Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS).</p> <p>Results</p> <p>In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief.</p> <p>Conclusions</p> <p>These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.</p

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 8.2m Subaru telescope on the summit of Maunakea 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 deg$^2$ in five broad bands ($grizy$), with a $5\,\sigma$ point-source depth of $r \approx 26$. The Deep layer covers a total of 26~deg$^2$ 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 deg$^2$). 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.Comment: 14 pages, 7 figures, 5 tables. Corrected for a typo in the coordinates of HSC-Wide spring equatorial field in Table

Cosmic Galaxy-IGM HI Relation at z similar to 2-3 Probed in the COSMOS/UltraVISTA 1.6 Deg(2) Field

We present spatial correlations of galaxies and IGM neutral hydrogen H i in the COSMOS/UltraVISTA 1.62 deg2 field. Our data consist of 13,415 photo-z galaxies at z ~ 2–3 with ${K}_{s}\lt 23.4$ and the Lyα forest absorption lines in the background quasar spectra selected from SDSS data with no signature of damped Lyα system contamination. We estimate a galaxy overdensity δ gal in an impact parameter of 2.5 (proper) Mpc, and calculate the Lyα forest fluctuations ${\delta }_{\langle F\rangle }$ whose negative values correspond to the strong Lyα forest absorption lines. We identify weak evidence of an anti-correlation between δ gal and ${\delta }_{\langle F\rangle }$ with a Spearman's rank correlation coefficient of −0.39 suggesting that the galaxy overdensities and the Lyα forest absorption lines positively correlate in space at the ~90% confidence level. This positive correlation indicates that high-z galaxies exist around an excess of H i gas in the Lyα forest. We find four cosmic volumes, dubbed A obs, B obs, C obs, and D obs, that have extremely large (small) values of δ gal sime 0.8 (−1) and ${\delta }_{\langle F\rangle }\simeq 0.1(-0.4)$, three of which, B obs–D obs, significantly depart from the δ gal–${\delta }_{\langle F\rangle }$ correlation, and weaken the correlation signal. We perform cosmological hydrodynamical simulations and compare with our observational results. Our simulations reproduce the δ gal–${\delta }_{\langle F\rangle }$ correlation, agreeing with the observational results. Moreover, our simulations have model counterparts of A obs–D obs, and suggest that the observations pinpoint, by chance, a galaxy overdensity like a proto-cluster, gas filaments lying on the quasar sightline, a large void, and orthogonal low-density filaments. Our simulations indicate that the significant departures of B obs–D obs are produced by the filamentary large-scale structures and the observation sightline effects

Cosmic Galaxy-IGM HI Relation at z similar to 2-3 Probed in the COSMOS/UltraVISTA 1.6 Deg(2) Field

We present spatial correlations of galaxies and IGM neutral hydrogen H i in the COSMOS/UltraVISTA 1.62 deg2 field. Our data consist of 13,415 photo-z galaxies at z ~ 2–3 with ${K}_{s}\lt 23.4$ and the Lyα forest absorption lines in the background quasar spectra selected from SDSS data with no signature of damped Lyα system contamination. We estimate a galaxy overdensity δ gal in an impact parameter of 2.5 (proper) Mpc, and calculate the Lyα forest fluctuations ${\delta }_{\langle F\rangle }$ whose negative values correspond to the strong Lyα forest absorption lines. We identify weak evidence of an anti-correlation between δ gal and ${\delta }_{\langle F\rangle }$ with a Spearman's rank correlation coefficient of −0.39 suggesting that the galaxy overdensities and the Lyα forest absorption lines positively correlate in space at the ~90% confidence level. This positive correlation indicates that high-z galaxies exist around an excess of H i gas in the Lyα forest. We find four cosmic volumes, dubbed A obs, B obs, C obs, and D obs, that have extremely large (small) values of δ gal sime 0.8 (−1) and ${\delta }_{\langle F\rangle }\simeq 0.1(-0.4)$, three of which, B obs–D obs, significantly depart from the δ gal–${\delta }_{\langle F\rangle }$ correlation, and weaken the correlation signal. We perform cosmological hydrodynamical simulations and compare with our observational results. Our simulations reproduce the δ gal–${\delta }_{\langle F\rangle }$ correlation, agreeing with the observational results. Moreover, our simulations have model counterparts of A obs–D obs, and suggest that the observations pinpoint, by chance, a galaxy overdensity like a proto-cluster, gas filaments lying on the quasar sightline, a large void, and orthogonal low-density filaments. Our simulations indicate that the significant departures of B obs–D obs are produced by the filamentary large-scale structures and the observation sightline effects

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

Small DNA Pieces in C. elegans Are Intermediates of DNA Fragmentation during Apoptosis

While studying small noncoding RNA in C. elegans, we discovered that protocols used for isolation of RNA are contaminated with small DNA pieces. After electrophoresis on a denaturing gel, the DNA fragments appear as a ladder of bands, ∼10 nucleotides apart, mimicking the pattern of nuclease digestion of DNA wrapped around a nucleosome. Here we show that the small DNA pieces are products of the DNA fragmentation that occurs during apoptosis, and correspondingly, are absent in mutant strains incapable of apoptosis. In contrast, the small DNA pieces are present in strains defective for the engulfment process of apoptosis, suggesting they are produced in the dying cell prior to engulfment. While the small DNA pieces are also present in a number of strains with mutations in predicted nucleases, they are undetectable in strains containing mutations in nuc-1, which encodes a DNase II endonuclease. We find that the small DNA pieces can be labeled with terminal deoxynucleotidyltransferase only after phosphatase treatment, as expected if they are products of DNase II cleavage, which generates a 3′ phosphate. Our studies reveal a previously unknown intermediate in the process of apoptotic DNA fragmentation and thus bring us closer to defining this important pathway

The Roles and Acting Mechanism of Caenorhabditis elegans DNase II Genes in Apoptotic DNA Degradation and Development

DNase II enzymes are acidic endonucleases that have been implicated in mediating apoptotic DNA degradation, a critical cell death execution event. C. elegans genome contains three DNase II homologues, NUC-1, CRN-6, and CRN-7, but their expression patterns, acting sites, and roles in apoptotic DNA degradation and development are unclear. We have conducted a comprehensive analysis of three C. elegans DNase II genes and found that nuc-1 plays a major role, crn-6 plays an auxiliary role, and crn-7 plays a negligible role in resolving 3′ OH DNA breaks generated in apoptotic cells. Promoter swapping experiments suggest that crn-6 but not crn-7 can partially substitute for nuc-1 in mediating apoptotic DNA degradation and both fail to replace nuc-1 in degrading bacterial DNA in intestine. Despite of their restricted and largely non-overlapping expression patterns, both CRN-6 and NUC-1 can mediate apoptotic DNA degradation in many cells, suggesting that they are likely secreted nucleases that are retaken up by other cells to exert DNA degradation functions. Removal or disruption of NUC-1 secretion signal eliminates NUC-1's ability to mediate DNA degradation across its expression border. Furthermore, blocking cell corpse engulfment does not affect apoptotic DNA degradation mediated by nuc-1, suggesting that NUC-1 acts in apoptotic cells rather than in phagocytes to resolve 3′ OH DNA breaks. Our study illustrates how multiple DNase II nucleases play differential roles in apoptotic DNA degradation and development and reveals an unexpected mode of DNase II action in mediating DNA degradation

Clinical, serologic and magnetic resonance imaging of 3 cases of inflammatory myopathy with abundant macrophages in the Japanese population

We report the first 3 cases of inflammatory myopathy with abundant macrophages (IMAM) to be found in an Asian country. Diagnosis of IMAM was based on the infiltration of CD68+ macrophages into biopsied specimens, particularly the fascia. Proximal skeletal muscle symptoms and signs, elevation of creatine kinase, and myogenic changes in electromyography were found in all of the cases, and magnetic resonance imaging clearly revealed thickening of the fascia. Since dermatomyositis (DM)-specific skin alterations were not found, none of the patients in this study fulfilled Bohan and Peter\u27s criteria for DM; however, anti-PL-7 antibody was detected in case number 1. In addition, CD20+ B-cell infiltration into the fascia was also detected in all of the cases, indicating further transition to DM. Severe illness, namely macrophage activation syndrome and acute respiratory distress syndrome, occurred in case 1 but was resolved with intensive combination therapy. The other 2 cases also required glucocorticoids to achieve remission

Resuscitation of Newborn Piglets. Short-Term Influence of FiO2 on Matrix Metalloproteinases, Caspase-3 and BDNF

Perinatal hypoxia-ischemia is a major cause of mortality and cerebral morbidity, and using oxygen during newborn resuscitation may further harm the brain. The aim was to examine how supplementary oxygen used for newborn resuscitation would influence early brain tissue injury, cell death and repair processes and the regulation of genes related to apoptosis, neurodegeneration and neuroprotection.Anesthetized newborn piglets were subjected to global hypoxia and then randomly assigned to resuscitation with 21%, 40% or 100% O(2) for 30 min and followed for 9 h. An additional group received 100% O(2) for 30 min without preceding hypoxia. The left hemisphere was used for histopathology and immunohistochemistry and the right hemisphere was used for in situ zymography in the corpus striatum; gene expression and the activity of various relevant biofactors were measured in the frontal cortex. There was an increase in the net matrix metalloproteinase gelatinolytic activity in the corpus striatum from piglets resuscitated with 100% oxygen vs. 21%. Hematoxylin-eosin (HE) staining revealed no significant changes. Nine hours after oxygen-assisted resuscitation, caspase-3 expression and activity was increased by 30-40% in the 100% O(2) group (n = 9/10) vs. the 21% O(2) group (n = 10; p<0.04), whereas brain-derived neurotrophic factor (BDNF) activity was decreased by 65% p<0.03.The use of 100% oxygen for resuscitation resulted in increased potentially harmful proteolytic activities and attenuated BDNF activity when compared with 21%. Although there were no significant changes in short term cell loss, hyperoxia seems to cause an early imbalance between neuroprotective and neurotoxic mechanisms that might compromise the final pathological outcome