Phase Equilibrium in the Er-Fe-O System at 1100℃

Phase equilibrium was established in the Er-Fe-O system at 1100℃ by altering the oxygen partial pressure from -log(Po_2/atm)= 15.00 to 0, allowing construction of a phase diagram at 1100℃ for the system Er_20_3-Fe-Fe_2O_3. In the system, two ternary compounds, ErFeO_3 and Er_3Fe_50_12, were deemed stable and had nonstoichiometric composition, whereas ErFe_20_4 was not found to be stable. The present result was different from that of previous studies at 1200 ℃, in which ErFe_20_4 was stable along with the above two ternary compounds. Lattice constants of ErFeO_3 and Er_3Fe_50_12, prepared in air by a quenching method, were determined and compared with previous values, and showed slight differences. The Gibbs energy changes of the reactions in the Fe-0 system, Fe + 1/2 O_2 = FeO, 3 FeO + 1/2 0_2 = Fe_30_4, and 2/3 Fe_30_4 + 1/6 0_2 = Fe_20_3, were determined, and the obtained values were compared with the previous values. The Gibbs energy changes of the reactions, Fe + 1/2 Er_20_3 + 3/4 0_2 = ErFe0_3, and 3 ErFeO_3 + 2/3 Fe_3O_4 + 1/6 0_2 = Er_3Fe_50_12, were calculated from the oxygen partial pressures in equilibrium

Genome-wide identification and annotation of HIF-1α binding sites in two cell lines using massively parallel sequencing

We identified 531 and 616 putative HIF-1α target sites by ChIP-Seq in the cancerous cell line DLD-1 and the non-cancerous cell line TIG-3, respectively. We also examined the positions and expression levels of transcriptional start sites (TSSs) in these cell lines using our TSS-Seq method. We observed that 121 and 48 genes in DLD-1 and TIG-3 cells, respectively, had HIF-1α binding sites in proximal regions of the previously reported TSSs that were up-regulated at the transcriptional level. In addition, 193 and 123 of the HIF-1α target sites, respectively, were located in proximal regions of previously uncharacterized TSSs, namely, TSSs of putative alternative promoters of protein-coding genes or promoters of putative non-protein-coding transcripts. The hypoxic response of DLD-1 cells was more significant than that of TIG-3 cells with respect to both the number of target sites and the degree of induced changes in transcript expression. The Nucleosome-Seq and ChIP-Seq analyses of histone modifications revealed that the chromatin formed an open structure in regions surrounding the HIF-1α binding sites, but this event occurred prior to the actual binding of HIF-1α. Different cellular histories may be encoded by chromatin structures and determine the activation of specific genes in response to hypoxic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11568-011-9150-9) contains supplementary material, which is available to authorized users

Lack of Modifying Effects of Intratracheal Instillation of Quartz or Dextran Sulfate Sodium (DSS) in Drinking Water on Lung Tumor Development Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Female A/J Mice

The purpose of the present study was to investigate the effects of inflammation, induced by intratracheal instillation (i.t.) of quartz as an environmental factor in the lung or drinking of dextran sulfate sodium (DSS) as an environmental factor in the colon on lung tumors in female A/J mice initiated with NNK. For comparison, colonic preneoplastic lesions, aberrant crypt foci (ACF), were also assessed. A/J mice at 6 weeks of age were divided into 5 groups, and Groups 1, 2 and 3 were pretreated with NNK (2 mg / 0.1 ml saline / mouse, intraperitoneal injection) at week 0. For a week, 2% DSS in drinking water was administered to the mice in Groups 2 and 4 beginning in week 1. In week 2, the mice of Groups 3 and 5 were exposed to intratracheal instillation of quartz (0.1 mg/rat) suspended in 25 μl saline. The experiment was terminated after 16 weeks. The results for the lung tumors and colonic ACFs showed a lack of modifying effects of the inflammation in either site. Hematologically and histopathologically, the inflammation induced by 0.1 mg quartz in the lung and 2% DSS in the colon was lacking or only mild at the end of 16 weeks. These results suggest that there may be differences in sensitivity to inflammation that determine tumor promoting potential

An Intratracheal Instillation Bioassay System for Detection of Lung Toxicity Due to Fine Particles in F344 Rats

It is an urgent priority to establish in vivo bioassays for detection of hazards related to fine particles, which can be inhaled into deep lung tissue by humans. In order to establish an appropriate bioassay for detection of lung damage after particle inhalation, several experiments were performed in rats using quartz as a typical lung toxic particle. The results of pilot experiments suggest that Days 1 and 28 after intratracheal instillation of 2 mg of fine test particles in vehicle are most appropriate for detection of acute and subacute inflammatory changes, respectively. Furthermore, the BrdU incorporation on Day 1 and the iNOS level on Day 28 proved to be suitable end-point markers for this purpose. An examination of the toxicity of a series of particles was performed with the developed bioassay. Although some materials, including nanoparticles, demonstrated toxicity that was too strong for sensitive assessment, a ranking order could be clarified. The bioassay thus appears suitable for rapid hazard identification with a possible ranking of the toxicity of various particles at single concentrations

Neuroprotective response after photodynamic therapy: Role of vascular endothelial growth factor

Background: Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood. Methods: We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively. Results: At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis. Conclusion: Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective

Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization

Purpose: To investigate the transcriptional factors associated with epithelial-mesenchymal transition (EMT) in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: Paraffin sections of CNV obtained from patients with AMD (n=12) were stained for transcriptional factors related to EMT, i.e., Snail, Slug, SIP1, and Twist. As a control, postmortem sections of ocular normal tissue were used. Furthermore, using a human retinal pigment epithelial (RPE) cell line (ARPE-19), reverse transcription–polymerase chain reaction (RT–PCR) and immunofluorescence microscopy were performed to explore the cellular localization and expression levels of EMT-associated transcriptional factors upon cytokine stimulation. Results: Of 12 specimens, 11 CNV tissues (91.6%) showed staining for Snail localized in cellular nuclei, particularly in those of RPE cells. Snail was strongly co-localized with α-smooth muscle antigen (SMA) in RPE cells. In contrast, postmortem human retina showed no Snail staining in RPE cells. Other transcriptional factors, Slug, Twist and SIP1 were not detected in CNV or normal human retina. In ARPE-19 cells, RT–PCR and immunofluorescence microscopy showed that Snail mRNA was upregulated by transforming growth factor (TGF)-β and VEGF stimulation. Furthermore, TGF-β induced relocalization of Snail to the nucleus in RPE cells. Conclusions: The current data indicate that Snail is a major transcriptional factor for EMT changes of RPE cells in human CNV

Lineage-level distribution models lead to more realistic climate change predictions for a threatened crayfish

Aim As climate change presents a major threat to biodiversity in the next decades, it is critical to assess its impact on species habitat suitability to inform biodiversity conservation. Species distribution models (SDMs) are a widely used tool to assess climate change impacts on species' geographical distributions. As the name of these models suggests, the species level is the most commonly used taxonomic unit in SDMs. However, recently it has been demonstrated that SDMs considering taxonomic resolution below (or above) the species level can make more reliable predictions of biodiversity change when different populations exhibit local adaptation. Here, we tested this idea using the Japanese crayfish (Cambaroides japonicus), a threatened species encompassing two geographically structured and phylogenetically distinct genetic lineages. Location Northern Japan. Methods We first estimated niche differentiation between the two lineages of C. japonicus using n-dimensional hypervolumes and then made climate change predictions of habitat suitability using SDMs constructed at two phylogenetic levels: species and intraspecific lineage. Results Our results showed only intermediate niche overlap, demonstrating measurable niche differences between the two lineages. The species-level SDM made future predictions that predicted much broader and severe impacts of climate change. However, the lineage-level SDMs led to reduced climate change impacts overall and also suggested that the eastern lineage may be more resilient to climate change than the western one. Main conclusions The two lineages of C. japonicus occupy different niche spaces. Compared with lineage-level models, species-level models can overestimate climate change impacts. These results not only have important implications for designing future conservation strategies for this threatened species, but also highlight the need for incorporating genetic information into SDMs to obtain realistic predictions of biodiversity change.Peer reviewe

Lung Carcinogenic Bioassay of CuO and TiO2 Nanoparticles with Intratracheal Instillation Using F344 Male Rats

Toxicity assessment of nanoparticles, now widespread in our environment, is an important issue. We have focused attention on the carcinogenic potential of copper oxide (CuO) and titanium dioxide (TiO2). In experiment 1, a sequential pilot study, the effectiveness of a carcinogenic bioassay featuring intraperitoneal injection (i.p.) of 20 mg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or 0.1% N-bis(2-hydroxypropyl)nitrosamine (DHPN) in drinking water for 2 weeks was examined. Based on the results, DHPN, as the lung carcinogen, and evaluation at week 30 were selected as the most appropriate for our purposes in Experiment 1. In experiment 2, the carcinogenic bioassay was used to assess the carcinogenic potentials of instilled nanoparticles of CuO and TiO2. There were no significant intergroup differences in the lung neoplastic lesions induced by DHPN, although the neoplastic lesions induced by the nanoparticles in the CuO or TiO2 intratracheal instillation (i.t.) groups, demonstrated a tendency to increase compared with the microparticles administration. At the very least, the carcinogenic bioassay with DHPN proved useful for assessment of the modifying effects of instilled particles, and further assessment of the carcinogenic potential of nanoparticles appears warranted

Oligomerization of Hepatitis C Virus Core Protein is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein

Bright X-ray flares from the BL Lac object Mrk 421, detected with MAXI in 2010 January and February

Strong X-ray flares from the blazar Mrk 421 were detected in 2010 January and February through the 7 month monitoring with the MAXI GSC. The maximum 2 -- 10 keV flux in the January and February flares was measured as 120 +- 10 mCrab and 164 +- 17 mCrab respectively; the latter is the highest among those reported from the object. A comparison of the MAXI and Swift BAT data suggests a convex X-ray spectrum with an approximated photon index of about 2. This spectrum is consistent with a picture that MAXI is observing near the synchrotron peak frequency. The source exhibited a spectral variation during these flares, slightly different from those in the previous observations, in which the positive correlation between the flux and hardness was widely reported. By equating the halving decay timescale in the January flare, $t_{\rm d} \sim 2.5 \times 10^{4}$ s, to the synchrotron cooling time, the magnetic field was evaluated as B = 0.045 G $(\delta/10)^{-1/3}$, where $\delta$ is the jet beaming factor. Assuming that the light crossing time of the emission region is shorter than the doubling rise time, $t_{\rm r} \lesssim 2 \times 10^{4}$ s, the region size was roughly estimated as $R < 6 \times 10^{15}$ cm $(\delta/10)$. These are consistent with the values previously reported. For the February flare, the rise time, $t_{\rm r} < 1.3 \times 10^{5}$ s, gives a loose upper limit on the size as $R < 4 \times 10^{16}$ cm $(\delta/10)$, although the longer decay time $t_{\rm d} \sim 1.4 \times 10^{5}$ s, indicates B = 0.015 G $(\delta/10)^{-1/3}$, which is weaker than the previous results. This could be reconciled by invoking a scenario that this flare is a superposition of unresolved events with a shorter timescale.Comment: 14 pages, 4 figures, accepted for PASJ (Vol. 62 No. 6