Umbilical Cord Blood and Cord Tissue Bank as a Source for Allogeneic Use

Recently, umbilical cord blood (CB) has received attention as the allogeneic optimum source for immunotherapies. More recently, the umbilical cord (UC) has been rapidly utilized as an abundant source of mesenchymal stromal cells (MSCs), which migrate toward the inflammatory and damaged tissue to subside the inflammation and support tissue repair. Both CB and UC can be provided “off-the-shelf” cell products for immunotherapies and regenerative medicine. As biomedical wastes, CB and UC can be obtained noninvasively without any risks to the donor. CB cells and UC-derived MSCs (UC-MSCs) also have higher proliferation potentials than other cells obtained from adult tissues. In addition, UC-MSCs are less immunogenic and have significant immunosuppressive ability. Several clinical trials with CB or UC-MSCs have been conducted based on these advantages. The establishment of a stable supply system of CB and UC-MSCs is critical now for their utilization in regenerative and immune cell therapies. We have thus established the cord blood/cord bank, “IMSUT CORD,” as a new type of biobank, to supply both frozen CB and UC tissues and derived cells for research and clinical uses. In this chapter, we will introduce the overall flow from collection to shipment and discuss several issues that need to be resolved in unrelated allogeneic stable supply system

Genomic and epigenomic mapping of leptin-responsive neuronal populations involved in body weight regulation.

Genome wide association studies (GWAS) in obesity have identified a large number of noncoding loci located near genes expressed in the central nervous system. However, due to the difficulties in isolating and characterizing specific neuronal subpopulations, few obesity-associated SNPs have been functionally characterized. Leptin responsive neurons in the hypothalamus are essential in controlling energy homeostasis and body weight. Here, we combine FACS-sorting of leptin-responsive hypothalamic neuron nuclei with genomic and epigenomic approaches (RNA-seq, ChIP-seq, ATAC-seq) to generate a comprehensive map of leptin-response specific regulatory elements, several of which overlap obesity-associated GWAS variants. We demonstrate the usefulness of our leptin-response neuron regulome, by functionally characterizing a novel enhancer near Socs3, a leptin response-associated transcription factor. We envision our data to serve as a useful resource and a blueprint for functionally characterizing obesity-associated SNPs in the hypothalamus

前哨 大阪毎日新聞社長 本山彦一

2018年度・2019年度関西大学創立130周年記念特別研究費（なにわ大阪研究）研究成果報告

Integration of multiple epigenomic marks improves prediction of variant impact in saturation mutagenesis reporter assay

The integrative analysis of highâ throughput reporter assays, machine learning, and profiles of epigenomic chromatin state in a broad array of cells and tissues has the potential to significantly improve our understanding of noncoding regulatory element function and its contribution to human disease. Here, we report results from the CAGI 5 regulation saturation challenge where participants were asked to predict the impact of nucleotide substitution at every base pair within five diseaseâ associated human enhancers and nine diseaseâ associated promoters. A library of mutations covering all bases was generated by saturation mutagenesis and altered activity was assessed in a massively parallel reporter assay (MPRA) in relevant cell lines. Reporter expression was measured relative to plasmid DNA to determine the impact of variants. The challenge was to predict the functional effects of variants on reporter expression. Comparative analysis of the full range of submitted prediction results identifies the most successful models of transcription factor binding sites, machine learning algorithms, and ways to choose among or incorporate diverse datatypes and cellâ types for training computational models. These results have the potential to improve the design of future studies on more diverse sets of regulatory elements and aid the interpretation of diseaseâ associated genetic variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151884/1/humu23797_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151884/2/humu23797.pd

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Apical Transport of Influenza A Virus Ribonucleoprotein Requires Rab11-positive Recycling Endosome

Influenza A virus RNA genome exists as eight-segmented ribonucleoprotein complexes containing viral RNA polymerase and nucleoprotein (vRNPs). Packaging of vRNPs and virus budding take place at the apical plasma membrane (APM). However, little is known about the molecular mechanisms of apical transport of newly synthesized vRNP. Transfection of fluorescent-labeled antibody and subsequent live cell imaging revealed that punctate vRNP signals moved along microtubules rapidly but intermittently in both directions, suggestive of vesicle trafficking. Using a series of Rab family protein, we demonstrated that progeny vRNP localized to recycling endosome (RE) in an active/GTP-bound Rab11-dependent manner. The vRNP interacted with Rab11 through viral RNA polymerase. The localization of vRNP to RE and subsequent accumulation to the APM were impaired by overexpression of Rab binding domains (RBD) of Rab11 family interacting proteins (Rab11-FIPs). Similarly, no APM accumulation was observed by overexpression of class II Rab11-FIP mutants lacking RBD. These results suggest that the progeny vRNP makes use of Rab11-dependent RE machinery for APM trafficking

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores

Magnetic Fields toward Ophiuchus-B Derived from SCUBA-2 Polarization Measurements

We present the results of dust emission polarization measurements of Ophiuchus-B (Oph-B) carried out using the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) camera with its associated polarimeter (POL-2) on the James Clerk Maxwell Telescope in Hawaii. This work is part of the B-fields in Star-forming Region Observations survey initiated to understand the role of magnetic fields in star formation for nearby star-forming molecular clouds. We present a first look at the geometry and strength of magnetic fields in Oph-B. The field geometry is traced over ~0.2 pc, with clear detection of both of the sub-clumps of Oph-B. The field pattern appears significantly disordered in sub-clump Oph-B1. The field geometry in Oph-B2 is more ordered, with a tendency to be along the major axis of the clump, parallel to the filamentary structure within which it lies. The degree of polarization decreases systematically toward the dense core material in the two sub-clumps. The field lines in the lower density material along the periphery are smoothly joined to the large-scale magnetic fields probed by NIR polarization observations. We estimated a magnetic field strength of 630 ± 410 μG in the Oph-B2 sub-clump using a Davis–Chandrasekhar–Fermi analysis. With this magnetic field strength, we find a mass-to-flux ratio λ = 1.6 ± 1.1, which suggests that the Oph-B2 clump is slightly magnetically supercritical