Effect of strong localization of doped holes in angle-resolved photoemission spectra of La1−x_{1-x}Srx_xFeO3_3

We have performed an angle-resolved photoemission spectroscopy study of La$_{0.6}$Sr$_{0.4}$FeO$_3$ using {\it in situ} prepared thin films and determined its band structure. The experimental band dispersions could be well explained by an empirical band structure assuming the G-type antiferromagnetic state. However, the Fe 3d bands were found to be shifted downward relative to the Fermi level ($E_F$) by $\sim 1$ eV compared with the calculation and to form a (pseudo)gap of $\sim 1$ eV at $E_F$. We attribute this observation to a strong localization effect of doped holes due to polaron formation.Comment: 5 pages, 5 figure

Hole-doping-induced changes in the electronic structure of La1−x_{1-x}Srx_xFeO3_3 : soft x-ray photoemission and absorption study of epitaxial thin films

We have studied the electronic structure of epitaxially grown thin films of La$_{1-x}$Sr$_x$FeO$_3$ by {\it in-situ} photoemission spectroscopy (PES) and x-ray absorption spectroscopy (XAS) measurements. The Fe 2$p$ and valence-band PES spectra and the O $1s$ XAS spectra of LaFeO$_3$ have been successfully reproduced by configuration-interaction cluster-model calculation and, except for the satellite structure, by band-structure calculation.From the shift of the binding energies of core levels, the chemical potential was found to be shifted downward as $x$ was increased. Among the three peaks in the valence-band spectra of La$_{1-x}$Sr$_x$FeO$_3$, the peak nearest to the Fermi level ($E_F$), due to the ``$e_{g}$ band'', was found to move toward $E_F$ and became weaker as $x$ was increased, whereas the intensity of the peak just above $E_F$ in the O $1s$ XAS spectra increased with $x$. The gap or pseudogap at $E_F$ was seen for all values of $x$. These results indicate that changes in the spectral line shape around $E_F$ are dominated by spectral weight transfer from below to above $E_F$ across the gap and are therefore highly non-rigid-band-like.Comment: 8 pages, 7 figure

Magnetic oxide semiconductors

Magnetic oxide semiconductors, oxide semiconductors doped with transition metal elements, are one of the candidates for a high Curie temperature ferromagnetic semiconductor that is important to realize semiconductor spintronics at room temperature. We review in this paper recent progress of researches on various magnetic oxide semiconductors. The magnetization, magneto-optical effect, and magneto-transport such as anomalous Hall effect are examined from viewpoint of feasibility to evaluate the ferromagnetism. The ferromagnetism of Co-doped TiO2 and transition metal-doped ZnO is discussed.Comment: 26 pages, 5 tables, 6 figure

Tumor-promoting functions of transforming growth factor-β in progression of cancer

Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling

Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling

Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy

The Anti-Proliferative Effects of the CHFR Depend on the Forkhead Associated Domain, but not E3 Ligase Activity Mediated by Ring Finger Domain

The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF) domain and is frequently downregulated in human colon and gastric cancers up to 50%. The loss of CHFR mRNA expression is a consequence of promoter methylation, suggesting a tumor suppressor role for this gene in gastrointestinal carcinogenesis. In terms of the biological functions of CHFR, it has been shown to activate cell cycle checkpoint when cells are treated with microtubule depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity and promote ubiquitination and degradation of oncogenic proteins such as Aurora A and polo-like kinase 1. However, molecular pathways involved in the tumor suppressive function of CHFR are not yet clear since the two established roles of this protein are likely to inhibit cell growth. In this study, we have identified that the FHA domain of CHFR protein is critical for growth suppressive properties, whereas the RF and cysteine rich domains (Cys) are not required for this function. In contrast, the RF and Cys domains are essential for E3 ligase activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed that the FHA domain of CHFR plays an important role in initiating a cell cycle arrest at G2/M, indicating a functional link exists between the anti-proliferative effects and checkpoint function of this tumor suppressor protein via this domain. Collectively, our data show that the checkpoint function of the FHA domain of CHFR is a core component of anti-proliferative properties against the gastrointestinal carcinogenesis

ChIP-seq Defined Genome-Wide Map of TGFβ/SMAD4 Targets: Implications with Clinical Outcome of Ovarian Cancer

Deregulation of the transforming growth factor-β (TGFβ) signaling pathway in epithelial ovarian cancer has been reported, but the precise mechanism underlying disrupted TGFβ signaling in the disease remains unclear. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate genome-wide screening of TGFβ-induced SMAD4 binding in epithelial ovarian cancer. Following TGFβ stimulation of the A2780 epithelial ovarian cancer cell line, we identified 2,362 SMAD4 binding loci and 318 differentially expressed SMAD4 target genes. Comprehensive examination of SMAD4-bound loci, revealed four distinct binding patterns: 1) Basal; 2) Shift; 3) Stimulated Only; 4) Unstimulated Only. TGFβ stimulated SMAD4-bound loci were primarily classified as either Stimulated only (74%) or Shift (25%), indicating that TGFβ-stimulation alters SMAD4 binding patterns in epithelial ovarian cancer cells. Furthermore, based on gene regulatory network analysis, we determined that the TGFβ-induced, SMAD4-dependent regulatory network was strikingly different in ovarian cancer compared to normal cells. Importantly, the TGFβ/SMAD4 target genes identified in the A2780 epithelial ovarian cancer cell line were predictive of patient survival, based on in silico mining of publically available patient data bases. In conclusion, our data highlight the utility of next generation sequencing technology to identify genome-wide SMAD4 target genes in epithelial ovarian cancer and link aberrant TGFβ/SMAD signaling to ovarian tumorigenesis. Furthermore, the identified SMAD4 binding loci, combined with gene expression profiling and in silico data mining of patient cohorts, may provide a powerful approach to determine potential gene signatures with biological and future translational research in ovarian and other cancers