382 research outputs found

    Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5

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    Meningiomas are a diverse group of tumors with a broad spectrum of histologic features. There are over 12 variants of meningioma, whose genetic features are just beginning to be described. Angiomatous meningioma is a World Health Organization (WHO) meningioma variant with a predominance of blood vessels. They are uncommon and confirming the histopathologic classification can be challenging. Given a lack of biomarkers that define the angiomatous subtype and limited understanding of the genetic changes underlying its tumorigenesis, we compared the genomic characteristics of angiomatous meningioma to more common meningioma subtypes. While typical grade I meningiomas demonstrate monosomy of chromosome 22 or lack copy number aberrations, 13 of 14 cases of angiomatous meningioma demonstrated a distinct copy number profile – polysomies of at least one chromosome, but often of many, especially in chromosomes 5, 13, and 20. WHO grade II atypical meningiomas with angiomatous features have both polysomies and genetic aberrations characteristic of other atypical meningiomas. Sequencing of over 560 cancer-relevant genes in 16 cases of angiomatous meningioma showed that these tumors lack common mutations found in other variants of meningioma. Our study demonstrates that angiomatous meningiomas have distinct genomic features that may be clinically useful for their diagnosis

    Integrated top-down and bottom-up mass spectrometry characterization of Escherichia coli ribosomal protein heterogeneity: identification of protein isoforms and post-translational modifications

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    The bacterial genome exhibits notable plasticity but is relatively static when compared to the proteome. Protein expression can vary significantly depending on environmental factors, growth stage or stochastic processes within cells. This highly variable character, coupled with the large dynamic range of protein expression levels and the complexity achieved through processes such as post-translational modification (PTM), necessitate accurate, sensitive and high-throughput methods of analysis. The primary aim of this research was to develop an integrated experimental and analysis workflow that combines the analytical power of top-down and bottom-up mass spectrometry towards protein isoform and PTM characterization. We apply this approach to a comprehensive characterization of Escherichia coli ribosomal protein isoform heterogeneity. Our findings uncovered a significant level of heterogeneity in the post-translational modification of a number of ribosomal proteins, revealing a possible mechanism for the regulation of ribosomal protein function both within and beyond the ribosome

    Customer engagement in tourism and hospitality research

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    Customer engagement (CE), defined as a customer's resource investment in his/her brand or firm interactions, has evolved into an important tourism and hospitality marketing metric in the last decade. However, despite existing insight in this area, dynamic CE remains in flux, requiring further investigation. In this chapter, we discuss CE's key theoretical foundation/underpinnings, perspectives, operationalization(s)/measurement, antecedents, consequences, mediators, moderators, approaches and methods, thus offering a foundation upon which the remainder of this book is built.info:eu-repo/semantics/acceptedVersio

    MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME)

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    Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function

    Modulation of delayed fluorescence pathways via rational molecular engineering

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    One of the key challenges in developing efficient organic light-emitting diodes (OLEDs) is overcoming the loss channel of triplet excitons. A common approach to mitigate these losses to enhance the external quantum efficiency of OLEDs is employing emitter molecules optimized for thermally activated delayed fluorescence (TADF) or triplet-triplet annihilation (TTA). However, achieving both in the solid state from the same organic chromophore poses a formidable challenge due to energetic and structural requirements needing to be met simultaneously. Here, we demonstrate TADF and TTA in donor-acceptor phthalimide derivatives by employing triphenylamine (TPA) or phenyl carbazole (PhCz) as a donor. Thin films of the TPA-substituted phthalimides doped in the poly(methyl methacrylate) matrix exhibit TADF emission from the singlet charge-transfer (CT) state. On the contrary, PhCz-substituted emitters display dominant TTA-induced delayed fluorescence in the neat film due to long-range molecular ordering that facilitates efficient triplet diffusion. The present study provides insight into how dual TADF-TTA delayed fluorescence can be realized in thin films of molecular semiconductors via rational molecular design

    Characterisation of dust emissions from machined engineered stones to understand the hazard for accelerated silicosis

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    Engineered stones are novel construction materials associated with a recent upsurge in silicosis cases among workers in the stonemason industry. In order to understand the hazard for the short latency of lung disease among stonemasons, we simulated real-time dust exposure scenario by dry-machining engineered stones in controlled conditions, capturing and analysing the respirable dust generated for physical and chemical characteristics. Natural granite and marble were included for comparison. Cutting engineered stones generated high concentrations of very fine particles ( 80% respirable crystalline silica content, in the form of quartz and cristobalite. Engineered stones also contained 8–20% resin and 1–8% by weight metal elements. In comparison, natural stones had far lower respirable crystalline silica (4- 30%) and much higher metal content, 29–37%. Natural stone dust emissions also had a smaller surface area than engineered stone, as well as lower surface charge. This study highlighted the physical and chemical variability within engineered stone types as well as between engineered and natural stones. This information will ultimately help understand the unique hazard posed by engineered stone fabrication work and help guide the development of specific engineering control measures targeting lower exposure to respirable crystalline silica.Chandnee Ramkissoon, Sharyn Gaskin, Leigh Thredgold, Tony Hall, Shelley Rowett, Richard Gu
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