Pertussis Toxin Stimulates IL-17 Production in Response to Bordetella pertussis Infection in Mice

In a mouse model of respiratory tract infection by Bordetella pertussis, bacteria multiply in the airways over the first week and are then cleared over the next 3–4 weeks by the host immune response. Pertussis toxin (PT), a virulence factor secreted exclusively by B. pertussis, promotes bacterial growth in the airways by suppression and modulation of host immune responses. By comparison of wild type and PT-deficient strains, we examined the role of PT in modulating airway cytokine and chemokine responses affecting neutrophil recruitment during B. pertussis infection in mice. We found that, despite early inhibition of neutrophil recruitment by PT, high numbers of neutrophils were recruited to the airways by 4 days post-infection with the wild type strain, but not with the PT-deficient strain, and that this correlated with upregulation of neutrophil-attracting chemokine gene expression. In addition, there was similar upregulation of genes expressing the cytokines IL-17A (IL-17), TNF-α and IFN-γ, indicating a mixed Th1/Th17 response. Expression of IL-6, a cytokine involved in Th17 induction, was upregulated earlier than the IL-17 response. We showed that PT, rather than bacterial numbers, was important for induction of these responses. Flow cytometric analysis revealed that the IL-17-producing cells were macrophages and neutrophils as well as T cells, and were present predominantly in the airways rather than the lung tissue. Antibody neutralization of IL-17 significantly reduced chemokine gene expression and neutrophil recruitment to the airways, but only modestly increased peak bacterial loads. These data indicate that PT stimulates inflammatory responses by induction of Th1- and Th17-associated cytokines, including IL-17, during B. pertussis infection in mice, but a role for IL-17 in protection against the infection remains to be established

On the Influence of Ionic Strength on Radium and Strontium Sorption to Sandy Loam Soils

Models which can estimate environmental transport of radioactive contaminants in natural and engineered systems are required to 1) deploy effective remediation strategies for contaminated sites, 2) design waste repositories for future waste streams, and 3) ensure protection of human and environmental health in all cases. These models require accurate transport parameters in order to correctly predict how these contaminants will move in the subsurface. This work aimed to determine more accurately the distribution coefficients for radium and strontium sorption to Savannah River Site (SRS) soils. Radium and strontium sorption to the soils was found to be highly dependent upon ionic strength due to competition for ion exchange sites. Radium distribution coefficients (Kd) for the clayey soil were determined to be 185.1 ± 25.63 L kg-1 and 30.35 ± 0.66 L kg-1 for ionic strengths of 0.02M and 0.1M as NaCl which is the approximate ionic strength of groundwater at the SRS. Radium distribution coefficients for the sandy soil were determined to be 24.95 ± 2.97 L kg-1 and 9.05 ± 0.36 L kg-1 for ionic strengths of 0.02M and 0.1M as NaCl. Sorption of Ra2+ was generally greater than Sr2+, consistent with the frequent use of higher distribution coefficients for Ra in performance assessments

A Brachistochrone Approach to Reconstruct the Inflaton Potential

We propose a new way to implement an inflationary prior to a cosmological dataset that incorporates the inflationary observables at arbitrary order. This approach employs an exponential form for the Hubble parameter $H(\phi)$ without taking the slow-roll approximation. At lowest non-trivial order, this $H(\phi)$ has the unique property that it is the solution to the brachistochrone problem for inflation.Comment: 13 pages, 2 figures, version matches published versio

Geographic Proximity Not a Prerequisite for Invasion: Hawaii Not the Source of California Invasion by Light Brown Apple Moth (Epiphyas postvittana)

BACKGROUND: The light brown apple moth (LBAM), Epiphyas postvittana (Walker), is native to Australia but invaded England, New Zealand, and Hawaii more than 100 years ago. In temperate climates, LBAM can be a major agricultural pest. In 2006 LBAM was discovered in California, instigating eradication efforts and quarantine against Hawaiian agriculture, the assumption being that Hawaii was the source of the California infestation. Genetic relationships among populations in Hawaii, California, and New Zealand are crucial to understanding LBAM invasion dynamics across the Pacific. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced mitochondrial DNA (mtDNA) from 1293 LBAM individuals from California (695), Hawaii (448), New Zealand (147), and Australia (3) to examine haplotype diversity and structure among introduced populations, and evaluate the null hypothesis that invasive populations are from a single panmictic source. However, invasive populations in California and New Zealand harbor deep genetic diversity, whereas Hawaii shows low level, shallow diversity. CONCLUSIONS/SIGNIFICANCE: LBAM recently has established itself in California, but was in Hawaii and New Zealand for hundreds of generations, yet California and New Zealand show similar levels of genetic diversity relative to Hawaii. Thus, there is no clear relationship between duration of invasion and genetic structure. Demographic statistics suggest rapid expansion occurring in California and past expansions in New Zealand; multiple introductions of diverse, genetically fragmented lineages could contribute to these patterns. Hawaii and California share no haplotypes, therefore, Hawaii is not the source of the California introduction. Paradoxically, Hawaii and California share multiple haplotypes with New Zealand. New Zealand may be the source for the California and Hawaii infestations, but the introductions were independent, and Hawaii was invaded only once. This has significant implications for quarantine, and suggests that probability of invasion is not directly related to geographic distance. Surprisingly, Hawaiian LBAM populations have much lower genetic diversity than California, despite being older

Community cleavages: gay and bisexual men's perceptions of gay and mainstream community acceptance in the post-AIDS, post-rights era

Changes in gay and bisexual men's connectedness to the gay community are related to the declining public visibility of HIV/AIDS and greater acceptance for homosexuality and bisexuality in mainstream society. Little work, however, has focused on perceived acceptance for subgroups within the gay community or broader society. Using interviews (n = 20) and a survey (n = 202) of gay and bisexual men in a mid-sized Canadian city, we find perceived hierarchies of acceptance for the various subgroups as well as an age effect wherein middle-aged men perceive the least acceptance for all groups. These differences are linked with the uneven impact of social, political, and institutional changes relevant to gay and bisexual men in Canada

Is there an association between spatial access to parks/green space and childhood overweight/obesity in Calgary, Canada?

<p>Abstract</p> <p>Background</p> <p>The recent increase in childhood obesity is expected to add significantly to the prevalence of chronic diseases. We used multivariate multilevel analysis to examine associations between parks/green space and childhood overweight/obesity across communities in Calgary, Canada, a city characterized by intensified urban sprawl and high car use.</p> <p>Methods</p> <p>Body Mass Index was calculated from measured height and weight data obtained from 6,772 children (mean age = 4.95 years) attending public health clinics for pre-school vaccinations. Each child's home postal code was geocoded using ESRI ArcGIS 9.2. We examined four measures of spatial access to parks/green space (based on Geographic Information Systems): 1) the number of parks/green spaces per 10,000 residents, 2) the area of parks/green space as a proportion of the total area within a community, 3) average distance to a park/green space, and 4) the proportion of parks/green space service area as a proportion of the total area within a community. Analyses were adjusted for dissemination area median family income (as a proxy for an individual child's family income) community-level education, and community-level proportion of visible minorities.</p> <p>Results</p> <p>In general, parks/green space at the community level was not associated with overweight/obesity in Calgary, with the exception of a marginally significant effect whereby a moderate number of parks/green spaces per 10,000 residents was associated with lower odds of overweight/obesity. This effect was non-significant in adjusted analyses.</p> <p>Conclusion</p> <p>Our null findings may reflect the popularity of car travel in Calgary, Canada and suggest that the role built environment characteristics play in explaining health outcomes may differ depending on the type of urban environment being studied.</p

Laboratory And Lysimeter Experimentation And Transport Modeling Of Neptunium And Strontium In Savannah River Site Sediments

The Savannah River Site (SRS) conducts performance assessment (PA) calculations to determine the appropriate amount of low-level radiological waste that can be safely disposed on site. Parameters are included in these calculations that account for the interaction between the immobile solid phase and the mobile aqueous phase. These parameters are either the distribution coefficient (K{sub d} value) or the apparent solubility value (K{sub sp}). These parameters are readily found in the literature and are used throughout the DOE complex. One shortcoming of K{sub d} values is that they are only applicable to a given set of solid and aqueous phase conditions. Therefore, a given radionuclide may have several K{sub d} values as it moves between formations and comes into contact with different solids and different aqueous phases. It is expected that the K{sub d} construct will be appropriate to use for a majority of the PA and for a majority of the radionuclides. However, semi-mechanistic models would be more representative in isolated cases where the chemistry is especially transitory or the radionuclide chemistry is especially complex, bringing to bear multiple species of varying sorption tendencies to the sediment. Semi-mechanistic models explicitly accommodate the dependency of K{sub d} values, or other sorption parameters, on contaminant concentration, competing ion concentrations, pH-dependent surface charge on the adsorbent, and solute species distribution. Incorporating semi-mechanistic concepts into geochemical models is desirable to make the models more robust and technically defensible. Furthermore, these alternative models could be used to augment or validate a Kd?based DOE Order 435.1 Performance Assessment. The objectives of this study were to: 1) develop a quantitative thermodynamically-based model for neptunium sorption to SRS sediments, and 2) determine a sorption constant from an SRS 11-year lysimeter study. The modeling studies were conducted with existing data sets. The first data set used laboratory generated Np sorption data as a function of concentration (three orders of magnitude) and as a function of pH (four orders of magnitude of proton concentration). In this modeling exercise, a very simple solution was identified by assuming that all sorption occurred only to the iron oxides in the sediment and that all the added NpO{sub 4}{sup -} remained in the oxidized state and was not reduced to the Np(IV) state (as occurs rapidly with Pu(V)). With rather limited input data, very good agreement between experimental and modeling results was observed. This modeling approach would be easy to add to the PA with little additional data requirements. This model would be useful in a system where pH is expected to change greatly, such as directly beneath a grout or concrete structure. The second model discussed in the report was to derive strontium K{sub d} values from data collected in an 11-year-old field transport study. In this controlled lysimeter study, a sensitivity analysis was conducted of hydrological and chemical processes that influence contaminant transport, including diffusion coefficients, seepage velocity, and K{sub d} value. The best overall K{sub d} derived from the model fit to the data was 32 L kg{sup -1}, which was the same value that was previously measured in traditional laboratory batch sorption studies. This was an unexpected result given the differences in experimental conditions between the batch test and the lysimeter flow through test, in particular the differences between strontium adsorption and desorption processes occurring in the latter test and not in the former. There were some trends in the lysimeter strontium data that were not predicted by the K{sub d} model, which suggest that other geochemical processes are likely also controlling strontium transport. Strontium release and cation exchange are being evaluated. These results suggest that future modeling efforts (e.g., PAs) could be improved by employing a more robust semi-empirical modeling approach to transient or complex conditions

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies