L_X-T Relation and Related Properties of Galaxy Clusters

An observational approach is presented to constrain the global structure and evolution of the intracluster medium based on the ROSAT and ASCA distant cluster sample. From statistical analysis of the gas density profile and the connection to the LX-T relation under the beta-model, the scaled gas profile is nearly universal for the outer region and the LX(>0.2r500) is tightly related to the temperature through T^3 rather than T^2. On the other hand, a large density scatter exists in the core region and there is clearly a deviation from the self-similar scaling for clusters with a small core size. A direct link between the core size and the radiative cooling timescale suggest that t_cool is a parameter to control the gas structure and the appearance of small cores in regular clusters may be much connected with the thermal evolution. We derive the luminosity-ambient temperature (T') relation, assuming the universal temperature profile to find the dispersion around the relation significantly decreases: L_1keV is almost constant for a wide range of t_cool. We further examined the LX-Tbeta and LX-T'beta relations and showed a trend that merging clusters segregate from the regular clusters on the planes. A good correlation between t_cool and the X-ray morphology on the L_1keV-t_cool/t_age plane leads us to define three phases according to the different level of cooling, and draw a phenomenological picture: after a cluster collapses and t_cool falls below t_age, the core cools radiatively with quasi-hydrostatic balancing in the gravitational potential, and the central density gradually becomes higher to evolve from an outer-core-dominant cluster to inner-core-dominant cluster.Comment: 39 pages, 37 figures. Accepted for publication in ApJ. Version with high-quality color figures at http://cosmic.riken.jp/ota/publications/index.htm

ASCA Observations of the Supernova Remnant IC 443: Thermal Structure and Detection of Overionized Plasma

We present the results of X-ray spatial and spectral studies of the ``mixed-morphology'' supernova remnant IC 443 using ASCA. IC 443 has a center-filled image in X-ray band, contrasting with the shell-like appearance in radio and optical bands. The overall X-ray emission is thermal, not from a synchrotron nebula. ASCA observed IC 443 three times, covering the whole remnant. From the image analysis, we found that the softness-ratio map reveals a shell-like structure. At the same time, its spectra require two (1.0 keV and 0.2 keV) plasma components; the emission of the 0.2 keV plasma is stronger in the region near the shell than the center. These results can be explained by a simple model that IC 443 has a hot (1.0 keV) interior surrounded by a cool (0.2 keV) outer shell. From the emission measures, we infer that the 0.2 keV plasma is denser than the 1.0 keV plasma, suggesting pressure equilibrium between the two. In addition, we found that the ionization temperature of sulfur, obtained from H-like K$\alpha$ to He-like K$\alpha$ intensity ratio, is 1.5 keV, significantly higher than the gas temperature of 1.0 keV suggested from the continuum spectrum. The same can be concluded for silicon. Neither an additional, hotter plasma component nor a multi-temperature plasma successfully accounts for this ratio, and we conclude that the 1.0 keV plasma is overionized. This is the first time that overionized gas has been detected in a SNR. For the gas to become overionized in the absence of a photoionizing flux, it must cool faster than the ions recombine. Thermal conduction from the 1.0 keV plasma to the 0.2 keV one could cause the 1.0 keV plasma to become overionized, which is plausible within an old (3$\times10^4$ yr) SNR.Comment: 11 pages, 15 figures, 2 tables, accepted for publication in The Astrophysical Journa

Enhanced abundances in three large-diameter mixed-morphology supernova remnants

We present an X-ray study of three mixed-morphology supernova remnants (SNRs), HB 21, CTB 1 and HB 3, using archival ASCA and ROSAT data. These data are complemented by archival Chandra X-ray Observatory data for CTB 1 and XMM-Newton X-ray Observatory data for HB 3. The spectra from HB 21 and HB 3 are well-described with a single-temperature thermal plasma in ionization equilibrium, while a two-temperature thermal plasma is found in CTB 1. We found enhanced abundances in all three SNRs. The elemental abundance of Mg is clearly enhanced in CTB 1, while HB 21 has enhanced abundances of Si and S. The situation is not so clear in HB 3 -- the plasma in this SNR either has significantly enhanced abundances of O, Ne and Mg, or it has marginally enhanced abundances of Mg and under-abundant Fe. We discuss the plausibility of mixed-morphology SNR models for the three SNRs and the presence of enhanced abundances. We revise a list of MM SNRs and their properties, compare the three SNRs studied here with other members of this class, and discuss the presence of enhanced elemental abundances in MM SNRs. We also report the ASCA detection of a compact source in the southern part of HB 3. The source spectrum is consistent with a power law with a photon index of ~2.7, and an unabsorbed X-ray flux of ~10^{-12} erg/cm^2/s in the 0.5--10.0 keV band. The column density towards this source differs from that towards the SNR, and it is therefore unlikely they are related.Comment: 26 pages, 15 figures, revised version (minor changes), accepted for publication in ApJ (10 Aug 2006

Suzaku broad-band spectroscopy of RX J1347.5-1145: constraints on the extremely hot gas and non-thermal emission

We present the results from the analysis of long Suzaku observations of the most X-ray luminous galaxy cluster RX J1347.5-1145 at z=0.451. Aims: We study physical properties of the hot (~20 keV) gas clump in the south-east (SE) region discovered by the Sunyaev-Zel'dovich (SZ) effect observations, to understand the gas physics of a violent cluster merger. We also explore a signature of non-thermal emission using the hard X-ray data. Results: We find that the single-temperature model fails to reproduce the continuum emission and Fe-K lines measured by XIS simultaneously. The two-temperature model with a very hot component improves the fit, although the XIS data can only give a lower bound on its temperature. We detect the hard X-ray emission in the 12-40 keV band at the 7 sigma level; however, the significance becomes marginal when the systematic error in the background estimation is included. With the Suzaku + Chandra joint analysis, we determine the temperature of the SE excess component to be 25.3^{+6.1}_{-4.5} ^{+6.9}_{-9.5} keV (90% statistical and systematic errors), which is in an excellent agreement with the previous SZ + X-ray analysis. This is the first time that the X-ray spectroscopy alone gives a good measurement of the temperature of the hot component in the SE region, which is made possible by Suzaku's unprecedented sensitivity to the wide X-ray band. These results strongly indicate that the cluster has undergone a recent, violent merger. The spectral analysis shows that the SE component is consistent with being thermal. We find the 3 sigma upper limit on the non-thermal flux, F < 8e-12 erg s^{-1} cm^{-2} in the 12-60 keV band. Combining this limit with a recent discovery of the radio mini halo at 1.4 GHz, we find a lower limit on the strength of the intracluster magnetic field, B > 0.007 micro G.Comment: 15 pages, 13 figures. Accepted for publication in A&

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Mechanism of Cancer Cell Death Induced by Depletion of an Essential Replication Regulator

Background: Depletion of replication factors often causes cell death in cancer cells. Depletion of Cdc7, a kinase essential for initiation of DNA replication, induces cancer cell death regardless of its p53 status, but the precise pathways of cell death induction have not been characterized. Methodology/Principal Findings: We have used the recently-developed cell cycle indicator, Fucci, to precisely characterize the cell death process induced by Cdc7 depletion. We have also generated and utilized similar fluorescent cell cycle indicators using fusion with other cell cycle regulators to analyze modes of cell death in live cells in both p53-positive and-negative backgrounds. We show that distinct cell-cycle responses are induced in p53-positive and-negative cells by Cdc7 depletion. p53-negative cells predominantly arrest temporally in G2-phase, accumulating CyclinB1 and other mitotic regulators. Prolonged arrest at G2-phase and abrupt entry into aberrant M-phase in the presence of accumulated CyclinB1 are followed by cell death at the post-mitotic state. Abrogation of cytoplasmic CyclinB1 accumulation partially decreases cell death. The ATR-MK2 pathway is responsible for sequestration of CyclinB1 with 14-3-3s protein. In contrast, p53-positive cancer cells do not accumulate CyclinB1, but appear to die mostly through entry into aberrant S-phase after Cdc7 depletion. The combination of Cdc7 inhibition with known anti-cancer agents significantly stimulates cell death effects in cancer cells in a genotype-dependent manner, providing a strategic basis for future combination therapies

Interactions of the Human MCM-BP Protein with MCM Complex Components and Dbf4

MCM-BP was discovered as a protein that co-purified from human cells with MCM proteins 3 through 7; results which were recapitulated in frogs, yeast and plants. Evidence in all of these organisms supports an important role for MCM-BP in DNA replication, including contributions to MCM complex unloading. However the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood. Here we show that human MCM-BP is capable of interacting with individual MCM proteins 2 through 7 when co-expressed in insect cells and can greatly increase the recovery of some recombinant MCM proteins. Glycerol gradient sedimentation analysis indicated that MCM-BP interacts most strongly with MCM4 and MCM7. Similar gradient analyses of human cell lysates showed that only a small amount of MCM-BP overlapped with the migration of MCM complexes and that MCM complexes were disrupted by exogenous MCM-BP. In addition, large complexes containing MCM-BP and MCM proteins were detected at mid to late S phase, suggesting that the formation of specific MCM-BP complexes is cell cycle regulated. We also identified an interaction between MCM-BP and the Dbf4 regulatory component of the DDK kinase in both yeast 2-hybrid and insect cell co-expression assays, and this interaction was verified by co-immunoprecipitation of endogenous proteins from human cells. In vitro kinase assays showed that MCM-BP was not a substrate for DDK but could inhibit DDK phosphorylation of MCM4,6,7 within MCM4,6,7 or MCM2-7 complexes, with little effect on DDK phosphorylation of MCM2. Since DDK is known to activate DNA replication through phosphorylation of these MCM proteins, our results suggest that MCM-BP may affect DNA replication in part by regulating MCM phosphorylation by DDK

Characterization of Leishmania donovani MCM4: Expression Patterns and Interaction with PCNA

Events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. Nuclear DNA replication in trypanosomatids has thus far remained a largely uninvestigated area. While several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms. Here, we characterize the expression of Leishmania donovani MCM4, and find that while it broadly resembles other eukaryotes, noteworthy differences exist. MCM4 is constitutively nuclear, signifying that, unlike what is seen in S.cerevisiae, varying subcellular localization of MCM4 is not a mode of replication regulation in Leishmania. Overexpression of MCM4 in Leishmania promastigotes causes progress through S phase faster than usual, implicating a role for MCM4 in the modulation of cell cycle progression. We find for the first time in eukaryotes, an interaction between any of the proteins of the MCM2-7 (MCM4) and PCNA. MCM4 colocalizes with PCNA in S phase cells, in keeping with the MCM2-7 complex being involved not only in replication initiation, but fork elongation as well. Analysis of a LdMCM4 mutant indicates that MCM4 interacts with PCNA via the PIP box motif of MCM4 - perhaps as an integral component of the MCM2-7 complex, although we have no direct evidence that MCM4 harboring a PIP box mutation can still functionally associate with the other members of the MCM2-7 complex- and the PIP box motif is important for cell survival and viability. In Leishmania, MCM4 may possibly help in recruiting PCNA to chromatin, a role assigned to MCM10 in other eukaryotes

DNA replication licensing and cell cycle kinetics of oligodendroglial tumours

The convergence point of growth-signalling pathways that control cell proliferation is the initiation of genome replication, the core of which is the assembly of pre-replicative complexes (pre-RCs), resulting in chromatin being ‘licensed’ for DNA replication in the subsequent S phase. The Mcm2–7 complex is a core constituent of the pre-RC, whose recruitment to replication origins is dependent on the Cdt1 loading factor. Geminin is a potent inhibitor of the initiation of DNA replication by preventing Mcm2–7 assembly at origins via its interaction with Cdt1, ensuring genomic integrity through suppression of re-initiation events in S phase. Here we investigate the regulation of Ki67, Mcm2, p21, caspase 3 and Geminin in a series of 55 oligodendrogliomas to provide an integrated picture of how cellular proliferation and programmed cell death are dysregulated in these tumours. Geminin does not behave as an inhibitor of cell proliferation, its labelling index rising with increasing growth fraction as defined by Ki67 or Mcm2 expression. Geminin is expressed in a higher proportion of cells in higher grade tumours (P<0.001) and shows a strong correlation to proliferation and replication licensing (P<0.01), but not apoptosis. Increasing tumour anaplasia is not associated with loss of Geminin. Importantly, the G1 phase of the proliferative cell cycle, as assessed by the Geminin/Ki67 ratio, shortens with increasing anaplasia, providing new potential algorithms for prognostic assessment. Origin licensing proteins thus provide powerful novel tools for assessment of tumour cell cycle kinetics in routinely processed surgical biopsy material