Travel Far: A Collection of Sonic Narratives

“Travel Far” is a 6 song EP immersing the listener into a fantastical realm of songwriting and sound-writing, with themes and emotions influenced by experiences in the real world.https://remix.berklee.edu/graduate-studies-production-technology/1081/thumbnail.jp

Cytolytic toxin production by \u3ci\u3eStaphylococcus aureus\u3c/i\u3e is dependent upon the activity of the protoheme IX farnesyltransferase

Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins

Regulation of Star Formation by a Hot Circumgalactic Medium

Galactic outflows driven by supernovae (SNe) are thought to be a powerful regulator of a galaxy's star-forming efficiency. Mass, energy, and metal outflows ($\eta_M$, $\eta_E$, and $\eta_Z$, here normalized by the star formation rate, the SNe energy and metal production rates, respectively) shape galaxy properties by both ejecting gas and metals out of the galaxy and by heating the circumgalactic medium (CGM), preventing future accretion. Traditionally, models have assumed that galaxies self-regulate by ejecting a large fraction of the gas which enters the interstellar medium (ISM), even though such high mass-loadings are in growing tension with observations. To better understand how the relative importance of ejective (i.e. high mass-loading) vs preventative (i.e. high energy-loading) feedback affects the present-day properties of galaxies, we develop a simple gas-regulator model of galaxy evolution, where the stellar mass, ISM, and CGM are modeled as distinct reservoirs which exchange mass, metals, and energy at different rates within a growing halo. Focusing on the halo mass range from $10^{10}$ to $10^{12} M_{\odot}$, we demonstrate that, with reasonable parameter choices, we can reproduce the stellar-to-halo mass relation and the ISM-to-stellar mass relation with low mass-loaded ($\eta_M \sim 0.1-10$) but high energy-loaded ($\eta_E \sim 0.1-1$) winds, with self-regulation occurring primarily through heating and cooling of the CGM. We show that the model predictions are robust against changes to the mass-loading of outflows but are quite sensitive to our choice of the energy-loading, preferring $\eta_E \sim 1$ for the lowest mass halos and $\sim 0.1$ for Milky Way-like halos.Comment: 19 pages, 9 Figures, submitted to Ap

NMR Analysis of a Stress Response Metabolic Signaling Network

We previously hypothesized that Staphylococcus epidermidis senses a diverse set of environmental and nutritional factors associated with biofilm formation through a modulation in the activity of the tricarboxylic acid (TCA) cycle. Herein, we report our further investigation of the impact of additional environmental stress factors on TCA cycle activity and provide a detailed description of our NMR methodology. S. epidermidis wild-type strain 1457 was treated with stressors that are associated with biofilm formation, a sub-lethal dose of tetracycline, 5% NaCl, 2% glucose and autoinducer-2 (AI-2). As controls and to integrate our current data with our previous study, 4% ethanol stress and iron-limitation were also used. Consistent with our prior observations, the effect of many environmental stress factors on the S. epidermidis metabolome was essentially identical to the effect of TCA cycle inactivation in the aconitase mutant strain 1457-acnA::tetM. A detailed quantitative analysis of metabolite concentration changes using 2D 1H-13C HSQC and 1H-1H TOCSY spectra identified a network of 37 metabolites uniformly affected by the stressors and TCA cycle inactivation. We postulate that the TCA cycle acts as the central pathway in a metabolic signaling network

Impact of the Histidine‐Containing Phosphocarrier Protein HPr on Carbon Metabolism and Virulence in Staphylococcus aureus

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading frame or harbor a ptsH variant carrying a thymidine to guanosine mutation at position 136, and the effects of these mutations on growth and metabolism were assessed. Inactivation of ptsH altered bacterial physiology and decreased the ability of S. aureus to form a biofilm and cause infections in mice. These data demonstrate that HPr affects central metabolism and virulence in S. aureus independent of its influence on CcpA regulation

Activity of the Lactate Dehydrogenase Inhibitor Oxamic Acid against the Fermentative Bacterium \u3ci\u3eStreptococcus mitis/oralis\u3c/i\u3e: Bactericidal Effects and Prevention of Daptomycin Resistance In Vitro and in an Ex Vivo Model

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro– derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor oxamic acid (OXA) to assess its efficacy against DAP-S S. mitis/oralis strain 351 during DAP exposures in vitro and ex vivo. As expected, OXA was growth inhibitory to S. mitis/oralis in a dose-dependent manner in vitro; however, it did not alter in vitro DAP susceptibility profiles. In contrast, OXA did prevent the emergence of DAP-R in an ex vivo model of simulated endocardial vegetations. These data suggest that metabolic inhibitors directed against this fermentative bacterium with limited metabolic capabilities could enhance killing and potentially forestall the emergence of DAP resistance

Self-regulation of black hole accretion via jets in early protogalaxies

The early growth of black holes (BHs) in high-redshift galaxies is likely regulated by their feedback on the surrounding gas. While radiative feedback has been extensively studied, the role of mechanical feedback has received comparatively less scrutiny to date. Here we use high-resolution parsec-scale hydrodynamical simulations to study jet propagation and its effect on BH accretion onto 100 ${\rm M_\odot}$ BHs in the dense, low-metallicity gas expected in early protogalaxies. As the jet propagates, it shocks the surrounding gas and forms a jet cocoon. The cocoon consists of a rapidly-cooling cold phase at the interface with the background gas and an over-pressured subsonic phase of reverse shock-heated gas filling the cocoon interior. We systematically vary the background gas density and temperature, BH feedback efficiency, and the jet model. We found that the jet cocoon width roughly follows a scaling derived by assuming momentum conservation in the jet propagation direction, and energy conservation in the lateral directions. Depending on the assumed gas and jet properties, the cocoon either stays elongated out to a large radius or isotropizes before reaching the Bondi radius, forming a nearly spherical bubble. Lower jet velocities and higher background gas densities result in self-regulation to higher momentum fluxes and elongated cocoons. In all cases, the outward momentum flux of the cocoon balances the inward momentum flux of the inflowing gas near the Bondi radius, which ultimately regulates BH accretion. The larger the distance the jet cocoon reaches, the longer the variability timescale of the BH accretion rate. Overall, the average accretion rate always remains below the Bondi rate, and exceeds the Eddington rate only if the ambient medium is dense and cold, and/or the jet is weak. We derive the combination of jet and ambient gas parameters yielding super-Eddington growth.Comment: 16 pages, 11 figure

Galaxy Size Problem at z=3: Simulated Galaxies Are Too Small

Using state-of-the-art adaptive mesh refinement cosmological hydrodynamic simulations with a spatial resolution of proper 0.21kpc/h in refined subregions embedded within a comoving cosmological volume (27.4Mpc/h)^3, we investigate the sizes of galaxies at z=3 in the standard cold dark matter model where reionization is assumed to complete at zri~6. Our simulated galaxies are found to be significantly smaller than the observed ones: while more than one half of the galaxies observed by HST and VLT ranging from rest-frame UV to optical bands with stellar masses larger than 2E10 Msun have half-light radii larger than 2kpc/h, none of the simulated massive galaxies in the same mass range have half-light radii larger than 2kpc/h, after taking into account dust extinction. Corroborative evidence is provided by the rotation curves of the simulated galaxies with total masses of 1E11-1E12Msun, which display values 300-1000km/s at small radii (0.5kpc/h) due to high stellar concentration in the central regions, larger than those of any well observed galaxies. Possible physical mechanisms to resolve this serious problem include: (1) an early reionization at zri>>6 to suppress gas condensation hence star formation, (2) a strong, internal energetic feedback from stars or central black holes to reduce the overall star formation efficiency, or (3) a substantial small-scale cutoff in the matter power spectrum.Comment: high resolution pdf file is available at http://www.astro.princeton.edu/~cen/galaxysize.pdf 15 pages, 3 figures, in press of ApJ Letter

Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis

Background: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non- susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non- susceptible through serial passage in the presence of daptomycin. Background: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non- susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non- susceptible through serial passage in the presence of daptomycin. Conclusions: S. mitis-oralis metabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated in Staphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non- susceptibility. By preventing these metabolic adaptations in S. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility