Tobramycin-Treated Pseudomonas aeruginosa PA14 Enhances Streptococcus constellatus 7155 Biofilm Formation in a Cystic Fibrosis Model System

Cystic fibrosis (CF) is a human genetic disorder which results in a lung environment that is highly conducive to chronic microbial infection. Over the past decade, deep-sequencing studies have demonstrated that the CF lung can harbor a highly diverse polymicrobial community. We expanded our existing in vitro model of Pseudomonas aeruginosa biofilm formation on CF-derived airway cells to include this broader set of CF airway colonizers to investigate their contributions to CF lung disease, particularly as they relate to the antibiotic response of the population. Using this system, we identified an interspecies interaction between P. aeruginosa, a bacterium associated with declining lung function and worsening disease, and Streptococcus constellatus, a bacterium correlated with the onset of pulmonary exacerbations in CF patients. The growth rate and cytotoxicity of S. constellatus 7155 and P. aeruginosa PA14 were unchanged when grown together as mixed biofilms in the absence of antibiotics. However, the addition of tobramycin, the frontline maintenance therapy antibiotic for individuals with CF, to a mixed biofilm of S. constellatus 7155 and P. aeruginosa PA14 resulted in enhanced S. constellatus biofilm formation. Through a candidate genetic approach, we showed that P. aeruginosa rhamnolipids were reduced upon tobramycin exposure, allowing for S. constellatus 7155 biofilm enhancement, and monorhamnolipids were sufficient to reduce S. constellatus 7155 biofilm viability in the absence of tobramycin. While the findings presented here are specific to a biofilm of S. constellatus 7155 and P. aeruginosa PA14, they highlight the potential of polymicrobial interactions to impact antibiotic tolerance in unanticipated ways

Direct measurements of dust attenuation in z~1.5 star-forming galaxies from 3D-HST: Implications for dust geometry and star formation rates

The nature of dust in distant galaxies is not well understood, and until recently few direct dust measurements have been possible. We investigate dust in distant star-forming galaxies using near-infrared grism spectra of the 3D-HST survey combined with archival multi-wavelength photometry. These data allow us to make a direct comparison between dust around star-forming regions ($A_{V,\mathrm{HII}}$) and the integrated dust content ($A_{V,\mathrm{star}}$). We select a sample of 163 galaxies between $1.36\le{}z\le1.5$ with H$\alpha$ signal-to-noise ratio $\ge5$ and measure Balmer decrements from stacked spectra to calculate $A_{V,\mathrm{HII}}$. First, we stack spectra in bins of $A_{V,\mathrm{star}}$, and find that $A_{V,\mathrm{HII}}=1.86\,A_{V,\mathrm{star}}$, with a significance of $\sigma=1.7$. Our result is consistent with the two-component dust model, in which galaxies contain both diffuse and stellar birth cloud dust. Next, we stack spectra in bins of specific star formation rate ($\log\,\mathrm{SSFR}$), star formation rate ($\log\,\mathrm{SFR}$), and stellar mass ($\log{}M_*$). We find that on average $A_{V,\mathrm{HII}}$ increases with SFR and mass, but decreases with increasing SSFR. Interestingly, the data hint that the amount of extra attenuation decreases with increasing SSFR. This trend is expected from the two-component model, as the extra attenuation will increase once older stars outside the star-forming regions become more dominant in the galaxy spectrum. Finally, using Balmer decrements we derive dust-corrected H$\alpha$ SFRs, and find that stellar population modeling produces incorrect SFRs if rapidly declining star formation histories are included in the explored parameter space.Comment: Accepted for publication in the Astrophysical Journal (13 pages, 9 figures

Mannitol Does Not Enhance Tobramycin Killing of Pseudomonas aeruginosa in a Cystic Fibrosis Model System of Biofilm Formation

Cystic Fibrosis (CF) is a human genetic disease that results in the accumulation of thick, sticky mucus in the airways, which results in chronic, life-long bacterial biofilm infections that are difficult to clear with antibiotics. Pseudomonas aeruginosa lung infection is correlated with worsening lung disease and P. aeruginosa transitions to an antibiotic tolerant state during chronic infections. Tobramycin is an aminoglycoside currently used to combat lung infections in individuals with CF. While tobramycin is effective at eradicating P. aeruginosa in the airways of young patients, it is unable to completely clear the chronic P. aeruginosa infections in older patients. A recent report showed that co-addition of tobramycin and mannitol enhanced killing of P. aeruginosa grown in vitro as a biofilm on an abiotic surface. Here we employed a model system of bacterial biofilms formed on the surface of CF-derived airway cells to determine if mannitol would enhance the antibacterial activity of tobramycin against P. aeruginosa grown on a more clinically relevant surface. Using this model system, which allows the growth of robust biofilms with high-level antibiotic tolerance analogous to in vivo biofilms, we were unable to find evidence for enhanced antibacterial activity of tobramycin with the addition of mannitol, supporting the observation that this type of co-treatment failed to reduce the P. aeruginosa bacterial load in a clinical setting

The MOSFIRE Deep Evolution Field (MOSDEF) Survey: Rest-Frame Optical Spectroscopy for ~1500 H-Selected Galaxies at 1.37 < z < 3.8

In this paper we present the MOSFIRE Deep Evolution Field (MOSDEF) survey. The MOSDEF survey aims to obtain moderate-resolution (R=3000-3650) rest-frame optical spectra (~3700-7000 Angstrom) for ~1500 galaxies at 1.37<z<3.80 in three well-studied CANDELS fields: AEGIS, COSMOS, and GOODS-N. Targets are selected in three redshift intervals: 1.37<z<1.70, 2.09<z<2.61, and 2.95<z<3.80, down to fixed H_AB (F160W) magnitudes of 24.0, 24.5 and 25.0, respectively, using the photometric and spectroscopic catalogs from the 3D-HST survey. We target both strong nebular emission lines (e.g., [OII], Hbeta, [OIII], 5008, Halpha, [NII], and [SII]) and stellar continuum and absorption features (e.g., Balmer lines, Ca-II H and K, Mgb, 4000 Angstrom break). Here we present an overview of our survey, the observational strategy, the data reduction and analysis, and the sample characteristics based on spectra obtained during the first 24 nights. To date, we have completed 21 masks, obtaining spectra for 591 galaxies. For ~80% of the targets we derive a robust redshift from either emission or absorption lines. In addition, we confirm 55 additional galaxies, which were serendipitously detected. The MOSDEF galaxy sample includes unobscured star-forming, dusty star-forming, and quiescent galaxies and spans a wide range in stellar mass (~10^9-10^11.5 Msol) and star formation rate (~10^0-10^3 Msol/yr). The spectroscopically confirmed sample is roughly representative of an H-band limited galaxy sample at these redshifts. With its large sample size, broad diversity in galaxy properties, and wealth of available ancillary data, MOSDEF will transform our understanding of the stellar, gaseous, metal, dust, and black hole content of galaxies during the time when the universe was most active.Comment: Accepted for publication in ApJS; 28 pages, 19 figures; MOSDEF spectroscopic redshifts available at http://mosdef.astro.berkeley.edu/Downloads.htm

Inferring More from Less: Prospector as a Photometric Redshift Engine in the Era of JWST

The advent of the James Webb Space Telescope (JWST) signals a new era in exploring galaxies in the high-$z$ universe. Current and upcoming JWST imaging will potentially detect galaxies out to $z \sim 20$, creating a new urgency in the quest to infer accurate photometric redshifts (photo-$z$) for individual galaxies from their spectral energy distributions, as well as masses, ages and star formation rates. Here we illustrate the utility of informed priors encoding previous observations of galaxies across cosmic time in achieving these goals. We construct three joint priors encoding empirical constraints of redshifts, masses, and star formation histories in the galaxy population within the \prospector\ Bayesian inference framework. In contrast with uniform priors, our model breaks an age-mass-redshift degeneracy, and thus reduces the mean bias error in masses from 0.3 to 0.1 dex, and in ages from 0.6 to 0.2 dex in tests done on mock JWST observations. Notably, our model recovers redshifts at least as accurately as the state-of-the-art photo-$z$ code \eazy\ in deep JWST fields, but with two advantages: tailoring a model based on a particular survey renders mostly unnecessary given well-motivated priors; obtaining joint posteriors describing stellar, active galactic nuclei, gas, and dust contributions becomes possible. We can now confidently use the joint distribution to propagate full non-Gaussian redshift uncertainties into inferred properties of the galaxy population. This model, ``\prospector-$\beta$'', is intended for fitting galaxy photometry where the redshift is unknown, and will be instrumental in ensuring the maximum science return from forthcoming photometric surveys with JWST. The code is made publicly available online as a part of \prospector.Comment: Accepted for publication in ApJL. 13 pages, 6 figures, 2 tables. The code is made publicly available online as a part of Prospector; the version used in this work corresponds to the state of the Git repository at commit 820ad7

Quantifying the Effects of Known Unknowns on Inferred High-redshift Galaxy Properties: Burstiness, the IMF, and Nebular Physics

The era of the James Webb Space Telescope ushers stellar populations models into uncharted territories, particularly at the high-redshift frontier. In a companion paper, we apply the \texttt{Prospector} Bayesian framework to jointly infer galaxy redshifts and stellar populations properties from broad-band photometry as part of the UNCOVER survey. Here we present a comprehensive error budget in spectral energy distribution (SED) modeling. Using a $z_{\rm phot}>9$ sample, we quantify the systematic shifts stemming from various model choices in inferred stellar mass, star formation rate (SFR), and age. These choices encompass different timescales for changes in the star formation history (SFH), non-universal stellar initial mass functions (IMF), and the inclusion of variable nebular abundances, gas density and ionizing photon budget. We find that the IMF exerts the strongest influence on the inferred properties: the systematic uncertainties can be as much as 1 dex, 2--5 times larger than the formal reported uncertainties in mass and SFR; and importantly, exceed the scatter seen when using different SED fitting codes. This means that a common practice in the literature of assessing uncertainties in SED-fitting processes by comparing multiple codes is substantively underestimating the true systematic uncertainty. Highly stochastic SFHs change the inferred SFH by much larger than the formal uncertainties, and introduce $\sim 0.8$ dex systematics in SFR and $\sim 0.3$ dex systematics in average age. Finally, employing a flexible nebular emission model causes $\sim 0.2$ dex systematic increase in mass, comparable to the formal uncertainty. This paper constitutes one of the initial steps toward a complete uncertainty estimate in SED modeling.Comment: Submitted to ApJ. 18 pages, 8 figures, 2 table

An ALMA Search for Substructure, Fragmentation, and Hidden Protostars in Starless Cores in Chamaeleon I

We present an Atacama Large Millimeter/submillimeter Array (ALMA) 106 GHz (Band 3) continuum survey of the complete population of dense cores in the Chamaeleon I molecular cloud. We detect a total of 24 continuum sources in 19 different target fields. All previously known Class 0 and Class I protostars in Chamaeleon I are detected, whereas all of the 56 starless cores in our sample are undetected. We show that the Spitzer+Herschel census of protostars in Chamaeleon I is complete, with the rate at which protostellar cores have been misclassified as starless cores calculated as <1/56, or < 2%. We use synthetic observations to show that starless cores collapsing following the turbulent fragmentation scenario are detectable by our ALMA observations when their central densities exceed ~10^8 cm^-3, with the exact density dependent on the viewing geometry. Bonnor-Ebert spheres, on the other hand, remain undetected to central densities at least as high as 10^10 cm^-3. Our starless core non-detections are used to infer that either the star formation rate is declining in Chamaeleon I and most of the starless cores are not collapsing, matching the findings of previous studies, or that the evolution of starless cores are more accurately described by models that develop less substructure than predicted by the turbulent fragmentation scenario, such as Bonnor-Ebert spheres. We outline future work necessary to distinguish between these two possibilities.Comment: Accepted by Ap

2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline

Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread

Unique Microbial Communities Persist in Individual Cystic Fibrosis Patients throughout a Clinical Exacerbation

Cystic fibrosis (CF) is caused by inherited mutations in the cystic fibrosis transmembrane conductance regulator gene and results in a lung environment that is highly conducive to polymicrobial infection. Over a lifetime, decreasing bacterial diversity and the presence of Pseudomonas aeruginosa in the lung are correlated with worsening lung disease. However, to date, no change in community diversity, overall microbial load or individual microbes has been shown to correlate with the onset of an acute exacerbation in CF patients. We followed 17 adult CF patients throughout the course of clinical exacerbation, treatment and recovery, using deep sequencing and quantitative PCR to characterize spontaneously expectorated sputum sample

Nurses\u27 Alumnae Association Bulletin - Volume 6 Number 9

Remember the Relief Fund Welcome! Miss Childs Financial Report Calendar of Coming Events Lest You Forget! Attention Review of the Alumnae Association Meetings Institutional Staff Nurses\u27 Section Report of Staff Activities - 1947-1948 Private Duty Section The White Haven Division Barton Memorial Division Remember the Relief Fund Student Nurses\u27 Activities Jefferson Scores Again The Clara Melville Scholarship Fund Interesting Activities of the Nurses\u27 Home Committee of the Women\u27s Board Exclusive for Nurses Changes in the Maternity Division Gray Lady Musical Therapy Service Memorial Service Honoring Mrs. Bessie Dobson Altemus The Blood Donor Center The Hospital Pharmacy Medical College News Remember the Relief Fund Administrative Staff and Faculty of the School of Nursing Streptomycin Changes in the Staff at Jefferson Hospital Care of the Thoracic Surgical Patient Miscellaneous Items Marriages New Arrivals Deaths The Bulletin Committee Attention, Alumnae New Addresse