CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses

A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment

オリエンタルケイ ユリ ‘カサブランカ’ ノ ヨクセイサイバイ デ ミラレル シュート オヨビ ハ ノ ショウガイハッセイ ト ソノ ケイゲンホウ

オリエンタル系ユリ‘カサブランカ’を用い，球根の氷温貯蔵前の予冷方法，長期氷温貯蔵後の解凍あるいは芽伸ばし処理時の温度を変えることにより，シュートおよび葉の障害発生に及ぼす影響を調べ，障害発生の軽減法を検討した。1℃のみで予冷する場合は8～12週間とし，12℃から1℃へと次第に温度を下げて予冷する慣行法では6℃以下の期間を8週間以内とすれば，致死あるいは不開花個体の発生率および葉の障害発生率が低く保たれることが明らかにされた。また，予冷期間中の温度上昇は不開花個体や葉の障害発生率を高める危険性が認められた。長期氷温貯蔵した球根を1℃で解凍すると5，20℃に比べ障害葉の発生を著しく抑制することができた。また，芽伸ばし処理時の温度を変えても切り花品質には差がなく，葉の障害発生率にも差はみられなかった。Occurrence of black shoots, non-flowering plants, and damaged leaves are often found in retarding culture of Oriental hybrid lilies after long-term storage at a subzero temperature. To reduce their damage, bulbs of ‘Casa Blanca’ produced in Niigata were packed in polyethylene bags with wet peat moss and subjected to pre-chilling at 1℃ for 8 to 20 weeks or conventional method of pre-chilling in which the temperature was gradually lowered from 12℃ to 1℃ at 4-week intervals before storing at －2.0℃. After storage at －2.0℃ for 5 to 7 months, they were planted in a plastic container and grown in a plastic house maintained at min. 14℃. Rates of black shoots, non-flowered plants, and damaged leaves were maintained low when bulbs were pre-chilled at 1℃ for 8 to 12 weeks or at low temperatures below 3℃ within 8 weeks in the conventional method. Temperature rise during the conventional method caused the increase rates of non-flowered plants and damaged leaves.Bulbs produced in Hokkaido and pre-chilled at 1℃ for 14 weeks were stored at －2.0℃ for 7 months and thereafter grown in an artificial growth room controlled at a temperature of 20℃ and a day length of 8 hours (12,000 lux). Occurrence of damaged leaves was reduced remarkably when they were defrosted at 1℃ as compared with defrosting at 5 or 20℃. Treatment by subjecting to temperatures of 5, 8 and 20℃ for 2 weeks to allow rooting and sprouting in a plastic pot filled with wet peat moss before planting resulted in decreased rate of damaged leaves irrespective of treated temperature

Cryo-EM structure of a Ca2⁺-bound photosynthetic LH1-RC complex containing multiple αβ-polypeptides

The light-harvesting-reaction center complex (LH1-RC) from the purple phototrophic bacterium Thiorhodovibrio strain 970 exhibits an LH1 absorption maximum at 960nm, the most red-shifted absorption for any bacteriochlorophyll (BChl) a-containing species. Here we present a cryo-EM structure of the strain 970 LH1-RC complex at 2.82 angstrom resolution. The LH1 forms a closed ring structure composed of sixteen pairs of the αβ-polypeptides. Sixteen Ca ions are present in the LH1 C-terminal domain and are coordinated by residues from the αβ -polypeptides that are hydrogen-bonded to BChl a. The Ca2⁺-facilitated hydrogen-bonding network forms the structural basis of the unusual LH1 redshift. The structure also revealed the arrangement of multiple forms of α- and β -polypeptides in an individual LH1 ring. Such organization indicates a mechanism of interplay between the expression and assembly of the LH1 complex that is regulated through interactions with the RC subunits inside

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

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 8.2-m Subaru telescope on the summit of Mauna Kea 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 deg2 in five broad bands (grizy), with a 5 σ point-source depth of r ≈ 26. The Deep layer covers a total of 26 deg2 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 deg2). 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

(Main Section: Ecological Planning)

The administrator of a city park must respond to various needs pertaining to parks as a provider of social and ecological services for city sustainability, through both profitable and non-profitable services. Especially for a large city park, it is difficult to cover all requirements through a single administrative party. Thus, a joint venture (JV) constituting multiple parties is one promising way to administer a large city park. This study aims to clarify the effectiveness and tasks of a JV in the designated administration of city parks. The results of questionnaires received from 69 designated administrators of large city parks (43.7% cover rate in study targets) indicated that JVs tended to actively seek new relationships with parties that have never interacted before to realize better park administration. The merits of constituting a JV included complementing limited know-how of park administration and accumulating new know-how in constituent parties. On the other hand, some disadvantages were highlighted, such as an insufficient number of new projects created through collaboration and vertically divided administration due to role sharing. To cope with these problems, better communication among constituent parties and the establishment of a collaborative environment are necessary

Tumor-derived interleukin-34 creates an immunosuppressive and chemoresistant tumor microenvironment by modulating myeloid-derived suppressor cells in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by a lack of therapeutic targets. The paucity of effective treatment options motivated a number of studies to tackle this problem. Immunosuppressive cells infiltrated into the tumor microenvironment (TME) of TNBC are currently considered as candidates for new therapeutic targets. Myeloid-derived suppressor cells (MDSCs) have been reported to populate in the TME of TNBC, but their roles in the clinical and biological features of TNBC have not been clarified. This study identified that interleukin-34 (IL-34) released by TNBC cells is a crucial immunomodulator to regulate MDSCs accumulation in the TME. We provide evidence that IL-34 induces a differentiation of myeloid stem cells into monocytic MDSCs (M-MDSCs) that recruits regulatory T (Treg) cells, while suppressing a differentiation into polymorphonuclear MDSCs (PMN-MDSCs). As a result, the increase in M-MDSCs contributes to the creation of an immunosuppressive TME, and the decrease in PMN-MDSCs suppresses angiogenesis, leading to an acquisition of resistance to chemotherapy. Accordingly, blockade of M-MDSC differentiation with an estrogen receptor inhibitor or anti-IL-34 monoclonal antibody suppressed M-MDSCs accumulation causing retardation of tumor growth and restores chemosensitivity of the tumor by promoting PMN-MDSCs accumulation. This study demonstrates previously poorly understood mechanisms of MDSCs-mediated chemoresistance in the TME of TNBC, which is originated from the existence of IL-34, suggesting a new rationale for TNBC treatment