p42MAPK-mediated phosphorylation of xEIAP/XLX in Xenopus cytostatic factor-arrested egg extracts

BACKGROUND: BIR family proteins are evolutionarily conserved anti-apoptotic molecules. One member of Xenopus BIR family proteins, xEIAP/XLX, is a weak apoptosis inhibitor and rapidly degraded in a cell-free apoptotic execution system derived from interphase egg extracts. However, unfertilized eggs are naturally arrested at the metaphase of meiosis II by the concerted activities of Mos-MEK-p42MAPK-p90Rsk kinase cascade (cytostatic factor pathway) and many mitotic kinases. Previous studies suggest that cytostatic factor-arrested egg extracts are more resistant to spontaneous apoptosis than interphase egg extracts in a p42MAPK-dependent manner. We tested whether xEIAP/XLX might be phosphorylated in cytostatic factor-arrested egg extracts, and also examined whether xEIAP/XLX could be functionally regulated by phosphorylation. RESULTS: We found that p42MAPK was the major kinase phosphorylating xEIAP/XLX in cytostatic factor-arrested egg extracts, and three Ser residues (Ser 235/251/254) were identified as p42MAPK-mediated phosphorylation sites. We characterized the behaviors of various xEIAP/XLX mutants that could not be phosphorylated by p42MAPK. However, neither protein stability nor anti-apoptotic ability of xEIAP/XLX was significantly altered by the substitution of Ser with either Ala or Asp at these three sites. CONCLUSION: xEIAP/XLX is physiologically phosphorylated by p42MAPK in Xenopus unfertilized eggs. However, this protein may not serve as an essential mediator of p42MAPK-dependent anti-apoptotic activity

A Non-notewise Melody Editing Method for Supporting Musically Untrained People's Music Composition

There have been many systems that automatically create a melody. However, when the created melody is not satisfactory, it is difficult for musically untrained people to manually edit it on a conventional MIDI sequencer. Therefore, we propose a melody editing method based on a melodic outline, which represents the overall shape of a melody. Given a melody, its melodic outline is obtained by applying the Fourier transform to the melody's pitch trajectory and extracting low-order Fourier coefficients. After the outline is redrawn, it is transformed into a note sequence by the inverse procedure of the extraction and a hidden Markov model. Experimental results showed that (1) for novice participants, our system was easier than the conventional piano-roll interface, (2) generated melodies were satisfactory for both novice and intermediate participants, and (3) novice participants' ideas about what melody they want became clearer as they experienced melody editing everyday

Endoscopic Ultrasonography-Guided Gastroenterostomy Techniques for Treatment of Malignant Gastric Outlet Obstruction

Gastric outlet obstruction (GOO) can be caused by periampullary malignancies and often leads to a reduction in a patient’s quality of life. Recently, endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) using a lumen-apposing self-expandable metal stent (LAMS) has been developed as a minimally invasive and durable endoscopic treatment for GOO. There are three types of EUS-GE technique: (1) the direct technique; (2) device-assisted techniques, such as a balloon catheter, nasobiliary drainage tube, and ultraslim endoscopy; and (3) EUS-guided double balloon-occluded gastrojejunostomy bypass. Previous reports of EUS-GE with LAMS have shown technical and clinical success rates (regardless of technique and etiology) of 87%–100% and 84%–100%, respectively. Studies comparing EUS-GE and surgical gastrojejunostomy have shown similar success rates, reintervention rates, and cost benefits, with a lower rate of early adverse events in EUS-GE. A comparison of EUS-GE and endoscopic enteral stent placement revealed similar technical success rates, but initial clinical success rate was higher and the rate of stent failure requiring reintervention was lower with EUS-GE

Effect of endothelin-1 (1-31) on the renal resistance vessels

Human chymase produces not only angiotensin II but also endothelin(ET)-1(1-31). We previously reported that ET-1(1-31) had several biological activities in vascular smooth muscle cells. In this study, we investigated the vasoconstrictor effect of ET-1(1-31) on the renal resistance vessels using in vitro micro perfused rabbit afferent and efferent arterioles.ET-1(1-31) decreased the lumen diameter of the afferent and efferent arterioles dose-dependently.ET-1(1-31)-induced afferent arteriolar vasoconstriction was not affected by phosphoramidon, an ET converting enzyme inhibitor. ET-1(1-31)-induced renal arteriolar vasoconstriction was inhibited by BQ123, an ETA receptor inhibitor, but not by BQ788, an ETB receptor inhibitor. These results suggest that ET-1(1-31)-induced renal arteriolar vasoconstriction may be mediated by ETA-like receptors

Adenosine receptors in the isolated rabbit afferent and efferent arterioles

Adenosine has been noted as one of the endogenous modulators of renal hemodynamics. Renal hemodynamic was mainly regulated by two resistance vessels, the afferent arteriole and efferent arteriole. However, there is still no consensus as to the intrarenal vascular action site of adenosine. In this study, we examined the direct effect of adenosine on the isolated microperfused rabbit afferent and efferent arterioles. Adenosine decreased the lumen diameter of microperfused afferent arterioles dose-dependently (Control : 14.35±0.97μm, adenosine 10-7M : 12.73±1.40μm, 10-6M : 8.18±1.21μm, 10-5M : 4.33±1.16μm, n=6). Adenosine increased the lumen diameter of adenosine A1 antagonist, 8-(normantan-3-yl)-1,3-dipropylxanthin (KW-3902), pretreated-microperfused afferent arterioles preconstricted by norepinephrine. Pretreatment with adenosine A2 antagonist, (E)-1,3,-dipropyl-8-(3,4-dimethoxystyryl)-7-methylxanthin (KF-7837), enhanced adenosine induced-afferent arteriolar vasoconstrictor effect. Adenosine did not change the lumen diameter of microperfused efferent arterioles, but adenosine increased the lumen diameter of norepinephrine preconstricted-microperfused efferent arterioles. The present data suggest that the afferent arterioles possesses both adenosine A1 and A2 receptors and the efferent arterioles possesses predominantly adenosine A2 receptors at least in the rabbit kidney

Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids

Housekeeping metabolic pathways such as glycolysis are active in all cell types. In addition, many types of cells are equipped with cell-specific metabolic pathways. To properly perform their functions, housekeeping and cell-specific metabolic pathways must function cooperatively. However, the regulatory mechanisms that couple metabolic pathways remain largely unknown. Recently, we showed that the steroidogenic cell-specific nuclear receptor Ad4BP/ SF-1, which regulates steroidogenic genes, also regulates housekeeping glycolytic genes. Here, we identify cholesterogenic genes as the targets of Ad4BP/SF-1. Further, we reveal that Ad4BP/SF-1 regulates Hummr, a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria. Given that cholesterol is the starting material for steroidogenesis and is synthesized from acetyl-CoA, which partly originates from glucose, our results suggest that multiple biological processes involved in synthesizing steroid hormones are governed by Ad4BP/SF-1. To our knowledge, this study provides the first example where housekeeping and cell-specific metabolism are coordinated at the transcriptional level.This work was supported by Grants 16H05142 (K.M.), 17H06427 (K.M.), 16K08593 (T.B.), and 17J03270 (M.I.) from the Japan Society for the Promotion of Science (JSPS) KAKENHI; The Uehara Memorial Foundation (K.M.); Takeda Science Foundation (T.B.); The Shin-Nihon of Advanced Medical Research (T.B.).Supplementary information accompanies this paper at https://doi.org/10.1038/s42003-018-0020-z

Geologic structures of the Berrheia, the Balchen Fjella, Sør Rondane Mountains, East Antarctica

第2回極域科学シンポジウム/第31回極域地学シンポジウム 11月17日（木） 国立極地研究所　2階大会議室前フロ

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML