Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus

Nuclear respiratory factor-1 (NRF-1) stimulates the transcription of nuclear-encoded genes that regulate mitochondrial (mt) genome transcription and biogenesis. We reported that estradiol (E2) and 4-hydroxytamoxifen (4-OHT) stimulate NRF-1 transcription in an estrogen receptor ? (ER?)- and ER?-dependent manner in human breast cancer cells. The aim of this study was to determine whether E2 and 4-OHT increase NRF-1 in vivo. Here, we report that E2 and 4-OHT increase NRF-1 expression in mammary gland (MG) and uterus of ovariectomized C57BL/6 mice in a time-dependent manner. E2 increased NRF-1 protein in the uterus and MG; however, in MG, 4-OHT increased Nrf1 mRNA but not protein. Chromatin immunoprecipitation assays revealed increased in vivorecruitment of ER? to the Nrf1 promoter and intron 3 in MG and uterus 6 h after E2 and 4-OHT treatment, commensurate with increased NRF-1 expression. E2- and 4-OHT-induced increases in NRF-1 and its target genes Tfam, Tfb1m, and Tfb2m were coordinated in MG but not in uterus due to uterine-selective inhibition of the expression of the NRF-1 coactivators Ppargc1a and Ppargc1b by E2 and 4-OHT. E2 transiently increased NRF-1 and PGC-1? nuclear staining while reducing PGC-1? in uterus. E2, not 4-OHT, activates mt biogenesis in MG and uterus in a time-dependent manner. E2 increased mt outer membrane Tomm40 protein levels in MG and uterus whereas 4-OHT increased Tomm40 only in uterus. These data support the hypothesis of tissue-selective regulation of NRF-1 and its downstream targets by E2 and 4-OHT in vivo

A New Hardware Correlator in Korea: Performance Evaluation using KVN observations

We report results of the performance evaluation of a new hardware correlator in Korea, the Daejeon correlator, developed by the Korea Astronomy and Space Science Institute (KASI) and the National Astronomical Observatory of Japan (NAOJ). We conducted Very Long Baseline Interferometry (VLBI) observations at 22~GHz with the Korean VLBI Network (KVN) in Korea and the VLBI Exploration of Radio Astrometry (VERA) in Japan, and correlated the aquired data with the Daejeon correlator. For evaluating the performance of the new hardware correlator, we compared the correlation outputs from the Daejeon correlator for KVN observations with those from a software correlator, the Distributed FX (DiFX). We investigated the correlated flux densities and brightness distributions of extragalactic compact radio sources. The comparison of the two correlator outputs show that they are consistent with each other within $<8\%$, which is comparable with the amplitude calibration uncertainties of KVN observations at 22~GHz. We also found that the 8\% difference in flux density is caused mainly by (a) the difference in the way of fringe phase tracking between the DiFX software correlator and the Daejeon hardware correlator, and (b) an unusual pattern (a double-layer pattern) of the amplitude correlation output from the Daejeon correlator. The visibility amplitude loss by the double-layer pattern is as small as 3\%. We conclude that the new hardware correlator produces reasonable correlation outputs for continuum observations, which are consistent with the outputs from the DiFX software correlator.Comment: 13 pagee, 9 figures, 3 tables, to appear in JKAS (received February 9, 2015; accepted March 16, 2015

P-wave Quarkonium Decays to Meson Pairs

The processes of P-wave Quarkonium exclusive decays to two mesons are investigated, in which the final state vector mesons with various polarizations are considered separately. In the calculation, the initial heavy quarkonia are treated in the framework of non-relativistic quantum chromodynamics, whereas for light mesons, the light cone distribution amplitudes up to twist-3 are employed. It turns out that the higher twist contribution is significant and provides a possible explanation for the observation of the hadron helicity selection rule violated processes $\chi_{c1}\rightarrow \phi\phi,\omega\omega$ by the BESIII collaboration in recently. We also evaluate the $\chi_{b1}\to J/\psi J/\psi$ process and find that its branching ratio is big enough to be measured at the B-factories.Comment: more results and discussions adde

The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state

Orientia tsutsugamushi (Ot) is an obligate intracellular bacterium in the family Rickettsiaceae that causes scrub typhus, a severe mite-borne human disease. Its mechanism of cell exit is unusual amongst Rickettsiaceae, as Ot buds off the surface of infected cells enveloped in plasma membrane. Here, we show that Ot bacteria that have budded out of host cells are in a distinct developmental stage compared with intracellular bacteria. We refer to these two stages as intracellular and extracellular bacteria (IB and EB, respectively). These two forms differ in physical properties: IB is both round and elongated, and EB is round. Additionally, IB has higher levels of peptidoglycan and is physically robust compared with EB. The two bacterial forms differentially express proteins involved in bacterial physiology and host-pathogen interactions, specifically those involved in bacterial dormancy and stress response, and outer membrane autotransporter proteins ScaA and ScaC. Whilst both populations are infectious, entry of IB Ot is sensitive to inhibitors of both clathrin-mediated endocytosis and macropinocytosis, whereas entry of EB Ot is only sensitive to a macropinocytosis inhibitor. Our identification and detailed characterization of two developmental forms of Ot significantly advances our understanding of the intracellular lifecycle of an important human pathogen

OGLE-2016-BLG-1227L: A Wide-separation Planet from a Very Short-timescale Microlensing Event

We present the analysis of the microlensing event OGLE-2016-BLG-1227. The light curve of this short-duration event appears to be a single-lens event affected by severe finite-source effects. Analysis of the light curve based on single-lens single-source (1L1S) modeling yields very small values of the event timescale, t_E ∼ 3.5 days, and the angular Einstein radius, θ_E ∼ 0.009 mas, making the lens a candidate of a free-floating planet. Close inspection reveals that the 1L1S solution leaves small residuals with amplitude ΔI ≲ 0.03 mag. We find that the residuals are explained by the existence of an additional widely-separated heavier lens component, indicating that the lens is a wide-separation planetary system rather than a free-floating planet. From Bayesian analysis, it is estimated that the planet has a mass of _p = 0.79^(+1.30)_(−0.39) M_J and it is orbiting a low-mass host star with a mass of M_(host) = 0.10+0.17−0.05 M_⊙ located with a projected separation of a_ = 3.4^(+2.1)_(−1.0) au. The planetary system is located in the Galactic bulge with a line-of-sight separation from the source star of D_(LS) = 1.21^(+0.96)_(−0.63) kpc. The event shows that there are a range of deviations in the signatures of host stars for apparently isolated planetary lensing events and that it is possible to identify a host even when a deviation is subtle

The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/?-Catenin Pathway in Skin Epidermis In Vivo

The contribution of the Wnt signaling pathway to human papilloma virus (HPV)-induced carcinogenesis is poorly understood. In high-grade dysplastic lesions that are caused by high-risk HPVs (HR-HPV), ?-catenin is often located in the cell nucleus, which suggests that Wnt pathway may be involved in the development of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain of the HPV16-E6 oncoprotein induces the nuclear accumulation of ?-catenin due to its capacity to degrade PDZ-containing cellular targets. To test this hypothesis, we evaluated the staining pattern of ?-catenin in the skin epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6 mice) and measured LacZ gene expression in K14E6 mice that were crossed with a strain expressing LacZ that was knocked into the Axin2 locus (Axin2+/LacZ mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of ?-catenin, the accumulation of cellular ?-catenin–responsive genes, and the expression of LacZ. None of these effects were observed when a truncated E6 oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6?PDZ mice) or in combination with Axin2+/LacZ. Conversely, cotransfection with either E6 or E6?PDZ similarly enhanced canonical Wnt signaling in short-term in vitro assays that used a luciferase Wnt/?-catenin/TCF-dependent promoter. We propose that the activation of canonical Wnt signaling could be induced by the HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain seems to be important in in vivo models only. Mol Cancer Res; 10(2); 250–8. ©2011 AACR