GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation

AMiBA: scaling relations between the integrated Compton-y and X-ray derived temperature, mass, and luminosity

We investigate the scaling relations between the X-ray and the thermal Sunyaev-Zel'dovich Effect (SZE) properties of clusters of galaxies, using data taken during 2007 by the Y.T. Lee Array for Microwave Background Anisotropy (AMiBA) at 94 GHz for the six clusters A1689, A1995, A2142, A2163, A2261, and A2390. The scaling relations relate the integrated Compton-y parameter Y_{2500} to the X-ray derived gas temperature T_{e}, total mass M_{2500}, and bolometric luminosity L_X within r_{2500}. Our results for the power-law index and normalization are both consistent with the self-similar model and other studies in the literature except for the Y_{2500}-L_X relation, for which a physical explanation is given though further investigation may be still needed. Our results not only provide confidence for the AMiBA project but also support our understanding of galaxy clusters.Comment: Accepted by ApJ; 8 pages, 3 figures, 5 table

AMiBA Wideband Analog Correlator

A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.Comment: 28 pages, 23 figures, ApJ in press

Mass and Hot Baryons in Massive Galaxy Clusters from Subaru Weak Lensing and AMiBA SZE Observations

We present a multiwavelength analysis of a sample of four hot (T_X>8keV) X-ray galaxy clusters (A1689, A2261, A2142, and A2390) using joint AMiBA Sunyaev-Zel'dovich effect (SZE) and Subaru weak lensing observations, combined with published X-ray temperatures, to examine the distribution of mass and the intracluster medium (ICM) in massive cluster environments. Our observations show that A2261 is very similar to A1689 in terms of lensing properties. Many tangential arcs are visible around A2261, with an effective Einstein radius \sim 40 arcsec (at z \sim 1.5), which when combined with our weak lensing measurements implies a mass profile well fitted by an NFW model with a high concentration c_{vir} \sim 10, similar to A1689 and to other massive clusters. The cluster A2142 shows complex mass substructure, and displays a shallower profile (c_{vir} \sim 5), consistent with detailed X-ray observations which imply recent interaction. The AMiBA map of A2142 exhibits an SZE feature associated with mass substructure lying ahead of the sharp north-west edge of the X-ray core suggesting a pressure increase in the ICM. For A2390 we obtain highly elliptical mass and ICM distributions at all radii, consistent with other X-ray and strong lensing work. Our cluster gas fraction measurements, free from the hydrostatic equilibrium assumption, are overall in good agreement with published X-ray and SZE observations, with the sample-averaged gas fraction of = 0.133 \pm 0.027, for our sample = (1.2 \pm 0.1) \times 10^{15} M_{sun} h^{-1}. When compared to the cosmic baryon fraction f_b = \Omega_b/\Omega_m constrained by the WMAP 5-year data, this indicates /f_b = 0.78 \pm 0.16, i.e., (22 \pm 16)% of the baryons are missing from the hot phase of clusters.Comment: accepted for publication in ApJ; high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/ms_highreso.pd

AMiBA: Sunyaev-Zel'Dovich Effect-derived Properties and Scaling Relations of Massive Galaxy Clusters

99學年度劉國欽研究獎助論文 100學年度劉國欽升等參考著作[[abstract]]The Sunyaev-Zel'dovich Effect (SZE) has been observed toward six massive galaxy clusters, at redshifts 0.091 ≤ z ≤ 0.322 in the 86-102 GHz band with the Y. T. Lee Array for Microwave Background Anisotropy (AMiBA). We modify an iterative method, based on the isothermal β models, to derive the electron temperature T e, total mass M t, gas mass M g, and integrated Compton Y within r 2500, from the AMiBA SZE data. Non-isothermal universal temperature profile (UTP) β models are also considered in this paper. These results are in good agreement with those deduced from other observations. We also investigate the embedded scaling relations, due to the assumptions that have been made in the method we adopted, between these purely SZE-deduced T e, M t, M g, and Y. Our results suggest that cluster properties may be measurable with SZE observations alone. However, the assumptions built into the pure-SZE method bias the results of scaling relation estimations and need further study.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子版[[countrycodes]]US

Tests of AMiBA Data Integrity

We describe methods used to validate data from the Y.T. Lee Array for Microwave Background Anisotropy (AMiBA), an interferometric array designed to measure the Sunyaev-Zel'dovich effect and the anisotropy of the Cosmic Microwave Background (CMB). We perform several statistical tests on data from pointed galaxy cluster observations taken in 2007 and noise data from long-term blank sky observations and measurements with the feeds covered by the absorbers. We apply power spectrum analysis, cross power spectrum analysis among different outputs with different time lags in our analog correlator, and sample variance law tests to noise data. We find that (1) there is no time variation of electronic offsets on the time scale of our two-patch observations (~10 minutes); (2) noise is correlated by less than 10% between different lags; and (3) the variance of noise scales with the inverse of time. To test the Gaussianity of the data, we apply Kolmogorov-Smirnov (K-S) tests to cluster data, and find that a 5% significance level efficiently detects data sets with known hardware problems without rejecting an excess of acceptable data. We also calculate third- and fourth-order moments and cumulants for the noise residual visibilities and find that about 95% of our data are within the 99% confidence regions of Gaussianity.Comment: 15 pages, 5 figures, accepted for publication in Ap

AMiBA: System Performance

The Y.T. Lee Array for Microwave Background Anisotropy (AMiBA) started scientific operation in early 2007. This work describes the optimization of the system performance for the measurements of the Sunyaev-Zel'dovich effect for six massive galaxy clusters at redshifts $0.09 - 0.32$. We achieved a point source sensitivity of $63\pm 7$ mJy with the seven 0.6m dishes in 1 hour of on-source integration in 2-patch differencing observations. We measured and compensated for the delays between the antennas of our platform-mounted interferometer. Beam switching was used to cancel instrumental instabilities and ground pick up. Total power and phase stability were good on time scales of hours, and the system was shown to integrate down on equivalent timescales of 300 hours per baseline/correlation, or about 10 hours for the entire array. While the broadband correlator leads to good sensitivity, the small number of lags in the correlator resulted in poorly measured bandpass response. We corrected for this by using external calibrators (Jupiter and Saturn). Using Jupiter as the flux standard, we measured the disk brightness temperature of Saturn to be $149^{+5}_{-12}$ K.Comment: 9 pages, 7 figures, 1 table, accepted for publication in Ap

Multiple Regulatory Mechanisms to Inhibit Untimely Initiation of DNA Replication Are Important for Stable Genome Maintenance

Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase is genotoxic and induces genomic instability in the budding yeast Saccharomyces cerevisiae. Our data indicate that cells preserve a low level of the initiation factor Sld2 to prevent untimely initiation during the normal cell cycle in addition to controlling the phosphorylation of Sld2 and Sld3 by cyclin-dependent kinase. Although untimely activation of origin is inhibited on multiple levels, we show that deregulation of a single pathway can cause genomic instability, such as gross chromosome rearrangements (GCRs). Furthermore, simultaneous deregulation of multiple pathways causes an even more severe phenotype. These findings highlight the importance of having multiple inhibitory mechanisms to prevent the untimely initiation of chromosome replication to preserve stable genome maintenance over generations in eukaryotes

The Non-Catalytic Carboxyl-Terminal Domain of ARFGAP1 Regulates Actin Cytoskeleton Reorganization by Antagonizing the Activation of Rac1

The regulation of the actin cytoskeleton and membrane trafficking is coordinated in mammalian cells. One of the regulators of membrane traffic, the small GTP-binding protein ARF1, also activates phosphatidylinositol kinases that in turn affect actin polymerization. ARFGAP1 is a GTPase activating protein (GAP) for ARF1 that is found on Golgi membranes. We present evidence that ARFGAP1 not only serves as a GAP for ARF1, but also can affect the actin cytoskeleton.As cells attach to a culture dish foci of actin appear prior to the cells flattening and spreading. We have observed that overexpression of a truncated ARFGAP1 that lacks catalytic activity for ARF, called GAP273, caused these foci to persist for much longer periods than non-transfected cells. This phenomenon was dependent on the level of GAP273 expression. Furthermore, cell spreading after re-plating or cell migration into a previously scraped area was inhibited in cells transfected with GAP273. Live cell imaging of such cells revealed that actin-rich membrane blebs formed that seldom made protrusions of actin spikes or membrane ruffles, suggesting that GAP273 interfered with the regulation of actin dynamics during cell spreading. The over-expression of constitutively active alleles of ARF6 and Rac1 suppressed the effect of GAP273 on actin. In addition, the activation of Rac1 by serum, but not that of RhoA or ARF6, was inhibited in cells over-expressing GAP273, suggesting that Rac1 is a likely downstream effector of ARFGAP1. The carboxyl terminal 65 residues of ARFGAP1 were sufficient to produce the effects on actin and cell spreading in transfected cells and co-localized with cortical actin foci.ARFGAP1 functions as an inhibitor upstream of Rac1 in regulating actin cytoskeleton. In addition to its GAP catalytic domain and Golgi binding domain, it also has an actin regulation domain in the carboxyl-terminal portion of the protein