ASU Scholarship Showcase

The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was investigated. We used a three-dimensional (3-D) organotypic model of human colonic epithelium that was previously validated and applied to study interactions between S. Typhimurium and the intestinal epithelium that lead to enteric salmonellosis. Using this model system, we show that L. reuteri protects the intestinal cells against the early stages of Salmonella infection and that this effect is significantly increased when L. reuteri is stimulated to produce reuterin from glycerol. More specifically, the reuterin-containing ferment of L. reuteri caused a reduction in Salmonella adherence and invasion (1 log unit), and intracellular survival (2 log units). In contrast, the L. reuteri ferment without reuterin stimulated growth of the intracellular Salmonella population with 1 log unit. The short-term exposure to reuterin or the reuterin-containing ferment had no observed negative impact on intestinal epithelial cell health. However, long-term exposure (24 h) induced a complete loss of cell-cell contact within the epithelial aggregates and compromised cell viability. Collectively, these results shed light on a potential role for reuterin in inhibiting Salmonella-induced intestinal infections and may support the combined application of glycerol and L. reuteri. While future in vitro and in vivo studies of reuterin on intestinal health should fine-tune our understanding of the mechanistic effects, in particular in the presence of a complex gut microbiota, this the first report of a reuterin effect on the enteric infection process in any mammalian cell type.

Background: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S.

Methods: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods.

Results: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period.

Conclusions: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.

Background: Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics.

In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico.

Methods: We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset) on the risk of death by multivariate logistic regression.

Results: Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P < 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41).

Conclusions: Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

Background: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru.

Methods: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases.

Results: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity.

Conclusions: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.

Atmospheric radiocarbon (¹⁴C) represents an important observational constraint on emissions of fossil-fuel derived carbon into the atmosphere due to the absence of ¹⁴C in fossil fuel reservoirs. The high sensitivity and precision that accelerator mass spectrometry (AMS) affords in atmospheric ¹⁴C analysis has greatly increased the potential for using such measurements to evaluate bottom-up emissions inventories of fossil fuel CO₂(CO₂ff), as well as those for other co-emitted species. Here we use observations of ¹⁴CO₂ and a series of primary hydrocarbons and combustion tracers from discrete air samples collected between June 2009 and September 2010 at the National Oceanic and Atmospheric Administration Boulder Atmospheric Observatory (BAO; Lat: 40.050° N, Lon: 105.004° W) to derive emission ratios of each species with respect to CO₂ff. The BAO tower is situated at the boundary of the Denver metropolitan area to the south and a large industrial and agricultural region to the north and east, making it an ideal location to study the contrasting mix of emissions from the activities in each region. The species considered in this analysis are carbon monoxide (CO), methane (CH₄), acetylene (C₂H₂), benzene (C₆H₆), and C₃–C₅ alkanes. We estimate emissions for a subset of these species by using the Vulcan high resolution CO2ff emission data product as a reference. We find that CO is overestimated in the 2008 National Emissions Inventory (NEI08) by a factor of ~2. A close evaluation of the inventory suggests that the ratio of CO emitted per unit fuel burned from on-road gasoline vehicles is likely over-estimated by a factor of 2.5. Using a wind-directional analysis of the data, we find enhanced concentrations of CH₄, relative to CO₂ff, in air influenced by emissions to the north and east of the BAO tower when compared to air influenced by emissions in the Denver metro region to the south. Along with enhanced CH₄, the strongest enhancements of the C₃–C₅ alkanes are also found in the north and east wind sector, suggesting that both the alkane and CH₄ enhancements are sourced from oil and gas fields located to the northeast, though it was not possible to rule out the contribution of non oil and gas CH₄ sources.

Urban environments are the primary contributors to global anthropogenic carbon emissions. Because much of the growth in CO₂ emissions will originate from cities, there is a need to develop, assess, and improve measurement and modeling strategies for quantifying and monitoring greenhouse gas emissions from large urban centers. In this study the uncertainties in an aircraft-based mass balance approach for quantifying carbon dioxide and methane emissions from an urban environment, focusing on Indianapolis, IN, USA, are described. The relatively level terrain of Indianapolis facilitated the application of mean wind fields in the mass balance approach. We investigate the uncertainties in our aircraft-based mass balance approach by (1) assessing the sensitivity of the measured flux to important measurement and analysis parameters including wind speed, background CO₂ and CH₄, boundary layer depth, and interpolation technique, and (2) determining the flux at two or more downwind distances from a point or area source (with relatively large source strengths such as solid waste facilities and a power generating station) in rapid succession, assuming that the emission flux is constant. When we quantify the precision in the approach by comparing the estimated emissions derived from measurements at two or more downwind distances from an area or point source, we find that the minimum and maximum repeatability were 12 and 52%, with an average of 31%. We suggest that improvements in the experimental design can be achieved by careful determination of the background concentration, monitoring the evolution of the boundary layer through the measurement period, and increasing the number of downwind horizontal transect measurements at multiple altitudes within the boundary layer.

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

Salmonella enterica serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike “classical” non-typhoidal Salmonella (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates. A better understanding of the key environmental factors regulating these systemic infections is urgently needed. Our previous studies using dynamic Rotating Wall Vessel (RWV) bioreactor technology demonstrated that physiological levels of fluid shear regulate virulence, gene expression, and stress response profiles of classic S. Typhimurium. Here we provide the first demonstration that fluid shear alters the virulence potential and pathogenesis-related stress responses of ST313 strain D23580 in a manner that differs from classic NTS.

Large urban emissions of greenhouse gases result in large atmospheric enhancements relative to background that are easily measured. Using CO₂ mole fractions and Δ¹⁴C and δ¹³C values of CO₂ in the Los Angeles megacity observed in inland Pasadena (2006–2013) and coastal Palos Verdes peninsula (autumn 2009–2013), we have determined time series for CO₂ contributions from fossil fuel combustion (C_ff) for both sites and broken those down into contributions from petroleum and/or gasoline and natural gas burning for Pasadena. We find a 10 % reduction in Pasadena C_ff during the Great Recession of 2008–2010, which is consistent with the bottom-up inventory determined by the California Air Resources Board. The isotopic variations and total atmospheric CO₂ from our observations are used to infer seasonality of natural gas and petroleum combustion. The trend of CO₂ contributions to the atmosphere from natural gas combustion is out of phase with the seasonal cycle of total natural gas combustion seasonal patterns in bottom-up inventories but is consistent with the seasonality of natural gas usage by the area's electricity generating power plants. For petroleum, the inferred seasonality of CO₂ contributions from burning petroleum is delayed by several months relative to usage indicated by statewide gasoline taxes. Using the high-resolution Hestia-LA data product to compare C_ff from parts of the basin sampled by winds at different times of year, we find that variations in observed fossil fuel CO₂ reflect seasonal variations in wind direction. The seasonality of the local CO₂ excess from fossil fuel combustion along the coast, on Palos Verdes peninsula, is higher in autumn and winter than spring and summer, almost completely out of phase with that from Pasadena, also because of the annual variations of winds in the region. Variations in fossil fuel CO₂ signals are consistent with sampling the bottom-up Hestia-LA fossil CO₂ emissions product for sub-city source regions in the LA megacity domain when wind directions are considered.

Recent advances in fossil fuel CO₂ (FFCO₂) emission inventories enable sensitivity tests of simulated atmospheric CO₂ concentrations to sub-annual variations in FFCO₂ emissions and what this implies for the interpretation of observed CO₂. Six experiments are conducted to investigate the potential impact of three cycles of FFCO₂ emission variability (diurnal, weekly and monthly) using a global tracer transport model. Results show an annual FFCO₂ rectification varying from −1.35 to +0.13 ppm from the combination of all three cycles. This rectification is driven by a large negative diurnal FFCO₂ rectification due to the covariation of diurnal FFCO₂ emissions and diurnal vertical mixing, as well as a smaller positive seasonal FFCO₂ rectification driven by the covariation of monthly FFCO₂ emissions and monthly atmospheric transport. The diurnal FFCO₂ emissions are responsible for a diurnal FFCO₂ concentration amplitude of up to 9.12 ppm at the grid cell scale. Similarly, the monthly FFCO₂ emissions are responsible for a simulated seasonal CO₂ amplitude of up to 6.11 ppm at the grid cell scale. The impact of the diurnal FFCO₂ emissions, when only sampled in the local afternoon, is also important, causing an increase of +1.13 ppmv at the grid cell scale. The simulated CO₂ concentration impacts from the diurnally and seasonally varying FFCO₂ emissions are centered over large source regions in the Northern Hemisphere, extending to downwind regions. This study demonstrates the influence of sub-annual variations in FFCO₂ emissions on simulated CO₂ concentration and suggests that inversion studies must take account of these variations in the affected regions.