494 results found
Xavier GDS, Bellomo EA, McGinty JA, et al., 2013, Animal Models of GWAS-Identified Type 2 Diabetes Genes, Journal of Diabetes Research, Vol: 2013, ISSN: 2314-6753
More than 65 loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notably TCF7L2 and ZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.
Myatt SS, Kongsema M, Man CW-Y, et al., 2013, SUMOylation inhibits FOXM1 activity and delays mitotic transition, Oncogene, Vol: 33, Pages: 4316-4329, ISSN: 1476-5594
The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response.
Kelly DJ, Alibhai D, Warren S, et al., 2013, An automated flim multiwell plate reader for high content analysis
We report an automated fluorescence lifetime imaging multiwell plate reader for high content analysis, capable of subcellular mapping of protein interactions. This instrument can acquire FLIM data from 96 wells in less than 15 minutes.©2013 The Optical Society (OSA).
Warren S, Kimberley C, Margineanu A, et al., 2013, Flim-fret of cell signalling in chemotaxis
We demonstrate the application of Fluorescence Lifetime Imaging (FLIM) to read out Förster resonant energy transfer (FRET) based biosensors for studying the spatio-temporal dynamics of signalling pathways in cells undergoing chemotaxis. ©2013 The Optical Society (OSA).
Coda S, Kelly DJ, Lagarto JL, et al., 2013, Autofluorescence lifetime imaging and metrology for medical research and clinical diagnosis
We report the development of instrumentation to utilise autofluorescence lifetime for the study and diagnosis of disease including cancer and osteoarthritis. ©2013 The Optical Society (OSA).
Roper JC, Yerolatsitis S, Birks TA, et al., 2013, Minimising group index variations in a multicore endoscope fibre
We describe a multicore endoscope fibre with minimised group index variation between cores that is obtained at a V parameter of 3. Tapering the fibre input enables us to achieve single-mode propagation. © OSA 2013.
Nickdel MB, Lagarto JL, Kelly DJ, et al., 2013, Detection of cartilage matrix degradation by autofluorescence lifetime, Spring Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL, Pages: A12-A13, ISSN: 0959-9673
Xavier GDS, Mondragon A, Mitchell R, et al., 2013, Defective glucose homeostasis in mice inactivated selectively for Tcf7l2 in the adult beta cell with an Ins1-controlled Cre, 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S142-S142, ISSN: 0012-186X
Warren SC, Margineanu A, Alibhai D, et al., 2013, Rapid Global Fitting of Large Fluorescence Lifetime Imaging Microscopy Datasets, PLOS ONE, Vol: 8, ISSN: 1932-6203
Seidenari S, Arginelli F, Dunsby C, et al., 2013, Multiphoton Laser Tomography and Fluorescence Lifetime Imaging of Melanoma: Morphologic Features and Quantitative Data for Sensitive and Specific Non-Invasive Diagnostics, PLOS ONE, Vol: 8, ISSN: 1932-6203
Arginelli F, Manfredini M, Bassoli S, et al., 2013, High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: 194-204, ISSN: 0909-752X
Alibhai D, Kelly DJ, Warren S, et al., 2013, Automated fluorescence lifetime imaging plate reader and its application to Forster resonant energy transfer readout of Gag protein aggregation, Journal of Biophotonics, Vol: 6, Pages: 398-408, ISSN: 1864-0648
Fluorescence lifetime measurements can provide quantitativereadouts of local fluorophore environment andcan be applied to biomolecular interactions via Fo¨ rsterresonant energy transfer (FRET). Fluorescence lifetimeimaging (FLIM) can therefore provide a high contentanalysis (HCA) modality to map protein-protein interactions(PPIs) with applications in drug discovery, systemsbiology and basic research. We present here an automatedmultiwell plate reader able to perform rapid unsupervisedoptically sectioned FLIM of fixed and livebiological samples and illustrate its potential to assayPPIs through application to Gag protein aggregationduring the HIV life cycle. We demonstrate both heteroFRETand homo-FRET readouts of protein aggregationand report the first quantitative evaluation of a FLIMHCA assay by generating dose response curves throughaddition of an inhibitor of Gag myristoylation. Z0 factorsexceeding 0.6 are realised for this FLIM FRET assay.Fluorescence lifetime plate map with representativeimages of high and low FRET cells and correspondingdose response plot.
Chen L, Andrews N, Kumar S, et al., 2013, Simultaneous angular multiplexing optical projection tomography at shifted focal planes, OPTICS LETTERS, Vol: 38, Pages: 851-853, ISSN: 0146-9592
Manfredini M, Arginelli F, Dunsby C, et al., 2013, High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: E433-E443, ISSN: 0909-752X
Manning HB, Nickdel MB, Yamamoto K, et al., 2013, Detection of cartilage matrix degradation by autofluorescence lifetime, MATRIX BIOLOGY, Vol: 32, Pages: 32-38, ISSN: 0945-053X
Roper JC, Yerolatsitis S, Birks TA, et al., 2013, Minimising group index variations in a multicore endoscope fibre, Conference on Lasers and Electro-Optics (CLEO), Publisher: IEEE, ISSN: 2160-9020
Martins M, Warren S, Kimberley C, et al., 2012, Activity of PLC epsilon contributes to chemotaxis of fibroblasts towards PDGF, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 5758-5769, ISSN: 0021-9533
Chen L, McGinty J, Taylor HB, et al., 2012, Improved OPT reconstructions based on the MTF and extension to FLIM-OPT
We demonstrate the improved reconstruction of OPT datasets by incorporating the measured MTF in the reconstruction process. We also extend OPT to FLIM-OPT and demonstrate its use for imaging live zebrafish embryos displaying autofluorescence. © 2012 OSA.
Laine R, Stuckey DW, Manning H, et al., 2012, Fluorescence Lifetime Readouts of Troponin-C-Based Calcium FRET Sensors: A Quantitative Comparison of CFP and mTFP1 as Donor Fluorophores, PLOS ONE, Vol: 7, ISSN: 1932-6203
Seidenari S, Arginelli F, Dunsby C, et al., 2012, Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics, EXPERIMENTAL DERMATOLOGY, Vol: 21, Pages: 831-836, ISSN: 0906-6705
Xavier GDS, Mondragon A, Sun G, et al., 2012, Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice, DIABETOLOGIA, Vol: 55, Pages: 2667-2676, ISSN: 0012-186X
Patalay R, Talbot C, Alexandrov Y, et al., 2012, Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas, PLOS One, Vol: 7, ISSN: 1932-6203
We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm2 is also presented, demonstrating the potential for tumour margin delineation.Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425–515 nm spectral emission) to 39.8% (620–655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83.We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice.
Brown AC, Oddos S, Dobbie IM, et al., 2012, Correction: Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy., PLoS Biol, Vol: 10
[This corrects the article on p. e1001152 in vol. 9.].
Patalay R, Chu A, Dunsby C, et al., 2012, A noninvasive imaging study of skin using two photon microscopy of cellular autofluorescence, 70th Annual Meeting of the American-Academy-of-Dermatology (AAD), Publisher: MOSBY-ELSEVIER, Pages: AB83-AB83, ISSN: 0190-9622
Chen L, McGinty J, Taylor HB, et al., 2012, Incorporation of an experimentally determined MTF for spatial frequency filtering and deconvolution during optical projection tomography reconstruction, OPTICS EXPRESS, Vol: 20, Pages: 7323-7337, ISSN: 1094-4087
Thompson AJ, Coda S, Sorensen MB, et al., 2012, In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 240-254, ISSN: 1864-063X
Sardini A, Stuckey DW, McGinty J, et al., 2012, In Vivo Investigation of Calpain Activity by Lifetime Imaging of Genetically Encoded FRET Sensors, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 159A-159A, ISSN: 0006-3495
Esseling M, Kemper B, Antkowiak M, et al., 2012, Multimodal biophotonic workstation for live cell analysis, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 9-13, ISSN: 1864-063X
Antkowiak M, Torres-Mapa ML, McGinty J, et al., 2012, Towards gene therapy based on femtosecond optical transfection, BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE III, Vol: 8427, ISSN: 0277-786X
Seidenari S, Arginelli F, Bassoli S, et al., 2012, Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin., Dermatol Res Pract, Vol: 2012
Multiphoton laser microscopy is a new, non-invasive technique providing access to the skin at a cellular and subcellular level, which is based both on autofluorescence and fluorescence lifetime imaging. Whereas the former considers fluorescence intensity emitted by epidermal and dermal fluorophores and by the extra-cellular matrix, fluorescence lifetime imaging (FLIM), is generated by the fluorescence decay rate. This innovative technique can be applied to the study of living skin, cell cultures and ex vivo samples. Although still limited to the clinical research field, the development of multiphoton laser microscopy is thought to become suitable for a practical application in the next few years: in this paper, we performed an accurate review of the studies published so far, considering the possible fields of application of this imaging method and providing high quality images acquired in the Department of Dermatology of the University of Modena.
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