Hierarchical Cluster and Region of Interest Analyses Based on Mass Spectrometry Imaging of Human Brain Tumours

Imaging mass spectrometry (IMS) has been rarely used to examine specimens of human brain tumours. In the current study, high quality brain tumour samples were selected by tissue observation. Further, IMS analysis was combined with a new hierarchical cluster analysis (IMS-HCA) and region of interest analysis (IMS-ROI). IMS-HCA was successful in creating groups consisting of similar signal distribution images of glial fibrillary acidic protein (GFAP) and related multiple proteins in primary brain tumours. This clustering data suggested the relation of GFAP and these identified proteins in the brain tumorigenesis. Also, high levels of histone proteins, haemoglobin subunit α, tubulins, and GFAP were identified in a metastatic brain tumour using IMS-ROI. Our results show that IMS-HCA and IMS-ROI are promising techniques for identifying biomarkers using brain tumour samples

Time-Dependent Interaction between Differentiated Embryo Chondrocyte-2 and CCAAT/Enhancer-Binding Protein ␣ Underlies the Circadian Expression of CYP2D6 in Serum- Shocked HepG2 Cells

ABSTRACT Differentiated embryo chondrocyte-2 (DEC2), also known as bHLHE41 or Sharp1, is a pleiotropic transcription repressor that controls the expression of genes involved in cellular differentiation, hypoxia responses, apoptosis, and circadian rhythm regulation. Although a previous study demonstrated that DEC2 participates in the circadian control of hepatic metabolism by regulating the expression of cytochrome P450, the molecular mechanism is not fully understood. We reported previously that brief exposure of HepG2 cells to 50% serum resulted in 24-h oscillation in the expression of CYP3A4 as well as circadian clock genes. In this study, we found that the expression of CYP2D6, a major drug-metabolizing enzyme in humans, also exhibited a significant oscillation in serum-shocked HepG2 cells. DEC2 interacted with CCAAT/enhancer-binding protein (C/EBP␣), accompanied by formation of a complex with histone deacetylase-1, which suppressed the transcriptional activity of C/EBP␣ to induce the expression of CYP2D6. The oscillation in the protein levels of DEC2 in serum-shocked HepG2 cells was nearly antiphase to that in the mRNA levels of CYP2D6. Transfection of cells with small interfering RNA against DEC2 decreased the amplitude of CYP2D6 mRNA oscillation in serumshocked cells. These results suggest that DEC2 periodically represses the promoter activity of CYP2D6, resulting in its circadian expression in serum-shocked cells. DEC2 seems to constitute a molecular link through which output components from the circadian clock are associated with the time-dependent expression of hepatic drug-metabolizing enzyme

1/2, 1/4 and 1/8 BPS Equations in SUSY Yang-Mills-Higgs Systems -- Field Theoretical Brane Configurations --

We systematically classify 1/2, 1/4 and 1/8 BPS equations in SUSY gauge theories in d=6, 5, 4, 3 and 2 with eight supercharges, with gauge groups and matter contents being arbitrary. Instantons (strings) and vortices (3-branes) are only allowed 1/2 BPS solitons in d=6 with N=1 SUSY. We find two 1/4 BPS equations and the unique 1/8 BPS equation in d=6 by considering configurations made of these field theory branes. All known BPS equations are rederived while several new 1/4 and 1/8 BPS equations are found in dimension less than six by dimensional reductions.Comment: 41 pages, no figures, v2: 49 pages, no figures, typos corrected, references added, the final version in NP

Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials : Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice

Use of fine-grained shredder dust as a cement admixture after a melting, rapid-cooling and pulverizing process

Shredder dust is a residue, which is removed from valuable ferrous metals found in scrap automobile and electronic waste. It is also an industrial waste byproduct which, under legislation in place since April 1996, must be disposed of in landfill sites. One method of disposing shredder dust is by scorification, however, this is a costly process and therefore impractical. Costs could be reduced if the shredder dust had a valuable use, and, in this paper, the authors examine its effectiveness as a cement admixture. First, molten shredder dust was crushed for use as a cement admixture. However, it was difficult to crush it completely because metallic grains were mixed in with molten shredder dust. These particles were removed by sifting and the molten shredder dust was crushed once again. Eventually, a fine 75 [mu]m and less powder type of slag was obtained. This slag was mixed with Ordinary Portland Cement (OPC) to form a cement mortar and subsequently a mortar test was conducted. From the test results, it was found that the long-term strength of the cement did not deteriorate even when it included 30% by weight of the pulverized molten shredder dust.Shredder dust Quenched granulated slag Evaluation test Crush Cement admixture

Hierarchical Cluster and Region of Interest Analyses Based on Mass Spectrometry Imaging of Human Brain Tumours

Imaging mass spectrometry (IMS) has been rarely used to examine specimens of human brain tumours. In the current study, high quality brain tumour samples were selected by tissue observation. Further, IMS analysis was combined with a new hierarchical cluster analysis (IMS-HCA) and region of interest analysis (IMS-ROI). IMS-HCA was successful in creating groups consisting of similar signal distribution images of glial fibrillary acidic protein (GFAP) and related multiple proteins in primary brain tumours. This clustering data suggested the relation of GFAP and these identified proteins in the brain tumorigenesis. Also, high levels of histone proteins, haemoglobin subunit α, tubulins, and GFAP were identified in a metastatic brain tumour using IMS-ROI. Our results show that IMS-HCA and IMS-ROI are promising techniques for identifying biomarkers using brain tumour samples

Region of Interest analysis using mass spectrometry imaging of mitochondrial and sarcomeric proteins in acute cardiac infarction tissue

Matrix-assisted laser desorption ionization image mass spectrometry (MALDI-IMS) has been developed for the identification of peptides in various tissues. The MALDI-IMS signal distribution patterns and quantification of the signal intensities of the regions of interest (ROI) with healthy regions were compared for identification of the disease specific biomarkers. We performed a new ROI analysis using the conventional t-test and data number independent Cohen’s d-value analysis. Using these techniques, we analysed heart tissues after acute myocardial infarction (AMI). As a result, IMS signals of mitochondrial adenosine triphosphate synthase alpha subunit (ATP5A), myosin-6/7(MYH6/7), aortic actin, and the myosin light chain 3 (MYL3) were identified in the infarcted region. In particular, the signals of MYH7 are significantly greater in the infarcted region using ROI analysis. ROI analysis using MALDI-IMS may be a promising technique for the identification of biomarkers for pathological studies that involve the comparison of diseased and control areas