MOIRCS Deep Survey III: Active Galactic Nuclei in Massive Galaxies at z=2-4

We investigate the X-ray properties of the K-band-selected galaxies at redshift 2 < z < 4 by using our deep near-infrared images obtained in the MOIRCS Deep Survey project and the published Chandra X-ray source catalog. 61 X-ray sources with the 2-10 keV luminosity L_X = 10^{42}-10^{44} erg/s are identified with the K-selected galaxies and we found that they are exclusively (90%) associated with the massive objects with stellar mass larger than 10^{10.5} Msun. Our results are consistent with the idea that the M_BH/M_str ratio of the galaxies at z=2-4 is similar to the present-day value. On the other hand, the AGN detection rate among the very massive galaxies with the stellar mass larger than 10^{11} Msun is high, 33% (26/78). They are active objects in the sense that the black-hole mass accretion rate is ~ 1-50% of the Eddington limit if they indeed have similar M_BH/M_str ratio with those observed in the local universe. The active duration in the AGN duty cycle of the high-redshift massive galaxies seems large.Comment: 33 pages, 12 figures, accepted for publication in Ap

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

MOIRCS deep survey. VI. Near-infrared spectroscopy of K-selected star-forming galaxies at z ~ 2

We present the results of near-infrared multi-object spectroscopic observations for 37 BzK-color-selected star-forming galaxies conducted with MOIRCS on the Subaru Telescope. The sample is drawn from the Ks -band-selected catalog of the MOIRCS Deep Survey in the GOODS-N region. About half of our samples are selected from the publicly available 24 μm-source catalog of the Multiband Imaging Photometer for Spitzer on board the Spitzer Space Telescope. Hα emission lines are detected from 23 galaxies, of which the median redshift is 2.12. We derived the star formation rates (SFRs) from extinction-corrected Hα luminosities. The extinction correction is estimated from the spectral energy distribution (SED) fitting of multiband photometric data covering UV to near-infrared wavelengths. The Balmer decrement of the stacked emission lines shows that the amount of extinction for the ionized gas is larger than that for the stellar continuum. From a comparison of the extinction-corrected Hα luminosity and other SFR indicators, we found that the relation between the dust properties of stellar continuum and ionized gas is different depending on the intrinsic SFR (differential extinction). We compared SFRs estimated from extinction-corrected Hα luminosities with stellar masses estimated from SED fitting. The comparison shows no correlation between SFR and stellar mass. Some galaxies with stellar mass smaller than ~1010 M sun show SFRs higher than ~100 M sun yr-1. The specific SFRs (SSFRs) of these galaxies are remarkably high; galaxies which have SSFR higher than ~10-8 yr-1 are found in eight of the present sample. From the best-fit parameters of SED fitting for these high-SSFR galaxies, we find that the average age of the stellar population is younger than 100 Myr, which is consistent with the implied high SSFR. The large SFR implies the possibility that the high-SSFR galaxies significantly contribute to the cosmic SFR density of the universe at z ~ 2. When we apply the larger extinction correction for the ionized gas or the differential extinction correction, the total SFR density estimated from the Hα-emission-line galaxies is 0.089-0.136 M sun yr-1 Mpc-3, which is consistent with the total SFR densities in the literature. The metallicity of the high-SSFR galaxies, which is estimated from the N2 index, is larger than that expected from the mass-metallicity relation of UV-selected galaxies at z ~ 2 by Erb et al. This study is based on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan