Ferrous Iron Sensing and Responding in Pseudomonas aeruginosa

Controlling iron distribution is important for all organisms, and is key in bacterial pathogenesis. It has long been understood that cystic fibrosis (CF) patient sputum contains elevated iron concentrations. However, anaerobic bacteria have been isolated from CF sputum and hypoxic zones in sputum have been measured. Because ferrous iron [Fe(II)] is stable in reducing, acidic conditions, it could exist in the CF lung. I show that a two-component system, BqsRS, specifically responds to Fe(II) in the CF pathogen, Pseudomonas aeruginosa. Concurrently, a clinical study found that Fe(II) is present in CF sputum at all stages of lung function decline. Fe(II), not Fe(III) correlates with patients in the most severe disease state. Furthermore, transcripts of the newly identified BqsRS were detected in sputum. Two component systems are the main method bacteria interact with their extracellular environment. A typical two-component system contains a sensor histidine kinase, which upon activation phosphorylates a response regulator that then acts as a transcription factor to elicit a cellular response to stimuli. To explore the mechanism of BqsRS, I describe the Fe(II)-sensing RExxE motif in the sensor BqsS and determine the consensus DNA sequence BqsR binds. With the BqsR binding sequence, I identify novel regulon members through bioinformatic and molecular biology techniques. From the predicted function of new BqsR regulon members, I find that Fe(II) elicits a response that globally protects the cells against cationic stressors, including clinically relevant antibiotics. Subsequently, I use BqsR as a case study to determine if promoter outputs can accurately be predicted based only on a deep understanding of a transcriptional activator’s operator or if a broader regulatory context is required for accurate predictions at all genomic loci. This work highlights the importance of Fe(II) as a (micro)environmental factor, even in conditions typically thought of as aerobic. Since the presence of Fe(II) can alter P. aeruginosa’s antibiotic susceptibility, combining the current strategy of targeting Fe(III) with a new approach targeting Fe(II) may help eradicate infections in the CF lung in the future

Nursing Department Newsletters 2011-2019

Regularly updated newsletters from the Department of Nursing at Messiah College. It especially highlights the Integrative classroom and Clinical-based learning. Some issues are missing from 2011 to 2019

A Local Historic Village Goes Online: Transforming English and Social Studies Methods Courses for a Virtual Setting

In this article, two teacher-educators share their experience of navigating the shift of a service learning project from being an in-person project to an entirely remote learning experience caused by the COVID-19 pandemic. We discuss instructional adjustments, provide student samples, and consider lessons learned

An Analysis of Pedestrian-Vehicular Crashes Near Public Schools in the City of Baltimore, Maryland

In previous research, children have been shown to be involved in pedestrian-vehicular crashes in high numbers due to improper pedestrian behaviors. Little research has been conducted to examine the relationship between schools and pedestrian crashes. This study analyzes pedestrian-vehicular crashes in the City of Baltimore, Maryland to determine any relationships that may exist between crashes near public schools and the physical and social attributes of these schools. It was found that the presence of a driveway decreases crash occurrence and severity. A setback from the road will decrease crash occurrence but increase the severity of the crashes. The presence of off-street parking was shown to increase the severity of a crash, particularly for children ages 16-18. Recreational facilities are shown to increase the crash occurrence and severity of crashes. This study however, is limited as it does not include pedestrian demand data and the results should be interpreted as such

Hydrochemical determination of source water contributions to Lake Lungo and Lake Ripasottile (central Italy)

Lake Lungo and Lake Ripasottile are two shallow (4-5 m) lakes located in the Rieti Basin, central Italy, that have been described previously as surface outcroppings of the groundwater table. In this work, the two lakes as well as springs and rivers that represent their potential source waters are characterized physio-chemically and isotopically, using a combination of environmental tracers. Temperature and pH were measured and water samples were analyzed for alkalinity, major ion concentration, and stable isotope (δ2H, δ18O, δ13C of dissolved inorganic carbon, and δ34S and δ18O of sulfate) composition. Chemical data were also investigated in terms of local meteorological data (air temperature, precipitation) to determine the sensitivity of lake parameters to changes in the surrounding environment. Groundwater represented by samples taken from Santa Susanna Spring was shown to be distinct with SO4 2- and Mg2+ content of 270 and 29 mg/L, respectively, and heavy sulfate isotopic composition (δ34S=15.2‰ and δ18O=10‰). Outflow from the Santa Susanna Spring enters Lake Ripasottile via a canal and both spring and lake water exhibits the same chemical distinctions and comparatively low seasonal variability. Major ion concentrations in Lake Lungo are similar to the Vicenna Riara Spring and are interpreted to represent the groundwater locally recharged within the plain. The δ13CDIC exhibit the same groupings as the other chemical parameters, providing supporting evidence of the source relationships. Lake Lungo exhibited exceptional ranges of δ13CDIC (±5‰) and δ2H, δ18O (±5 ‰ and ±7 ‰, respectively), attributed to sensitivity to seasonal changes. The hydrochemistry results, particularly major ion data, highlight how the two lakes, though geographically and morphologically similar, represent distinct hydrochemical facies. These data also show a different response in each lake to temperature and precipitation patterns in the basin that may be attributed to lake water retention time. The sensitivity of each lake to meteorological patterns can be used to understand the potential effects from long-term climate variability

Credit and Liquidity in the Macroeconomy

This dissertation studies the role of credit and liquidity in macroeconomic fluctuations. Chapter 1 analyzes the effect of endogenous unemployment risk on the dynamics of recovery from a liquidity trap. In a liquidity trap, an adverse demand shock raises unemployment and produces a period of slow hiring. Slow hiring further reduces demand, both for standard precautionary reasons and because credit conditions endogenously worsen, reducing households' ability to borrow and consume. Multiple equilibrium paths exist, and which one the economy follows depends on household expectations and the policy rule adopted by the central bank after the economy exits the trap. Employment remains depressed for a substantial period after an adverse shock because high unemployment increases the dispersion of household debt holdings, slowing the recovery of demand. I find that the initial household debt distribution significantly affects the economy's sensitivity to a demand shock, and study the role of central bank policy in mitigating the initial fall in employment and promoting faster recovery. Chapter 2 explores a novel channel through which financial shocks affect the real economy through the supply of liquidity. I consider a model in which firms require uncertain ongoing financing, and agency costs limit their ability to raise new funds. To secure future financing, firms hold assets to sell if needed, and purchase credit lines from financial intermediaries. I collectively refer to these instruments as liquidity. Financial intermediaries' ability to commit future funds depends on their capital. This creates a linkage between bank balance sheets and the aggregate supply of liquidity. Bank losses raise the liquidity premium and reduce investment. I analyze the optimal supply of public liquidity, and find that when private liquidity is scarce the government should issue bonds for their liquidity properties. I further find that the optimal supply of government debt is decreasing in bank capital. This suggests that in the wake of a financial crisis in which financial intermediaries suffer large losses, governments should increase debt issuance. Chapter 3 considers the distributive implications of financial regulation. It develops a model in which the financial sector benefits from financial risk-taking by earning greater expected returns. However, risk-taking also increases the incidence of large losses that lead to credit crunches and impose negative externalities on the real economy. A regulator has to trade off efficiency in the financial sector, which is aided by deregulation, against efficiency in the real economy, which is aided by tighter regulation and a more stable supply of credit

Predicting the impact of promoter variability on regulatory outputs

The increased availability of whole genome sequences calls for quantitative models of global gene expression, yet predicting gene expression patterns directly from genome sequence remains a challenge. We examine the contributions of an individual regulator, the ferrous iron-responsive regulatory element, BqsR, on global patterns of gene expression in Pseudomonas aeruginosa. The position weight matrix (PWM) derived for BqsR uncovered hundreds of likely binding sites throughout the genome. Only a subset of these potential binding sites had a regulatory consequence, suggesting that BqsR/DNA interactions were not captured within the PWM or that the broader regulatory context at each promoter played a greater role in setting promoter outputs. The architecture of the BqsR operator was systematically varied to understand how binding site parameters influence expression. We found that BqsR operator affinity was predicted by the PWM well. At many promoters the surrounding regulatory context, including overlapping operators of BqsR or the presence of RhlR binding sites, were influential in setting promoter outputs. These results indicate more comprehensive models that include local regulatory contexts are needed to develop a predictive understanding of global regulatory outputs