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Hypertensive disorders of pregnancy, intrauterine growth restriction (IUGR), and reduced pancreatic β‐cell area increases risk of offspring developing type 2 diabetes (T2D). Our previous studies using rat reduced uteroplacental perfusion pressure (RUPP) model of gestational hypertension and IUGR demonstrated reduced pancreatic β‐cell area in offspring at embryonic day 19 and postnatal day 13 (PD13). We hypothesized reduced β‐cell area early in life would manifest as hyperglycemia and glucose intolerance as animals aged. However, glucose intolerance did not differ in RUPP versus control offspring to 1 year of life, whether intraperitoneal or oral glucose challenge. At PD28, female RUPP offspring show normalized β‐cell area compared to controls and improved ability to clear glucose following oral challenge. Oral glucose challenge results in significant increase in incretin GLP‐1 in RUPP female offspring compared to control. Insulin tolerance did not differ amongst control and RUPP offspring, except at PD28 where insulin reduced blood glucose more effectively in RUPP female offspring versus control. Insulin‐induced vasodilation in isolated aorta and insulin signaling in fat are more pronounced in RUPP PD28 female offspring versus control. Thus, our studies demonstrate compensatory mechanisms protect IUGR offspring of a hypertensive pregnancy from long‐term metabolic effects and development of T2D.

Integrated, quantitative expressions of anthropogenic stress over large geographic regions can be valuable tools in environmental research and management. Despite the fundamental appeal of a regional approach, development of regional stress measures remains one of the most important current challenges in environmental science. Using publicly available, pre-existing spatial datasets, we developed a geographic information system database of 86 variables related to five classes of anthropogenic stress in the U.S. Great Lakes basin: agriculture, atmospheric deposition, human population, land cover, and point source pollution. The original variables were quantified by a variety of data types over a broad range of spatial and classification resolutions. We summarized the original data for 762 watershed-based units that comprise the U.S. portion of the basin and then used principal components analysis to develop overall stress measures within each stress category. We developed a cumulative stress index by combining the first principal component from each of the five stress categories. Maps of the stress measures illustrate strong spatial patterns across the basin, with the greatest amount of stress occurring on the western shore of Lake Michigan, southwest Lake Erie, and southeastern Lake Ontario. We found strong relationships between the stress measures and characteristics of bird communities, fish communities, and water chemistry measurements from the coastal region. The stress measures are taken to represent the major threats to coastal ecosystems in the U.S. Great Lakes. Such regional-scale efforts are critical for understanding relationships between human disturbance and ecosystem response, and can be used to guide environmental decision-making at both regional and local scales.

The Floristic Quality Index (FQI) has been proposed as a tool that can be used to identify areas of high conservation value, monitor sites over time, assess the anthropogenic impacts affecting an area, and measure the ecological condition of an area. FQI is based on the Coefficient of Conservatism (C), which is a numerical score assigned to each plant species in a local flora, primarily from best professional judgment, that reflects the likelihood that a species is found in natural habitats. FQI is computed by multiplying the mean Coefficient of Conservatism (C) by the square root of species richness for an observational unit. Great Lakes coastal wetlands were used to assess the properties and performance of various species richness, Coefficient of Conservatism, and Floristic Quality indices, as well as compare C-value assignments from two U.S. states (Wisconsin and Michigan). FQI and species richness increased with sampling area according to a power function, but C more or less remained constant. Sampling schemes should therefore focus on controlling sampling area and minimally sampling each community type at a site. In some cases, Wisconsin and Michigan assigned different values of C to the same species, highlighting possible effects due to the somewhat subjective nature of C-value assignment. Coefficient of Conservatism and Floristic Quality indices were better at discriminating differences between sites, independent of a condition gradient, than species richness alone, but neither index type outperformed the other. Both types of indices were also found to be acceptable ecological indicators of condition, although Floristic Quality indices consistently outperformed Coefficient of Conservatism indices in this capacity. Regardless of the subjectivity involved with the assignment of C-values and that ‘floristic quality’ is a human concept and not a true ecosystem property, both Coefficient of Conservatism and Floristic Quality indices seem to be effective indicators of condition in Great Lakes coastal wetlands.

We determined the influence of habitat, landscape, geographic, and climate variables on Sedge Wren ( Cistothorus platensis ) and Marsh Wren ( C. palustris ) occurrence in 840 coastal wetland survey points throughout the Great Lakes. Variables included surrounding land use and configuration out to 2000 m; latitude; longitude; temperature; precipitation; and vegetation characteristics within 100 m. Classification trees predicted Sedge Wren occurrence at points in the western Great Lakes with < 11 km of roads within 1000 m. Emergent herbaceous wetland within 500 m, woody wetland within various distances, and sedge within 100 m were also positively associated with Sedge Wren occurrence. Marsh Wren occurrence was predicted at points in the southern Great Lakes with < 42% developed land within 500 m. Emergent herbaceous wetland within 500 m, cropland within various distances, and cattail within 100 m were also positively associated with Marsh Wren occurrence. Our results suggest limiting development around wetlands is important for conserving these bird species throughout Great Lakes coastal wetlands. Landscape-scale land cover variables are easily obtainable and significantly increase our ability to predict occurrence of these species across a broad geographic scale.

A better understanding of relationships between human activities and water chemistry is needed to identify and manage sources of anthropogenic stress in Great Lakes coastal wetlands. The objective of the study described in this article was to characterize relationships between water chemistry and multiple classes of human activity (agriculture, population and development, point source pollution, and atmospheric deposition). We also evaluated the influence of geomorphology and biogeographic factors on stressor-water quality relationships. We collected water chemistry data from 98 coastal wetlands distributed along the United States shoreline of the Laurentian Great Lakes and GIS-based stressor data from the associated drainage basin to examine stressor-water quality relationships. The sampling captured broad ranges (1.5-2 orders of magnitude) in total phosphorus (TP), total nitrogen (TN), dissolved inorganic nitrogen (DIN), total suspended solids (TSS), chlorophyll a (Chl a), and chloride; concentrations were strongly correlated with stressor metrics. Hierarchical partitioning and all-subsets regression analyses were used to evaluate the independent influence of different stressor classes on water quality and to identify best predictive models. Results showed that all categories of stress influenced water quality and that the relative influence of different classes of disturbance varied among water quality parameters. Chloride exhibited the strongest relationships with stressors followed in order by TN, Chl a, TP, TSS, and DIN. In general, coarse scale classification of wetlands by morphology (three wetland classes: riverine, protected, open coastal) and biogeography (two ecoprovinces: Eastern Broadleaf Forest [EBF] and Laurentian Mixed Forest [LMF]) did not improve predictive models. This study provides strong evidence of the link between water chemistry and human stress in Great Lakes coastal wetlands and can be used to inform management efforts to improve water quality in Great Lakes coastal ecosystems.

To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a randomized, double-blind, placebo-controlled trial. Adult primary care patients in Duluth, Minnesota, were screened for vitamin D deficiency in February 2007. Participants completed questionnaires pertaining to a variety of symptoms, vitamin D intake, and selected medical conditions. Patients with mild to moderate vitamin D deficiency (25-hydroxyvitamin D [25(OH)D], 10-25 ng/mL) participated in a randomized controlled trial (RCT) of vitamin D replacement and its effect on symptoms. Participants were randomly assigned to receive 50 000 units of cholecalciferol (vitamin D3) weekly or placebo for 8 weeks. Patients with severe vitamin D deficiency (25[OH]D <10 ng/mL) were treated in an unblinded fashion, and symptoms were reevaluated post treatment. A total of 610 patients underwent initial screening, and 100 patients with mild to moderate vitamin D deficiency participated in the RCT. Thirty-eight severely deficient patients were treated in an unblinded fashion. On initial screening, 46.2% of participants were deficient in vitamin D. Self-reported vitamin D supplementation, milk intake, celiac disease, gastric bypass, and chronic pancreatitis were predictive of vitamin D status. Severely deficient participants reported increased musculoskeletal symptoms, depression (including seasonal), and higher (worse) scores on a fibromyalgia assessment questionnaire. In the RCT, the treated group showed significant improvement in fibromyalgia assessment scores (P = 0.03), whereas the placebo-treated participants did not. Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later. Compared with participants in the placebo group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living.

Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data usingAspergillus as allergen to identify putative asthma 'signature genes', i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.

Understanding the relationship between human disturbance and ecological response is essential to the process of indicator development. For large-scale observational studies, sites should be selected across gradients of anthropogenic stress, but such gradients are often unknown for apopulation of sites prior to site selection. Stress data available from public sources can be used in a geographic information system (GIS) to partially characterize environmental conditions for large geographic areas without visiting the sites. We divided the U.S. Great Lakes coastal region into 762 units consisting of a shoreline reach and drainage-shed and then summarized over 200 environmental variables in seven categories for the units using a GIS. Redundancy within the categories of environmental variables was reduced using principal components analysis. Environmental strata were generated from cluster analysis using principal component scores as input. To protect against site selection bias, sites were selected in random order from clusters. The site selection process allowed us to exclude sites that were inaccessible and was shown to successfully distribute sites across the range of environmental variation in our GIS data. This design has broad applicability when the goal is to develop ecological indicators using observational data from large-scale surveys.

NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

Dietary samples from nestling Tree Swallows (Tachycineta bicolor) in northwestern Minnesota were compared to invertebrate availability as measured by aerial tow nets. The majority of the biomass in the nestlings' diet was adult insects with larval stages of aquatic origin, while absolute numbers of insects of both aquatic and terrestrial origin were similar. Orders of invertebrates in the diet and available were similar in number but not in biomass. Diet showed little variation by time of day, date of sampling or the age of the nestling. The mean number of odonates in the nestling Tree Swallows' diet increased exponentially as the percentage of open water and open water + cattail marsh increased within a 400-m foraging radius. Dieta de los Pichones de Tachycineta bicolor Resumen. Se compararon muestras dietarias de pichones de la golondrina Tachycineta bicolor tomadas en el noroeste de Minnesota con la disponibilidad de invertebrados medida con redes aéreas. La mayor parte de la biomasa en la dieta de los pichones correspondió a insectos adultos con estadíos larvales de origen acuá tico, mientras que los números absolutos de insectos de origen acuático y no acuático fueron similares. Los órdenes de invertebrados presentes en la dieta y disponibles en el ambiente fueron similares en números pero no en biomasa. La dieta mostró poca variación entre horas del día, fechas de muestreo o edad de los pichones. El número promedio de odonatos en la dieta de los pichones de T. bicolor aumentó exponencialmente a medida que se incrementó el porcentaje de agua abierta y de agua abierta + pantanos de espadañas dentro de un radio de forrajeo de 400 m.