2D graphics environment", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>33</sup>", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "<sup>33</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33 and lmfit libraries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5281/zenodo.11813", "author" : [ { "dropping-particle" : "", "family" : "Newville", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stensitzki", "given" : "Till", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allen", "given" : "Daniel B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingargiola", "given" : "Antonino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Zendo", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "LMFIT: Non-Linear Least-Square Minimization and Curve-Fitting for Python", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>34</sup>", "plainTextFormattedCitation" : "34", "previouslyFormattedCitation" : "<sup>34</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34.Image analysisBased on 12 (~3-4 plaques taken from each sample) images showing the spatial distribution of β-sheets, our computations aimed at the determination of four ~4-micron-thick layers around the deposits to define their surrounding areas. For the sake of further computations, to define the coordinates of an Aβ deposit, the binarization with the binarization threshold of 0.16 was found to robustly mark the plaque-like areas. Additional median filtering step (4 pixel × 4 pixel mask) was included to remove any single-pixel binarization artifacts (see Fig 6a and b). The binarized image was then subjected to the dilation transformation. The mask of 4 × 4 pixels (around 4.4 ?m × 4.4 ?m) resulted in the plaques’ area enlarged by ~ 4 ?m in each direction. Finally, to determine the first 4-?m-thick layer around the Aβ core, the dilated image was then subtracted from the binarized one. The whole procedure was repeated additional three times to determine all four areas of the same width around the deposits (cf. Fig 6c). The scripts for image transformations were written in Python 2.7 with scipy, numpy ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1109/MCSE.2011.37", "ISBN" : "1521-9615 VO - 13", "ISSN" : "15219615", "abstract" : "In the Python world, NumPy arrays are the standard representation for numerical data and enable efficient implementation of numerical computations in a high-level language. As this effort shows, NumPy performance can be improved through three techniques: vectorizing calculations, avoiding copying data in memory, and minimizing operation counts.", "author" : [ { "dropping-particle" : "", "family" : "Walt", "given" : "St\u00e9fan", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colbert", "given" : "S. Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varoquaux", "given" : "Ga\u00ebl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Computing in Science and Engineering", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "22-30", "title" : "The NumPy array: A structure for efficient numerical computation", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>29</sup>", "plainTextFormattedCitation" : "29", "previouslyFormattedCitation" : "<sup>29</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29, matplotlib ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1109/MCSE.2007.55", "ISBN" : "1521-9615 VO - 9", "ISSN" : "15219615", "PMID" : "1000044628", "abstract" : "Matplotlib is a 2D graphics package used for Python for application development, interactive scripting,and publication-quality image generation across user interfaces and operating systems", "author" : [ { "dropping-particle" : "", "family" : "Hunter", "given" : "John D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Computing in Science and Engineering", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "99-104", "title" : "Matplotlib: A 2D graphics environment", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>33</sup>", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "<sup>33</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33 and scikit-image ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.7717/peerj.453", "ISBN" : "2167-9843", "ISSN" : "2167-8359", "PMID" : "25024921", "abstract" : "scikit-image is an image processing library that implements algorithms and utilities for use in research, education and industry applications. It is released under the liberal Modified BSD open source license, provides a well-documented API in the Python programming language, and is developed by an active, international team of collaborators. In this paper we highlight the advantages of open source to achieve the goals of the scikit-image library, and we showcase several real-world image processing applications that use scikit-image. More information can be found on the project homepage, .", "author" : [ { "dropping-particle" : "", "family" : "Walt", "given" : "St\u00e9fan", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00f6nberger", "given" : "Johannes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nunez-Iglesias", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulogne", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warner", "given" : "Joshua D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yager", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouillart", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PeerJ", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "e453", "title" : "scikit-image: image processing in Python.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>35</sup>", "plainTextFormattedCitation" : "35", "previouslyFormattedCitation" : "<sup>35</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35 libraries.Principal Component AnalysisPrincipal Component Analysis (PCA), involving the fractions of protein secondary structure components computed as highlighted above, was used to compare the protein composition and variability of the spectra taken from the plaque (PLAQUE) and outer (Out) layers. First two PCA variables (PCA1 and PCA2), explaining 45% and 35% of the variance, were taken into account. The scripts for PCA have been written in Python 2.7 using the above-mentioned packages.Molecular factorsTo describe the lipid and protein related processes occurring within and in close proximity of the Aβ deposits, some additional molecular parameters were determined. One of these, the integration area of the νas(-PO42-) band in phospholipids and phosphodiesters was computed within the 1200 – 1260 cm-1 integration range (baseline 1200 – 1260 cm-1). In turn, the ν=(CH)/ νas(CH3) parameter to describe the level of lipid unsaturation was computed as a ratio of the ν=(CH) oleofinic band area (integration between: 3000 cm-1-3020 cm-1; baseline 3000 cm-1-3020 cm-1) to the νas(CH3) band area (integration between: 2948 cm-1-2990 cm-1; baseline 2800 cm-1-3000 cm-1). So-called lipid to protein ratio was computed as the integration area of the C-H str (integration between: 2800 – 3000 cm-1; baseline: 2800 – 3000 cm-1) and the area of amide I (integration between: 1600 – 1700 cm-1; baseline: 1600 – 1700cm-1). The level of lipid oxidation was expressed as a ratio of the C-H stretch area (integration between: 2800 – 3000 cm-1; baseline: 2800 – 3000 cm-1) and the C=O ester band centered at 1730 cm-1 (integration between: 1715 – 1740 cm-1; baseline: 1715 -1740 cm-1). Statistical data analysisThe spectra, protein secondary contents and additional molecular factors computed were divided onto six classes as follows: PLAQUE, 1st layer, 2nd layer, 3rd layer, 4rd layer and Outer. The protein secondary structure contents were finally expressed as the mean ± mean standard error. The statistical data analysis was carried out using an in-house code written in Python using the scipy library with the assistance of the above-mentioned Python libraries.Results and discussionPrevious work has demonstrated that FTIR spectroscopy is a very versatile molecular imaging method for studying different protein- and lipid-related effects underlying Aβ-related neurotoxicity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroimage.2011.11.033", "ISBN" : "1053-8119", "ISSN" : "10538119", "PMID" : "22119649", "abstract" : "In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. ?? 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Caine", "given" : "Sally", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heraud", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobin", "given" : "Mark J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNaughton", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernard", "given" : "Claude C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "3624-3640", "title" : "The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue", "type" : "article", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>10</sup>", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "<sup>10</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10. Currently, the significance of the interplay between these two molecular components is gradually emerging as alternative means to explain AD pathology at different clinical stages of the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/bs.irn.2015.05.008", "ISBN" : "9780128047620", "ISSN" : "00747742", "PMID" : "26358893", "abstract" : "Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as \"the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation.\" Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. ?? 2015 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Naud??", "given" : "Alba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabr??", "given" : "Rosanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jov??", "given" : "Mariona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ayala", "given" : "Victoria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonzalo", "given" : "Hugo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Portero-Ot??n", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrer", "given" : "Isidre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pamplona", "given" : "Reinald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Neurobiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "133-189", "title" : "Lipidomics of Human Brain Aging and Alzheimer's Disease Pathology", "type" : "chapter", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>36</sup>", "plainTextFormattedCitation" : "36", "previouslyFormattedCitation" : "<sup>36</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36. Importantly, the increasingly growing spatial resolution of micro-imaging experiments by FTIR allows acquisition of the data at the sub-micron pixel size, which is a pre-requisite for studying pathological processes at the sub-cellular level ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c4an02053g", "ISBN" : "0003-2654", "ISSN" : "1364-5528", "PMID" : "25738183", "abstract" : "A new optical system has recently been developed that enables infrared images to be obtained with a pixel resolution of 1 micron on a bench-top instrument using a thermal source. We present here imaging data from two contrasting cellular systems that represent different challenges. Renal carcinoma cells cytospun onto CaF2 have a largely rounded morphology and thus suffer from strong resonant Mie scattering. Skin fibroblast cells, cultured onto CaF2 on the other hand are very spread out so scatter less strongly but are so thin they deliver extremely weak signals. Using suitable pre-processing methods, including PCA noise reduction and RMieS correction, we demonstrate that useful high resolution images can be obtained from either sample.", "author" : [ { "dropping-particle" : "", "family" : "Hughes", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kansiz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorling", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jimenez-Hernandez", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "N W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2080-5", "title" : "Enhanced FTIR bench-top imaging of single biological cells.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/c4an01982b", "ISSN" : "1364-5528", "PMID" : "25600495", "abstract" : "A recent upgrade to the optics configuration of a thermal source FTIR microscope equipped with a focal plane array detector has enabled rapid acquisition of high magnification spectrochemical images, in transmission, with an effective geometric pixel size of \u223c1 \u00d7 1 \u03bcm(2) at the sample plane. Examples, including standard imaging targets for scale and accuracy, as well as biomedical tissues and microorganisms, have been imaged with the new system and contrasted with data acquired at normal magnification and with a high magnification multi-beam synchrotron instrument. With this optics upgrade, one can now conduct rapid biodiagnostic ex vivo tissue imaging in-house, with images collected over larger areas, in less time (minutes) and with comparable quality and resolution to the best synchrotron source FTIR imaging capabilities.", "author" : [ { "dropping-particle" : "", "family" : "Findlay", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiens", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedlmair", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mundy", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kansiz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2493-503", "title" : "Rapid biodiagnostic ex vivo imaging at 1 \u03bcm pixel resolution with thermal source FTIR FPA.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nmeth.1585", "ISBN" : "1548-7105 (Electronic) 1548-7091 (Linking)", "ISSN" : "1548-7105", "PMID" : "21423192", "abstract" : "Conventional Fourier-transform infrared (FTIR) microspectroscopic systems are limited by an inevitable trade-off between spatial resolution, acquisition time, signal-to-noise ratio (SNR) and sample coverage. We present an FTIR imaging approach that substantially extends current capabilities by combining multiple synchrotron beams with wide-field detection. This advance allows truly diffraction-limited high-resolution imaging over the entire mid-infrared spectrum with high chemical sensitivity and fast acquisition speed while maintaining high-quality SNR.", "author" : [ { "dropping-particle" : "", "family" : "Nasse", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Eric C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reininger", "given" : "Ruben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kajdacsy-Balla", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macias", "given" : "Virgilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature methods", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "413-6", "title" : "High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>20,22,37</sup>", "plainTextFormattedCitation" : "20,22,37" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,22,37. By benchtop FTIR imaging at 6.25 μm pixel size, Kong et al. probed large area stromal regions surrounding the melanoma skin tumour. The authors concluded noticeable pathological changes appear 50-100 μm away from the cancerous tissue, which was linked to the commonly known field effect observed when highly malignant tumours progress ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c0an00112k", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Kong", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Rohith K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1569", "title" : "Characterization of tumor progression in engineered tissue using infrared spectroscopic imaging", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>38</sup>", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "<sup>39</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38. A more recent study by Kumar et al. set out to gain more insight into breast cancer pathology at the cellular level with particular scrutiny placed upon the analysis of the extracellular matrix by synchrotron FTIR imaging at the pixel size of around 3 μm. With the aid of multivariate methods, collagen-induced modifications in the extracellular matrix were found, and proposed as possible markers of tumour’s progression ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0111137", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Kumar", "given" : "Saroj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shabi", "given" : "Thankaraj Salammal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Ahmad", "given" : "Aamir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014", "11", "12" ] ] }, "page" : "e111137", "title" : "A FTIR Imaging Characterization of Fibroblasts Stimulated by Various Breast Cancer Cell Lines", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/c3an00241a", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Kumar", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desmedt", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsimont", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sotiriou", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "14", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "4058", "title" : "Change in the microenvironment of breast cancer studied by FTIR imaging", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>39,40</sup>", "plainTextFormattedCitation" : "39,40", "previouslyFormattedCitation" : "<sup>40,41</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,40. Kwak et al., in turn, proposed the paradigm of FTIR chemical imaging at 6.25 μm pixel size for prognosis of prostate cancer recurrence. By analysing a large cohort of large area tissue microarrays (186 patients), the prediction method was found to outperform commonly used methods ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/srep08758", "ISSN" : "2045-2322", "author" : [ { "dropping-particle" : "", "family" : "Kwak", "given" : "Jin Tae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kajdacsy-Balla", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macias", "given" : "Virgilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinha", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientific Reports", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "3", "4" ] ] }, "page" : "8758", "title" : "Improving Prediction of Prostate Cancer Recurrence using Chemical Imaging", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>41</sup>", "plainTextFormattedCitation" : "41", "previouslyFormattedCitation" : "<sup>42</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }41. In our study, as compared in Fig 1e-f, we took advantage of high-magnification benchtop FTIR-FPA imaging at the pixel size of of 1.1 μm justified by radically higher fidelity of sub-cellular histological details that could be resolved with a stand–alone laboratory instrument coupled with state-of-the-art IR optics. As compared with the above-mentioned studies, the goal of the present study was to unravel spectral changes in small tissue areas (up to 100 μm x 100 μm). Since the diameters of the plaques were found to range from 10-40 μm (i.e. Fig 5a), the higher sub-cellular resolution was a prerequisite to providing with relevant chemical information. It was also to separate out inflammation-related changes which could be attributable to tiny engulfing microglial cells with around 1-2 μm in diameter ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1742-2094-11-12", "ISSN" : "1742-2094", "author" : [ { "dropping-particle" : "", "family" : "Torres-Platas", "given" : "Susana G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comeau", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rachalski", "given" : "Adeline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bo", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruceanu", "given" : "Cristiana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turecki", "given" : "Gustavo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giros", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mechawar", "given" : "Naguib", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neuroinflammation", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "12", "title" : "Morphometric characterization of microglial phenotypes in human cerebral cortex", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>42</sup>", "plainTextFormattedCitation" : "42", "previouslyFormattedCitation" : "<sup>43</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }42. However, a careful assessment of the results may play a pivotal role as other factors, such as Mie scattering, reflection contributions, electric-field-standing wave artifacts, may obscure the biologically relevant spectroscopic information ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1366/000370209789806902", "ISSN" : "19433530", "PMID" : "19891839", "abstract" : "We have been investigating the mid-infrared (MIR) reflection spectrum of microparticles on mirrored substrates. Gold-coated porous alumina filters were used as a substrate to layer the particles and provide consistent reflection spectra. Polystyrene spheres with measured diameters of 0.42 microm were studied using Fourier transform infrared (FT-IR) reflection microspectroscopy, and spectra are shown for coverages in the range 0.5-6 monolayers (ML). Results show that absorption has a nonlinear, stairstep-like dependence on particle coverage and a wavelength dependence that can be explained by electric field standing waves (EFSW) caused by the mirrored substrate. The same effect is found to cause progressive weakening of the observed spectra as a function of increasing wavelength in sub-monolayer coverage measurements. Scattering effects in the spectra are consistent with surface scattering at the antinodes of the EFSW. These observations provide explanations for differences seen between optical properties of particles calculated using the specular-reflection method versus those calculated using traditional aerosol methods. A simple multilayer method for estimating particle absorption coefficients is demonstrated that compares well with values reported using ellipsometry for bulk polystyrene. Another simple method based on submonolayer coverage spectra provides spectra suitable for classification analysis but is only semi-quantitative at determining absorption coefficients.", "author" : [ { "dropping-particle" : "", "family" : "Brooke", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Bronk", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCutcheon", "given" : "J. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "S. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myrick", "given" : "M. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Applied spectroscopy", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1293-1302", "title" : "A study of electric field standing waves on reflection microspectroscopy of polystyrene particles.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/b821349f", "ISBN" : "0003-2654", "ISSN" : "0003-2654", "PMID" : "19475144", "abstract" : "Fourier transform infrared spectra of a single cell in transflection geometry are seen to vary significantly with position on the cell, showing a distorted derivative-like lineshape in the region of the optically dense nucleus. A similar behaviour is observable in a model system of the protein albumin doped in a potassium bromide disk. It is demonstrated that the spectrum at any point is a weighted sum of the sample reflection and transmission and that the dominance of the reflection spectrum in optically dense regions can account for some of the spectral distortions previously attributed to dispersion artefacts. Rather than being an artefact, the reflection contribution is ever present in transflection spectra and it is further demonstrated that the reflection characteristics can be used for cellular mapping.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byrne", "given" : "Hugh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnier", "given" : "Franck", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Colin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gazi", "given" : "Ehsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1171-1175", "title" : "Reflection contributions to the dispersion artefact in FTIR spectra of single biological cells.", "type" : "article-journal", "volume" : "134" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1039/c4an01975j", "ISSN" : "1364-5528", "PMID" : "25672838", "abstract" : "FTIR microscopy is a powerful technique which has become popular due to its ability to provide complementary information during histopathological assessment of biomedical tissue samples. Recently however, questions have been raised on the suitability of the transflection mode of operation for clinical diagnosis due to the so called Electric Field Standing Wave (EFSW) effect. In this paper we compare chemical images measured in transmission and transflection from prostate tissue obtained from five different patients, and discuss the variability of the spectra acquired with each sampling modality. We find that spectra obtained in transflection undergo a non-linear distortion, i.e. non-linear variations in absorption band strength across the spectra, and that there are significant differences in spectra measured from the same area of tissue depending on the mode of operation. Principal Component Analysis (PCA) is used to highlight that poorer discrimination between benign and cancerous tissue is obtained in transflection mode. In addition we show that use of second derivatives, while qualitatively improves spectral discrimination, does not completely alleviate the underlying problem.", "author" : [ { "dropping-particle" : "", "family" : "Pilling", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2383-92", "title" : "Comparison of transmission and transflectance mode FTIR imaging of biological tissue.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>43\u201345</sup>", "plainTextFormattedCitation" : "43\u201345", "previouslyFormattedCitation" : "<sup>44\u201346</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }43–45. This is due to radically different optical properties of mature Aβ plaques visible as dark spots under the microscope ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c3an00295k", "ISBN" : "1204237409", "ISSN" : "1364-5528", "PMID" : "23586070", "abstract" : "While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and A\u03b2 peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 \u00d7 0.54 \u00b5m(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3\u00d7Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Catherine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Jillian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unger", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "Benedict C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "3991-7", "title" : "Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>18</sup>", "plainTextFormattedCitation" : "18", "previouslyFormattedCitation" : "<sup>18</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }18. The approximated formula to describe the scattering cross-section is presented below:Q=2-4ρsinρ+4ρ21-cosρ (4)ρ=4πan-1λ (5)Where: λ – wavelength [?m], n – the relative refractive indexOne can conclude that the presence of the objects with radically different optical (and physical) properties in tissue sections may result in the presence of multiple undulating baselines. To get rid of the artifacts arising from the Mie-like behavior observed in FTIR spectra, a number of approaches have been developed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1529/biophysj.104.057950", "ISBN" : "0006-3495", "ISSN" : "00063495", "PMID" : "15749767", "abstract" : "We report infrared microspectral features of nuclei in a completely inactive and contracted (pyknotic) state, and of nuclei of actively dividing cells. For pyknotic nuclei, the very high local concentration of DNA leads to opaqueness of the chromatin and, consequently, the absence of DNA signals in the IR spectra of very small nuclei. However, these nuclei can be detected by their scattering properties, which can be described by the Mie theory of scattering from dielectric spheres. This scattering depends on the size of the nucleus; consequently, quite different scattering cross-sections are calculated and observed for pyknotic and mitotic nuclei.", "author" : [ { "dropping-particle" : "", "family" : "Mohlenhoff", "given" : "Brian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romeo", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diem", "given" : "Max", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Bayden R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biophysical journal", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "3635-3640", "title" : "Mie-type scattering and non-Beer-Lambert absorption behavior of human cells in infrared microspectroscopy.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/C5AN00401B", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Lukacs", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bl\u00fcmel", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmerman", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ba\u011fc\u0131o\u011flu", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "3273-3284", "title" : "Recovery of absorbance spectra of micrometer-sized biological and inanimate particles", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>46,47</sup>", "plainTextFormattedCitation" : "46,47", "previouslyFormattedCitation" : "<sup>47,48</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,47. The RMieS-EMSC algorithm, proposed by Bassan et al, has been shown to give acceptable performance and is commonly used in the field ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jbio.201000036", "ISBN" : "1864-0648 (Electronic)\\r1864-063X (Linking)", "ISSN" : "1864063X", "PMID" : "20414907", "abstract" : "In the field of biomedical infrared spectroscopy it is often desirable to obtain spectra at the cellular level. Samples consisting of isolated single biological cells are particularly unsuited to such analysis since cells are strong scatterers of infrared radiation. Thus measured spectra consist of an absorption component often highly distorted by scattering effects. It is now known that the predominant contribution to the scattering is Resonant Mie Scattering (RMieS) and recently we have shown that this can be corrected for, using an iterative algorithm based on Extended Multiplicative Signal Correction (EMSC) and a Mie approximation formula. Here we present an iterative algorithm that applies full Mie scattering theory. In order to avoid noise accumulation in the iterative algorithm a curve-fitting step is implemented on the new reference spectrum. The new algorithm increases the computational time when run on an equivalent processor. Therefore parallel processing by a Graphics Processing Unit (GPU) was employed to reduce computation time. The optimised RMieS-EMSC algorithm is applied to an IR spectroscopy data set of cultured single isolated prostate cancer (PC-3) cells, where it is shown that spectral distortions from RMieS are removed.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lockyer", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Biophotonics", "id" : "ITEM-1", "issue" : "8-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "609-620", "title" : "RMieS-EMSC correction for infrared spectra of biological cells: Extension using full Mie theory and GPU computing", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nprot.2014.110", "ISBN" : "1750-2799 (Electronic)\\r1750-2799 (Linking)", "ISSN" : "1750-2799", "PMID" : "24992094", "abstract" : "IR spectroscopy is an excellent method for biological analyses. It enables the nonperturbative, label-free extraction of biochemical information and images toward diagnosis and the assessment of cell functionality. Although not strictly microscopy in the conventional sense, it allows the construction of images of tissue or cell architecture by the passing of spectral data through a variety of computational algorithms. Because such images are constructed from fingerprint spectra, the notion is that they can be an objective reflection of the underlying health status of the analyzed sample. One of the major difficulties in the field has been determining a consensus on spectral pre-processing and data analysis. This manuscript brings together as coauthors some of the leaders in this field to allow the standardization of methods and procedures for adapting a multistage approach to a methodology that can be applied to a variety of cell biological questions or used within a clinical setting for disease screening or diagnosis. We describe a protocol for collecting IR spectra and images from biological samples (e.g., fixed cytology and tissue sections, live cells or biofluids) that assesses the instrumental options available, appropriate sample preparation, different sampling modes as well as important advances in spectral data acquisition. After acquisition, data processing consists of a sequence of steps including quality control, spectral pre-processing, feature extraction and classification of the supervised or unsupervised type. A typical experiment can be completed and analyzed within hours. Example results are presented on the use of IR spectra combined with multivariate data processing.", "author" : [ { "dropping-particle" : "", "family" : "Baker", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trevisan", "given" : "J\u00falio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Rohit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butler", "given" : "Holly J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorling", "given" : "Konrad M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fielden", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fogarty", "given" : "Simon W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fullwood", "given" : "Nigel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heys", "given" : "Kelly a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Caryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lasch", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin-Hirsch", "given" : "Pierre L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obinaju", "given" : "Blessing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sockalingum", "given" : "Ganesh D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sul\u00e9-Suso", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strong", "given" : "Rebecca J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Bayden R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Francis L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature protocols", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1771-91", "title" : "Using Fourier transform IR spectroscopy to analyze biological materials.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>11,26</sup>", "plainTextFormattedCitation" : "11,26", "previouslyFormattedCitation" : "<sup>11,26</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11,26. Our results demonstrate the oscillating baseline is also present in the FTIR spectra taken from the Aβ deposits indicating the inherent problem of Mie-like distortions likely to affect the pure absorbance spectra (cf. Fig 2a). In Fig 2b, there is a 2D distribution of the scattering intensities measured at 2500 cm-1 (unlikely to be assigned to any vibration modes but arising from fluctuations in the baseline) for a selected plaque. From this data, we can see that the (dense) core of the plaque is of radically elevated absorbance. Once corrected, as in Fig 2c, the intensities computed at 2500 cm-1 become 95% lower than the maximum absorbance in the spectra, so that one could assume their influence to the spectroscopic information (here proteomic-related) should be negligible. In addition, the histogram presented in Fig 2d shows up the corrected data (blue boxes) are of significantly lower heterogeneity, and their baselines’ oscillations are of markedly reduced amplitude as compared with the uncorrected values (red boxes). These results come as no surprise since the previous studies have demonstrated that FTIR spectra taken from the cells were of very high variability in their chemical and physical properties (refractive index, density) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jbio.201000036", "ISBN" : "1864-0648 (Electronic)\\r1864-063X (Linking)", "ISSN" : "1864063X", "PMID" : "20414907", "abstract" : "In the field of biomedical infrared spectroscopy it is often desirable to obtain spectra at the cellular level. Samples consisting of isolated single biological cells are particularly unsuited to such analysis since cells are strong scatterers of infrared radiation. Thus measured spectra consist of an absorption component often highly distorted by scattering effects. It is now known that the predominant contribution to the scattering is Resonant Mie Scattering (RMieS) and recently we have shown that this can be corrected for, using an iterative algorithm based on Extended Multiplicative Signal Correction (EMSC) and a Mie approximation formula. Here we present an iterative algorithm that applies full Mie scattering theory. In order to avoid noise accumulation in the iterative algorithm a curve-fitting step is implemented on the new reference spectrum. The new algorithm increases the computational time when run on an equivalent processor. Therefore parallel processing by a Graphics Processing Unit (GPU) was employed to reduce computation time. The optimised RMieS-EMSC algorithm is applied to an IR spectroscopy data set of cultured single isolated prostate cancer (PC-3) cells, where it is shown that spectral distortions from RMieS are removed.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohler", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lockyer", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Biophotonics", "id" : "ITEM-1", "issue" : "8-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "609-620", "title" : "RMieS-EMSC correction for infrared spectra of biological cells: Extension using full Mie theory and GPU computing", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/b821349f", "ISBN" : "0003-2654", "ISSN" : "0003-2654", "PMID" : "19475144", "abstract" : "Fourier transform infrared spectra of a single cell in transflection geometry are seen to vary significantly with position on the cell, showing a distorted derivative-like lineshape in the region of the optically dense nucleus. A similar behaviour is observable in a model system of the protein albumin doped in a potassium bromide disk. It is demonstrated that the spectrum at any point is a weighted sum of the sample reflection and transmission and that the dominance of the reflection spectrum in optically dense regions can account for some of the spectral distortions previously attributed to dispersion artefacts. Rather than being an artefact, the reflection contribution is ever present in transflection spectra and it is further demonstrated that the reflection characteristics can be used for cellular mapping.", "author" : [ { "dropping-particle" : "", "family" : "Bassan", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byrne", "given" : "Hugh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnier", "given" : "Franck", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Colin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gazi", "given" : "Ehsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Michael D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Noel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1171-1175", "title" : "Reflection contributions to the dispersion artefact in FTIR spectra of single biological cells.", "type" : "article-journal", "volume" : "134" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>26,44</sup>", "plainTextFormattedCitation" : "26,44", "previouslyFormattedCitation" : "<sup>26,45</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26,44. RMieS depends on the scattering particle size and refractive index, therefore any variations either in samples’ morphology or density may distort pure absorbance FTIR spectra which is the case in our raw data taken from the Aβ plaques ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1366/000370209789806902", "ISSN" : "19433530", "PMID" : "19891839", "abstract" : "We have been investigating the mid-infrared (MIR) reflection spectrum of microparticles on mirrored substrates. Gold-coated porous alumina filters were used as a substrate to layer the particles and provide consistent reflection spectra. Polystyrene spheres with measured diameters of 0.42 microm were studied using Fourier transform infrared (FT-IR) reflection microspectroscopy, and spectra are shown for coverages in the range 0.5-6 monolayers (ML). Results show that absorption has a nonlinear, stairstep-like dependence on particle coverage and a wavelength dependence that can be explained by electric field standing waves (EFSW) caused by the mirrored substrate. The same effect is found to cause progressive weakening of the observed spectra as a function of increasing wavelength in sub-monolayer coverage measurements. Scattering effects in the spectra are consistent with surface scattering at the antinodes of the EFSW. These observations provide explanations for differences seen between optical properties of particles calculated using the specular-reflection method versus those calculated using traditional aerosol methods. A simple multilayer method for estimating particle absorption coefficients is demonstrated that compares well with values reported using ellipsometry for bulk polystyrene. Another simple method based on submonolayer coverage spectra provides spectra suitable for classification analysis but is only semi-quantitative at determining absorption coefficients.", "author" : [ { "dropping-particle" : "", "family" : "Brooke", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Bronk", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCutcheon", "given" : "J. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "S. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myrick", "given" : "M. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Applied spectroscopy", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1293-1302", "title" : "A study of electric field standing waves on reflection microspectroscopy of polystyrene particles.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>43</sup>", "plainTextFormattedCitation" : "43", "previouslyFormattedCitation" : "<sup>44</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }43. This issue becomes important when the goal is to bring deeper insight into pure proteomic related information which is encoded within FTIR spectra. In particular, the amide I band of peptides has been shown to contain a myriad of subtle information on innumerable protein backbone C=O vibration modes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0033583502003815", "ISBN" : "0033-5835 (Print)", "ISSN" : "00335835", "PMID" : "12621861", "abstract" : "This review deals with current concepts of vibrational spectroscopy for the investigation of protein structure and function. While the focus is on infrared (IR) spectroscopy, some of the general aspects also apply to Raman spectroscopy. Special emphasis is on the amide I vibration of the polypeptide backbone that is used for secondary-structure analysis. Theoretical as well as experimental aspects are covered including transition dipole coupling. Further topics are discussed, namely the absorption of amino-acid side-chains, 1H/2H exchange to study the conformational flexibility and reaction-induced difference spectroscopy for the investigation of reaction mechanisms with a focus on interpretation tools.", "author" : [ { "dropping-particle" : "", "family" : "Barth", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zscherp", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Quarterly Reviews of Biophysics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "S0033583502003815", "title" : "What vibrations tell about proteins", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>48</sup>", "plainTextFormattedCitation" : "48", "previouslyFormattedCitation" : "<sup>49</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }48. One should mention that other ranges within the fingerprint region are also commonly used in the proteomic research, but the intensity of underlying modes of vibrations of proteins’ backbones is markedly reduced, compared with those observed within amide I ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4AN01867B", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Surowka", "given" : "A. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczerbowska-Boruchowska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2428-2438", "title" : "The combination of artificial neural networks and synchrotron radiation-based infrared micro-spectroscopy for a study on the protein composition of human glial tumors", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1529/biophysj.105.072017", "ISBN" : "3226505386", "ISSN" : "0006-3495", "PMID" : "16428280", "abstract" : "Fourier-transform infrared spectroscopy is a method of choice for the experimental determination of protein secondary structure. Numerous approaches have been developed during the past 15 years. A critical parameter that has not been taken into account systematically is the selection of the wavenumbers used for building the mathematical models used for structure prediction. The high quality of the current Fourier-transform infrared spectrometers makes the absorbance at every single wavenumber a valid and almost noiseless type of information. We address here the question of the amount of independent information present in the infrared spectra of proteins for the prediction of the different secondary structure contents. It appears that, at most, the absorbance at three distinct frequencies of the spectra contain all the nonredundant information that can be related to one secondary structure content. The ascending stepwise method proposed here identifies the relevance of each wavenumber of the infrared spectrum for the prediction of a given secondary structure and yields a particularly simple method for computing the secondary structure content. Using the 50-protein database built beforehand to contain as little fold redundancy as possible, the standard error of prediction in cross-validation is 5.5% for the alpha-helix, 6.6% for the beta-sheet, and 3.4% for the beta-turn.", "author" : [ { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruysschaert", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raussens", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biophysical journal", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "2946-57", "title" : "Evaluation of the information content in infrared spectra for protein secondary structure determination.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ab.2004.10.016", "ISSN" : "00032697", "author" : [ { "dropping-particle" : "", "family" : "Navea", "given" : "Susana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tauler", "given" : "Rom\u00e0", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "de", "family" : "Juan", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Analytical Biochemistry", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "page" : "231-242", "title" : "Application of the local regression method interval partial least-squares to the elucidation of protein secondary structure", "type" : "article-journal", "volume" : "336" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>49\u201351</sup>", "plainTextFormattedCitation" : "49\u201351", "previouslyFormattedCitation" : "<sup>50\u201352</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49–51. To extract the proteomic related information from amide I many solutions have been proposed, be it different machine-learning-based approaches (including artificial neural networks), chemometric approaches (partial least squares) and curve fitting ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4AN01867B", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Surowka", "given" : "A. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczerbowska-Boruchowska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2428-2438", "title" : "The combination of artificial neural networks and synchrotron radiation-based infrared micro-spectroscopy for a study on the protein composition of human glial tumors", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/pmic.200300808", "ISBN" : "1441162577", "ISSN" : "16159853", "PMID" : "15274125", "abstract" : "Fourier transform infrared (FTIR) spectroscopy is an attractive tool for proteomics research as it can be used to rapidly characterize protein secondary structure in aqueous solution. Recently, a number of secondary structure prediction methods based on reference sets of FTIR spectra from proteins with known structure from X-ray crystallography have been suggested. These prediction methods, often referred to as pattern recognition based approaches, demonstrated good prediction accuracy using some error measure, e.g., the standard error of prediction (SEP). However, to avoid possible adverse effects from differences in recording, the analysis has been mostly based on reference sets of FTIR spectra from proteins recorded in one laboratory only. As a result, these studies were based on reference sets of FTIR spectra from a limited number of proteins. Pattern recognition based approaches, however, rely on reference sets of FTIR spectra from as many proteins as possible representing all possible band shape variation to be related to the diversity of protein structural classes. Hence, if we want to build reliable pattern recognition based systems to support proteomics research, which are capable of making good predictions from spectral data of any unknown protein, one common goal should be to build a comprehensive protein infrared spectra databank (PISD) containing FTIR spectra of proteins of known structure. We have started the process of developing a comprehensive PISD composed of spectra recorded in different laboratories. As part of this work, here we investigate possible effects on prediction accuracy achieved by a neural network analysis when using reference sets composed of FTIR spectra from different laboratories. Surprisingly low magnitude of difference in SEPs throughout all our experiments suggests that FTIR spectra recorded in different laboratories may be safely combined into one reference set with only minor deterioration of prediction accuracy in the worst case.", "author" : [ { "dropping-particle" : "", "family" : "Hering", "given" : "Joachim A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Innocent", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haris", "given" : "Parvez I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proteomics", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "2310-2319", "title" : "Towards developing a protein infrared spectra databank (PISD) for proteomics research", "type" : "paper-conference", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ab.2004.06.030", "ISSN" : "00032697", "PMID" : "15325291", "abstract" : "Secondary structures of proteins have been predicted using neural networks from their Fourier transform infrared spectra. To improve the generalization ability of the neural networks, the training data set has been artificially increased by linear interpolation. The leave-one-out approach has been used to demonstrate the applicability of the method. Bayesian regularization has been used to train the neural networks and the predictions have been further improved by the maximum-likelihood estimation method. The networks have been tested and standard error of prediction (SEP) of 4.19% for ?? helix, 3.49% for ?? sheet, and 3.15% for turns have been achieved. The results indicate that there is a significant decrease in the SEP for each type of structure parameter compared to previous works. ?? 2004 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Severcan", "given" : "Mete", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haris", "given" : "Parvez I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severcan", "given" : "Feride", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Analytical Biochemistry", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "238-244", "title" : "Using artificially generated spectral data to improve protein secondary structure prediction from Fourier transform infrared spectra of proteins", "type" : "article-journal", "volume" : "332" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>49,52,53</sup>", "plainTextFormattedCitation" : "49,52,53", "previouslyFormattedCitation" : "<sup>50,53,54</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49,52,53. The former, representing so-called supervised techniques, involve the training using the spectra of known secondary structure components (target values), so that the appropriate optimization may even mirror the results obtained with sophisticated crystallographic measurements ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4AN01867B", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Surowka", "given" : "A. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczerbowska-Boruchowska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2428-2438", "title" : "The combination of artificial neural networks and synchrotron radiation-based infrared micro-spectroscopy for a study on the protein composition of human glial tumors", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>49</sup>", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "<sup>50</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49. The latter represent the unsupervised solutions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/C4AN01867B", "ISSN" : "0003-2654", "author" : [ { "dropping-particle" : "", "family" : "Surowka", "given" : "A. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczerbowska-Boruchowska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2428-2438", "title" : "The combination of artificial neural networks and synchrotron radiation-based infrared micro-spectroscopy for a study on the protein composition of human glial tumors", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/pmic.200300808", "ISBN" : "1441162577", "ISSN" : "16159853", "PMID" : "15274125", "abstract" : "Fourier transform infrared (FTIR) spectroscopy is an attractive tool for proteomics research as it can be used to rapidly characterize protein secondary structure in aqueous solution. Recently, a number of secondary structure prediction methods based on reference sets of FTIR spectra from proteins with known structure from X-ray crystallography have been suggested. These prediction methods, often referred to as pattern recognition based approaches, demonstrated good prediction accuracy using some error measure, e.g., the standard error of prediction (SEP). However, to avoid possible adverse effects from differences in recording, the analysis has been mostly based on reference sets of FTIR spectra from proteins recorded in one laboratory only. As a result, these studies were based on reference sets of FTIR spectra from a limited number of proteins. Pattern recognition based approaches, however, rely on reference sets of FTIR spectra from as many proteins as possible representing all possible band shape variation to be related to the diversity of protein structural classes. Hence, if we want to build reliable pattern recognition based systems to support proteomics research, which are capable of making good predictions from spectral data of any unknown protein, one common goal should be to build a comprehensive protein infrared spectra databank (PISD) containing FTIR spectra of proteins of known structure. We have started the process of developing a comprehensive PISD composed of spectra recorded in different laboratories. As part of this work, here we investigate possible effects on prediction accuracy achieved by a neural network analysis when using reference sets composed of FTIR spectra from different laboratories. Surprisingly low magnitude of difference in SEPs throughout all our experiments suggests that FTIR spectra recorded in different laboratories may be safely combined into one reference set with only minor deterioration of prediction accuracy in the worst case.", "author" : [ { "dropping-particle" : "", "family" : "Hering", "given" : "Joachim A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Innocent", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haris", "given" : "Parvez I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proteomics", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "2310-2319", "title" : "Towards developing a protein infrared spectra databank (PISD) for proteomics research", "type" : "paper-conference", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>49,52</sup>", "plainTextFormattedCitation" : "49,52", "previouslyFormattedCitation" : "<sup>50,53</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49,52. Although they are commonly used, fast, fairly simple and hassle-free for implementation, the proteomic related information they provide is semi-quantitative. This is because the intensities of vibration modes underlying amide I arise from the changes in the dipole moment of the entire peptide during resonant absorption of infrared radiation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0033583502003815", "ISBN" : "0033-5835 (Print)", "ISSN" : "00335835", "PMID" : "12621861", "abstract" : "This review deals with current concepts of vibrational spectroscopy for the investigation of protein structure and function. While the focus is on infrared (IR) spectroscopy, some of the general aspects also apply to Raman spectroscopy. Special emphasis is on the amide I vibration of the polypeptide backbone that is used for secondary-structure analysis. Theoretical as well as experimental aspects are covered including transition dipole coupling. Further topics are discussed, namely the absorption of amino-acid side-chains, 1H/2H exchange to study the conformational flexibility and reaction-induced difference spectroscopy for the investigation of reaction mechanisms with a focus on interpretation tools.", "author" : [ { "dropping-particle" : "", "family" : "Barth", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zscherp", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Quarterly Reviews of Biophysics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "S0033583502003815", "title" : "What vibrations tell about proteins", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>48</sup>", "plainTextFormattedCitation" : "48", "previouslyFormattedCitation" : "<sup>49</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }48. Usually, asymmetric modes produce the strongest changes in the dipole moment and result in the highest peaks, whilst the symmetric modes are significantly (even several orders of magnitude) weaker making the interaction of IR light with a sample a very complicated quantum-mechanical phenomenon ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0033583502003815", "ISBN" : "0033-5835 (Print)", "ISSN" : "00335835", "PMID" : "12621861", "abstract" : "This review deals with current concepts of vibrational spectroscopy for the investigation of protein structure and function. While the focus is on infrared (IR) spectroscopy, some of the general aspects also apply to Raman spectroscopy. Special emphasis is on the amide I vibration of the polypeptide backbone that is used for secondary-structure analysis. Theoretical as well as experimental aspects are covered including transition dipole coupling. Further topics are discussed, namely the absorption of amino-acid side-chains, 1H/2H exchange to study the conformational flexibility and reaction-induced difference spectroscopy for the investigation of reaction mechanisms with a focus on interpretation tools.", "author" : [ { "dropping-particle" : "", "family" : "Barth", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zscherp", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Quarterly Reviews of Biophysics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "S0033583502003815", "title" : "What vibrations tell about proteins", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.vibspec.2010.01.015", "ISSN" : "09242031", "abstract" : "The vibrational spectra of molecules contain a wealth of information, if only one can find the key. Our current efforts are directed towards interpretation of spatially resolved IR, Raman and SERS spectra from our various biological and inorganic samples, and computational modeling of the spectra as aids in analysis and interpretation. We have performed hybrid Density Functional Theory/Hartree-Fock calculations with B3LYP/6-31+G(d) on glycine homopeptides with 2-9 amino acid residues formed into straight chain, ??-helix and ??-sheet arrangements to explore some of the basic features underlying the amide I profile. The calculations give complete normal modes and intensities based on the molecular wavefunction. We discuss the general principles of carbonyl bond alignment and normal mode phase that dominate the calculated profiles. We compare computational results to experimental spectra from brain tissue of the TgCRND8 transgenic mouse model for Alzheimer disease, recorded with synchrotron-source single pixel detector and 10 ??m spatial resolution, and with a focal plane array and detector elements of 5.5 ??m. Spectra from dense core plaques imaged with both systems sometimes show radically different amide I profiles. While numerical methods can be applied to image the plaques in each case, the results illustrate the continued importance of developing instrument and target-specific parameters. ?? 2010 Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzadu", "given" : "Lsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kastyak", "given" : "Marzena Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuzyk", "given" : "Alexandra C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Julian", "given" : "Robert L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Vibrational Spectroscopy", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "71-76", "title" : "Theoretical and experimental considerations for interpretation of amide I bands in tissue", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>48,54</sup>", "plainTextFormattedCitation" : "48,54", "previouslyFormattedCitation" : "<sup>49,55</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }48,54. Therefore, one should realise that the fraction of a specific amide I band is at least proportional to the number of residues of a particular conformational state ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.vibspec.2010.01.015", "ISSN" : "09242031", "abstract" : "The vibrational spectra of molecules contain a wealth of information, if only one can find the key. Our current efforts are directed towards interpretation of spatially resolved IR, Raman and SERS spectra from our various biological and inorganic samples, and computational modeling of the spectra as aids in analysis and interpretation. We have performed hybrid Density Functional Theory/Hartree-Fock calculations with B3LYP/6-31+G(d) on glycine homopeptides with 2-9 amino acid residues formed into straight chain, ??-helix and ??-sheet arrangements to explore some of the basic features underlying the amide I profile. The calculations give complete normal modes and intensities based on the molecular wavefunction. We discuss the general principles of carbonyl bond alignment and normal mode phase that dominate the calculated profiles. We compare computational results to experimental spectra from brain tissue of the TgCRND8 transgenic mouse model for Alzheimer disease, recorded with synchrotron-source single pixel detector and 10 ??m spatial resolution, and with a focal plane array and detector elements of 5.5 ??m. Spectra from dense core plaques imaged with both systems sometimes show radically different amide I profiles. While numerical methods can be applied to image the plaques in each case, the results illustrate the continued importance of developing instrument and target-specific parameters. ?? 2010 Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzadu", "given" : "Lsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kastyak", "given" : "Marzena Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuzyk", "given" : "Alexandra C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Julian", "given" : "Robert L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Vibrational Spectroscopy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "71-76", "title" : "Theoretical and experimental considerations for interpretation of amide I bands in tissue", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>54</sup>", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "<sup>55</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54. Nevertheless, much work involving the curve-fitting approach took advantage of showing the importance of the proteomic related conclusions drawn from the semi-quantitative results ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.sbi.2010.07.007", "ISBN" : "0959-440X", "ISSN" : "0959440X", "PMID" : "20739176", "abstract" : "Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X-ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in bridging the gap towards 'functional biology' is discussed based upon recent achievements, with a critical assessment of the contributions to biological and biomedical research. ?? 2010.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Structural Biology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "649-656", "title" : "From structure to cellular mechanism with infrared microspectroscopy", "type" : "article", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1529/biophysj.105.072017", "ISBN" : "3226505386", "ISSN" : "0006-3495", "PMID" : "16428280", "abstract" : "Fourier-transform infrared spectroscopy is a method of choice for the experimental determination of protein secondary structure. Numerous approaches have been developed during the past 15 years. A critical parameter that has not been taken into account systematically is the selection of the wavenumbers used for building the mathematical models used for structure prediction. The high quality of the current Fourier-transform infrared spectrometers makes the absorbance at every single wavenumber a valid and almost noiseless type of information. We address here the question of the amount of independent information present in the infrared spectra of proteins for the prediction of the different secondary structure contents. It appears that, at most, the absorbance at three distinct frequencies of the spectra contain all the nonredundant information that can be related to one secondary structure content. The ascending stepwise method proposed here identifies the relevance of each wavenumber of the infrared spectrum for the prediction of a given secondary structure and yields a particularly simple method for computing the secondary structure content. Using the 50-protein database built beforehand to contain as little fold redundancy as possible, the standard error of prediction in cross-validation is 5.5% for the alpha-helix, 6.6% for the beta-sheet, and 3.4% for the beta-turn.", "author" : [ { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruysschaert", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raussens", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biophysical journal", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "2946-57", "title" : "Evaluation of the information content in infrared spectra for protein secondary structure determination.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1039/c0an00513d", "ISSN" : "1364-5528", "PMID" : "20927459", "abstract" : "Malignant gliomas are very aggressive tumors, highly angiogenic and invading heterogeneously the surrounding brain parenchyma, making their resection very difficult. To overcome the limits of current diagnostic imaging techniques used for gliomas, we proposed using FTIR imaging, with a spatial resolution from 6 to 10 \u03bcm, to provide molecular information for their histological examination, based on discrimination between normal and tumor vasculature. Differentiation between normal and tumor blood vessel spectra by hierarchical cluster analysis was performed on tissue sections obtained from xenografted brain tumors of Rag-gamma mice 28 days after intracranial implantation of glioma cells, as well as for human brain tumors obtained in clinics. Classical pathological examination and immunohistochemistry were performed in parallel to the FTIR spectral imaging of brain tissues. First on the animal model, classification of FTIR spectra of blood vessels could be performed using spectral intervals based on fatty acyl (3050-2800 cm(-1)) and carbohydrate (1180-950 cm(-1)) absorptions, with the formation of two clusters corresponding to healthy and tumor parts of the tissue sections. Further data treatments on these two spectral intervals provided interpretable information about the molecular contents involved in the differentiation between normal and tumor blood vessels, the latter presenting a higher level of fatty acyl chain unsaturation and an unexpected loss of absorption from osidic residues. This classification method was further successfully tested on human glioma tissue sections. These findings demonstrate that FTIR imaging could highlight discriminant molecular markers to distinguish between normal and tumor vasculature, and help to delimitate areas of corresponding tissue.", "author" : [ { "dropping-particle" : "", "family" : "Wehbe", "given" : "Katia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pineau", "given" : "Raphael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eimer", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vital", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loiseau", "given" : "Hugues", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00e9l\u00e9ris", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "3052-9", "title" : "Differentiation between normal and tumor vasculature of animal and human glioma by FTIR imaging.", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1371/journal.pone.0139854", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Saeed", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raouf", "given" : "Gehan A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nafee", "given" : "Sherif S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaheen", "given" : "Salem A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hadeethi", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLOS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Perc", "given" : "Matjaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10", "5" ] ] }, "page" : "e0139854", "title" : "Effects of Very Low Dose Fast Neutrons on Cell Membrane And Secondary Protein Structure in Rat Erythrocytes", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.3390/molecules200712599", "ISSN" : "14203049", "abstract" : "Infrared spectroscopy is a powerful tool in protein science due to its sensitivity to changes in secondary structure or conformation. In order to take advantage of the full power of infrared spectroscopy in structural studies of proteins, complex band contours, such as the amide I band, have to be decomposed into their main component bands, a process referred to as curve fitting. In this paper, we report on an improved curve fitting approach in which absorption spectra and second derivative spectra are fitted simultaneously. Our approach, which we name co-fitting, leads to a more reliable modelling of the experimental data because it uses more spectral information than the standard approach of fitting only the absorption spectrum. It also avoids that the fitting routine becomes trapped in local minima. We have tested the proposed approach using infrared absorption spectra of three mixed \u03b1/\u03b2 proteins with different degrees of spectral overlap in the amide I region: ribonuclease A, pyruvate kinase, and aconitase.", "author" : [ { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Maurizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Chenge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eremina", "given" : "Nadejda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecules", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "12599-12622", "title" : "Simultaneous fitting of absorption spectra and their second derivatives for an improved analysis of protein infrared spectra", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.tibtech.2006.08.005", "ISBN" : "0167-7799 (Print)", "ISSN" : "01677799", "PMID" : "16935373", "abstract" : "Fourier-transform infrared (FT-IR) spectro-imaging enables global analysis of samples, with resolution close to the cellular level. Recent studies have shown that FT-IR imaging enables determination of the biodistribution of several molecules of interest (carbohydrates, lipids, proteins) for tissue analysis without pre-analytical modification of the sample such as staining. Molecular structure information is also available from the same analysis, notably for protein secondary structure and fatty acyl chain peroxidation level. Thus, several cancer markers can be identified from FT-IR tissue images, enabling accurate discrimination between healthy and tumor areas. FT-IR imaging applications are now able to provide unique chemical and morphological information about tissue status. With the fast image acquisition provided by modern mid-infrared imaging systems, it is now envisaged to analyze cerebral tumor exereses in delays compatible with neurosurgery. Accordingly, we propose to take FT-IR imaging into consideration for the development of new molecular histopathology tools. ?? 2006 Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Petibois", "given" : "Cyril", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deleris", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in Biotechnology", "id" : "ITEM-6", "issue" : "10", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "455-462", "title" : "Chemical mapping of tumor progression by FT-IR imaging: towards molecular histopathology", "type" : "article", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>32,50,55\u201358</sup>", "plainTextFormattedCitation" : "32,50,55\u201358", "previouslyFormattedCitation" : "<sup>32,51,56\u201359</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32,50,55–58. In this proof-of-principle paper, the preliminary results demonstrate the feasibility of the amide I curve-fitting for protein secondary structure imaging of the Aβ plaques. The spectroscopic data presented are important to the extent to demonstrate that variation in relative amide I peak areas assigned to alpha-helices, β-turns, random coils and β-sheets is enough to localize and correlate the results with other molecular components found in FTIR spectra of the Aβ deposits. We first optimized our model, fixed the parameters in their optimal range, and subsequently performed the analysis of the FTIR maps for all the plaques. Fig 4a and 4b show the results of curve fitting for two spectra taken from the core of the plaque (Fig 4a) and from its surrounding (3b). In the deposits, the peaks assigned to β-turns, β-sheets and random coils are elevated, while the band attributed to alpha-helices is reduced, compared with the surrounding (cf. 3a-b). Interestingly, in the amide I spectrum taken from the deposit, the spectral signatures arising from both elevated β-sheets and random coils were present, which is in line with previous work ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/bip.20820", "ISBN" : "0006-3525 (Print)\\r0006-3525 (Linking)", "ISSN" : "00063525", "PMID" : "17680701", "abstract" : "Plaques composed of the A\u03b2 peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of A\u03b2, showing all the classical properties of amyloid including \u03b2-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an early age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a \u03b2-sheet conformation. The amide I maximum of plaque cores was at 1623 cm\u22121, and unlike for in vitro A\u03b2 fibrils, the high-frequency (1680\u20131690 cm\u22121) component attributed to antiparallel \u03b2-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.", "author" : [ { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bigio", "given" : "Marc R.", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mai", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westaway", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biopolymers", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "207-217", "title" : "Dense-core and diffuse A?? plaques in TgCRND8 mice studied with synchrotron FTIR microspectroscopy", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/c3an00295k", "ISBN" : "1204237409", "ISSN" : "1364-5528", "PMID" : "23586070", "abstract" : "While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and A\u03b2 peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 \u00d7 0.54 \u00b5m(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3\u00d7Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Catherine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Jillian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unger", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "Benedict C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "3991-7", "title" : "Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>15,18</sup>", "plainTextFormattedCitation" : "15,18", "previouslyFormattedCitation" : "<sup>15,18</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15,18. Net peak areas attributed to β-turns, alpha-helices, random coils and β-sheets were finally expressed as the relative fraction of amide I (cf. Fig 5a-e). One selected deposit was graphically presented in Fig 5a-e. What is interesting in this data is that alpha-helices are dramatically reduced within the deposit. On the contrary, β-sheets, turns and random coils appear to be somewhat increased, while the random coils seem to surround the region of increased fraction of β-sheets in this case. By using those images, the main challenge behind our work was to extract the information on protein-related chemical effects within and in close proximity of the plaques. We found image-processing-assisted methods (see the algorithm in Fig 6) to utilize the images showing the spatial variation in β-sheets very convenient. As demonstrated in Fig 4a and Fig 6, the β-sheets’ fraction of 0.16 discriminates between the areas of increased β-sheets and surrounding regions. The image-processing procedure to determine the immediate areas of the deposits was highlighted in Fig 6. Given the six adjacent layers (PLAQUE, 1st, 2nd, 3rd, 4th and Out), we calculated the average fraction of each protein secondary structure component vs. its position (the layer it falls into). The results (cf. Fig 7a-b) indicate the plaques are co-localized to increased β-sheets, turns, random coils, and reduced fraction of alpha-helices. In turn, the surrounding regions are enriched in alpha-helices. The transition between alpha-helices and β-sheets is indicative of aggregated proteins and was recently proposed using amide I band fitting of pure Aβ spectra ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bbamem.2013.01.014", "ISBN" : "0005-2736", "ISSN" : "0006-3002", "PMID" : "23357359", "abstract" : "Protein misfolding and aggregation are the hallmark of a number of diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and the prion diseases. In all cases, a naturally-occurring protein misfolds and forms aggregates that are thought to disrupt cell function through a wide range of mechanisms that are yet to be fully unraveled. Fourier transform infrared (FTIR) spectroscopy is a technique that is sensitive to the secondary structure of proteins and has been widely used to investigate the process of misfolding and aggregate formation. This review focuses on how FTIR spectroscopy and spectroscopic microscopy are being used to evaluate the structural changes in disease-related proteins both in vitro and directly within cells and tissues. Finally, ongoing technological advances will be presented that are enabling time-resolved FTIR imaging of protein aggregation directly within living cells, which can provide insight into the structural intermediates, time scale, and mechanisms of cell toxicity associated with aggregate formation. This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bourassa", "given" : "Megan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Randy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimica et biophysica acta", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2339-46", "title" : "FTIR spectroscopic imaging of protein aggregation in living cells.", "type" : "article-journal", "volume" : "1828" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.bpj.2012.07.046", "ISSN" : "00063495", "PMID" : "23009851", "abstract" : "Fibrin is a protein polymer that forms the viscoelastic scaffold of blood clots and thrombi. Despite the critical importance of fibrin deformability for outcomes of bleeding and thrombosis, the structural origins of the clot's elasticity and plasticity remain largely unknown. However, there is substantial evidence that unfolding of fibrin is an important part of the mechanism. We used Fourier transform infrared spectroscopy to reveal force-induced changes in the secondary structure of hydrated fibrin clots made of human blood plasma in vitro. When extended or compressed, fibrin showed a shift of absorbance intensity mainly in the amide I band (1600-1700 cm-1) as well as in the amide II and III bands, indicating an increase of the ??-sheets and a corresponding reduction of the ??-helices. The structural conversions correlated directly with the strain or pressure and were partially reversible at the conditions applied. The additional absorbance observed at 1612-1624 cm -1 was characteristic of the nascent interchain ??-sheets, consistent with protein aggregation and fiber bundling during clot deformation observed using scanning electron microscopy. We conclude that under extension and/or compression an ??-helix to ??-sheet conversion of the coiled-coils occurs in the fibrin clot as a part of forced protein unfolding. ?? 2012 Biophysical Society.", "author" : [ { "dropping-particle" : "", "family" : "Litvinov", "given" : "Rustem I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faizullin", "given" : "Dzhigangir A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zuev", "given" : "Yuriy F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weisel", "given" : "John W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biophysical Journal", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1020-1027", "title" : "The ??-helix to ??-sheet transition in stretched and compressed hydrated fibrin clots", "type" : "article-journal", "volume" : "103" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>59,60</sup>", "plainTextFormattedCitation" : "59,60", "previouslyFormattedCitation" : "<sup>60,61</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }59,60. This data is also in accord with other work showing FTIR spectra of dense core-plaques exhibiting a characteristic shoulder around 1630 cm-1 suggesting highly aggregated amyloid enriched in β-sheets ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jsb.2005.09.004", "ISBN" : "1047-8477", "ISSN" : "10478477", "PMID" : "16325427", "abstract" : "Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (A??). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 ??m was achieved. FTIRM results showed that the amyloid plaques have elevated ??-sheet content, as demonstrated by a strong amide I absorbance at 1625 cm-1. Using SXRF microprobe, we find that AD tissue also contains \"hot spots\" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The \"hot spots\" of accumulated Zn and Cu were co-localized with ??-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated ??-sheet content in A?? plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD. ?? 2005 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Telivala", "given" : "Tejas P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Randy J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanzirotti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miklossy", "given" : "Judit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Structural Biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "30-37", "title" : "Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with ??-amyloid deposits in Alzheimer's disease", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/c3an00295k", "ISBN" : "1204237409", "ISSN" : "1364-5528", "PMID" : "23586070", "abstract" : "While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and A\u03b2 peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 \u00d7 0.54 \u00b5m(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3\u00d7Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Catherine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Jillian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unger", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "Benedict C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "3991-7", "title" : "Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.sbi.2010.07.007", "ISBN" : "0959-440X", "ISSN" : "0959440X", "PMID" : "20739176", "abstract" : "Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X-ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in bridging the gap towards 'functional biology' is discussed based upon recent achievements, with a critical assessment of the contributions to biological and biomedical research. ?? 2010.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumas", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Structural Biology", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "649-656", "title" : "From structure to cellular mechanism with infrared microspectroscopy", "type" : "article", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>13,18,32</sup>", "plainTextFormattedCitation" : "13,18,32", "previouslyFormattedCitation" : "<sup>13,18,32</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13,18,32. Some recent studies using ATR-FTIR have also corroborated that Aβ fragments possess increased amounts of anti-parallel β-sheets ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bbamem.2013.04.012", "ISSN" : "00052736", "PMID" : "23746423", "abstract" : "Amyloid refers to insoluble protein aggregates that are responsible for amyloid diseases but are also implicated in important physiological functions (functional amyloids). The widespread presence of protein aggregates but also, in most of the cases, their deleterious effects explain worldwide efforts made to understand their formation, structure and biological functions. We emphasized the role of FTIR and especially ATR-FTIR techniques in amyloid protein and/or peptide studies. The multiple advantages provided by ATR-FTIR allow an almost continuous structural view of protein/peptide conversion during the aggregation process. Moreover, it is now well-established that infrared can differentiate oligomers from fibrils simply on their spectral features. ATR-FTIR is certainly the fastest and easiest method to obtain this information. ATR-FTIR occupies a key position in the analysis and comprehension of the complex aggregation mechanism(s) at the oligomer and/or fibril level. These mechanism(s) seem to present strong similarities between different amyloid proteins and might therefore be extremely important to understand for both disease-associated and functional amyloid proteins. This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies. ?? 2013 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Sarroukh", "given" : "Rabia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruysschaert", "given" : "Jean Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raussens", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimica et Biophysica Acta - Biomembranes", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2328-2338", "title" : "ATR-FTIR: A \"rejuvenated\" tool to investigate amyloid proteins", "type" : "article", "volume" : "1828" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>61</sup>", "plainTextFormattedCitation" : "61", "previouslyFormattedCitation" : "<sup>62</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }61. Using the amide I curve fitting results, the PCA analysis demonstrated a good separation between the deposits and surrounding ‘Out’ regions along PCA1 (cf. Fig 8a-b). The points attributed to the Aβ plaques are in the negative PC1 space, whilst the surrounding ones are in the positive space. Fig 8b shows the corresponding scores plot of the data. One can surmise that the cause for this clustering is mainly due to β-sheets and β-turns. Their loadings are both of the highest amplitude and negative, which supports the idea that these components are co-localized in the Aβ plaques. One possible explanation for this might be that fibrillar Aβ displays additional shoulder at around 1690 cm-1, which could contribute to the β-turns peak ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1042/BJ20090379", "ISBN" : "1470-8728 (Electronic)\\r0264-6021 (Linking)", "ISSN" : "1470-8728", "PMID" : "19435461", "abstract" : "AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either Abeta oligomers or fibrils, suggesting that structural differences between these forms of Abeta exist. Using conditions which yield well-defined Abeta-(1-42) oligomers or fibrils, we studied the secondary structure of these species by ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy. Whereas fibrillar Abeta was organized in a parallel beta-sheet conformation, oligomeric Abeta displayed distinct spectral features, which were attributed to an antiparallel beta-sheet structure. We also noted striking similarities between Abeta oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel beta-sheets in Abeta oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.", "author" : [ { "dropping-particle" : "", "family" : "Cerf", "given" : "Emilie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarroukh", "given" : "Rabia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamamizu-Kato", "given" : "Shiori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Breydo", "given" : "Leonid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Derclaye", "given" : "Sylvie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dufr\u00eane", "given" : "Yves F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayanaswami", "given" : "Vasanthy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goormaghtigh", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruysschaert", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raussens", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Biochemical journal", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "415-423", "title" : "Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide", "type" : "article-journal", "volume" : "421" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>62</sup>", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "<sup>63</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62. The presence of this shoulder can therefore support the idea that fibrillar Aβ deposits to build up senile plaques adapts antiparallel β-sheets motif. However, as demonstrated both in the experimental and theoretical studies, the intensity of this high-wavenumber peak is up to five times weaker than the major one centered at around 1630 cm-1 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1097-0282", "abstract" : "Resonance vibrational interactions of amide I for the parallel-chain pleated-sheet structure have been treated on the basis of the perturbation theory in a dipole-dipole approxn. The infinite sheet and finite fragments of different types have been considered. The possibility of exptl. observation by ir spectra of parallel-chain pleated-sheet fragments in globular proteins is discussed. [on SciFinder (R)]", "author" : [ { "dropping-particle" : "", "family" : "Chirgadze", "given" : "Y N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nevskaya", "given" : "N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biopolymers", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1976" ] ] }, "page" : "627-636", "title" : "Infrared Spectra and Resonance Ineraction of Amide I Vibration of the Parallel-Chain Pleated Sheet", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>63</sup>", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "<sup>64</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63. Another possible scenario is that the phospholipid system, present in high concentrations in the neuropil (but not present in pure in vitro Aβ samples), could modify the Aβ aggregation. Indeed, some recent studies involving the POPC/POPS (1-palmitoyl-2-oleoylphospatidylcholine/ palmitoyl-2-oleoylphospatidylserine) system, using Raman spectroscopy, SR-FTIR, and micro XRD confirmed the aggregation of Aβ(25-35) results in detectable amounts of both antiparallel and parallel β-sheets motifs together with some possible β-turns ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/la500145r", "ISSN" : "0743-7463", "author" : [ { "dropping-particle" : "", "family" : "Accardo", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shalabaeva", "given" : "Victoria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotte", "given" : "Marine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burghammer", "given" : "Manfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krahne", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riekel", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dante", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Langmuir", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014", "3", "25" ] ] }, "page" : "3191-3198", "title" : "Amyloid \u03b2 Peptide Conformational Changes in the Presence of a Lipid Membrane System", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>64</sup>", "plainTextFormattedCitation" : "64", "previouslyFormattedCitation" : "<sup>65</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }64. In another study, Gough et al. reported some major obstacles with obtaining pure Aβ spectra in the dense core plaques found in the pristine brain tissue sections drawn from both humans and animal models of AD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.vibspec.2010.01.015", "ISSN" : "09242031", "abstract" : "The vibrational spectra of molecules contain a wealth of information, if only one can find the key. Our current efforts are directed towards interpretation of spatially resolved IR, Raman and SERS spectra from our various biological and inorganic samples, and computational modeling of the spectra as aids in analysis and interpretation. We have performed hybrid Density Functional Theory/Hartree-Fock calculations with B3LYP/6-31+G(d) on glycine homopeptides with 2-9 amino acid residues formed into straight chain, ??-helix and ??-sheet arrangements to explore some of the basic features underlying the amide I profile. The calculations give complete normal modes and intensities based on the molecular wavefunction. We discuss the general principles of carbonyl bond alignment and normal mode phase that dominate the calculated profiles. We compare computational results to experimental spectra from brain tissue of the TgCRND8 transgenic mouse model for Alzheimer disease, recorded with synchrotron-source single pixel detector and 10 ??m spatial resolution, and with a focal plane array and detector elements of 5.5 ??m. Spectra from dense core plaques imaged with both systems sometimes show radically different amide I profiles. While numerical methods can be applied to image the plaques in each case, the results illustrate the continued importance of developing instrument and target-specific parameters. ?? 2010 Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzadu", "given" : "Lsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kastyak", "given" : "Marzena Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuzyk", "given" : "Alexandra C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Julian", "given" : "Robert L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Vibrational Spectroscopy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "71-76", "title" : "Theoretical and experimental considerations for interpretation of amide I bands in tissue", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>54</sup>", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "<sup>55</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54. The authors mentioned that there is some overlap between adjacent FPA pixels blending the spectra taken from the Aβ deposits with the ones from the surrounding neuropil areas ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.vibspec.2010.01.015", "ISSN" : "09242031", "abstract" : "The vibrational spectra of molecules contain a wealth of information, if only one can find the key. Our current efforts are directed towards interpretation of spatially resolved IR, Raman and SERS spectra from our various biological and inorganic samples, and computational modeling of the spectra as aids in analysis and interpretation. We have performed hybrid Density Functional Theory/Hartree-Fock calculations with B3LYP/6-31+G(d) on glycine homopeptides with 2-9 amino acid residues formed into straight chain, ??-helix and ??-sheet arrangements to explore some of the basic features underlying the amide I profile. The calculations give complete normal modes and intensities based on the molecular wavefunction. We discuss the general principles of carbonyl bond alignment and normal mode phase that dominate the calculated profiles. We compare computational results to experimental spectra from brain tissue of the TgCRND8 transgenic mouse model for Alzheimer disease, recorded with synchrotron-source single pixel detector and 10 ??m spatial resolution, and with a focal plane array and detector elements of 5.5 ??m. Spectra from dense core plaques imaged with both systems sometimes show radically different amide I profiles. While numerical methods can be applied to image the plaques in each case, the results illustrate the continued importance of developing instrument and target-specific parameters. ?? 2010 Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzadu", "given" : "Lsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kastyak", "given" : "Marzena Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuzyk", "given" : "Alexandra C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Julian", "given" : "Robert L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Vibrational Spectroscopy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "71-76", "title" : "Theoretical and experimental considerations for interpretation of amide I bands in tissue", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>54</sup>", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "<sup>55</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54. Finally, to tackle the problem of protein-related biochemical processes occurring within and in close proximity of the deposits, we verified if there were any statistically significant (p<0.05) correlations between β/α ratios and additional molecular parameters computed for each consecutive layer. We found decreased lipid/protein ratio coincides with the elevated β/α ratio (cf. Fig 9b), though the correlation coefficient was not statistically significant (p=0.13) and the relation between those two parameters seemed to be non-linear. It is probably due to increased amount of protein-like material within the plaques. The single most interesting result to emerge from this data is that we observed a slight increase in the lipid/protein parameter in the first layer (around 4.4 ?m apart). This result, though very subtle, should draw our attention to increased accumulation of lipids around Aβ deposits reported elsewhere ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1039/c3an00295k", "ISBN" : "1204237409", "ISSN" : "1364-5528", "PMID" : "23586070", "abstract" : "While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and A\u03b2 peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tissue sections obtained with the mid-infrared beamline IRENI (InfraRed ENvironmental Imaging, Synchrotron Radiation Center, U Wisconsin-Madison), where the pixel resolution of 0.54 \u00d7 0.54 \u00b5m(2) permits analysis at sub-cellular dimensions. Spectrochemical images of dense core plaque found in hippocampus and cortex sections of two transgenic mouse models of AD (TgCRND8 and 3\u00d7Tg) are compared with plaque images from a 91 year old apoE43 human AD case. Spectral analysis was done in conjunction with histochemical stains of serial sections. A lipid membrane-like spectral signature surrounded and infiltrated the dense core plaques in all cases. Remarkable compositional similarities in early stage plaques suggest similar routes to plaque formation, regardless of genetic predisposition or mammalian origin.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Catherine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Jillian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unger", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albensi", "given" : "Benedict C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "Carol J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "Kathleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "3991-7", "title" : "Synchrotron FTIR reveals lipid around and within amyloid plaques in transgenic mice and Alzheimer's disease brain.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1039/c4an01982b", "ISSN" : "1364-5528", "PMID" : "25600495", "abstract" : "A recent upgrade to the optics configuration of a thermal source FTIR microscope equipped with a focal plane array detector has enabled rapid acquisition of high magnification spectrochemical images, in transmission, with an effective geometric pixel size of \u223c1 \u00d7 1 \u03bcm(2) at the sample plane. Examples, including standard imaging targets for scale and accuracy, as well as biomedical tissues and microorganisms, have been imaged with the new system and contrasted with data acquired at normal magnification and with a high magnification multi-beam synchrotron instrument. With this optics upgrade, one can now conduct rapid biodiagnostic ex vivo tissue imaging in-house, with images collected over larger areas, in less time (minutes) and with comparable quality and resolution to the best synchrotron source FTIR imaging capabilities.", "author" : [ { "dropping-particle" : "", "family" : "Findlay", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiens", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rak", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedlmair", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschmugl", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mundy", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kansiz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Analyst", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2493-503", "title" : "Rapid biodiagnostic ex vivo imaging at 1 \u03bcm pixel resolution with thermal source FTIR FPA.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>18,22</sup>", "plainTextFormattedCitation" : "18,22", "previouslyFormattedCitation" : "<sup>18,22</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }18,22. Previous studies appreciated the significance of glial infiltration which may enhance the accumulation of lipid-like material around the deposits. This result is likely to be related to lipid-rich membranes of microglia and astrocytes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1474-4422(15)70016-5", "ISBN" : "1474-4465 (Electronic)\\r1474-4422 (Linking)", "ISSN" : "14744465", "PMID" : "25792098", "abstract" : "Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.", "author" : [ { "dropping-particle" : "", "family" : "Heneka", "given" : "Michael T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carson", "given" : "Monica J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "El", "family" : "Khoury", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landreth", "given" : "Gary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brosseron", "given" : "Frederic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feinstein", "given" : "Douglas L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Andreas H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyss-Coray", "given" : "Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitorica", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ransohoff", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrup", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frautschy", "given" : "Sally A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finsen", "given" : "Bente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Guy C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verkhratsky", "given" : "Alexei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamanaka", "given" : "Koji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koistinaho", "given" : "Jari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Latz", "given" : "Eicke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halle", "given" : "Annett", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petzold", "given" : "Gabor C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Town", "given" : "Terrence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Dave", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shinohara", "given" : "Mari L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "V. Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "Clive", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bazan", "given" : "Nicolas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brooks", "given" : "David J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunot", "given" : "St??phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joseph", "given" : "Bertrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deigendesch", "given" : "Nikolaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garaschuk", "given" : "Olga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boddeke", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinarello", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Breitner", "given" : "John C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Greg M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golenbock", "given" : "Douglas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kummer", "given" : "Markus P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet Neurology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "388-405", "title" : "Neuroinflammation in Alzheimer's disease", "type" : "article", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>7</sup>", "plainTextFormattedCitation" : "7", "previouslyFormattedCitation" : "<sup>7</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7. The second remark that emerges from our data is related to the previous one. It turns out, the average values of β/α are positively correlated with the area of the νas(-PO42-) band (Fig 9a). It can lead to the conjecture that the gradual accumulation of β-sheets is associated with up-regulated abundance of phosphodiesters and/or lipid esters in the core of a plaque. This result, lends support to the recent study that demonstrated some protein-bound oxidation products of sugar oxidation (advanced glycation end products - AGEs) are secreted by glia surrounding Aβ plaques ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neurobiolaging.2014.09.025", "ISSN" : "15581497", "PMID" : "25448604", "abstract" : "Neurons that reenter the cell cycle die rather than divide, a phenomenon that is associated with neurodegeneration in Alzheimer's disease (AD). Reexpression of cell-cycle related genes in differentiated neurons in AD might be rooted in aberrant mitogenic signaling. Because microglia and astroglia proliferate in the vicinity of amyloid plaques, it is likely that plaque components or factors secreted from plaque-activated glia induce neuronal mitogenic signaling. Advanced glycation end products (AGEs), protein-bound oxidation products of sugar, might be one of those mitogenic compounds. Cyclin D1 positive neurons are colocalized with AGEs or directly surrounded by extracellular AGE deposits in AD brain. However, a direct proof of DNA replication in these cells has been missing. Here, we report by using fluorescent in situ hybridization that consistent with the expression of cell cycle proteins, hyperploid neuronal cells are in colocalization with AGE staining in AD brains but not in nondemented controls. To complement human data, we used apolipoprotein E-deficient mice as model of neurodegeneration and showed that increased oxidative stress caused an intensified neuronal deposition of AGEs, being accompanied by an activation of the MAPK cascade via RAGE. This cascade, in turn, induced the expression of cyclin D1 and DNA replication. In addition, reduction of oxidative stress by application of \u03b1-lipoic acid decreased AGE accumulations, and this decrease was accompanied by a reduction in cell cycle reentry and a more euploid neuronal genome.", "author" : [ { "dropping-particle" : "", "family" : "Kuhla", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ludwig", "given" : "Sophie C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhla", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcnch", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollmar", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurobiology of Aging", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "753-761", "title" : "Advanced glycation end products are mitogenic signals and trigger cell cycle reentry of neurons in Alzheimer's disease brain", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>65</sup>", "plainTextFormattedCitation" : "65", "previouslyFormattedCitation" : "<sup>66</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }65. In addition, Fig 9c highlights the lipids are significantly less unsaturated in the plaques as indicated by the decrease in the ν(=CH)/ νas(CH3) ratio. This observation fits in with the recent results by Benseny-Cases et al, showing the areas of human Aβ deposits exhibit reduced level of lipid unsaturation (the ν(=CH)/ νas(CH3) ratio) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/ac502667b", "ISBN" : "1520-6882 (Electronic)\\r0003-2700 (Linking)", "PMID" : "25415602", "abstract" : "Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.", "author" : [ { "dropping-particle" : "", "family" : "Benseny-Cases", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klementieva", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotte", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrer", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cladera", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anal Chem", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "12047-12054", "title" : "Microspectroscopy (muFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>19</sup>", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "<sup>19</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19. This interesting correlation points to processes associated with lipid peroxidation induced within Aβ-deposits. As mentioned, the redox-active metals, Cu and Fe, are extensively accumulated within the deposits due their improper chelation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jsb.2005.09.004", "ISBN" : "1047-8477", "ISSN" : "10478477", "PMID" : "16325427", "abstract" : "Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (A??). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 ??m was achieved. FTIRM results showed that the amyloid plaques have elevated ??-sheet content, as demonstrated by a strong amide I absorbance at 1625 cm-1. Using SXRF microprobe, we find that AD tissue also contains \"hot spots\" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The \"hot spots\" of accumulated Zn and Cu were co-localized with ??-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated ??-sheet content in A?? plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD. ?? 2005 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "Lisa M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Telivala", "given" : "Tejas P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Randy J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanzirotti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miklossy", "given" : "Judit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Structural Biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "30-37", "title" : "Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with ??-amyloid deposits in Alzheimer's disease", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>13</sup>", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "<sup>13</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. Fibrillar Aβ has a very strong positive reduction potential and is capable of simultaneous reduction of Cu2+ and Fe3+ to Cu+ and Fe2+ and subsequent generation of hyper-reactive free oxygen species (ROS) via Fenton or a Haber–Weiss reaction, recognized as major driving forces in the neuropathological processes to tip the scales towards gradual development of the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bbamem.2007.02.002", "ISBN" : "0006-3002 (Print)\\r0006-3002 (Linking)", "ISSN" : "00052736", "PMID" : "17433250", "abstract" : "There is a growing body of evidence to support a role for oxidative stress in Alzheimer's disease (AD), with increased levels of lipid peroxidation, DNA and protein oxidation products (HNE, 8-HO-guanidine and protein carbonyls respectively) in AD brains. The brain is a highly oxidative organ consuming 20% of the body's oxygen despite accounting for only 2% of the total body weight. With normal ageing the brain accumulates metals ions such iron (Fe), zinc (Zn) and copper (Cu). Consequently the brain is abundant in antioxidants to control and prevent the detrimental formation of reactive oxygen species (ROS) generated via Fenton chemistry involving redox active metal ion reduction and activation of molecular oxygen. In AD there is an over accumulation of the Amyloid \u03b2 peptide (A\u03b2), this is the result of either an elevated generation from amyloid precursor protein (APP) or inefficient clearance of A\u03b2 from the brain. A\u03b2 can efficiently generate reactive oxygen species in the presence of the transition metals copper and iron in vitro. Under oxidative conditions A\u03b2 will form stable dityrosine cross-linked dimers which are generated from free radical attack on the tyrosine residue at position 10. There are elevated levels of urea and SDS resistant stable linked A\u03b2 oligomers as well as dityrosine cross-linked peptides and proteins in AD brain. Since soluble A\u03b2 levels correlate best with the degree of degeneration [C.A. McLean, R.A. Cherny, F.W. Fraser, S.J. Fuller, M.J. Smith, K. Beyreuther, A.I. Bush, C.L. Masters, Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease, Ann. Neurol. 46 (1999) 860\u2013866] we suggest that the toxic A\u03b2 species corresponds to a soluble dityrosine cross-linked oligomer. Current therapeutic strategies using metal chelators such as clioquinol and desferrioxamine have had some success in altering the progression of AD symptoms. Similarly, natural antioxidants curcumin and ginkgo extract have modest but positive effects in slowing AD development. Therefore, drugs that target the oxidative pathways in AD could have genuine therapeutic efficacy.", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Danielle G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappai", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnham", "given" : "Kevin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimica et Biophysica Acta (BBA) - Biomembranes", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "1976-1990", "title" : "The redox chemistry of the Alzheimer's disease amyloid \u03b2 peptide", "type" : "article-journal", "volume" : "1768" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>14</sup>", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "<sup>14</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14. Recent evidence suggests that unsaturated lipids are particularly prone to free radicals-induced peroxidation because of their unsaturated chemical bonds in their long fatty acid β-chain ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0303-4240", "PMID" : "8533011", "author" : [ { "dropping-particle" : "", "family" : "Esterbauer", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Reviews of physiology, biochemistry and pharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "31-64", "title" : "Chemistry and pathophysiology of oxidation of LDL.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>66</sup>", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "<sup>67</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66. As shown in Fig 9d, the correlation coefficient between β/α and the level of lipid oxidation was found to be negative and highly significant (p<0.05). This is in good agreement with the latest work by Benseny-Cases et al. using SR-FTIR imaging, which demonstrated reduced level of lipid oxidation within human Aβ plaques raster-scanned at 6 μm pixel size in the brain tissue section taken from the aged human (non-AD tissue section) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/ac502667b", "ISBN" : "1520-6882 (Electronic)\\r0003-2700 (Linking)", "PMID" : "25415602", "abstract" : "Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.", "author" : [ { "dropping-particle" : "", "family" : "Benseny-Cases", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klementieva", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotte", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrer", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cladera", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anal Chem", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "12047-12054", "title" : "Microspectroscopy (muFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>19</sup>", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "<sup>19</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19. Notably, in our study we utilized an early-stage animal model, which might have not fully mirrored the changes occurring in advanced AD. Nevertheless, is can support the idea that early-stage AD may alter oxidation level of lipids within the deposits. The relationship between normal aging and expression of Aβ plaques has not yet been fully explained and currently remains the matter of debate ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pneurobio.2012.03.005", "ISBN" : "0301-0082", "ISSN" : "03010082", "PMID" : "22459297", "abstract" : "Since the description by Alois Alzheimer, more than 50 years have passed during which senile dementia and pre-senile dementia have been considered Alzheimer disease (AD) on the basis of their common neuropathological and clinical manifestations. AD now covers pre-senile dementia, senile dementia, mild cognitive impairment and pre-clinical AD, all of them within the context of AD-related pathology. However, there is still a gray area between normal aging with AD-related pathology and AD. Here it is proposed that Alzheimer (or alzheimer) is an age-related neurodegenerative process distinguished from normal aging by the presence of senile plaques and neurofibrillary tangles. Alzheimer affects about 80% of individuals aged 65 years but dementia only occurs in a small percentage of individuals at this age; prevalence of dementia in Alzheimer increases to 25% in individuals aged 80 years. The concepts derived from the ??-amyloid hypothesis support ??-amyloid as a conductor in the pathogenesis of familial AD and as a prodding factor in sporadic AD. Moreover, seeding of ??-amyloid and truncated tau explains incorporation, enhancement and perpetuation of AD-related changes. Therefore, the earliest Alzheimer changes confined to selected regions are the first grounds and the main risk factor for developing dementia. The term Alzheimer embraces this assumption and likens its meaning to other degenerative biological processes, such as atherosclerosis, that may eventually progress to disease. In this context, the first stages of Alzheimer should be considered as primary targets of therapeutic intervention in order to prevent progression to diseased states. ?? 2012 Elsevier Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Ferrer", "given" : "Isidro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Progress in Neurobiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "38-51", "title" : "Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia", "type" : "article", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>67</sup>", "plainTextFormattedCitation" : "67", "previouslyFormattedCitation" : "<sup>68</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }67. It is quite challenging to find one robust explanation on our remark, but it seems possible that aggregated Aβ may promote gliosis and subsequent over-production of different oxidation products with reduced abundance of C=O ester bands at the expense of lipid membranes therefore inducing oxidative stress in neurons ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00204-015-1556-z", "ISSN" : "1432-0738", "PMID" : "26126631", "abstract" : "Alzheimer disease (AD) is a neurodegenerative disease with many known pathological features, yet there is still much debate into the exact cause and mechanisms for progression of this degenerative disorder. The amyloid-beta (A\u03b2)-induced oxidative stress hypothesis postulates that it is the oligomeric A\u03b2 that inserts into membrane systems to initiate much of the oxidative stress observed in brain during the progression of the disease. In order to study the effects of oxidative stress on tissue from patients with AD and amnestic mild cognitive impairment (MCI), we have developed a method called redox proteomics that identifies specific brain proteins found to be selectively oxidized. Here, we discuss experimental findings of oxidatively modified proteins involved in three key cellular processes implicated in the pathogenesis of AD progression: energy metabolism, cell signaling and neurotransmission, as well as the proteasomal degradation pathways and antioxidant response systems. These proteomics studies conducted by our laboratory and others in the field shed light on the molecular changes imposed on the cells of AD and MCI brain, through the deregulated increase in oxidative/nitrosative stress inflicted by A\u03b2 and mitochondrial dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Swomley", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butterfield", "given" : "D Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of toxicology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "page" : "1669-80", "title" : "Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics.", "type" : "article-journal", "volume" : "89" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>68</sup>", "plainTextFormattedCitation" : "68", "previouslyFormattedCitation" : "<sup>69</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }68. In this study, the level of lipid oxidation was found to be around five times lower in the plaques as compared with the surrounding (cf. Fig 9d). This remark draws our attention to the fact that Aβ-driven gliosis at expense oxidation products with reduced abundance of C=O ester bands was recently proposed by Swomley et al. as one of the major mechanisms underlying progression of AD ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00204-015-1556-z", "ISSN" : "1432-0738", "PMID" : "26126631", "abstract" : "Alzheimer disease (AD) is a neurodegenerative disease with many known pathological features, yet there is still much debate into the exact cause and mechanisms for progression of this degenerative disorder. The amyloid-beta (A\u03b2)-induced oxidative stress hypothesis postulates that it is the oligomeric A\u03b2 that inserts into membrane systems to initiate much of the oxidative stress observed in brain during the progression of the disease. In order to study the effects of oxidative stress on tissue from patients with AD and amnestic mild cognitive impairment (MCI), we have developed a method called redox proteomics that identifies specific brain proteins found to be selectively oxidized. Here, we discuss experimental findings of oxidatively modified proteins involved in three key cellular processes implicated in the pathogenesis of AD progression: energy metabolism, cell signaling and neurotransmission, as well as the proteasomal degradation pathways and antioxidant response systems. These proteomics studies conducted by our laboratory and others in the field shed light on the molecular changes imposed on the cells of AD and MCI brain, through the deregulated increase in oxidative/nitrosative stress inflicted by A\u03b2 and mitochondrial dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Swomley", "given" : "Aaron M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butterfield", "given" : "D Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of toxicology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "page" : "1669-80", "title" : "Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics.", "type" : "article-journal", "volume" : "89" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>68</sup>", "plainTextFormattedCitation" : "68", "previouslyFormattedCitation" : "<sup>69</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }68. Interestingly, by analysing the levels of 4‐hydroxy‐nonenal, a major lipid peroxidation product identified in AD brains, McGrath et al. found its plasma displays around 4-5 times lower levels in the control group, suggesting the effect is about one order of magnitude stronger in the affected brains ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/qjmed/94.9.485", "ISSN" : "14602393", "author" : [ { "dropping-particle" : "", "family" : "McGrath", "given" : "L.T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "QJM", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2001", "9", "1" ] ] }, "page" : "485-490", "title" : "Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "<sup>69</sup>", "plainTextFormattedCitation" : "69", "previouslyFormattedCitation" : "<sup>70</sup>" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69.ConclusionsOur proof-of-principle study has demonstrated the usefulness of the presented approach by showing that proteomic related information could be drawn from FTIR-FPA imaging of Aβ plaques at an early-stage of the pathology. The combined approach was found very robust in research towards correlative studies on the interplay between the distance from the deposits and the extent to the molecular burden. Our results, although preliminary, demonstrate the areas affected by plaques display different protein and lipid-processes associated with oxidative stress pathology. Also, our data emphasized the areas adjacent to the deposits may play a critical role in the spread of the pathology.AcknowledgementsThe authors would like to kindly acknowledge J. Brooks, Z. Zhang, J. Doherty and A. Keen for technical assistance during FTIR-FPA measurements, and I. Berrueta Razo and E. Correia Faria-Billinton for access to preliminary data. This work was partly supported by the Polish Ministry of Science and Higher Education and its grants for Scientific Research, and partly by the EU ERASMUS+ funding. The FTIR instrumentation used was partly financed by the Williamson Trust.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1J. G?tz and L. M. Ittner, Nat. Rev. Neurosci., 2008, 9, 532–544.2C. Reitz and R. Mayeux, Biochem. Pharmacol., 2014, 88, 640–651.3H. Braak and E. Braak, Acta Neuropathol., 1991, 82, 239–59.4J. Brettschneider, K. Del Tredici, V. M.-Y. Y. Lee and J. Q. Trojanowski, Nat. Rev. Neurosci., 2015, 16, 109–20.5I. Kuperstein, K. Broersen, I. Benilova, J. Rozenski, W. Jonckheere, M. Debulpaep, A. Vandersteen, I. Segers-Nolten, K. Van Der Werf, V. Subramaniam, D. Braeken, G. Callewaert, C. Bartic, R. D’Hooge, I. C. Martins, F. Rousseau, J. Schymkowitz and B. De Strooper, EMBO J., 2010, 29, 3408–3420.6W. Kim and M. H. Hecht, J. Biol. Chem., 2005, 280, 35069–35076.7M. T. Heneka, M. J. Carson, J. El Khoury, G. E. Landreth, F. Brosseron, D. L. Feinstein, A. H. Jacobs, T. Wyss-Coray, J. Vitorica, R. M. Ransohoff, K. Herrup, S. A. Frautschy, B. Finsen, G. C. Brown, A. Verkhratsky, K. Yamanaka, J. Koistinaho, E. Latz, A. Halle, G. C. Petzold, T. Town, D. Morgan, M. L. Shinohara, V. H. Perry, C. Holmes, N. G. Bazan, D. J. Brooks, S. Hunot, B. Joseph, N. Deigendesch, O. Garaschuk, E. Boddeke, C. A. Dinarello, J. C. Breitner, G. M. Cole, D. T. Golenbock and M. P. Kummer, Lancet Neurol., 2015, 14, 388–405.8D. Allan Butterfield, A. Castegna, C. M. Lauderback and J. Drake, Neurobiol. Aging, 2002, 23, 655–664.9M. Arimon, S. Takeda, K. L. Post, S. Svirsky, B. T. Hyman and O. Berezovska, Neurobiol. Dis., 2015, 84, 109–119.10S. Caine, P. Heraud, M. J. Tobin, D. McNaughton and C. C. A. Bernard, Neuroimage, 2012, 59, 3624–3640.11M. J. Baker, J. Trevisan, P. Bassan, R. Bhargava, H. J. Butler, K. M. Dorling, P. R. Fielden, S. W. Fogarty, N. J. Fullwood, K. a Heys, C. Hughes, P. Lasch, P. L. Martin-Hirsch, B. Obinaju, G. D. Sockalingum, J. Sulé-Suso, R. J. Strong, M. J. Walsh, B. R. Wood, P. Gardner and F. L. Martin, Nat. Protoc., 2014, 9, 1771–91.12L. P. Choo, M. Jackson, W. C. Halliday and H. H. Mantsch, Biochim. Biophys. Acta, 1993, 1182, 333–337.13L. M. Miller, Q. Wang, T. P. Telivala, R. J. Smith, A. Lanzirotti and J. Miklossy, J. Struct. Biol., 2006, 155, 30–37.14D. G. Smith, R. Cappai and K. J. Barnham, Biochim. Biophys. Acta - Biomembr., 2007, 1768, 1976–1990.15M. Rak, M. R. Del Bigio, S. Mai, D. Westaway and K. M. Gough, Biopolymers, 2007, 87, 207–217.16R. Bhargava, Appl. Spectrosc., 2012, 66, 1091–1120.17M. Z. Kastyak-Ibrahim, M. J. Nasse, M. Rak, C. Hirschmugl, M. R. Del Bigio, B. C. Albensi and K. M. Gough, Neuroimage, 2012, 60, 376–383.18C. R. Liao, M. Rak, J. Lund, M. Unger, E. Platt, B. C. Albensi, C. J. Hirschmugl and K. M. Gough, Analyst, 2013, 138, 3991–7.19N. Benseny-Cases, O. Klementieva, M. Cotte, I. Ferrer and J. Cladera, Anal Chem, 2014, 86, 12047–12054.20M. J. Nasse, M. J. Walsh, E. C. Mattson, R. Reininger, A. Kajdacsy-Balla, V. Macias, R. Bhargava and C. J. Hirschmugl, Nat. Methods, 2011, 8, 413–6.21R. K. Reddy, M. J. Walsh, M. V. Schulmerich, P. S. Carney and R. Bhargava, Appl. Spectrosc., 2013, 67, 93–105.22C. R. Findlay, R. Wiens, M. Rak, J. Sedlmair, C. J. Hirschmugl, J. Morrison, C. J. Mundy, M. Kansiz and K. M. Gough, Analyst, 2015, 140, 2493–503.23S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari and F. M. LaFerla, Neuron, 2003, 39, 409–421.24T. van Dijk, D. Mayerich, R. Bhargava and P. S. Carney, Opt. Express, 2013, 21, 12822.25P. Bassan, A. Kohler, H. Martens, J. Lee, H. J. Byrne, P. Dumas, E. Gazi, M. Brown, N. Clarke and P. Gardner, Analyst, 2010, 135, 268–277.26P. Bassan, A. Kohler, H. Martens, J. Lee, E. Jackson, N. Lockyer, P. Dumas, M. Brown, N. Clarke and P. Gardner, J. Biophotonics, 2010, 3, 609–620.27P. Bassan, A. Sachdeva, A. Kohler, C. Hughes, A. Henderson, J. Boyle, J. H. Shanks, M. Brown, N. W. Clarke and P. Gardner, Analyst, 2012, 137, 1370–7.28D. Thain, T. Tannenbaum and M. Livny, Concurr. Comput. Pract. Exp., 2005, 17, 323–356.29S. Van Der Walt, S. C. Colbert and G. Varoquaux, Comput. Sci. Eng., 2011, 13, 22–30.30D. W. Marquardt, J. Soc. Ind. Appl. Math., 1963, 11, 431–441.31K. Levenberg, Q. Appl. Math., 1944, 2, 196–168.32L. M. Miller and P. Dumas, Curr. Opin. Struct. Biol., 2010, 20, 649–656.33J. D. Hunter, Comput. Sci. Eng., 2007, 9, 99–104.34M. Newville, T. Stensitzki, D. B. Allen and A. Ingargiola, Zendo, 2014.35S. van der Walt, J. L. Sch?nberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart and T. Yu, PeerJ, 2014, 2, e453.36A. Naudi, R. Cabre, M. Jove, V. Ayala, H. Gonzalo, M. Portero-Otin, I. Ferrer and R. Pamplona, in International Review of Neurobiology, 2015, vol. 122, pp. 133–189.37C. Hughes, A. Henderson, M. Kansiz, K. M. Dorling, M. Jimenez-Hernandez, M. D. Brown, N. W. Clarke and P. Gardner, Analyst, 2015, 140, 2080–5.38R. Kong, R. K. Reddy and R. Bhargava, Analyst, 2010, 135, 1569.39S. Kumar, T. S. Shabi and E. Goormaghtigh, PLoS One, 2014, 9, e111137.40S. Kumar, C. Desmedt, D. Larsimont, C. Sotiriou and E. Goormaghtigh, Analyst, 2013, 138, 4058.41J. T. Kwak, A. Kajdacsy-Balla, V. Macias, M. Walsh, S. Sinha and R. Bhargava, Sci. Rep., 2015, 5, 8758.42S. G. Torres-Platas, S. Comeau, A. Rachalski, G. Bo, C. Cruceanu, G. Turecki, B. Giros and N. Mechawar, J. Neuroinflammation, 2014, 11, 12.43H. Brooke, B. V. Bronk, J. N. McCutcheon, S. L. Morgan and M. L. Myrick, Appl. Spectrosc., 2009, 63, 1293–1302.44P. Bassan, H. J. Byrne, J. Lee, F. Bonnier, C. Clarke, P. Dumas, E. Gazi, M. D. Brown, N. W. Clarke and P. Gardner, Analyst, 2009, 134, 1171–1175.45M. J. Pilling, P. Bassan and P. Gardner, Analyst, 2015, 140, 2383–92.46B. Mohlenhoff, M. Romeo, M. Diem and B. R. Wood, Biophys. J., 2005, 88, 3635–3640.47R. Lukacs, R. Blümel, B. Zimmerman, M. Ba?c?o?lu and A. Kohler, Analyst, 2015, 140, 3273–3284.48A. Barth and C. Zscherp, Q. Rev. Biophys., 2002, 35, S0033583502003815.49A. D. Surowka, D. Adamek and M. Szczerbowska-Boruchowska, Analyst, 2015, 140, 2428–2438.50E. Goormaghtigh, J.-M. Ruysschaert and V. Raussens, Biophys. J., 2006, 90, 2946–57.51S. Navea, R. Tauler and A. de Juan, Anal. Biochem., 2005, 336, 231–242.52J. A. Hering, P. R. Innocent and P. I. Haris, in Proteomics, 2004, vol. 4, pp. 2310–2319.53M. Severcan, P. I. Haris and F. Severcan, Anal. Biochem., 2004, 332, 238–244.54K. M. Gough, L. Tzadu, M. Z. Kastyak, A. C. Kuzyk and R. L. Julian, Vib. Spectrosc., 2010, 53, 71–76.55K. Wehbe, R. Pineau, S. Eimer, A. Vital, H. Loiseau and G. Déléris, Analyst, 2010, 135, 3052–9.56A. Saeed, G. A. Raouf, S. S. Nafee, S. A. Shaheen and Y. Al-Hadeethi, PLoS One, 2015, 10, e0139854.57M. Baldassarre, C. Li, N. Eremina, E. Goormaghtigh and A. Barth, Molecules, 2015, 20, 12599–12622.58C. Petibois and G. Deleris, Trends Biotechnol., 2006, 24, 455–462.59L. M. Miller, M. W. Bourassa and R. J. Smith, Biochim. Biophys. Acta, 2013, 1828, 2339–46.60R. I. Litvinov, D. A. Faizullin, Y. F. Zuev and J. W. Weisel, Biophys. J., 2012, 103, 1020–1027.61R. Sarroukh, E. Goormaghtigh, J. M. Ruysschaert and V. Raussens, Biochim. Biophys. Acta - Biomembr., 2013, 1828, 2328–2338.62E. Cerf, R. Sarroukh, S. Tamamizu-Kato, L. Breydo, S. Derclaye, Y. F. Dufrêne, V. Narayanaswami, E. Goormaghtigh, J.-M. Ruysschaert and V. Raussens, Biochem. J., 2009, 421, 415–423.63Y. N. Chirgadze and N. A. Nevskaya, Biopolymers, 1976, 15, 627–636.64A. Accardo, V. Shalabaeva, M. Cotte, M. Burghammer, R. Krahne, C. Riekel and S. Dante, Langmuir, 2014, 30, 3191–3198.65A. Kuhla, S. C. Ludwig, B. Kuhla, G. Münch and B. Vollmar, Neurobiol. Aging, 2015, 36, 753–761.66H. Esterbauer and P. Ramos, Rev. Physiol. Biochem. Pharmacol., 1996, 127, 31–64.67I. Ferrer, Prog. Neurobiol., 2012, 97, 38–51.68A. M. Swomley and D. A. Butterfield, Arch. Toxicol., 2015, 89, 1669–80.69L. T. McGrath, QJM, 2001, 94, 485–490.Fig.1. (a) Large tissue area microscopic image; (b) microscopic image of the optically dense dark cortex deposit; (c) the distribution of the absorbance at 1660 cm-1 (amide I); (d) the distribution of the absorbance at 2960 cm-1 (CH str); (e) low resolution (5.5 μm) amide I imaging of the deposit; (f) high magnification (1.1 μm) amide I imaging of the deposit.Fig 2. The results of the scattering correction: a) FTIR spectra taken from the deposit before and after correction; the maps showing the distribution of the absorbance at 2500 cm-1: b) before and c) after correction; d) the distribution of the heights at 2500 cm-1 before and after correction.Fig 3. The optimization of the fitting procedure: a) the second order derivative FTIR spectrum to determine the peaks’ positions; b) the optimization of the FWHM for all the peaks included; c) the optimization of the Lorentzian fraction.Fig 4. The curve fitting of a single: a) neuropil point b) plaque point.Fig 5. The results of the curve fitting for one selected plaque: a) the microscopic picture of the plaque, b) the fraction of alpha-helices, c) the fraction of β-sheets, d) the fraction of random coils, e) the fraction of β-turns.Fig 6. The image processing procedure to determine the consecutive layers around Aβ plaques.Fig. 7. The percentage contents of protein secondary components within and in close proximity of the plaques for: a) β-sheets and α-helices; b) β-turns and random coils.Fig 8. PCA analysis of the protein composition of AB plaques: a) the projection of the data onto PCA1 vs. PC2; b) the corresponding loadings plot.Fig 9. The relation between β/α ratios and: a) the area of the νas(-PO42-) band; b) lipid to protein ratio; c) level of lipid unsaturation; d) level of lipid oxidation. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related download
Related searches
- the university of scranton address
- the university of hong kong
- wharton school of the university of pennsylvania
- the university of scranton tuition
- the university of scranton
- the university of hk
- the university of scranton jobs
- the university of north texas
- the university of philosophical research
- the university of scranton players
- the university of scranton calendar
- the university of chicago jobs