Paper published: Nasal immunity is an ancient arm of the mucosal immune system of vertebrates

Nasal immunity is an ancient arm of the mucosal immune system of vertebrates Luca Tacchi, Rami Musharrafieh, Erin T. Larragoite, Kyle Crossey, Erik B. Erhardt, Samuel A. M. Martin, Scott E. LaPatra, & Irene Salinas Nature Communications 5 (5205), pdf, doi: 10.1038/ncomms6205 Online 22 October 2014 http://www.nature.com/ncomms/2014/141022/ncomms6205/full/ncomms6205.html Abstract The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for millions of years. In terrestrial vertebrates such as birds and mammals, the nasopharynx-associated lymphoid tissue (NALT) represents a first line of immune defence. Here we propose that NALT is an ancient arm of the mucosal immune system not restricted to terrestrial vertebrates. We find that NALT is present in rainbow trout and that it resembles other teleost mucosa-associated lymphoid tissues. Trout NALT consists of diffuse lymphoid cells and lacks tonsils and adenoids. The predominant B-cell subset found in trout NALT are IgT + B cells, similar to skin and gut. The trout olfactory organ is colonized by abundant symbiotic bacteria, which are coated by trout secretory immunoglobulin. Trout NALT is capable of mounting strong anti-viral immune responses following nasal delivery of a live attenuated viral vaccine. Our results open up a new tool for the control of aquatic infectious diseases via nasal vaccination.
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Paper published: Parental Military Service, Agent Orange Exposure, and the Risk of Rhabdomyosarcoma in Offspring

Parental Military Service, Agent Orange Exposure, and the Risk of Rhabdomyosarcoma in Offspring Grufferman, S, PJ Lupo, RI Vogel, AF Olshan, EB Erhardt, and S Ognjanovic Journal of Pediatrics 2014 Dec; pdf, 165(6):1216–21 Online: September 18, 2014 http://www.jpeds.com/article/S0022-3476(14)00734-3/abstract DOI: 10.1016/j.jpeds.2014.08.009 Abstract OBJECTIVE: To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. STUDY DESIGN: Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. RESULTS: There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). CONCLUSIONS: We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.
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Paper published: Reporting rate variation of childhood diseases in the pre-vaccine era

Reporting rate variation of childhood diseases in the pre-vaccine era Gunning, C, EB Erhardt, and HJ Wearing Proceedings of the Royal Society B 281 (1794) pp. 1-–9 Online: September 17, 2014 http://rspb.royalsocietypublishing.org//content/281/1794/20140886.abstract DOI: 10.1098/rspb.2014.0886 Abstract Incomplete observation is an important yet often neglected feature of observational ecological timeseries. In particular, observational case report timeseries of childhood diseases have played an important role in the formulation of mechanistic dynamical models of populations and metapopulations. Yet to our knowledge, no comprehensive study of childhood disease reporting probabilities (commonly referred to as reporting rates) has been conducted to date. Here, we provide a detailed analysis of measles and whooping cough reporting probabilities in pre-vaccine United States cities and states, as well as measles in cities of England and Wales. Overall, we find the variability between locations and diseases greatly exceeds that between methods or time periods. We demonstrate a strong relationship within location between diseases and within disease between geographical areas. In addition, we find that demographic covariates such as ethnic composition and school attendance explain a non-trivial proportion of reporting probability variation. Overall, our findings show that disease reporting is both variable and non-random and that completeness of reporting is influenced by disease identity, geography and socioeconomic factors. We suggest that variations in incomplete observation can be accounted for and that doing so can reveal ecologically important features that are otherwise obscured.
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Paper published: Yield and Effects of Organic Nitrogen Fertilizer on Field-Grown Chinese Medicinal Plants in the United States

Yield and Effects of Organic Nitrogen Fertilizer on Field-Grown Chinese Medicinal Plants in the United States Gardner, Z, EB Erhardt, E Shaikouskaya, JP Baek, and LE Craker Journal of Herbs, Spices & Medicinal Plants 21(1) pp. 9–22 Online: August 13, 2014 http://www.tandfonline.com/doi/abs/10.1080/10496475.2014.891092 DOI: 10.1080/10496475.2014.891092 Abstract There is an increased demand for Chinese medicinal plants in the U.S., with little known about the feasibility of production of these species outside of China. The purpose of this study was to develop basic agronomic data for selected Chinese medicinal plant species. Agastache rugosa, Schizonepeta tenuifolia, Leonurus japonicus, and Leonurus sibiricus were grown in a randomized complete block design with 0, 100, or 200 kg.ha−1 of nitrogen (N). At 100 kg.ha−1 of N, a significant increase in yield of all species was observed as compared to the 0 kg.ha−1 control. Average dry yield per plant at 100 kg.ha−1 of N was 44.7 g for A. rugosa herb, 52.6 g for S. tenuifolia inflorescences, 42.7 g for L. japonicus basal rosette, and 46.9 g for L. sibiricus basal rosette. Yields of A. rugosa and both Leonurus species increased significantly again at 200 kg.ha−1 of N as compared to 100 kg.ha−1, while the increase in yield between these two levels was slight for S. tenuifolia. Results from these trials indicate that all four of the selected species are suitable for cultivation in the northeastern U.S.
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Paper published: Maternal and birth characteristics and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group

Maternal and birth characteristics and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group Lupo, PJ, HE Danysh, SX Skapek, DS Hawkins, LG Spector, RZhou, MF Okcu, K Papworth, EB Erhardt, and S Grufferman Cancer Causes and Control 25 (7) pp 905-913 http://link.springer.com/article/10.1007/s10552-014-0390-6 Online: August 1, 2013 DOI: 10.1007/s10552-014-0390-6 Abstract Purpose Previous assessments of childhood rhabdomyosarcoma have indicated maternal and birth characteristics may be associated with tumor development; however, much work remains to identify novel and confirm suspected risk factors. Our objective was to evaluate the associations between maternal and birth characteristics and childhood rhabdomyosarcoma. Methods This case–control study included 322 cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls were identified using random digit dialing and were individually matched to cases on race, sex, and age. Families of the case and control subjects participated in a telephone interview, which captured information on maternal characteristics (birth control use, number of prenatal visits, anemia, and abnormal bleeding during pregnancy) and birth characteristics [birth weight, preterm birth, and type of delivery (vaginal vs. cesarean)]. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95 % confidence interval (CI) for each exposure, adjusted for age, race, sex, household income, and parental education. As the two most common histologic types of rhabdomyosarcoma are embryonal (n = 215) and alveolar (n = 66), we evaluated effect heterogeneity of these exposures. Results The only characteristic that was associated with childhood rhabdomyosarcoma, and statistically significant, was abnormal vaginal bleeding during pregnancy (OR 1.75, 95 % CI 1.12–2.74). Birth control use (OR 1.45, 95 % CI 0.96–2.18), anemia during pregnancy (OR 1.27, 95 % CI 0.81–1.99), and preterm birth (OR 2.51, 95 % CI 0.74–8.49) were positively associated with childhood rhabdomyosarcoma, but were not statistically significant. Low birth weight [adjusted odds ratios (aOR) 4.46, 95 % CI 1.41–14.1] and high birth weight (aOR 2.41, 95 % CI 1.09–5.35) were strongly associated with alveolar rhabdomyosarcoma. However, these factors did not display significant effect heterogeneity between histologic types (p > 0.15 for all characteristics). Conclusions Overall, we found little evidence that these maternal and birth characteristics are strongly associated with childhood rhabdomyosarcoma.
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Paper published: Rates of Biotic Interactions Scale Predictably with Temperature Despite Variation

Rates of Biotic Interactions Scale Predictably with Temperature Despite Variation Burnside, W. R., Erhardt, E. B., Hammond, S. T. and Brown, J. H. Oikos, 123 pp. 1449–1456 Online: May 27, 2014 http://onlinelibrary.wiley.com/doi/10.1111/oik.01199/abstract DOI: 10.1111/oik.01199 Abstract Most biological processes are temperature dependent. To quantify the temperature dependence of biotic interactions and evaluate predictions of metabolic theory, we: 1) compiled a database of 81 studies that provided 112 measures of rates of herbivory, predation, parasitism, parasitoidy, or competition between two species at two or more temperatures; and 2) analyzed the temperature dependence of these rates in the framework of metabolic ecology to test our prediction that the “activation energy,” E, centers around 0.65 eV. We focused on studies that assessed rates or associated times of entire biotic interactions, such as time to consumption of all prey, rather than rates of components of these interactions, such as prey encounter rate. Results were: 1) the frequency distribution of E for each interaction type was typically peaked and right skewed; 2) the overall mean is E= 0.96 eV and median E= 0.78 eV; 3) there was significant variation in E within but not across interaction types; but 4) average values of E were not significantly different from 0.65 eV by interaction type and 5) studies with measurements at more temperatures were more consistent with E= 0.65 eV. These synthetic findings suggest that, despite the many complicating factors, the temperature-dependence of rates of biotic interactions broadly reflect of rates of metabolism, a relationship with important implications for a warming world.
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Paper published: Stable Isotope Sourcing using Sampling

Stable Isotope Sourcing using Sampling Erhardt, EB, BO Wolf, M Ben-David, and EJ Bedrick Open Journal of Ecology 4 (6) pp. 289–298 Online: May 2014 http://www.scirp.org/journal/PaperInformation.aspx?PaperID=46187 DOI: 10.4236/oje.2014.46027 Abstract Stable isotope mixing models are used to estimate proportional contributions of sources to a mixture, such as in the analysis of animal diets, plant nutrient use, geochemistry, pollution, and forensics. We describe an algorithm implemented as SISUS software for providing a user-specified number of probabilistic exact solutions derived quickly from the extended mixing model. Our method outperforms IsoSource, a deterministic algorithm for providing approximate solutions to represent the solution polytope. Our method is an approximate Bayesian large sample procedure. SISUS software is freely available at StatAcumen.com/sisus and as an R package at cran.r-project.org/web/packages/sisus.
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Paper published: Infectious, autoimmune, and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children’s Oncology Group (COG) study

Infectious, autoimmune, and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children’s Oncology Group (COG) study Linabery, A. M., Erhardt, E. B., Fonstad, R. K., Ambinder, R. F., Bunin, G. R., Ross, J. A., Spector, L. G. and Grufferman, S. International Journal of Cancer, 135: 1454–1469 Online: March 18, 2014 http://onlinelibrary.wiley.com/doi/10.1002/ijc.28785/abstract DOI: 10.1002/ijc.28785 Abstract An infectious origin for pediatric Hodgkin lymphoma (HL) has long been suspected and Epstein-Barr virus (EBV) has been implicated in a subset of cases. Increased HL incidence in children with congenital and acquired immunodeficiencies, consistent associations between autoimmune diseases and adult HL and genome-wide association and other genetic studies together suggest immune dysregulation is involved in lymphomagenesis. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL diagnosed in 1989-2003 at 0-14 years at Children’s Oncology Group institutions. Parents of 517 cases and 784 controls completed telephone interviews, including items regarding medical histories. Tumor EBV status was determined for 355 cases. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HL. Cases were more likely to have had an infection>1 year prior to HL diagnosis (OR=1.69, 95% CI: 0.98-2.91); case siblings were also more likely to have had a prior infection (OR=2.04, 95% CI: 1.01-4.14). Parental history of autoimmunity associated with increased EBV+ HL risk (OR=2.97, 95% CI: 1.34-6.58), while having a parent (OR=1.47, 95% CI: 1.01-2.14) or sibling (OR=1.62, 95% CI: 1.11-2.36) with an allergy was associated with EBV - HL. These results may indicate true increased risk for infections and increased risk with family history of autoimmune and allergic conditions that varies by tumor EBV status, or they may be attributable to inaccurate recall. In addition to employing biomarkers to confirm the role of immune-modulating conditions in pediatric HL, future studies should focus on family based designs.
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Paper published: Inference for stable isotope mixing models: a study of the diet of dunlin

Inference for stable isotope mixing models: a study of the diet of dunlin Erhardt, EB and EJ Bedrick Journal of the Royal Statistical Society: Series C. pp. 579–593 Online: February 4, 2014 http://onlinelibrary.wiley.com/doi/10.1111/rssc.12047/abstract doi: 10.1111/rssc.12047 Abstract Stable isotope sourcing is used to estimate proportional contributions of sources to a mixture, such as in the analysis of animal diets and plant nutrient use. Statistical methods for inference on the diet proportions by using stable isotopes have focused on the linear mixing model. Existing frequentist methods assume that the diet proportion vector can be uniquely solved for in terms of one or two isotope ratios. We develop large sample methods that apply to an arbitrary number of isotope ratios, assuming that the linear mixing model has a unique solution or is overconstrained. We generalize these methods to allow temporal modelling of the population mean diet, assuming that isotope ratio response data are collected over time. The methodology is motivated by a study of the diet of dunlin, a small migratory seabird.
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Paper published: Targeted 13C enrichment of lipid and protein pools in the body reveals circadian changes in oxidative fuel mixture during prolonged fasting: a case study using Japanese quail

Targeted 13C enrichment of lipid and protein pools in the body reveals circadian changes in oxidative fuel mixture during prolonged fasting: a case study using Japanese quail McCue, MD, JA Amaya, AS Yang, EB Erhardt, BO Wolf, and DT Hanson Comparative Biochemistry and Physiology – Part A: Molecular & Integrative Physiology 166 (4), pdf, pp. 546–554 Online: August 27, 2013 http://www.sciencedirect.com/science/article/pii/S1095643313002237 DOI: 10.1016/j.cbpa.2013.08.009 Abstract Many animals undergo extended periods of fasting. During these fasts, animals oxidize a ratio of macronutrients dependent on the nutritional, energetic, and hydric requirements of the fasting period. In this study, we use Japanese quail (Coturnix coturnix japonica), a bird with natural intermediate fasting periods, to examine macronutrient use during a 6 d fast. We raised groups of quail on isotopically labeled materials (13C-1-leucine, 13C-U-glucose, or 13C-1-palmitic acid) with the intent of labeling specific macronutrient/tissue pools in each treatment, and then traced their use as fuels by measuring the δ13C values of breath CO2. Based on changes in δ13C values during the fast, it appears that the carbohydrate label,13C-U-glucose, was largely incorporated into the lipid pool and thus breath samples ultimately reflected lipid use rather than carbohydrate use. In the lipid treatment, the 13C-1-palmitic acid faithfully labeled the lipid pool and was reflected in the kinetics δ13C values in breath CO2 during the fast. Endogenous lipid oxidation peaked after 24 h of fasting and remained constantly elevated thereafter. The protein label,13C-1-leucine, showed clear diurnal periods of protein sparing and degradation, with maximal rates of protein oxidation occurring at night and the lowest rates occurring during the day time. This stable isotope tracer method provides a noninvasive approach to study the nutrient dynamics of fasting animals and should provide new insights into how different types of animals use specific nutrient pools during fasting and possibly other non-steady physiological states.
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