Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo

For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13high cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Development of Intensity Modulated Extraction System in HIMAC Synchrotron

At HIMAC Synchrotron, we have developed a dynamic intensity control system toward spot scanning irradiation. In this system, the spill structure is controlled dynamically by controlling the amplitude modulation of the RF-knockout. In this paper, generation of amplitude modulation waveform for intensity control, the system for controlling amplitude modulation and experimental result are described.第2回日本加速器学会年

A versatile control system for irradiation and measurement for secondary beam experiments in a heavy ion accelerator, HIMAC

For spot-scanning irradiation, we have developed a new control system in the experiments involving secondary beams of short half-lives. Fast beam switching and spot-by-spot dose monitoring were incorporated into this system. The control system can interface with various instruments, perform sequencing of measurements, control the motion of instruments and data acquisition. Synchronized communications with the period of beam spills in the LAN are introduced in the system to avoid the conflicts among computer communications. As an example of measurement, the results of dose distribution in 3D spot-scanning irradiation are presented.8th European Conference on Accelerators in Applied Research and Technolog

Dynamic intensity control system with RF-knockout slow-extraction in the HIMAC synchrotron

We have developed a dynamic beam intensity control system intended for use in three-dimensional pencil-beam scanning irradiation. In this system, which controls the spill structure and intensities of the beams extracted from the synchrotron, the amplitude of the RF-knockout is controlled using a 10 kHz response. Its amplitude modulation function is generated based on an analytical onedimensional model of the RF-knockout slow-extraction. Using feedback control of the proportional and integral controls, this system allows us to control the beam current dynamically in response to the request, as was experimentally verified in the HIMAC synchrotron. In this paper, we describe the system for controlling the amplitude modulation through the inclusion of feedback, and we provide some experimental results

DEVELOPMENT OF NTENSITY MODULATED EXTRACTION SYSTEM IN HIMAC SYNCHROTRON

At HIMAC Synchrotron,we have developed a dynamic intensity control system toward spot scanning irradiation.in this system,the spil structure is controlled dynamic ally by controlling the amplitude modulation of the RF-knockout.In this paper,generation of amplitude modulation waveform intensity control,the system for controlling amplitude modulation and experimental result are described