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

Letter: immune checkpoint inhibitor‐induced colitis—shouldn’t we be checking more often? Authors’ reply

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151368/1/apt15448_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151368/2/apt15448.pd

The Ursinus Weekly, February 24, 1958

Martin Zippin to speak at Y seminar on art, Feb. 26 • Grundy crowned; Whitians named at annual Lorelei • Army med service topic at pre-med meeting tonite • Seniors present Gold in the hills March 7 and 8 • Campus Chest \u2758 charities • Ursinus photo enthusiast shows camera art in UC Library foyer • Freshman women get colors at ceremonies • Cub & Key Society requests outlines from junior men • WSGA names May queen - J. Martin; Molitor, manager • Tau Sig and Sig Rho dance held Saturday night • Editorial: Art and the student • Nothing new under Ur sun (us) • Ode to idiots • Letters to the editor • Ursinus wrestlers visit Wilkes for meet, Fri. and Sat. • Swimming and basketball finds belles victorious • U.C. cagers downed again; PMC & Swarthmore victors • Matmen trounce PMC; Record now 5 wins, one loss • Sophomores elect Drummond and Watson to MSGAhttps://digitalcommons.ursinus.edu/weekly/1400/thumbnail.jp

The Ursinus Weekly, January 13, 1958

Faculty, students get together for fireside chats • European views of Americans told at IRC meeting • Lantern contest offers prizes to writers and artists • Satellites topic at chem meeting tonight in S-12 • Library receives 400 dollar grant • Lorelei discussed, proctors named at MSGA meeting • Student teachers\u27 tales amuse SEAP meeting • Picasso exhibition opens at Philadelphia art museum • Tranquilizers subject of pre-med meeting, Jan. 8 • Podolak captains color guard • Sig Nu & Delta Pi to hold final fling January 18 • Editorial: It\u27s our move now • Trim the wick and brighten the Lantern • Prize poems • Picasso: Biography • Valentine Day opener set for girls\u27 badminton team • Girls\u27 basketball opener set for Feb. 12 with G\u27burg • UC grapplers beat Haverford 19-13 in season\u27s opener • Varsity cagers lose; J.V.s beat Swarthmore, Haverford • Bears scalped by Indians 81-69 in year-end game • Beta Sig mardi gras held • Frosh give dance: Beneath the sea • Many fields included in new library accessionshttps://digitalcommons.ursinus.edu/weekly/1397/thumbnail.jp

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

Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster. Induction of GFPRNAi construct also alters the response of lifespan to nutrition, exacerbating the lifespan-shortening effects of food containing a high quantity of yeast. Our study indicates that activation of the RNAi machinery may have sequence-independent side-effects on lifespan, and that caution needs to be exercised when employing ubiquitous RNAi in Drosophila ageing studies. However, we also show that RNAi restricted to certain tissues may not be detrimental to lifespan