87 research outputs found

    CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression

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    In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity

    Dynamic Critical Behavior of an Extended Reptation Dynamics for Self-Avoiding Walks

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    We consider lattice self-avoiding walks and discuss the dynamic critical behavior of two dynamics that use local and bilocal moves and generalize the usual reptation dynamics. We determine the integrated and exponential autocorrelation times for several observables, perform a dynamic finite-size scaling study of the autocorrelation functions, and compute the associated dynamic critical exponents zz. For the variables that describe the size of the walks, in the absence of interactions we find z2.2z \approx 2.2 in two dimensions and z2.1z\approx 2.1 in three dimensions. At the θ\theta-point in two dimensions we have z2.3z\approx 2.3.Comment: laTeX2e, 32 pages, 11 eps figure

    The dark energy spectrometer - A potential multi-fiber instrument for the Blanco 4-meter telescope

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    We describe the preliminary design of the Dark Energy Spectrometer (DESpec), a fiber-fed spectroscopic instrument concept for the Blanco 4-meter telescope at Cerro Tololo Inter-American Observatory (CTIO). DESpec would take advantage of the infrastructure recently deployed for the Dark Energy Camera (DECam). DESpec would be mounted in the new DECam prime focus cage, would be interchangeable with DECam, would share the DECam optical corrector, and would feature a focal plane with ∼4000 robotically positioned optical fibers feeding multiple high-throughput spectrometers. The instrument would have a field of view of 3.8 square degrees, a wavelength range of approximately 500<λ<1000 nm, and a spectral resolution of R∼3000. DESpec would provide a powerful spectroscopic follow-up system for sources in the Southern hemisphere discovered by the Dark Energy Survey and LSST

    Differential Growth of Francisella tularensis, Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of Ft SchuS4 to Immunized Animals

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    The gram-negative bacterium Francisella tularensis (Ft) is both a potential biological weapon and a naturally occurring microbe that survives in arthropods, fresh water amoeba, and mammals with distinct phenotypes in various environments. Previously, we used a number of measurements to characterize Ft grown in Brain-Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and (2) slightly more virulent in naïve animals, compared to Ft grown in Mueller Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB repress expression of select Ft virulence factors by an unknown mechanism. Here, we tested the hypotheses that Ft grown in BHI (BHI-Ft) accurately displays a full protein composition more similar to that reported for infection-derived Ft and that this similarity would make BHI-Ft more susceptible to pre-existing, vaccine-induced immunity than MHB-Ft. We performed comprehensive proteomic analysis of Ft grown in MHB, BHI, and BHI supplemented with casamino acids (BCA) and compared our findings to published “omics” data derived from Ft grown in vivo. Based on the abundance of ~1,000 proteins, the fingerprint of BHI-Ft is one of nutrient-deprived bacteria that—through induction of a stringent-starvation-like response—have induced the FevR regulon for expression of the bacterium's virulence factors, immuno-dominant antigens, and surface-carbohydrate synthases. To test the notion that increased abundance of dominant antigens expressed by BHI-Ft would render these bacteria more susceptible to pre-existing, vaccine-induced immunity, we employed a battery of LVS-vaccination and S4-challenge protocols using MHB- and BHI-grown Ft S4. Contrary to our hypothesis, these experiments reveal that LVS-immunization provides a barrier to infection that is significantly more effective against an MHB-S4 challenge than a BHI-S4 challenge. The differences in apparent virulence to immunized mice are profoundly greater than those observed with primary infection of naïve mice. Our findings suggest that tularemia vaccination studies should be critically evaluated in regard to the growth conditions of the challenge agent
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