A Small-Molecule Inhibitor of Mps1 Blocks the Spindle-Checkpoint Response to a Lack of Tension on Mitotic Chromosomes

SummaryThe spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1–3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5–7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy. We performed a phenotype-based chemical-genetic screen in budding yeast and identified an inhibitor of the spindle checkpoint, called cincreasin. We used a genome-wide collection of yeast gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]. Despite the requirement for Mps1 for sensing both the lack of microtubule attachment and tension at kinetochores, we find concentrations of cincreasin that selectively inhibit the tension-sensitive branch of the spindle checkpoint. At these concentrations, cincreasin causes lethal chromosome missegregation in mutants that display chromosomal instability. Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability

Nanomechanical-resonator-assisted induced transparency in a Cooper-pair-box system

We propose a scheme to demonstrate the electromagnetically induced transparency (EIT) in a system of a superconducting Cooper-pair box coupled to a nanomechanical resonator. In this scheme, the nanomechanical resonator plays an important role to contribute additional auxiliary energy levels to the Cooper-pair box so that the EIT phenomenon could be realized in such a system. We call it here resonator-assisted induced transparency (RAIT). This RAIT technique provides a detection scheme in a real experiment to measure physical properties, such as the vibration frequency and the decay rate, of the coupled nanomechanical resonator.Comment: To appear in New Journal of Physics: Special Issue "Mechanical Systems at the Quantum Limit

Fe–Fe bonding in the rhombic Fe 4 cores of the Zintl clusters [Fe 4 E 18 ] 4− (E = Sn and Pb) †

We report here the synthesis and characterization of two endohedral Zintl-ion clusters, [Fe4Sn18]4− and [Fe4Pb18]4−, which contain rhombic Fe4 cores. The Fe–Fe bond lengths are all below 2.5 Å, distinctly shorter than in the corresponding Cu clusters, indicating the presence of Fe–Fe bonding. Subtle differences in the structure of the Fe4 core between the two clusters suggest that the change in tetrel element causes a change in electronic ground state, with a very short Fe–Fe bond length of 2.328 Å present across the diagonal of the rhombus in the lead case

Influence of an external magnetic field on the decoherence of a central spin coupled to an antiferromagnetic environment

Using the spin wave approximation, we study the decoherence dynamics of a central spin coupled to an antiferromagnetic environment under the application of an external global magnetic field. The external magnetic field affects the decoherence process through its effect on the antiferromagnetic environment. It is shown explicitly that the decoherence factor which displays a Gaussian decay with time depends on the strength of the external magnetic field and the crystal anisotropy field in the antiferromagnetic environment. When the values of the external magnetic field is increased to the critical field point at which the spin-flop transition (a first-order quantum phase transition) happens in the antiferromagnetic environment, the decoherence of the central spin reaches its highest point. This result is consistent with several recent quantum phase transition witness studies. The influences of the environmental temperature on the decoherence behavior of the central spin are also investigated.Comment: 29 preprint pages, 4 figures, to appear in New Journal of Physic

The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding

AbstractPandemic influenza viral infections have been associated with viral pneumonia. Chimeric influenza viruses with the hemagglutinin segment of the 1918, 1957, 1968, or 2009 pandemic influenza viruses in the context of a seasonal H1N1 influenza genome were constructed to analyze the role of hemagglutinin (HA) in pathogenesis and cell tropism in a mouse model. We also explored whether there was an association between the ability of lung surfactant protein D (SP-D) to bind to the HA and the ability of the corresponding chimeric virus to infect bronchiolar and alveolar epithelial cells of the lower respiratory tract. Viruses expressing the hemagglutinin of pandemic viruses were associated with significant pathology in the lower respiratory tract, including acute inflammation, and showed low binding activity for SP-D. In contrast, the virus expressing the HA of a seasonal influenza strain induced only mild disease with little lung pathology in infected mice and exhibited strong in vitro binding to SP-D

A Dynamic-Order Fractional Dynamic System

Multi-system interaction is an important and difficult problem in physics. Motivated by the experimental result of an electronic circuit element "Fractor", we introduce the concept of dynamic-order fractional dynamic system, in which the differential-order of a fractional dynamic system is determined by the output signal of another dynamic system. The new concept offers a comprehensive explanation of physical mechanism of multi-system interaction. The properties and potential applications of dynamic-order fractional dynamic systems are further explored with the analysis of anomalous relaxation and diffusion processes.Comment: 10 pages, 5 figure

Aggregation‐induced emission luminogen: A new perspective in the photo‐degradation of organic pollutants

Both the variety and uniqueness of organic semiconductors has contributed to the rapid development of environmental engineering applications and renewable fuel production, typified by the photodegradation of organic pollutants or water splitting. This paper presents a rare example of an aggregation‐induced emission luminogen as a highly efficient photocatalyst for pollutant decomposition in an environmentally relevant application. Under irradiation, the tetraphenylethene‐based AIEgen (TPE‐Ca) exhibited high photo‐degradation efficiency of up to 98.7% of Rhodamine B (RhB) in aqueous solution. The possible photocatalytic mechanism was studied by electron paramagnetic resonance and X‐ray photoelectron spectroscopy spectra, electrochemistry, thermal imaging technology, ultra‐performance liquid chromatography and high‐definition mass spectrometry, as well as by density functional theory calculations. Among the many diverse AIEgens, this is the first AIEgen to be developed as a photocatalyst for the degradation of organic pollutants. This research will open up new avenues for AIEgens research, particularly for applications of environmental relevance

First-generation structure-activity relationship studies of 2,3,4,9-tetrahydro-1H-carbazol-1-amines as CpxA phosphatase inhibitors

Genetic activation of the bacterial two-component signal transduction system, CpxRA, abolishes the virulence of a number of pathogens in human and murine infection models. Recently, 2,3,4,9-tetrahydro-1H-carbazol-1-amines were shown to activate the CpxRA system by inhibiting the phosphatase activity of CpxA. Herein we report the initial structure-activity relationships of this scaffold by focusing on three approaches 1) A-ring substitution, 2) B-ring deconstruction to provide N-arylated amino acid derivatives, and 3) C-ring elimination to give 2-ethylamino substituted indoles. These studies demonstrate that the A-ring is amenable to functionalization and provides a promising avenue for continued optimization of this chemotype. Further investigations revealed that the C-ring is not necessary for activity, although it likely provides conformational constraint that is beneficial to potency, and that the (R) stereochemistry is required at the primary amine. Simplification of the scaffold through deconstruction of the B-ring led to inactive compounds, highlighting the importance of the indole core. A new lead compound 26 was identified, which manifests a ∼30-fold improvement in CpxA phosphatase inhibition over the initial hit. Comparison of amino and des-amino derivatives in bacterial strains differing in membrane permeability and efflux capabilities demonstrate that the amine is required not only for target engagement but also for permeation and accumulation in Escherichia coli

Colossal magnetoresistance and quenched disorder in manganese oxides

We give an overview on several recent topics of colossal magnetoresistive manganites in both experiments and theories, focusing on the effect of quenched disorder. The disorder is intrinsically involved since the compounds are solid solutions, and its importance has been pointed out in several experiments of transport and magnetic properties. Recent progress in the experimental control of the strength of disorder is also reviewed. Theoretically, the effect of the disorder has been explored within the framework of the double-exchange mechanism. Several efforts to understand the phase diagram and the electronic properties are reviewed. We also briefly discuss a recent topic on the effect of disorder on competing phases and the origin of colossal magnetoresistance.Comment: 5 pages, 4 figures, proceedings submitted to SPQS200