283 research outputs found

    Cytokine Profiles of Stimulated Blood Lymphocytes in Asthmatic and Healthy Adolescents Cross the School Year

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    T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-γ (IFN-γ), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th 1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-γ:IL-4 and IFN-γ:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation

    Precise Re–Os ages of organic-rich mudrocks and the Os isotope composition of Jurassic seawater

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    Rhenium and osmium isotope and abundance data have been obtained on precisely-located samples from three suites of immature, organic-rich mudrocks from Jurassic coastal outcrops in England, The data provide accurate whole-rode ages of 207 +/- 12 Ma, 181 +/- 13 Ma and 155 +/- 4.3 Ma for suites of Hettangian, Toarcian (exaratum Subzone) and Kimmeridgian (sensu anglico, wheatleyensis Subzone) samples. These new Re-Os ages are indistinguishable, within the assigned analytical uncertainties, from interpolated depositional ages estimated from published geological timescales, and establish the importance of the Re-Os dating technique for chronostratigraphic studies. Early-diagenetic pyrite nodules possess levels of Re and Os which are similar to 1-2 orders of magnitude lower than in the enclosing organic-rich mudrocks, indicating that these elements had already been removed from sediment pore waters at the time of nodule formation. Thus the Re-Os isotope system in these organic-rich mudrocks has been closed since, or from very soon after, the time of sediment deposition. Because most of the Re (98+%) and Os (95-99.8+%) in the mudrocks is shown to be hydrogenous, the Os-187/Os-188((i)) of the samples is interpreted to be that of contemporaneous seawater. The data thereby provide the first estimates of the Os isotope composition of Jurassic seawater. During the earliest Jurassic (Hettangian), the seawater Os-187/Os-188 ratio was extremely unradiogenic (similar to 0.15); it had increased to similar to 0.8 at the end of the Early Jurassic (Toarcian) similar to 20 Ma later, while in the Late Jurassic (Kimmeridgian) the seawater Os-187/Os-188 ratio was similar to 0.59. The most likely explanation for the unradiogenic Os isotope composition of Hettangian seawater is that the contribution of unradiogenic Os to the oceans from the hydrothermal alteration of oceanic crust greatly exceeded the input of radiogenic Os from the continents at that time. This interpretation is in Line with observations suggesting that global weathering rates were low in the Hettangian, and that increased hydrothermal and volcanic activity preceded the break-up of Pangea. The Re/Os ratios of Hettangian mudrocks (and by inference, of contemporaneous seawater) are similar to those of mudrocks deposited at later times during the Jurassic, and argues against the unradiogenic Os in Hettangian seawater being derived from extraterrestrial meteoritic sources

    Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women

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    Background The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study. Methods Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH. Results After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (β=-0.42, p<0.05) and IL-8 was positively associated with PGH (β=0.35, p<0.05) among the Black mothers only; neither were significantly associated with PGH in the White mothers. When extending models to birth outcomes, BMI was positively associated with birthweight corrected for gestational age (BWz) (β=0.24, p<0.05) and educational attainment was negatively associated with BWz (β=0.28, p<0.05) for infants of White women. In contrast, neither variable was predictive of BWz for infants of Black mothers. Conclusion Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth

    Investigating the tradeoffs between spatial resolution and diffusion sampling for brain mapping with diffusion tractography: Time well spent?: Spatial vs. Q-Space Sampling for Tractography

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    Interest in mapping white matter pathways in the brain has peaked with the recognition that altered brain connectivity may contribute to a variety of neurologic and psychiatric diseases. Diffusion tractography has emerged as a popular method for postmortem brain mapping initiatives, including the ex-vivo component of the human connectome project, yet it remains unclear to what extent computer-generated tracks fully reflect the actual underlying anatomy. Of particular concern is the fact that diffusion tractography results vary widely depending on the choice of acquisition protocol. The two major acquisition variables that consume scan time, spatial resolution, and diffusion sampling, can each have profound effects on the resulting tractography. In this analysis we determined the effects of the temporal tradeoff between spatial resolution and diffusion sampling on tractography in the ex-vivo rhesus macaque brain, a close primate model for the human brain. We used the wealth of autoradiography-based connectivity data available for the rhesus macaque brain to assess the anatomic accuracy of six time-matched diffusion acquisition protocols with varying balance between spatial and diffusion sampling. We show that tractography results vary greatly, even when the subject and the total acquisition time are held constant. Further, we found that focusing on either spatial resolution or diffusion sampling at the expense of the other is counterproductive. A balanced consideration of both sampling domains produces the most anatomically accurate and consistent results

    Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys

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    Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species

    A diffusion tensor MRI atlas of the postmortem rhesus macaque brain

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    The rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate for modeling the structure and function of the brain. Brain atlases, and particularly those based on magnetic resonance imaging (MRI), have become important tools for understanding normal brain structure, and for identifying structural abnormalities resulting from disease states, exposures, and/or aging. Diffusion tensor imaging (DTI) -based MRI brain atlases are widely used in both human and macaque brain imaging studies because of the unique contrasts, quantitative diffusion metrics, and diffusion tractography that they can provide. Previous MRI and DTI atlases of the rhesus brain have been limited by low contrast and/or low spatial resolution imaging. Here we present a microscopic resolution MRI/DTI atlas of the rhesus brain based on 10 postmortem brain specimens. The atlas includes both structural MRI and DTI image data, a detailed three-dimensional segmentation of 241 anatomic structures, diffusion tractography, cortical thickness estimates, and maps of anatomic variability amongst atlas specimens. This atlas incorporates many useful features from previous work, including anatomic label nomenclature and ontology, data orientation, and stereotaxic reference frame, and further extends prior analyses with the inclusion of high-resolution multi-contrast image data

    Deep soils modify environmental consequences of increased nitrogen fertilizer use in intensifying Amazon agriculture

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    Agricultural intensification offers potential to grow more food while reducing the conversion of native ecosystems to croplands. However, intensification also risks environmental degradation through emissions of the greenhouse gas nitrous oxide (N2O) and nitrate leaching to ground and surface waters. Intensively-managed croplands and nitrogen (N) fertilizer use are expanding rapidly in tropical regions. We quantified fertilizer responses of maize yield, N2O emissions, and N leaching in an Amazon soybean-maize double-cropping system on deep, highly-weathered soils in Mato Grosso, Brazil. Application of N fertilizer above 80 kg N ha−1 yr−1 increased maize yield and N2O emissions only slightly. Unlike experiences in temperate regions, leached nitrate accumulated in deep soils with increased fertilizer and conversion to cropping at N fertilization rates \u3e80 kg N ha−1, which exceeded maize demand. This raises new questions about the capacity of tropical agricultural soils to store nitrogen, which may determine when and how much nitrogen impacts surface waters

    Brain enlargement and increased behavioral and cytokine reactivity in infant monkeys following acute prenatal endotoxemia

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    Infections and inflammatory conditions during pregnancy can dysregulate neural development and increase the risk for developing autism and schizophrenia. The following research utilized a nonhuman primate model to investigate the potential impact of a mild endotoxemia during pregnancy on brain maturation and behavioral reactivity as well as the infants’ hormone and immune physiology. Nine pregnant female rhesus monkeys (Macaca mulatta) were administered nanogram concentrations of lipopolysaccharide (LPS) on two consecutive days, six weeks before term, and their offspring were compared to nine control animals. When tested under arousing challenge conditions, infants from the LPS pregnancies were more behaviorally disturbed, including a failure to show a normal attenuation of startle responses on tests of prepulse inhibition. Examination of their brains at one year of age with magnetic resonance imaging (MRI) revealed the unexpected finding of a significant 8.8% increase in global white matter volume distributed across many cortical regions compared to controls. More selective changes in regional gray matter volume and cortical thickness were noted in parietal, medial temporal, and frontal areas. While inhibited neural growth has been described previously after prenatal infection and LPS administration at higher doses in rodents, this low dose endotoxemia in the monkey is the first paradigm to produce a neural phenotype associated with augmented gray and white matter growth
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