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Arctic sea ice is rapidly decreasing during the recent period of global warming. One of the significant factors of the Arctic sea ice loss is oceanic heat transport from lower latitudes. For months of sea ice formation, the variations in the sea surface temperature over the Pacific Arctic region were highly correlated with the Pacific Decadal Oscillation (PDO). However, the seasonal sea surface temperatures recorded their highest values in autumn 2018 when the PDO index was neutral. It is shown that the anomalous warm seawater was a rapid ocean response to the southerly winds associated with episodic atmospheric blocking over the Bering Sea in September 2018. This warm seawater was directly observed by the R/V Mirai Arctic Expedition in November 2018 to significantly delay the southward sea ice advance. If the atmospheric blocking forms during the PDO positive phase in the future, the annual maximum Arctic sea ice extent could be dramatically reduced.

Mutations in genes that encode components of tuberous sclerosis complex 2 (TSC2) are associated with tuberous sclerosis complex disease. TSC2 interacts with tuberous sclerosis complex 1 to form a complex that negatively regulates cell growth and proliferation via the inactivation of mechanistic target of rapamycin complex 1. The activity of TSC2 is mainly regulated via posttranslational modifications such as phosphorylation. However, the control of TSC2 activity is not entirely achieved by phosphorylation. In this study, we show that TSC2 is methylated at R1457 and R1459 by protein arginine methyltransferase 1 (PRMT1). Methylation of these two residues can affect the phosphorylation status through protein kinase B (Akt) of TSC2 at T1462 and is essential for TSC2 stability. Taken together, these findings indicate that novel posttranslational modifications are important for the regulation of TSC2 stability through PRMT1-mediated methylation.

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The long-term trend of extreme ocean waves in the emerging ice-free waters of the summer Arctic is studied using ERA-Interim wave reanalysis, with validation by two drifting wave buoys deployed in summer 2016. The 38-year-long reanalysis dataset reveals an increase in the expected largest significant wave height from 2.3 m to 3.1 m in the ice-free water from the Laptev to the Beaufort Seas during October. The trend is highly correlated with the expected increase in highest wind speed from 12.0 m/s to 14.2 m/s over the ice-free ocean, and less so with the extent of the ice-free water. Since the storms in this area did not strengthen throughout the analysis period, the increase in the expected largest significant wave height follows from the enhanced probability of storms in ice-free waters, which is pertinent to the estimation of extreme sea conditions along the Northern Sea Route.

Bromodomain Containing 4 (BRD4) mediates transcriptional elongation of the oncogene MYC by binding to acetylated histones. BRD4 has been shown to play a critical role in tumorigenesis in several cancers, and the BRD4-NUT fusion gene is a driver of NUT midline carcinoma (NMC), a rare but highly lethal cancer. microRNAs (miRNAs) are endogenous small non-coding RNAs that suppress target gene expression by binding to complementary mRNA sequences. Here, we show that miR-3140, which was identified as a novel tumor suppressive miRNA by function-based screening of a library containing 1090 miRNA mimics, directly suppressed BRD4 by binding to its coding sequence (CDS). miR-3140 concurrently downregulated BRD3 by bind to its CDS as well as CDK2 and EGFR by binding to their 3’ untranslated regions. miR-3140 inhibited tumor cell growth in vitro in various cancer cell lines, including EGFR tyrosine kinase inhibitor-resistant cells. Interestingly, we found that miR-3140 downregulated the BRD4-NUT fusion protein and suppressed in vitro tumor cell growth in a NMC cell line, Ty-82 cells. Furthermore, administration of miR-3140 suppressed in vivo tumor growth in a xenograft mouse model. Our results suggest that miR-3140 is a candidate for the development of miRNA-based cancer therapeutics.

Recent research has demonstrated that additional winter radiosonde observations in Arctic regions enhance the predictability of mid-latitude weather extremes by reducing uncertainty in the flow of localised tropopause polar vortices. The impacts of additional Arctic observations during summer are usually confined to high latitudes and they are difficult to realize at mid-latitudes because of the limited scale of localised tropopause polar vortices. However, in certain climatic states, the jet stream can intrude remarkably into the mid-latitudes, even in summer; thus, additional Arctic observations might improve analysis validity and forecast skill for summer atmospheric circulations over the Northern Hemisphere. This study examined such cases that occurred in 2016 by focusing on the prediction of the intensity and track of tropical cyclones (TCs) over the North Atlantic and North Pacific, because TCs are representative of extreme weather in summer. The predictabilities of three TCs were found influenced by additional Arctic observations. Comparisons with ensemble reanalysis data revealed that large errors propagate from the data-sparse Arctic into the mid-latitudes, together with high-potential-vorticity air. Ensemble forecast experiments with different reanalysis data confirmed that additional Arctic observations sometimes improve the initial conditions of upper-level troposphere circulations.

Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1+MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1+MDSCs in comparison to those from healthy subjects (p +MDSCs were reduced by curative treatment for HCC (p +MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1+MDSCs were significantly increased compared with control (p +MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1+MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1+MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1+MDSCs as a new biomarker of HCC.

The differentiation of preadipocytes into adipocytes is controlled by several transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are known as master regulators of adipogenesis. BCL11B is a zinc finger-type transcription factor that regulates the development of the skin and central nervous and immune systems. Here, we found that BCL11B was expressed in the white adipose tissue (WAT), particularly the subcutaneous WAT and that BCL11B−/− mice had a reduced amount of subcutaneous WAT. During adipogenesis, BCL11B expression transiently increased in 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). The ability for adipogenesis was reduced in BCL11B knockdown 3T3-L1 cells and BCL11B−/− MEFs, whereas the ability for osteoblastogenesis was unaffected in BCL11B−/− MEFs. Luciferase reporter gene assays revealed that BCL11B stimulated C/EBPβ activity. Furthermore, the expression of downstream genes of the Wnt/β-catenin signaling pathway was not suppressed in BCL11B−/− MEFs during adipogenesis. Thus, this study identifies BCL11B as a novel regulator of adipogenesis, which works, at least in part, by stimulating C/EBPβ activity and suppressing the Wnt/β-catenin signaling pathway.

A high level of plasma low-density lipoprotein (LDL) cholesterol is considered a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) is essential for clearing plasma LDL cholesterol, activation of LDLR is a promising therapeutic target for patients with atherosclerotic disease. Here we demonstrated how the flavonoid kaempferol stimulated the gene expression and activity of LDLR in HepG2 cells. The kaempferol-mediated stimulation of LDLR gene expression was completely inhibited by knockdown of Sp1 gene expression. Treatment of HepG2 cells with kaempferol stimulated the recruitment of Sp1 to the promoter region of the LDLR gene, as well as the phosphorylation of Sp1 on Thr-453 and Thr-739. Moreover, these kaempferol-mediated processes were inhibited in the presence of U0126, an ERK pathway inhibitor. These results suggest that kaempferol may increase the activity of Sp1 through stimulation of Sp1 phosphorylation by ERK1/2 and subsequent induction of LDLR expression and activity.

During ice-free periods, the Northern Sea Route (NSR) could be an attractive shipping route. The decline in Arctic sea-ice extent, however, could be associated with an increase in the frequency of the causes of severe weather phenomena and high wind-driven waves and the advection of sea ice could make ship navigation along the NSR difficult. Accurate forecasts of weather and sea ice are desirable for safe navigation, but large uncertainties exist in current forecasts, partly owing to the sparse observational network over the Arctic Ocean. Here, we show that the incorporation of additional Arctic observations improves the initial analysis and enhances the skill of weather and sea-ice forecasts, the application of which has socioeconomic benefits. Comparison of 63-member ensemble atmospheric forecasts, using different initial data sets, revealed that additional Arctic radiosonde observations were useful for predicting a persistent strong wind event. The sea-ice forecast, initialised by the wind fields that included the effects of the observations, skilfully predicted rapid wind-driven sea-ice advection along the NSR.

UTokyo Research掲載「大豆のタンパク質1回摂取で代謝を改善する因子が急増」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/single-ingestion-of-soy-protein-improves-metabolism.html, UTokyo Research "Single ingestion of soy protein improves metabolism" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/single-ingestion-of-soy-protein-improves-metabolism.html