Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection.

A B S T R A C T rIPC (remote ischaemic preconditioning) is a phenomenon whereby short periods of ischaemia and reperfusion of a tissue or organ (e.g. mesentery, kidney) can protect a distant tissue or organ (e.g. heart) against subsequent, potentially lethal, ischaemia. We, and others, have shown that transient limb ischaemia can provide potent myocardial protection experimentally and clinically during cardiac surgery. Nonetheless, our understanding of the signal transduction from remote stimulus to local effect remains incomplete. The aim of the present study was to define the humoral nature of rIPC effector(s) from limb ischaemia and to study their local effects in isolated heart and cardiomyocyte models. Using a Langendorff preparation, we show that infarct size after coronary artery ligation and reperfusion was substantially reduced by rIPC in vivo, this stimulus up-regulating the MAPKs (mitogen-activating protein kinases) p42/p44, and inducing PKCε (protein kinase Cε) subcellular redistribution. Pre-treatment with the plasma and dialysate of plasma (obtained using 15 kDa cut-off dialysis membrane) from donor rabbits subjected to rIPC similarly protected against infarction. The effectiveness of the rIPC dialysate was abrogated by passage through a C 18 hydrophobic column, but eluate from this column provided the same level of protection. The dialysate of rIPC plasma from rabbits and humans was also tested in an isolated fresh cardiomyocyte model of simulated ischaemia and reperfusion. Necrosis in cardiomyocytes treated with rIPC dialysate was substantially reduced compared with control, and was similar to cells pre-treated by 'classical' preconditioning. This effect, by rabbit rIPC dialysate, was blocked by pretreatment with the opiate receptor blocker naloxone. In conclusion, in vivo transient limb ischaemia releases a low-molecular-mass (<15 kDa) hydrophobic circulating factor(s) which induce(s) a potent protection against myocardial ischaemia/reperfusion injury in Langendorff-perfused hearts and isolated cardiomyocytes in the same species. This cardioprotection is transferable across species, independent of local neurogenic activity, and requires opioid receptor activation

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

The Hyper Suprime-Cam SSP survey: Overview and survey design

Hyper Suprime-Cam (HSC) is a wide-field imaging camera on the prime focus of the 8.2-m Subaru telescope on the summit of Mauna Kea in Hawaii. A team of scientists from Japan, Taiwan, and Princeton University is using HSC to carry out a 300-night multi-band imaging survey of the high-latitude sky. The survey includes three layers: the Wide layer will cover 1400 deg2 in five broad bands (grizy), with a 5 σ point-source depth of r ≈ 26. The Deep layer covers a total of 26 deg2 in four fields, going roughly a magnitude fainter, while the UltraDeep layer goes almost a magnitude fainter still in two pointings of HSC (a total of 3.5 deg2). Here we describe the instrument, the science goals of the survey, and the survey strategy and data processing. This paper serves as an introduction to a special issue of the Publications of the Astronomical Society of Japan, which includes a large number of technical and scientific papers describing results from the early phases of this survey

Induction and persistence of cytogenetic damage in cultured peripheral blood lymphocytes following 15 Gy gamma-irradiation

In the conventional dicentric chromosome assay (DCA), the linear-quadratic dose response equation has been established for doses less than 6 Gy. At higher doses, DCA does not provide accurate dose response relationships due to mitotic delay, poor mitotic index and a high proportion of complex chromosomal aberrations. In case of partial body exposure, however, induction and transmission of chromosomal damage at high dose irradiation should be analyzed to assess the biological effects of radiation. The objective of this work is to characterize chromosomal aberrations induced by high-dose irradiation in cultured lymphocytes. Peripheral blood samples were exposed to 15 Gy gamma-ray (60Co source, 0.51 Gy/min). Isolated lymphocytes were cultured in RPMI1640 medium supplemented with 20% fetal bovine serum, 2% phytohaemagglutinin and 30 mM bromodeoxyuridine (BrdU). Cells were harvested at 48 h, 50 h, 52 h, 54 h, 56 h, 72 h and 96 h after culture initiation. For the 72 h sample, multicolor fluorescence in situ hybridization (M-FISH) was conducted to analyze complex chromosome aberrations. The first mitotic peak appeared at 52-54 h. Interestingly, cells containing aberrant chromosomes with as many as 8-10 centromeres were observed. Average dicentric equivalent count per cell ranged from 9.0 to 9.5 in 48 h – 56 h samples. In the 72 h sample, 20% of the dividing cells were in the 2nd metaphase. It should be noted that 70% of the 2nd metaphase cells were tetraploid cells including endoreduplicated cells. The high degree of polyploidy noted in our material suggests that irradiation may exert an effect on the replication process, in addition to the structural damage. M-FISH analyses revealed that in certain cells, aberrant chromosomes were accurately replicated in the polyploidization process. In the 96 h sample, cells at the third metaphase with octaploid chromosomes were found. In conclusion, a certain population of peripheral blood lymphocytes was found to transit to the second and even third mitoses after high-dose in vitro irradiation, persisting with severe chromosome aberrations. The occurrence of polyploidization and endoreduplication following high-dose irradiation described here validated the reported fact that after high dose radiotherapy, tetrapliod cells were observed in the circulating blood of patients.14th International Comgress of Radiation Researc

Establishment of a dose-response curve of 60Co gamma-ray irradiation by dicentric chromosome analysis

Ionizing radiation exposure causes DNA strand breaks that lead to chromosome aberrations. Among radiation-induced chromosome aberrations, multicentric chromosomes, as represented by dicentric chromosomes, are considered to be sensitive and specific biomarkers for assessing the radiation dose. For more than three decades, dicentric chromosome analysis (DCA) has been the Gold Standard of biodosimetry. In DCA, a dicentric yield per cell of a radiation-exposed patient is applied to a calibration curve (dose-response curve). Many dose-response curves have been proposed thus far, but most of them have been generated respectively from one healthy donor by one in vitro experiment. According to the result of international collaborative works on inter-laboratory comparisons, it has been reported that in DCA, the significant variation of dose estimation is partly attributed to different experimental protocols including the scoring criteria of chromosome aberrations among institutions / investigators. Thus, it is necessary for a biodosimetry laboratory to have and use its own dose-response curve under its own experimental conditions.In the present study, in order to evaluate the dose estimation of patients for better medical preparedness, a dose-response curve was established by analyzing 13 occupationally non-exposed healthy volunteers by DCA using peripheral blood samples irradiated in vitro with 60Co gamma-rays at seven different doses (0, 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 Gy). The result of the first-division metaphase scoring followed a linear-quadratic equation, Y=A+aD+bD2 (Y: the yield of dicentrics, D: the dose, A: the background frequency, a: the linear coefficient, b: the dose squared coefficient; IAEA Technical Reports Series No. 405 Cytogenetic Analysis for Radiation Dose Assessment, Vienna, 2001).Then, we established a practical biodosimetry protocol for radiation emergency medicine, tentatively called the NIRS DCA System (including sample collection, cell culture, chromosome preparation, automated metaphase image-capturing, chromosome aberration scoring in triage- and full estimation-modes, and a diagnostic report format), for conducting dose estimation within several days of receiving blood samples. The NIRS DCA System is now being used for actual radiation exposure accidents in Japan

Induction and Persistence of Multicentric Chromosomes in Cultured Human Peripheral Blood Lymphocytes Following High-Dose Gamma Irradiation

Among radiation-induced chromosome aberrations, multicentric chromosomes, as represented by dicentric chromosomes (dicentrics), are regarded as sensitive and specific biomarkers for assessing radiation dose in the 0 to 5 Gy range. The objective of this study was to characterize chromosome aberrations induced in vitro by a higher dose of radiation. Peripheral blood lymphocytes were exposed to 15 Gy gamma rays at a dose rate of 0.5 Gy/min and harvested at 48, 50, 52, 54, 56 and 72 h. The first mitotic peak appeared at 52-54 h, showing about a 6 h mitotic delay as compared with nonirradiated control cultures. Cell-cycle analysis of parallel and simultaneous cultures by sister-chromatid differentiation staining suggests that metaphase cells examined in 48-56 h cultures were in the first mitosis after culture initiation. The mean dicentric equivalent counts ranged from 9.0 to 9.3 in consecutively harvested cultures with no significant differences among them. At 72 h, about 20 % of dividing cells were tetraploid, persisting with faithfully replicated unstable chromosome aberrations. The nonrandom distribution of replicated chromosome pairs, deduced from multicolor fluorescence in situ hybridization analysis, led us to surmise that the predominant mechanism underlying the induction of tetraploid cells is endoreduplication. These findings suggest that a high-dose in vitro irradiation applied to peripheral blood lymphocytes may affect on the replication process, in addition to structural chromosome damage