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To reveal the origin of the mini-starbursts in the Milky Way, we carried out large-scale CO observations toward the RCW 106 giant molecular cloud (GMC) complex using the NANTEN2 4 m radio telescope operated by Nagoya University. We also analyzed the Mopra Southern Galactic Plane CO survey and Herschel infrared continuum archival data. The RCW 106 GMC complex contains the radial velocity components of −68 km s−1 and −50 km s−1 reported by H. Nguyen et al. (2015). Focusing on the RCW 106 East and West region with the massive star formation having the bright infrared dust emission, we found that these regions have three different velocity components with ∼10 km s−1 differences. The two out of three velocity components show morphological correspondence with the infrared cold dust emission and connect with the bridge feature on a position–velocity diagram. Therefore, two molecular clouds with ∼10 km s−1 differences are likely to be physically associated with massive star-forming regions in the GMC complex. Based on these observational results, we argue that mini-starbursts and massive star/cluster formation in the RCW 106 GMC complex are induced by supersonic cloud–cloud collisions in an agglomerate of molecular gas on the Scutum–Centaurus arm.

Epstein–Barr virus (EBV) predominantly infects B cells and causes B‐cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK‐cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV‐positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV‐encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV‐negative cells using the cells conditionally expressing LMP1, and on CAEBV‐derived EBV‐positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV‐negative cell line. We here found that Epstein–Barr virus (EBV) latent membrane protein 1 plays a role in growth promotion of chronic active EBV infection (CAEBV), a lymphoproliferative disease associated with poor prognosis. Such analysis contributes to understanding of oncogenesis and may provide basic information for development of anti‐cancer drug to EBV‐positive proliferative diseases and cancers.

To reveal the origin of the mini-starbursts in the Milky Way, we carried out large-scale CO observations toward the RCW 106 giant molecular cloud (GMC) complex using the NANTEN2 4-m radio telescope operated by Nagoya University. We also analyzed the Mopra Southern Galactic plane CO survey and Herschel infrared continuum archival data. The RCW 106 GMC complex contains the radial velocity components of \\(-68\\) km s\\(^-1\\) and \\(-50\\) km s\\(^-1\\) reported by Nguyen et al. (2015). Focusing on the RCW 106 East and West region with the massive star formation having the bright infrared dust emission, we found that these regions have three different velocity components with \\( 10\\) km s\\(^-1\\) differences. The two out of three velocity components show morphological correspondence with the infrared cold dust emission and connect with the bridge feature on a position-velocity diagram. Therefore, two molecular clouds (MCs) with \\( 10\\) km s\\(^-1\\) differences are likely to be physically associated with massive star-forming regions in the GMC complex. Based on these observational results, we argue that mini-starbursts and massive star/cluster formation in the RCW 106 GMC complex are induced by supersonic cloud-cloud collisions in an agglomerate of molecular gas on the Scutum-Centaurus arm.

Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Cardiovascular diseases are a major cause of death worldwide, and the development of novel therapeutic targets to treat it is urgently needed. We report that a zinc transporter, ZIP13, regulates cardiovascular homeostasis. We found that the expression level of Zip13 mRNA was diminished in both primary neonatal cardiomyocytes and mouse heart tissues treated with the cardiotoxic agent doxycycline. Primary neonatal cardiomyocytes from Zip13 gene-knockout (KO) mice exhibited abnormal irregular arrhythmic beating. RNA-seq analysis identified 606 differentially expressed genes in Zip13 -KO mouse-derived primary neonatal cardiomyocytes and Gene ontology (GO) analysis revealed that both inflammation- and cell adhesion-related genes were significantly enriched. In addition, telemetry echocardiography analysis suggested that arrhythmias were likely to occur in Zip13 -KO mice, in which elevated levels of the cardiac fibrosis marker Col1a1 , vascular inflammation-related gene eNOS , and Golgi-related molecule GM130 were observed. These results indicate the physiological importance of ZIP13—it maintains cardiovascular homeostasis by resolving inflammation and stress response. Our findings suggest that optimizing ZIP13 expression and/or function may improve cardiovascular disease management.

Spaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g ; AG) and microgravity (μ g ; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy-related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profiles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms.

Despite considerable scholarly attention on the institutional and normative aspects of development cooperation, its longitudinal dynamics unfolding at the global level have rarely been investigated. Focusing on aid, we examine the evolving global structure of development cooperation induced by aid flows in its entirety. Representing annual aid flows between donors and recipients from 1970 to 2013 as a series of networks, we apply hierarchical stochastic block models to extensive aid-flow data that cover not only the aid behavior of the major OECD donors but also that of other emerging donors, including China. Despite a considerable degree of external expansion and internal diversification of aid relations over the years, the analysis has uncovered a temporally persistent structure of aid networks. The latter comprises, on the one hand, a limited number of major donors with far-reaching resources and, on the other hand, a large number of mostly poor but globally well-connected recipients. The results cast doubt on the efficacy of recurrent efforts for “aid reform” in substantially changing the global aid flow pattern.

BackgroundNo prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality.MethodsWe conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores.ResultsWe enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05).ConclusionsWe derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available (https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android).

Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy. This study investigated the prognostic value of the expression of cereblon (CRBN)‐pathway genes on the clinical relevance of lenalidomide treatment and evaluated the levels of CRBN‐binding proteins, mutations in these genes, and the methylation status of the CRBN promoter sequence. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of lenalidomide and dexamethasone therapy.

Prion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrP C ) to the abnormal β-sheet rich form (PrP Sc ) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrP Sc , reduced PrP Sc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.