SIRT1 negatively regulates the expression of Prl2C3,a senescence-associated protein

SIRT1 is a mammalian homologue of yeast longevity protein Sir2. SIRT1 deacetylates transcription factors, cofactors, and histones in an NAD+-dependent manner, and promotes cell survival, anti-oxidative function, and DNA repair. Although some studies have indicated that SIRT1 is involved in longevity, the function of SIRT1 for preventing aging and senescence is still unclear. In mouse embryonic fibroblasts (MEFs), we found that SIRT1 expression decreased by aging and IRT1 reciprocally regulated the expression level of Prl2C3, one of the prolactin-like peptides. In young MEFs, purified Prl2C3 inhibited the growth and increased the number of senescence-associated β galactosidase-positive cells with enlarged and flattened shapes. Moreover, immunostaining of human skin sections showed the expression of Prl2C3 in the basal cells of the epidermis. These results indicate that SIRT1 negatively regulates a senescence-associated protein rl2C3

Mechanistic Insight on the Formation of GaN:ZnO Solid Solution from Zn–Ga Layered Double Hydroxide Using Urea as the Nitriding Agent

A solid solution of GaN and ZnO (GaN:ZnO) is promising as a photocatalyst for visible light-driven overall water splitting to produce H2. However, several obstacles still exist in the conventional preparation procedure of GaN:ZnO. For example, the atomic distributions of Zn and Ga are non-uniform in GaN:ZnO when a mixture of the metal oxides, i.e., Ga2O3 and ZnO, is used as a precursor. In addition, GaN:ZnO is generally prepared under harmful NH3 flow for long durations at high temperatures. Here, a facile synthesis of GaN:ZnO with homogeneous atomic composition via a simple and safe procedure is reported. A layered double hydroxide (LDH) containing Zn2+ and Ga3+ was used to increase the uniformity of the atomic distributions of Zn and Ga in GaN:ZnO. We employed urea as a nitriding agent instead of gaseous NH3 to increase the safety of the reaction. Through the optimization of reaction conditions such as heattreatment temperature and content of urea, single-phase GaN:ZnO was successfully obtained. In addition, the nitridation mechanism using urea was investigated in detail. NH3 released from the thermal decomposition of urea did not directly nitride the LDH precursor. X-ray absorption and infrared spectroscopies revealed that Zn(CN2)-like intermediate species were generated at the middle temperature range and Ga–N bonds formed at high temperature along with dissociation of CO and CO2.This file includes Supporting Information.This work was supported by JSPS KAKENHI Grant Number JP16H06438, JP16H06441, JP17H05483, JP17H03392. This work was partly supported by the Center for Functional Nano Oxide at Hiroshima University. The synchrotron radiation experiments were performed at the BL01B1 beamline of SPring-8 with the approval of the Japan Synchrotron Radiation Research 32 Institute (JASRI) (Proposal No. 2017B1043 and 2018A1749)

An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/ thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of transGolgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria

Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP

形態学的に骨髄腫細胞との鑑別に苦慮した plasmacytoid な形態を示した膀胱癌の多発骨転移の１例

　尿路上皮癌には，腫瘍細胞が形質細胞に酷似した形態を呈することがある．今回，形態学的に骨髄腫細胞との鑑別に苦慮したplasmacytoid な形態を示した膀胱癌の骨髄転移の一例を経験したので報告する．　症例は80歳代男性で，20XX 年10月に蛋白尿と腎機能障害が出現し，精査にて多発性骨髄腫（IgG-λ），ISS Ⅱ期と診断され，BD 療法（bortezomib+dexamethasone）を開始した．効果は良好で，３コース施行後にはVGPR（very good partial response）に到達した．20XX ＋１年２月間歇的に認めていた血尿の精査を行い，細胞診や膀胱鏡検査から膀胱癌の併発を確認した．骨髄腫治療は中断し，膀胱癌治療を優先した．PET/CT 検査ではリンパ節やその他臓器への転移は認めず，６月に膀胱全摘術が施行された．術後は経過良好であったため，全身状態の回復を待ち，骨髄腫治療を再開する予定であった．しかし，９月末頃から腰痛が出現し，10月には腰痛の増強を認めたため再度PET/CT 検査を施行したところ，多発する骨髄病変を認めた．骨髄腫の増悪を疑い骨髄検査を施行した．骨髄穿刺塗沫標本では，形質細胞様の異形細胞を多数認め，骨髄腫の増悪を推測させる所見であった．しかし同時に施行された骨髄腫関連検査では，IgG やその他の免疫グロブリンは正常であり，蛋白分画や免疫固定法でもM 蛋白は検出されなかった．骨髄生検の病理組織学的検査の結果，形質細胞様の異形細胞は尿路上皮系の腫瘍細胞であり，膀胱癌の骨転移と診断された．PET/CT 検査での多発骨髄病変は，多発性骨髄腫の増悪ではなく，膀胱癌の多発骨転移であった．　膀胱全摘後の再発は，遠隔転移が20～50% と遠隔転移が多く，遠隔転移部位として骨，リンパ節，肺，肝の順に多いと報告されている．そのため，骨髄塗抹標本検鏡の際，遭遇する可能性があり，骨髄腫細胞と見誤らないためには，免疫染色を含めた組織学的な検討，血清・尿の蛋白解析が必須と考えられた．　Urothelial cancer cells may appear similar to plasma cells. We present a case of plasmacytoid bladder cancer with bone marrow metastasis and difficult morphological differentiation from myeloma. A male in his 80s presented with proteinuria and renal dysfunction in October 20XX. Detailed examination led to a diagnosis of International Staging System Stage II multiple myeloma (IgG-λ), and BD (bortezomib + dexamethasone) therapy was started. Three courses of treatment resulted in a very good partial response. Intermittent hematuria was observed in February 20XX+1, and cytodiagnosis and cystoscopy confirmed bladder cancer. Myeloma treatment was discontinued, and treatment of bladder cancer was prioritized. There was no metastasis to lymph nodes or other organs on positron emission tomography-computed tomography (PET/CT) and cystectomy was performed in June. The postoperative course was good, and myeloma treatment was to resume once the patient had improved. However, in late September, he developed lower back pain that intensified in October. Repeat PET/ CT confirmed multiple bone marrow lesions. Exacerbation of myeloma was suspected. Bone marrow aspiration confirmed multiple plasma cell-like atypical cells, indicating exacerbation of myeloma. However, other myeloma-related tests performed at the same time, including IgG and immunoglobulins, were normal, and M protein was not detected on protein fractionation or immunofixation. Histopathological examination of a bone marrow biopsy showed that plasma cell-like atypical cells were urothelial tumor cells, and bone metastasis from bladder cancer was diagnosed. Multiple bone marrow lesions found on PET/CT were not an exacerbation of multiple myeloma but instead were multiple bone metastases from bladder cancer.　Recurrence following cystectomy has a high prevalence of distant metastasis (20 to 50%), and distant metastasis sites include bones, lymph nodes, lungs, and liver in the order of prevalence. Therefore, bone marrow aspiration and histological examination with immunostaining, in addition to serum and urine protein analysis are essential to prevent confusion with myeloma cells

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu}$as) astrometry in the near-infrared (NIR) Hw band (1.0–1.6 ${\mu}$m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions

A CASE OF DOUBLE RENAL PELVES AND URETERS ASSOCIATED WITH DOUBLE SUPERIOR VENAE CAVAE

A case of incomplete double renal pelves and ureters was found in a 78-year- old Japanese woman during an ordinary dissection by medical students at Nara Medical University in 2007. The double renal pelves and ureters were present in the left kidney. After two ureters were combined at the distal site, the combined ureter entered the urinary bladder. The number of renal calices was five and three in the upper and lower renal pelves of the left kidney, respectively. Furthermore, the right kidney and ureter were normal. The double superior venae cavae were also present in the woman

Quantitative Proteomic Analysis of the Response to Zinc, Magnesium, and Calcium Deficiency in Specific Cell Types of Arabidopsis Roots

The proteome profiles of specific cell types have recently been investigated using techniques such as fluorescence activated cell sorting and laser capture microdissection. However, quantitative proteomic analysis of specific cell types has not yet been performed. In this study, to investigate the response of the proteome to zinc, magnesium, and calcium deficiency in specific cell types of Arabidopsis thaliana roots, we performed isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics using GFP-expressing protoplasts collected by fluorescence-activated cell sorting. Protoplasts were collected from the pGL2-GFPer and pMGP-GFPer marker lines for epidermis or inner cell lines (pericycle, endodermis, and cortex), respectively. To increase the number of proteins identified, iTRAQ-labeled peptides were separated into 24 fractions by OFFGFEL electrophoresis prior to high-performance liquid chromatography coupled with mass spectrometry analysis. Overall, 1039 and 737 proteins were identified and quantified in the epidermal and inner cell lines, respectively. Interestingly, the expression of many proteins was decreased in the epidermis by mineral deficiency, although a weaker effect was observed in inner cell lines such as the pericycle, endodermis, and cortex. Here, we report for the first time the quantitative proteomics of specific cell types in Arabidopsis roots