Minimal charge gap in the ionic Hubbard model

We study the ionic Hubbard model at temperature T=0 within the mean-field approximation, and show that the charge gap does not close completely at the ionic-band insulator to antiferromagnetic insulator transition, contrary to previous expectations. Furthermore, we find an intermediate phase for on-site repulsions $U>U_c$ for different lattices, and calculate the phase diagram for the ionic Hubbard model with alternating U, corresponding to a Cu-O lattice.Comment: 5 pages with 7 figures; minor correction

Spin-dependent transport in metal/semiconductor tunnel junctions

This paper describes a model as well as experiments on spin-polarized tunnelling with the aid of optical spin orientation. This involves tunnel junctions between a magnetic material and gallium arsenide (GaAs), where the latter is optically excited with circularly polarized light in order to generate spin-polarized carriers. A transport model is presented that takes account of carrier capture in the semiconductor surface states, and describes the semiconductor surface in terms of a spin-dependent energy distribution function. The so-called surface spin-splitting can be calculated from the balance of the polarized electron and hole flow in the semiconductor subsurface region, the polarized tunnelling current across the tunnel barrier between the magnetic material and the semiconductor surface, and the spin relaxation at the semiconductor surface. Measurements are presented of the circular-polarization-dependent photocurrent (the so-called helicity asymmetry) in thin-film tunnel junctions of Co/Al2O3/GaAs. In the absence of a tunnel barrier, the helicity asymmetry is caused by magneto-optical effects (magnetic circular dichroism). In the case where a tunnel barrier is present, the data cannot be explained by magneto-optical effects alone; the deviations provide evidence that spin-polarized tunnelling due to optical spin orientation occurs. In Co/τ-MnAl/AlAs/GaAs junctions no deviations from the magneto-optical effects are observed, most probably due to the weak spin polarization of τ-MnAl along the tunnelling direction; the latter is corroborated by bandstructure calculations. Finally, the application of photoexcited GaAs for spin-polarized tunnelling in a scanning tunnelling microscope is discussed.

Single Spin Superconductivity: Formulation and Ginzburg-Landau Theory

We describe a novel superconducting phase that arises due to a pairing instability of the half-metallic antiferromagnetic (HM AFM) normal state. This single spin superconducting (SSS) phase contains broken time reversal symmetry in addition to broken gauge symmetry, the former due to the underlying magnetic order in the normal state. A classification of normal state symmetries leads to the conclusion that the HM AFM normal phase whose point group contains the inversion operator contains the least symmetry possible which still allows for a zero momentum pairing instability. The Ginzburg-Landau free energy for the superconducting order parameter is constructed consistent with the symmetry of the normal phase, electromagnetic gauge invariance and the crystallographic point group symmetry including inversion. For cubic, hexagonal and tetragonal point groups, the possible symmetries of the superconducting phase are classified, and the free energy is used to construct a generalized phase diagram. We identify the leading candidate out of the possible SSS phases for each point group. The symmetry of the superconducting phase is used to determine the cases where the gap function has generic zeros (point or line nodes) on the Fermi surface. Such nodes always occur, hence thermodynamic properties will have power-law behavior at low temperature.Comment: 39 pages, RevTeX, 4 PostScript figures included, submitted to Phys. Rev.

The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres

INCENP acts as a protein scaffold that integrates the functions of two crucial mitotic kinases, Aurora B and Polo, at centromeres of mitotic chromosomes

The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres

INCENP acts as a protein scaffold that integrates the functions of two crucial mitotic kinases, Aurora B and Polo, at centromeres of mitotic chromosomes

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

<p>Abstract</p> <p>Background</p> <p>Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of <it>Curcuma longa</it>. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.</p> <p>Methods</p> <p>Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an <it>in vitro </it>APC activity assay.</p> <p>Results</p> <p>We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells.</p> <p>Conclusions</p> <p>We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin.</p

Polo-Like Kinase-1 Controls Aurora A Destruction by Activating APC/C-Cdh1

Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase activity and the E3 ubiquitin ligase SCF-βTrCP. Here, we show that Plk1 is also required for the timely destruction of its activator Aurora A in late anaphase. It has been shown that Aurora A destruction is controlled by the auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C). Remarkably, we found that Plk1-depletion prevented the efficient dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1, at least in part, through direct phosphorylation of the human phosphatase Cdc14A, controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A

B-Cyclin/CDKs Regulate Mitotic Spindle Assembly by Phosphorylating Kinesins-5 in Budding Yeast

Although it has been known for many years that B-cyclin/CDK complexes regulate the assembly of the mitotic spindle and entry into mitosis, the full complement of relevant CDK targets has not been identified. It has previously been shown in a variety of model systems that B-type cyclin/CDK complexes, kinesin-5 motors, and the SCFCdc4 ubiquitin ligase are required for the separation of spindle poles and assembly of a bipolar spindle. It has been suggested that, in budding yeast, B-type cyclin/CDK (Clb/Cdc28) complexes promote spindle pole separation by inhibiting the degradation of the kinesins-5 Kip1 and Cin8 by the anaphase-promoting complex (APCCdh1). We have determined, however, that the Kip1 and Cin8 proteins are present at wild-type levels in the absence of Clb/Cdc28 kinase activity. Here, we show that Kip1 and Cin8 are in vitro targets of Clb2/Cdc28 and that the mutation of conserved CDK phosphorylation sites on Kip1 inhibits spindle pole separation without affecting the protein's in vivo localization or abundance. Mass spectrometry analysis confirms that two CDK sites in the tail domain of Kip1 are phosphorylated in vivo. In addition, we have determined that Sic1, a Clb/Cdc28-specific inhibitor, is the SCFCdc4 target that inhibits spindle pole separation in cells lacking functional Cdc4. Based on these findings, we propose that Clb/Cdc28 drives spindle pole separation by direct phosphorylation of kinesin-5 motors

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations