Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice

Background

Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity.

Methods

Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ in vitro.

Results

OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression in vivo. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our in vivo findings.

Conclusions

Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice.     

Fibrocytes and the tissue niche in lung repair

Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.     

Food composition of the diet in relation to changes in waist circumference adjusted for body mass index

Background

Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity. A better understanding of which food groups/items contribute to these associations is necessary.

Objective

To ascertain the association of food groups/items consumption on prospective annual changes in “waist circumference for a given BMI” (WC_BMI), a proxy for abdominal adiposity.

Design

We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC_BMI was defined as the residuals of waist circumference regressed on BMI, and annual change in WC_BMI (ΔWC_BMI, cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between food groups/items and ΔWC_BMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates.

Results

Higher fruit and dairy products consumption was associated with a lower gain in WC_BMI whereas the consumption of white bread, processed meat, margarine, and soft drinks was positively associated with ΔWC_BMI. When these six food groups/items were analyzed in combination using a summary score, those in the highest quartile of the score – indicating a more favourable dietary pattern –showed a ΔWC_BMI of −0.11 (95% CI −0.09 to −0.14) cm/y compared to those in the lowest quartile.

Conclusion

A dietary pattern high in fruit and dairy and low in white bread, processed meat, margarine, and soft drinks may help to prevent abdominal fat accumulation.     

Trend in obesity prevalence in European adult cohort populations during follow-up since 1996 and their predictions to 2015

Objective

To investigate trends in obesity prevalence in recent years and to predict the obesity prevalence in 2015 in European populations.

Methods

Data of 97 942 participants from seven cohorts involved in the European Prospective Investigation into Cancer and Nutrition (EPIC) study participating in the Diogenes project (named as “Diogenes cohort” in the following) with weight measurements at baseline and follow-up were used to predict future obesity prevalence with logistic linear and non-linear (leveling off) regression models. In addition, linear and leveling off models were fitted to the EPIC-Potsdam dataset with five weight measures during the observation period to find out which of these two models might provide the more realistic prediction.

Results

During a mean follow-up period of 6 years, the obesity prevalence in the Diogenes cohort increased from 13% to 17%. The linear prediction model predicted an overall obesity prevalence of about 30% in 2015, whereas the leveling off model predicted a prevalence of about 20%. In the EPIC-Potsdam cohort, the shape of obesity trend favors a leveling off model among men (R² = 0.98), and a linear model among women (R² = 0.99).

Conclusion

Our data show an increase in obesity prevalence since the 1990ies, and predictions by 2015 suggests a sizeable further increase in European populations. However, the estimates from the leveling off model were considerably lower.     

The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis

Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs in the nematode C. elegans, named paqr-1, paqr-2 and paqr-3. These are differently expressed in the intestine (the main fat-storing tissue), hypodermis, muscles, neurons and secretory tissues, from which they could exert systemic effects. Analysis of mutants revealed that paqr-1 and -2 are novel metabolic regulators in C. elegans and that they act redundantly but independently from paqr-3. paqr-2 is the most important of the three paqr genes: mutants grow poorly, fail to adapt to growth at low temperature, and have a very high fat content with an abnormal enrichment in long (C20) poly-unsaturated fatty acids when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations in aak-2, the C. elegans homolog of AMPK, or nhr-80, another nuclear hormone receptor gene, suppress the growth phenotype of paqr-2 mutants, probably because they restore the balance between energy expenditure and storage. We conclude that paqr-1 and paqr-2 are receptors that regulate fatty acid metabolism and cold adaptation in C. elegans, that their main function is to promote energy utilization rather than storage, and that PAQR class proteins have regulated metabolism in metazoans for at least 700 million years.     

The effect of cleft lip on adults' responses to faces: cross-species findings

Cleft lip and palate is the most common of the congenital conditions affecting the face and cranial bones and is associated with a raised risk of difficulties in infant-caregiver interaction; the reasons for such difficulties are not fully understood. Here, we report two experiments designed to explore how adults respond to infant faces with and without cleft lip, using behavioural measures of attractiveness appraisal ('liking') and willingness to work to view or remove the images ('wanting'). We found that infants with cleft lip were rated as less attractive and were viewed for shorter durations than healthy infants, an effect that was particularly apparent where the cleft lip was severe. Women rated the infant faces as more attractive than men did, but there were no differences in men and women's viewing times of these faces. In a second experiment, we found that the presence of a cleft lip in domestic animals affected adults' 'liking' and 'wanting' responses in a comparable way to that seen for human infants. Adults' responses were also remarkably similar for images of infants and animals with cleft lip, although no gender difference in attractiveness ratings or viewing times emerged for animals. We suggest that the presence of a cleft lip can substantially change the way in which adults respond to human and animal faces. Furthermore, women may respond in different ways to men when asked to appraise infant attractiveness, despite the fact that men and women 'want' to view images of infants for similar durations.     

Re-structuring of marine communities exposed to environmental change: a global study on the interactive effects of species and functional richness

Species richness is the most commonly used but controversial biodiversity metric in studies on aspects of community stability such as structural composition or productivity. The apparent ambiguity of theoretical and experimental findings may in part be due to experimental shortcomings and/or heterogeneity of scales and methods in earlier studies. This has led to an urgent call for improved and more realistic experiments. In a series of experiments replicated at a global scale we translocated several hundred marine hard bottom communities to new environments simulating a rapid but moderate environmental change. Subsequently, we measured their rate of compositional change (re-structuring) which in the great majority of cases represented a compositional convergence towards local communities. Re-structuring is driven by mortality of community components (original species) and establishment of new species in the changed environmental context. The rate of this re-structuring was then related to various system properties. We show that availability of free substratum relates negatively while taxon richness relates positively to structural persistence (i.e., no or slow re-structuring). Thus, when faced with environmental change, taxon-rich communities retain their original composition longer than taxon-poor communities. The effect of taxon richness, however, interacts with another aspect of diversity, functional richness. Indeed, taxon richness relates positively to persistence in functionally depauperate communities, but not in functionally diverse communities. The interaction between taxonomic and functional diversity with regard to the behaviour of communities exposed to environmental stress may help understand some of the seemingly contrasting findings of past research.