Suzaku X-Ray Imaging and Spectroscopy of Cassiopeia A

Suzaku X-ray observations of a young supernova remnant, Cassiopeia A, were carried out. K-shell transition lines from highly ionized ions of various elements were detected, including Chromium (Cr-Kalpha at 5.61 keV). The X-ray continuum spectra were modeled in the 3.4--40 keV band, summed over the entire remnant, and were fitted with a simplest combination of the thermal bremsstrahlung and the non-thermal cut-off power-law models. The spectral fits with this assumption indicate that the continuum emission is likely to be dominated by the non-thermal emission with a cut-off energy at > 1 keV. The thermal-to-nonthermal fraction of the continuum flux in the 4-10 keV band is best estimated as ~0.1. Non-thermal-dominated continuum images in the 4--14 keV band were made. The peak of the non-thermal X-rays appears at the western part. The peak position of the TeV gamma-rays measured with HEGRA and MAGIC is also shifted at the western part with the 1-sigma confidence. Since the location of the X-ray continuum emission was known to be presumably identified with the reverse shock region, the possible keV-TeV correlations give a hint that the accelerated multi-TeV hadrons in Cassiopeia A are dominated by heavy elements in the reverse shock region.Comment: Publ. Astron. Soc. Japan 61, pp.1217-1228 (2009

High-temperature performance of ferritic steels in fireside corrosion regimes: temperature and deposits

The paper reports high temperature resistance of ferritic steels in fireside corrosion regime in terms of temperature and deposits aggressiveness. Four candidate power plant steels: 15Mo3, T22, T23 and T91 were exposed under simulated air-fired combustion environment for 1000 h. The tests were conducted at 600, 650 and 700 °C according to deposit-recoat test method. Post-exposed samples were examined via dimensional metrology (the main route to quantify metal loss), and mass change data were recorded to perform the study of kinetic behavior at elevated temperatures. Microstructural investigations using ESEM-EDX were performed in order to investigate corrosion degradation and thickness of the scales. The ranking of the steels from most to the least damage was 15Mo3 > T22 > T23 > T91 in all three temperatures. The highest rate of corrosion in all temperatures occurred under the screening deposit

mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function.

細胞質における鉄の出納はiron regulatory protein 1および2（IRP1/2）を介する鉄輸送の制御によって維持されるが，鉄が重要な役割を果たすミトコンドリアにおける鉄欠乏への適応機構は不明であった．本研究では，mRNA結合蛋白tristetraprolin（TTP）が鉄欠乏により発現誘導され，ミトコンドリア電子伝達系における鉄含有蛋白の発現量を鉄利用に合わせて適切に制御することによりミトコンドリア機能を維持することを明らかにした

Inhibition of ICAM2 induces radiosensitisation in oral squamous cell carcinoma cells

We recently identified genes and molecular pathways related to radioresistance of oral squamous cell carcinoma (OSCC) using Affymetrix GeneChip. The current study focused on the association between one of the target genes, intercellular adhesion molecule 2 (ICAM2), and resistance to X-ray irradiation in OSCC cells, and evaluated the antitumor efficacy of combining ICAM2 small interfering RNA (siRNA) and X-ray irradiation. Downregulation of ICAM2 expression by siRNA enhanced radiosensitivity of OSCC cells with the increased apoptotic phenotype via phosphorylation (ser473) of AKT and activation of caspase-3. Moreover, overexpression of ICAM2 induced greater OSCC cell resistance to the X-ray irradiation with the radioresistance phenotype. These results suggested that ICAM2 silencing is closely related to sensitivity of OSCC cells to radiotherapy, and that ICAM2 may be an effective radiotherapeutic target for this disease

Role of ER Stress in Ventricular Contractile Dysfunction in Type 2 Diabetes

BACKGROUND: Diabetes mellitus (DM) is associated with an increased risk of ischemic heart disease and of adverse outcomes following myocardial infarction (MI). Here we assessed the role of endoplasmic reticulum (ER) stress in ventricular dysfunction and outcomes after MI in type 2 DM (T2DM). METHODOLOGY AND PRINCIPAL FINDINGS: In hearts of OLETF, a rat model of T2DM, at 25∼30 weeks of age, GRP78 and GRP94, markers of ER stress, were increased and sarcoplasmic reticulum calcium ATPase (SERCA)2a protein was reduced by 35% compared with those in LETO, a non-diabetic control. SERCA2a mRNA levels were similar, but SERCA2a protein was more ubiquitinated in OLETF than in LETO. Left ventricular (LV) end-diastolic elastance (Eed) was higher in OLETF than in LETO (53.9±5.2 vs. 20.2±5.6 mmHg/µl), whereas LV end-systolic elastance and positive inotropic responses to β-adrenergic stimulation were similar in OLETF and LETO. 4-Phenylbutyric acid (4-PBA), an ER stress modulator, suppressed both GRP up-regulation and SERCA2a ubiquitination and normalized SERCA2a protein level and Eed in OLETF. Sodium tauroursodeoxycholic acid, a structurally different ER stress modulator, also restored SERCA2a protein level in OLETF. Though LV dysfunction was modest, mortality within 48 h after coronary occlusion was markedly higher in OLETF than in LETO (61.3% vs. 7.7%). Telemetric recording showed that rapid progression of heart failure was responsible for the high mortality rate in OLETF. ER stress modulators failed to reduce the mortality rate after MI in OLETF. CONCLUSIONS: ER stress reduces SERCA2a protein via its augmented ubiquitination and degradation, leading to LV diastolic dysfunction in T2DM. Even at a stage without systolic LV dysfunction, susceptibility to lethal heart failure after infarction is markedly increased, which cannot be explained by ER stress or change in myocardial response to sympathetic nerve activation

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions

Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer

Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase–polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK

Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.</p> <p>Methods</p> <p>We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of <it>EFNA1 </it>in cases with 1q gain, and <it>EFNA1 </it>expression was correlated with the expression of a target gene (<it>VEGF</it>). The <it>BOP1 </it>gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. <it>SMAD2 </it>was the most down-regulated gene on 18q, and on 20q, <it>STMN3 </it>and <it>TGIF2 </it>were highly up-regulated. Immunohistochemistry for SMAD4 correlated with <it>SMAD2 </it>gene expression and 18q loss.</p> <p>Conclusion</p> <p>On basis of integrative analysis this study identified one well known CRC gene (<it>SMAD2</it>) and several other genes (<it>EFNA1, BOP1, TGIF2 </it>and <it>STMN3</it>) that possibly could be used for rectal cancer characterization.</p