The molecular epidemiology and characteristics of methicillin resistant Staphylococcus aureus sequence type 22 in a local, national and international context.

The globally distributed, ciprofloxacin resistant hospital associated methicillin resistant Staphylococcus aureus (MRSA) lineage epidemic (E)MRSA-15 (sequence type 22) continues to expand into new healthcare systems around the world. To further understand the evolution of EMRSA-15, which has been proposed to have emerged in the West Midlands, a large collection of contemporaneous and historical Birmingham isolates were studied alongside a collection of International genomes. Through generation of phylogentic trees this study has been able to determine that EMRSA-15 emerged in c1984 and that during this time a highly related healthcare associated ciprofloxacin sensitive ST22 population was present in Birmingham. A dominant, geographically restricted EMRSA-15 clone was also identified in Birmingham (designated the BHM clone). Analysis of the impact of fluoroquinolone use on the Birmingham EMRSA-15 phylogeny showed increasing use of fluoroquinolones (the introduction of ofloxacin) coincided with the emergence of the BHM clone. Further evidence of geographically restricted EMRSA-15 clones were found in Guernsey and Hong Kong; demonstrating localized evolution giving rise to distinct island populations. Comparison of the desiccation tolerance of geographically restricted and non-restricted EMRSA-15 clones indicated enhanced environmental survival as a possible reason for the spread and dominance of the restricted lineages

Optimisation of ultrafast laser assisted etching in fused silica

Observations of runout distances combined with velocity measurements suggest that “major” dry-mixed avalanches show a scale invariance to the total drop height HSC. This is in accordance to the proposed upper-limit envelope of the maximum velocity by McClung and Schaerer (2006). The observations are also supported by a simple scaling analysis using a simple mass block model on cycloidal and parabolic tracks (Gauer, 2018b), concluding Umax~ gHSC/2 . In this supplementary paper, a simple mass block model is presented that includes basic observations of major dry-mixed avalanches, such as mass entrainment and deposition, and that reflects this scale invariance. Almost all model parameters can principally be observed in the field. Model results are compared with a series of avalanche observations of runout and velocity and match well, considering that the model is a first order approximation

Pro-inflammatory role of monocyte-derived CX3CR1int macrophages in Helicobacter hepaticus-induced colitis

Cells of the monocyte-macrophage lineage play important roles in the pathogenesis of inflammatory bowel diseases, but they are also present in the normal healthy intestine, where they are critical for maintaining homeostasis. It has been unclear whether the pro-inflammatory roles of intestinal macrophages reflect altered behaviour of the existing resident cells, or if they involve recruitment of a distinct cell type. Here we have explored these ideas using the model of colitis induced by Helicobacter hepaticus (Hh) in the context of neutralisation or deletion of interleukin 10 (IL-10). Granulocytes and monocytes made up most of the inflammatory myeloid infiltrates found in the colon of Hh-infected colitic mice, rising to a peak within 2 weeks of Hh inoculation, but taking several months to resolve completely. The inflammatory response was dependent on the combined presence of Hh and absence of IL-10, and was accompanied by increased production of inflammatory mediators such as IL-1β, TNFα, IL-6 and IL-23p19 by infiltrating myeloid cells, mostly relatively immature cells of the macrophage lineage that express intermediate levels of CX3CR1. In contrast, the population of mature CX3CR1hi macrophages did not expand as markedly during colitis, and these cells made little contribution to inflammatory mediator production. Taking into account their numerical dominance in the myeloid compartment, we conclude that newly recruited monocytes are the main source of pro-inflammatory mediators in colitis induced in the absence of IL-10 signalling, and that altered behaviour of mature macrophages is not a major component of this pathology

A Miniature Fibre-Optic Raman Probe Fabricated by Ultrafast Laser-Assisted Etching

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope

SIGMA: A System for Integrative Genomic Microarray Analysis of Cancer Genomes

BACKGROUND: The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. RESULTS: We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. CONCLUSION: In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA) of cancer genomes, can be accessed at

Multi-core fibre-fed integral field spectrograph (MCIFU) IV:The fiber link

The Multi-Core Integral-Field Unit (MCIFU) is a diffraction-limited near-infrared integral-field spectrograph designed to detect and characterise exoplanets and disks in combination with extreme adaptive optics (xAO) instruments. It has been developed by an extended consortium as an experimental path finder for medium resolution spectroscopic upgrades for xAO systems. To allow it to achieve its goals we manufactured a fibre link system composed of a custom integrated fiber, with 3D printed microlenses and an ultrafast laser inscribed reformatter. Here we detail the specific requirements of the fibre link, from its design parameters, through its manufacture the laboratory performance and discuss upgrades for the future. © 2020 SPIE.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.This research was funded by the Prostate Cancer Research Centre charity (registered UK charity no. 1156027), Grant Number AA1. A small financial contribution was also made through intra-mural funds from the Royal Veterinary College.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.016110

願書留（正月より十二月まで、名主上野新右衛門外）

Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate cancer exist. Using an unbiased, quantitative approach, this study evaluates the potential of three proteins of the 40S ribosomal protein complex as putative biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi-automated Ox-DAB signal quantification using ImageJ software revealed a significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non-malignant tissue (p<0.0001). Receiver operating characteristics curves were calculated to evaluate the potential of each protein as a biomarker of malignancy in prostate cancer. Positive likelihood ratios for RPS19, RPS21 and RPS24 were calculated as 2.99, 4.21, and 2.56 respectively, indicating that the overexpression of the protein is correlated with the presence of disease. Triple-labelled, quantitative, immunofluorescence (with RPS19, RPS21 and RPS24) showed significant changes (p<0.01) in the global intersection coefficient, a measure of how often two fluorophore signals intersect, for RPS19 and RPS24 only. No change was observed in the co-localization of any other permutations of the three proteins. Our results show that RPS19, RPS21 or RPS24 are upregulated in malignant tissue and may serve as putative biomarkers for prostate cancer