Stabilization of P/CAF, as a ubiquitin ligase toward MDM2, suppresses mitotic cell death through p53-p21 activation in HCT116 cells with SIRT2 suppression

We previously reported that the suppression of SIRT2, an NAD + -dependent protein deacetylases, induces p53 accumulation via degradation of p300 and the subsequent MDM2 degradation, eventually leading to apoptosis in HeLa cells. The present study identified a novel pathway of p53 accumulation by SIRT2 suppression in HCT116(p53+/+) cells in which SIRT2 suppression led to escape from mitotic cell death caused by spindle assembly checkpoint activation induced by microtubule inhibitors such as nocodazole but not apoptosis or G1 or G2 arrest. We found that SIRT2 interacts with P/CAF, a histone acetyltransferase, which also acts as a ubiquitin ligase against MDM2. SIRT2 suppression led to an increase of P/CAF acetylation and its stabilization followed by a decrease in MDM2 and activation of the p53-p21 pathway. Depression of mitotic cell death in HCT116(p53+/+) cells with SIRT2 suppression was released by suppression of P/CAF or p21. Thus, the P/CAF-MDM2-p53-p21 axis enables the escape from mitotic cell death and confers resistance to nocodazole in HCT116(p53+/+) cells with SIRT2 suppression. As SIRT2 has attracted attention as a potential target for cancer therapeutics for p53 regulation, the present study provides a molecular basis for the efficacy of SIRT2 for future cancer therapy based on p53 regulation. These findings also suggest an undesirable function of the SIRT2 suppression associated with activation of the p53-p21 pathway in the suppression of mitotic cell death caused by spindle assembly checkpoint activation

Liquid Level Indicator for Metal Dewar

A simple liquid level indicator for a metal dewar has been constructed with the use of superconducting elemental Ta and Nb-Ti alloy as well as carbon resistor. Electrical and superconducting properties, repeatability, sensitivity, and a practical operation of the indicator have been investigated at 78°K and 4.2°K. The hysteresis or instability effect of the resistance for Nb-Ti wire was found at the magnetic field of 17 kG. Evaporation rate of liquid helium can be estimated in the dewar with a few indicators

LOW TEMPERATURE NMR APPARATUS WITH MOSFETS (3SK45) AND A1 20 27

Thermal hysteresis tests have been made between 300 and 77 K for the static characteristics of commercial MOSFETs (3SK45) which are to be used as active elements in our steady-state NMR apparatus. The newly constructed apparatus using this type of FETs works well at low temperatures, with respect to the reproducibility, stability, and signal-to-noise ratio. With this device, the A127 NMR in ruby crystal (A1203:cr3+) has been measured at 77 K and liquid helium temperatures. Both the dipolar splitting width and the absorption intensity in the NMR spectrum depend on temperature and the angle between the magnetic field and the trigonal axis. These results are explained by the spin diffusion model, in which the A127 nuclei see the local fields arising from identical nucear spins and the paramagnetic electron spins of cr3+ ions existing in the crystal

Low Field Superconducting Magnet with Nb-Ti Wire

A low-field square ended superconducting magnet has been constructed with Nb-Ti alloy as a coil, which is to be used for the nuclear magnetic resonance experiment at helium temperatures. The wire is wound around a brass bobbin (the inner diameter 10 mm and the length 60 mm). To operate the magnet in a persistent mode, a persistent current switch with the same wire is attached The magnetic field strength at the exciting current 20 A is about 12kG, which is measured by a Bi-sensor. No decay of the persistent current is observed with time. The field strength vs. the current and the field distribution in the magnet are measured, which are in good agreement with the calculated values

Muscle Thickness of Anterior Mid-Thigh in Hospitalized Patients : Comparison of Supine and Standing Postures

Objectives: To compare the magnitude changes in muscle thickness (MTH) of the anterior mid-thigh between the supine and standing postures.Design: Experimental.Setting: University hospital laboratory.Participants: Inpatients (N=283) between the ages of 29 and 93 years (193 men, 90 women) with cardiovascular disease who volunteered for this study.Interventions: Not applicable.Main Outcome Measures: MTH of the anterior mid-thigh was measured with a 10 MHz ultrasound probe while the participants stood or lay supine in a relaxed position with their arms extended and by their sides.Results: Age and percentage of body fat were greater (P<.01) in women than in men (74.3±12.3 vs 67.7±12.1y and 32.6±10.3% vs 27.4±7.4%, respectively), but standing height, body weight, and body mass index were greater (P<.01) in men than in women (164.9±6.3 vs 149.1±7.5 cm, 65.4±12.7 vs 49.5±11.1 kg, and 23.8±3.9 vs 22.1±4.4 kg/㎡, respectively). Correlations were found between the standing posture and supine position in the anterior-mid thigh MTH for both men (r=0.85; P<.01) and women (r=0.82; P<.01). In the anterior-mid thigh for men and women, MTH was greater in the standing posture (3.7±1.0 vs 2.5±0.7 cm) than in supine position (3.1±0.8 vs 2.1±0.7 cm) (both P<.01).Conclusions: In this study, MTH of the anterior mid-thigh during prolonged hospitalization was approximately 16% higher in men than in women regardless of posture, and was approximately 32% higher in standing posture than in the supine position regardless of sex

Not only Body Weight Perception but also Body Mass Index is Relevant to Suicidal Ideation and Self-Harming Behavior in Japanese Adolescents

Whether a low body mass index (BMI) is directly associated with a high risk of suicidal ideation or self-harming behavior in adolescents is still inconclusive. This study has, therefore, evaluated the relevance of BMI to suicidal ideation and self-harming behavior after controlling for body weight perception (BWP) and other potential confounding factors. BMI, BWP, suicidal ideation, and self-harming behavior were all assessed using a self-report questionnaire administered to 18,104 Japanese adolescents. Potential confounding factors were also evaluated. The data were then analyzed using bi-variate and multivariate logistic regression. Low BMI was associated with suicidal ideation and deliberate self-harm when controlling for sex, age, drug use, emotional distress, and BWP. Low BMI may be an independent risk factor for suicidal ideation and deliberate self-harming behavior in Japanese adolescents.ArticleJOURNAL OF NERVOUS AND MENTAL DISEASE. 200(4):305-309 (2012)journal articl

Mechanism of delayed seed germination caused by high temperature during grain filling in rice (Oryza sativa L.)

High temperature during grain filling considerably reduces yield and quality in rice (Oryza sativa L.); however, how high temperature affects seed germination of the next generation is not yet well understood. Here, we report that seeds from plants exposed to high temperature during the grain filling stage germinated significantly later than seeds from unstressed plants. This delay remained even after dormancy release treatments, suggesting that it was not due to primary seed dormancy determined during grain filling. In imbibed embryos of heat-stressed seeds, expression of abscisic acid (ABA) biosynthesis genes (OsNCEDs) was higher than in those of control seeds, whereas that of ABA catabolism genes (OsABA8′OHs) was lower. In the aleurone layer, despite no change in GA signaling as evidenced by no effect of heat stress on OsGAMYB gene expression, the transcripts of α-amylase genes OsAmy1C, OsAmy3B, and OsAmy3E were significantly down-regulated in heat-stressed seeds in comparison with controls. Changes in promoter methylation levels were consistent with transcriptional changes of ABA catabolism-related and α-amylase genes. These data suggest that high temperature during grain filling results in DNA methylation of ABA catabolism-related and α-amylase gene promoters, delaying germination of heat-stressed seeds