Detection of the Far-infrared [O III] and Dust Emission in a Galaxy at Redshift 8.312: Early Metal Enrichment in the Heart of the Reionization Era

We present the Atacama Large Millimeter/submillimeter Array (ALMA) detection of the [O III] 88 $\mu$m line and rest-frame 90 $\mu$m dust continuum emission in a Y-dropout Lyman break galaxy (LBG), MACS0416_Y1, lying behind the Frontier Field cluster MACS J0416.1-2403. This [O III] detection confirms the LBG with a spectroscopic redshift of $z = 8.3118 \pm 0.0003$, making this object one of the furthest galaxies ever identified spectroscopically. The observed 850 $\mu$m flux density of $137 \pm 26$ $\mu$Jy corresponds to a de-lensed total infrared (IR) luminosity of $L_{\rm IR} = (1.7 \pm 0.3) \times 10^{11} L_{\odot}$ if assuming a dust temperature of $T_{\rm dust} = 50$ K and an emissivity index of $\beta = 1.5$, yielding a large dust mass of $4 \times 10^6 M_{\odot}$. The ultraviolet-to-far IR spectral energy distribution modeling where the [O III] emissivity model is incorporated suggests the presence of a young ($\tau_{\rm age} \approx 4$ Myr), star-forming (SFR $\approx 60 M_{\odot}$ yr$^{-1}$), moderately metal-polluted ($Z \approx 0.2 Z_{\odot}$) stellar component with a mass of $M_{\rm star} = 3 \times 10^8 M_{\odot}$. An analytic dust mass evolution model with a single episode of star-formation does not reproduce the metallicity and dust mass in $\tau_{\rm age} \approx 4$ Myr, suggesting a pre-existing evolved stellar component with $M_{\rm star} \sim 3 \times 10^9 M_{\odot}$ and $\tau_{\rm age} \sim 0.3$ Gyr as the origin of the dust mass.Comment: Accepted by ApJ. 18 pages, 10 figures, 5 table

〔研究ノート〕卵巣摘除された慢性腎臓病モデルラットの骨代謝維持に 対する食餌アルギニンあるいは大豆イソフラボン抽出物 投与の有効性評価に関する基礎的研究

The present study was carried out to elucidate the protective effects of dietary L-arginine and soy isoflavone-extracted on the bone metabolism in the ovariectomized chronic kidney disease model rats.　　Nine-week-old female rats received 360mg/kg BW of adenine intragastrally for four consecutive days so that they would develop chronic kidney disease（CKD）. After six days of recovery, rats received ovariectomies（OVX）under anesthesia. A sham operation was carried out on another group of rats（group Intact）.　　Seven days after the OVX, the rats were given either a control diet（20％ casein protein diet（group CA）; 0.5％ L-arginine supplemented diet（group Arg）; or 0.20％ soy isoflavone-extracted supplemented diet（group IF）, 13g per day for 12 weeks. Rats in group Intact were, like group CA, given the control diet.　　The results were as follows: 1）Group CA developed moderate chronic kidney disease which was manifested as elevated kidney weight, increased serum creatinine, relatively lower creatinine clearance and reduced femoral-BMD than that of group Intact.2）The L-Arginine supplemented diet did not improve renal function and femoral BMD-loss. But, increased mRNA expression levels of IGF-1, BMP-2 and Osterix were observed in the femurs.3）Soy isoflavone-extracted supplemented diet had no preventative effects on BMD loss, although estrogen receptor-beta mRNA expression levels in the femurs were elevated.　　From these results, bone-protective functions of L-arginine via activation of osteoblast differentiation and bone formation process were suggested. Further investigation to clarify the efficacy of L-arginine-IGF-1 signal transduction on the bone metabolism is required to determine whether a therapy based on this approach can help people suffering from osteoporosis in CKD patients

Temporal Dynamics of Nitrous Oxide Emission and Nitrate Leaching in Renovated Grassland with Repeated Application of Manure and/or Chemical Fertilizer

Managed grassland is occasionally renovated to maintain plant productivity by killing old vegetation, ploughing, and reseeding. This study aimed to investigate the combined effect of grassland renovation and long-term manure application on the temporal dynamics of nitrous oxide (N2O) emission and nitrate nitrogen (NO3--N) leaching. The study was conducted from September 2013 to September 2016 in a managed grassland renovated in September 2013. In this grassland, two treatments were managedchemical fertilizer application (F treatment) and the combined application of chemical fertilizer and beef cattle manure (MF treatment)for eight years before the renovation. The control treatment without fertilization (CT) was newly established in the F treatment. The soil N2O flux was measured using a closed chamber method. A leachate sample was collected using a tension-free lysimeter that was installed at the bottom of the Ap horizon (25 cm deep), and total NO3--N leaching was calculated from leachate NO3--N concentration and drainage volume was estimated by the water balance method. In the first year after renovation, the absence of plant nitrogen uptake triggered NO3--N leaching following rainfall during renovation and increased drainage water after thawing. NO3--N movement from topsoil to deeper soil enhanced N2O production and emission from the soil. N2O emission in MF treatment was 1.6-2.0 times larger than those of CT and F treatments, and NO3--N leaching in MF treatment was 2.3-2.6 times larger than those of CT and F treatments in the first year. Mineral nitrogen release derived from long-term manure application increased NO3--N leaching and N2O emission. In the second year, N2O emission and NO3--N leaching significantly decreased from the first year because of increased plant N uptake and decreased mineral nitrogen surplus, and no significant differences in N2O emission and NO3--N leaching were observed among the treatments. In the second and third years, NO3--N leaching was regulated by plant nitrogen uptake. There were no significant differences in NO3--N leaching among the treatments, but N2O emission in MF treatment was significantly smaller than in the F treatment. Long-term manure application could be a possible option to mitigate N2O emission in permanent grassland; however, the risk of increased NO3--N leaching and N2O emission in the renovation year induced by manure nitrogen release should be noted

Indole Editing Enabled by HFIP‐Mediated Ring‐Switch Reactions of 3‐Amino‐2‐Hydroxyindolines

This work reports the novel reactivity of hemiaminal as a precursor for indole editing at the multi-site. The HFIP-promoted indole editing of indoline hemiaminals affords 2-arylindoles through a ring-switch sequence. The key to success of this transformation is to use a cyclic hemiaminal as an alpha-amino aldehyde surrogate under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance. The utility of this transformation is presented through the one-pot protocol and the synthesis of isocryptolepine

Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic differentiation through Foxg1

Abstract Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. We previously reported that Pro-Hyp promotes the differentiation of osteoblasts by increasing Runx2, osterix and Col1α1 mRNA expression levels. Here, to elucidate the mechanism of Pro-Hyp promotion of osteoblast differentiation, we focus on the involvement of Foxo1 in osteoblast differentiation via Runx2 regulation and the role of Foxg1 in Foxo1 regulation. The addition of Pro-Hyp had no effect on MC3T3-E1 cell proliferation in Foxo1- or Foxg1-knockdown cells. In Foxo1-knockdown cells, the addition of Pro-Hyp increased ALP activity, but in Foxg1-knockdown cells, it had no effect on ALP activity. An enhancing effect of Pro-Hyp on the Runx2 and osterix expression levels was observed in Foxo1-knockdown cells. However, no enhancing effect of Pro-Hyp on osteoblastic gene expression was observed when Foxg1 was knocked down. These results demonstrate that Pro-Hyp promotes osteoblastic MC3T3-E1 cell differentiation and upregulation of osteogenic genes via Foxg1 expression

A Case of Significant Response to Olaparib in a Patient with Primary Peritoneal Carcinosarcoma Diagnosed by Laparoscopic Surgery

Primary peritoneal carcinosarcomas which arise from extragenital locations are extremely rare. Carinosarcomas contain both carcinomatous and sarcomatous elements and can be mainly detected in the female genital tract. We herein report a case of primary peritoneal carcinosarcoma diagnosed by laparoscopic surgery and treated with olaparib. A 62-year-old woman referred to our hospital due to abdominal distension. From imaging findings, we suspected advanced primary peritoneal carcinoma, and laparoscopic surgery was thereafter performed. The pathological diagnosis was carcinosarcoma, and the patient received chemotherapy with docetaxel and carboplatin. After three cycles of chemotherapy, the interval debulking surgery was attempted but resulted in suboptimal results. Because the bilateral ovaries were observed with a normal size and normal findings, we considered that the most likely diagnosis was primary peritoneal carcinosarcoma. After the additional chemotherapy and a 6-month observation period, the tumor relapsed. The patient received chemotherapy again, and the peritoneal carcinosarcoma was judged to be a platinum-sensitive tumor. Oral administration of olaparib was thus initiated. Although a dose reduction was needed due to anemia, olaparib was effective, and the patient could continue the drug for another 7 months. This is the first report of primary peritoneal carcinosarcoma treated with olaparib and shows that it could be a treatment option for platinum-sensitive tumors

Indirect CRISPR screening with photoconversion revealed key factors of drug resistance with cell–cell interactions

Abstract Comprehensive screenings to clarify indirect cell–cell interactions, such as those in the tumor microenvironment, especially comprehensive assessments of supporting cells’ effects, are challenging. Therefore, in this study, indirect CRISPR screening for drug resistance with cell–cell interactions was invented. The photoconvertible fluorescent protein Dendra2 was inducted to supporting cells and explored the drug resistance responsible factors of supporting cells with CRISPR screenings. Random mutated supporting cells co-cultured with leukemic cells induced drug resistance with cell–cell interactions. Supporting cells responsible for drug resistance were isolated with green-to-red photoconversion, and 39 candidate genes were identified. Knocking out C9orf89, MAGI2, MLPH, or RHBDD2 in supporting cells reduced the ratio of apoptosis of cancer cells. In addition, the low expression of RHBDD2 in supporting cells, specifically fibroblasts, of clinical pancreatic cancer showed a shortened prognosis, and a negative correlation with CXCL12 was observed. Indirect CRISPR screening was established to isolate the responsible elements of cell–cell interactions. This screening method could reveal unknown mechanisms in all kinds of cell–cell interactions by revealing live phenotype-inducible cells, and it could be a platform for discovering new targets of drugs for conventional chemotherapies