Genetic variants of TSLP and asthma in an admixed urban population

Background

Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.

Objectives

To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population.

Methodology and Main Results

Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09–2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04–3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93–1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10–2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07–1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08–1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94–1.17, p = 0.33).

Conclusions

Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.     

Pikas (Ochotona princeps : Lagomorpha) as allogenic engineers in an alpine ecosystem

Pikas (Ochotona princeps: Lagomorpha) build caches of vegetation (“haypiles”), which serve as a food source during winter in alpine and subalpine habitats. Haypiles appear to degrade over time and form patches of nutrient-rich soils in barren talus and scree areas. We sampled soils underneath and next to haypiles, and plants growing on and near haypiles in an alpine cirque in northwestern Wyoming, USA, to determine the effects of pika food caches on N, C, and C/N ratios in soils and plants. We found that (1) haypile soils had significantly higher carbon and nitrogen levels and lower C/N ratios than both adjacent soils and soils in the general study area, (2) two of three plant species tested (Polemonium viscosum and Oxyria digyna) had significantly higher levels of tissue percent N when growing on haypile soils, and (3) total standing plant biomass at the study site increased with soil percent N suggesting that vegetation was nitrogen limited. Pikas may therefore function as allogenic ecosystem engineers by modulating nutrient availability to plants. Received: 5 July 1997 / Accepted: 30 November 1997     

Erwinia carotovora subsp. carotovora and Erwinia-derived elicitors HrpN and PehA trigger distinct but interacting defense responses and cell death in Arabidopsis

We have used an hrp-positive strain of the soft rot pathogen Erwinia carotovora subsp. carotovora to elucidate plant responses to this bacterial necrotroph. Purified virulence determinants, harpin (HrpN) and polygalacturonase (PehA), were used as tools to facilitate this analysis. We show that HrpN elicits lesion formation in Arabidopsis and tobacco and triggers systemic resistance in Arabidopsis. Establishment of resistance is accompanied by the expression of salicylic acid (SA)-dependent, but also jasmonate/ethylene (JA/ET)-dependent, marker genes PR1 and PDF1.2, respectively, suggesting that both SA-dependent and JA/ET-dependent defense pathways are activated. Use of pathway-specific mutants and transgenic NahG plants show that both pathways are required for the induction of resistance. Arabidopsis plants treated simultaneously with both elictors PehA, known to trigger only JA/ET-dependent defense signaling, and HrpN react with accelerated and enhanced induction of the marker genes PR1 and PDF1.2 both locally and systemically. This mutual amplification of defense gene expression involves both SA-dependent and JA/ET-dependent defense signaling. The two elicitors produced by E. carotovora subsp. carotovora also cooperate in triggering increased production of superoxide and lesion formation.     

Effects of ultraviolet-B radiation on growth, mycorrhizas and mineral nutrition of silver birch (Betula pendula Roth) seedlings grown in low-nutrient conditions

The effects of increased ultraviolet‐B (UV‐B) radiation on the growth, mycorrhizas and mineral nutrition of silver birch (Betula pendula Roth) seedlings were studied in greenhouse conditions. Seedlings—planted in a birch‐forest top soil and sand substrate—were grown without additional nutrient supply. Ultraviolet treatment started immediately after the seedlings emerged and the daily integrated biologically effective UV‐B irradiance on the UV‐B‐treated plants was equivalent to a 25% depletion of stratospheric ozone under clear sky conditions. Visible symptoms of UV‐B damage or nutrient deficiency were not observed throughout the experiment. Seedling height and dry weight (DW) (measured after 58 days and 76 days of treatment) were not affected by increased UV‐B. However, a significant shift in DW allocation toward roots resulted in a lower shoot/root ratio and leaf area ratio in UV‐B‐treated plants compared to control plants. At the first harvest (after 58 days of treatment), the percentage of various mycorrhizal morphotypes and the number of short roots per unit of root length or weight were not affected by increased UV‐B despite significantly increased DW allocation toward roots. Subtle reduction in the allocation of nitrogen (N) to leaves and increased allocation of phosphorus (P) to roots may suggest cumulative effects that could affect the plant performance over the long‐term.     

Amplitude and frequency modulation of pulsatile luteinizing hormone-releasing hormone release

Summary 1. A variety of neuroendocrine approaches has been used to characterize cellular mechanisms governing luteinizing hormone-releasing hormone (LHRH) pulse generation. We review recentin vivo microdialysis,in vitro superfusion, andin situ hybridization experiments in which we tested the hypothesis that the amplitude and frequency of LHRH pulses are subject to independent regulation via distinct and identifiable cellular pathways.2. Augmentation of LHRH pulse amplitude is proposed as a central feature of preovulatory LHRH surges. Three mechanisms are described which may contribute to this increase in LHRH pulse amplitude: (a) increased LHRH gene expression, (b) augmentation of facilitatory neurotransmission, and (c) increased responsiveness of LHRH neurons to afferent synaptic signals. Neuropeptide Y (NPY) is examined as a prototypical afferent transmitter regulating the generation of LHRH surges through the latter two mechanisms.3. Retardation of LHRH pulse generator frequency is postulated to mediate negative feedback actions of gonadal hormones. Evidence supporting this hypothesis is reviewed, including results ofin vivo monitoring experiments in which LHRH pulse frequency, but not amplitude, is shown to be increased following castration. A role for noradrenergic neurons as intervening targets of gonadal hormone negative feedback actions is discussed.4. Future directions for study of the LHRH pulse generator are suggested.     

Neuronostatin, a novel peptide encoded by somatostatin gene, regulates cardiac contractile function and cardiomyocyte survival

Neuronostatin, a recently discovered peptide encoded by somatostatin gene, is involved in regulation of neuronal function, blood pressure, food intake, and drinking behavior. However, the biological effects of neuronostatin on cardiac myocytes are not known, and the intracellular signaling mechanisms induced by neuronostatin remain unidentified. We analyzed the effect of neuronostatin in isolated perfused rat hearts and in cultured primary cardiomyocytes. Neuronostatin infusion alone had no effect on left ventricular (LV) contractile function or on isoprenaline- or preload-induced increase in cardiac contractility. However, infusion of neuronostatin significantly decreased the positive inotropic response to endothelin-1 (ET-1). This was associated with an increase in phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK). Treatment of both neonatal and adult cardiomyocytes with neuronostatin resulted in reduced cardiomyocyte viability. Inhibition of JNK further increased the neuronostatin-induced cell death. We conclude that neuronostatin regulates cardiac contractile function and cardiomyocyte survival. Receptors for neuronostatin need to be identified to further characterize the biological functions of the peptide.     

Long-term dynamics of voles and lemmings at the timberline and above the willow limit as a test of hypotheses on trophic interactions

We have monitored population fluctuations of microtine rodents since 1977 in two habitat complexes in Finnmark, northernmost Norway - a low arctic plains landscape, with patches of willow scrubland embedded in lichen-dwarf birch tundra, and in adjacent highlands, occupied by scrub-free heaths, snow-beds and bogs. In the plains landscape, voles were cyclic, with a period of five years, and with wave-like density fluctuations. This pattern is consistent with time trajectory of prey in a predator-prey limit cycle. Autoregression analysis implies that the prey pattern is cleanest in the most productive plains habitats, while dynamics in the prevailing heath and bog habitats are governed by two significant lags, implying that even vole-plant interactions count. In the highlands, lemmings had two outbreaks, characterized by J-shaped growth curves, and separated by long periods of low density. The fluctuation pattern of lemmings in highlands was consistent with the predicted time trajectory of a predator. The implications of time trajectories are corroborated by direct evidence on microtine impacts upon the vegetation and on spatial patterns in predator activity. Even the strong dispersal tendency of lemmings during population peaks is consistent with the conjecture that they are adapted to play the role of a predator in a sustained predator-prey cycle. As a whole, the pattern supports T. Oksanen's modification of the hypothesis of exploitation ecosystems, where both local productivity and the structure of the landscape are taken in account.     

Genotype × Herbivore Effect on Leaf Litter Decomposition in Betula Pendula Saplings: Ecological and Evolutionary Consequences and the Role of Secondary Metabolites

Plant genetic variation and herbivores can both influence ecosystem functioning by affecting the quantity and quality of leaf litter. Few studies have, however, investigated the effects of herbivore load on litter decomposition at plant genotype level. We reduced insect herbivory using an insecticide on one half of field-grown Betula Pendula saplings of 17 genotypes, representing random intrapopulation genetic variation, and allowed insects to naturally colonize the other half. We hypothesized that due to induced herbivore defence, saplings under natural herbivory produce litter of higher concentrations of secondary metabolites (terpenes and soluble phenolics) and have slower litter decomposition rate than saplings under reduced herbivory. We found that leaf damage was 89 and 53% lower in the insecticide treated saplings in the summer and autumn surveys, respectively, which led to 73% higher litter production. Litter decomposition rate was also affected by herbivore load, but the effect varied from positive to negative among genotypes and added up to an insignificant net effect at the population level. In contrast to our hypothesis, concentrations of terpenes and soluble phenolics were higher under reduced than natural herbivory. Those genotypes, whose leaves were most injured by herbivores, produced litter of lowest mass loss, but unlike we expected, the concentrations of terpenes and soluble phenolics were not linked to either leaf damage or litter decomposition. Our results show that (1) the genetic and herbivore effects on B. pendula litter decomposition are not mediated through variation in terpene or soluble phenolic concentrations and suggest that (2) the presumably higher insect herbivore pressure in the future warmer climate will not, at the ecological time scale, affect the mean decomposition rate in genetically diverse B. pendula populations. However, (3) due to the significant genetic variation in the response of decomposition to herbivory, evolutionary changes in mean decomposition rate are possible.     

Permanent night workers´ sleep and psychosocial factors in hospital work. A comparison to day and shift work

ABSTRACT

We aimed to study whether permanent night workers sleep and psychosocial factors differ from day workers and shift workers. The participants (n = 9 312, 92% females, average age 45 years, most commonly nurses and departmental secretaries) were day workers (DW, n = 2 672), shift workers (SW, n = 6 486) and permanent night workers (PNW, n = 154). The Finnish Public Sector survey responses from six hospital districts from 2012 were combined to payroll data from 91 days preceding the survey. The data were analyzed using Pearson χ²-test, one-way ANOVA and multinomial logistic regression analysis. The PNWs reported slightly longer average sleep length than the SWs or the DWs (7:27 vs. 7:13 and 7:10 h, p < 0.001). The PNWs reported least often difficulties in maintaining sleep (p < 0.001) compared to the SWs and the DWs. The PNWs reported most often difficulties to fall asleep and fatigue during free-time (p-values <0.001). The DWs and PNWs experienced less often work-life conflict than the SWs (25 and 26 vs. 38%, p < 0.001). The PNWs were more often satisfied with autonomy at work and appreciation and fair treatment by colleagues than the DWs or the SWs (p < 0.001). The SWs and PNWs reported remarkably higher occurrence of verbal (p < 0.001, OR 3.71, 95% CI 3.23–4.27 and OR 7.67, 95% CI 5.35–10.99, respectively) and physical workplace violence (p < 0.001, OR 9.24, 95% CI 7.17–11.90 and OR 28.34, 95% CI 16.64–43.06, respectively) compared to DWs. Conclusively, PNWs reported contradictory differences in sleep quality compared to DWs and SWs. PNWs are more often satisfied with their colleagues and autonomy at work than DWs or SWs but face workplace violence remarkably more often.