Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics

Heat shock protein 90 (Hsp90) is a promising cancer drug target as a molecular chaperone critical for stabilization and activation of several of the oncoproteins that drive cancer progression. Its actions depend upon its essential ATPase, an activity fortuitously inhibited with a very high degree of selectivity by natural antibiotics: notably the actinomycete-derived benzoquinone ansamycins (e.g. geldanamycin) and certain fungal-derived resorcyclic acid lactones (e.g. radicicol). The molecular interactions made by these antibiotics when bound within the ADP/ATP-binding site of Hsp90 have served as templates for the development of several synthetic Hsp90 inhibitor drugs. Much attention now focuses on the clinical trials of these drugs. However, because microbes have evolved antibiotics to target Hsp90, it is probable that they often exploit Hsp90 inhibition when interacting with each other and with plants. Fungi known to produce Hsp90 inhibitors include mycoparasitic, as well as plant-pathogenic, endophytic and mycorrhizal species. The Hsp90 chaperone may, therefore, be a prominent target in establishing a number of mycoparasitic (interfungal), fungal pathogen–plant and symbiotic fungus–plant relationships. Furthermore the Hsp90 family proteins of the microbes that produce Hsp90 inhibitor antibiotics are able to reveal how drug resistance can arise by amino acid changes in the highly conserved ADP/ATP-binding site of Hsp90

Vectors for N- or C-terminal positioning of the yeast Gal4p DNA binding or activator domains

EMTREE drug terms: fungal protein; heat shock protein 90; hybrid protein; transcription factor EMTREE medical terms: amino terminal sequence; article; carboxy terminal sequence; DNA binding; DNA binding domain; expression vector; Gal4p domain; gene activation; gene activation domain; gene expression; nonhuman; plasmid; plasmid ADC; plasmid BDC; protein domain; protein protein interaction; technique; two hybrid system; yeast MeSH: Binding Sites; DNA-Binding Proteins; Genetic Vectors; Protein Structure, Tertiary; Recombinant Fusion Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Trans-Activation (Genetics); Transcription Factors; Two-Hybrid System Techniqu

The gravitational wave rocket

Einstein's equations admit solutions corresponding to photon rockets. In these a massive particle recoils because of the anisotropic emission of photons. In this paper we ask whether rocket motion can be powered only by the emission of gravitational waves. We use the double series approximation method and show that this is possible. A loss of mass and gain in momentum arise in the second approximation because of the emission of quadrupole and octupole waves.Comment: 10 pages LaTe

Ion-Beam Induced Current in High-Resistance Materials

The peculiarities of electric current in high-resistance materials, such as semiconductors or semimetals, irradiated by ion beams are considered. It is shown that after ion--beam irradiation an unusual electric current may arise directed against the applied voltage. Such a negative current is a transient effect appearing at the initial stage of the process. The possibility of using this effect for studying the characteristics of irradiated materials is discussed. A new method for defining the mean projected range of ions is suggested.Comment: 1 file, 7 pages, RevTex, no figure

Transition from electron accumulation to depletion at InGaN surfaces

The composition dependence of the Fermi-level pinning at the oxidized (0001) surfaces of n-type InxGa1−xN films (0<=x<=1) is investigated using x-ray photoemission spectroscopy. The surface Fermi-level position varies from high above the conduction band minimum (CBM) at InN surfaces to significantly below the CBM at GaN surfaces, with the transition from electron accumulation to depletion occurring at approximately x=0.3. The results are consistent with the composition dependence of the band edges with respect to the charge neutrality level

Struggling and juggling: a comparison of assessment loads in research and teaching-intensive universities

In spite of the rising tide of metrics in UK higher education, there has been scant attention paid to assessment loads, when evidence demonstrates that heavy demands lead to surface learning. Our study seeks to redress the situation by defining assessment loads and comparing them across research-and teaching intensive universities. We clarify the concept of ‘assessment load’ in response to findings about high volumes of summative assessment on modular degrees. We define assessment load across whole undergraduate degrees, according to four measures: the volume of summative assessment; volume of formative assessment; proportion of examinations to coursework; number of different varieties of assessment. All four factors contribute to the weight of an assessment load, and influence students’ approaches to learning. Our research compares programme assessment data from 73 programmes in 14 UK universities, across two institutional categories. Research-intensives have higher summative assessment loads and a greater proportion of examinations; teaching-intensives have higher varieties of assessment. Formative assessment does not differ significantly across both university groups. These findings pose particular challenges for students in different parts of the sector. Our study questions the wisdom that ‘more’ is always better, proposing that lighter assessment loads may make room for ‘slow’ and deep learning

Band anticrossing in GaNxSb1–x

Fourier transform infrared absorption measurements are presented from the dilute nitride semiconductor GaNSb with nitrogen incorporations between 0.2% and 1.0%. The divergence of transitions from the valence band to E– and E+ can be seen with increasing nitrogen incorporation, consistent with theoretical predictions. The GaNSb band structure has been modeled using a five-band k·p Hamiltonian and a band anticrossing fitting has been obtained using a nitrogen level of 0.78 eV above the valence band maximum and a coupling parameter of 2.6 eV