Interplay between Transcription and RNA Degradation

Amount of mRNA depends on the both the rates of mRNA transcription in the nucleus and mRNA degradation in the cytoplasm. Although each of the processes was studied independently, recent studies demonstrated the interplay between transcription and mRNA degradation in various cellular processes, such as cell-cycle, cellular differentiation, and stress responses. In this review, we discuss the benefit of the interplay in the gene expressions and the mechanisms how these two processes are coupled. We also review recent genome-wide methods to measure the rates of transcription and degradation

Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes

AbstractSterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinemia in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-1a activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance

The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. High-fat diet (HFD) and obesity, which is now endemic, increase breast cancer risk and have been associated with worse prognosis. HFD accelerated the onset of tumors with more advanced lesions and increased triple-negative spontaneous breast tumors and HDAC activity in MMTV-PyMT transgenic mice. Oral administration of clinically relevant doses of FTY720 suppressed development, progression and aggressiveness of spontaneous breast tumors in these mice, reduced HDAC activity and strikingly reversed HFD-induced loss of estrogen and progesterone receptors in advanced carcinoma. In ERα-negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, treatment with FTY720 also re-expressed ERα and increased therapeutic sensitivity of ERα-negative syngeneic breast tumors to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that a multipronged attack with FTY720 is a novel combination approach for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer

Momentum-resolved charge excitations in high-Tc cuprates studied by resonant inelastic x-ray scattering

We report a Cu K-edge resonant inelastic x-ray scattering (RIXS) study of high-Tc cuprates. Momentum-resolved charge excitations in the CuO2 plane are examined from parent Mott insulators to carrier-doped superconductors. The Mott gap excitation in undoped insulators is found to commonly show a larger dispersion along the [pi,pi] direction than the [pi,0] direction. On the other hand, the resonance condition displays material dependence. Upon hole doping, the dispersion of the Mott gap excitation becomes weaker and an intraband excitation appears as a continuum intensity below the gap at the same time. In the case of electron doping, the Mott gap excitation is prominent at the zone center and a dispersive intraband excitation is observed at finite momentum transfer

Quantum fluctuation and geometrical frustration effects on electric polarization

We examine theoretically a possibility of ferroelectricity caused by electronic charge order without inversion symmetry, motivated by layered iron oxides. Quantum electronic models in a paired-triangular lattice are analyzed by utilizing the variational Monte Carlo simulation. Our calculation demonstrates that combined effects of electron transfer between the layers, corresponding to quantum fluctuation between the potential minima, and geometrical frustration promote appearance of an electric polarization. Present results are in contrast to the conventional manner of quantum fluctuation in ferroelectricity.Comment: 5 pages, 4 figure

Present Status in the Development of 6 MeV Heavy Ion Beam Probe on LHD

In order to measure the potential in Large Helical Device (LHD), we have been developing a heavy ion beam probe (HIBP). For probing beam, gold beam is used, which is accelerated by a tandem accelerator up to the energy of 6 MeV. The experiments for calibration of beam orbit were done, and experimental results were compared with orbit calculations. The experimental results coincided fairly with the calculation results. After the calibration of the beam orbit, the potential in plasma was tried to measure with the HIBP. The experimental data showed positive potential in a neutral beam heating phase on the condition of ne ? 5 × 10^18 m^-3, and the increase of potential was observed when the additional electron cyclotron heating was applied to this plasma. The time constant for this increase was about a few tens ms, which was larger than a theoretical expectation. In the spatial position of sample volume, we might have an ambiguity in this experiment

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)

Introduction: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. Methods and analysis: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoint are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. Ethics and dissemination: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals