Linkage disequilibrium patterns and tagSNP transferability among European populations

The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of approximately 2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.     

Ligand depletion negatively controls the mitogenic activity of epidermal growth factor

EGF activates the ErbB1 receptor, but there appears only a limited correlation between its receptor binding affinity and mitogenic activity. This is indicated by our present observation that in cells with high ErbB1 expression, including SUM102 breast tumor cells, low affinity EGF/Notch chimeras have similarly high mitogenic activity as EGF, in spite of the fact that EGF is superior in inducing receptor tyrosine phosphorylation and p42/p44 MAP-kinase activity. However, as a result of receptor-mediated internalisation high-affinity ligands such as EGF are depleted much more rapidly from the extracellular medium than low-affinity EGF/Notch chimeras. As a consequence, the mitogenic activity of EGF on ErbB1 overexpressing cells is limited by substantial degradation of internalised ligand in the period before cells enter S-phase, a phenomenon that is not observed for low affinity mutant ligands. The mitogenic activity of EGF on ErbB1 overexpressing cells does therefore not only depend on the applied concentration but also on the total amount of ligand added, and is strongly underestimated when tested in a limited assay volume. No such dependence on the incubation volume was observed for EGF activity on cells with low ErbB1 expression levels and on cells for which EGF is growth inhibitory.     

The composition and taxonomic significance of fatty acid patterns in three white rust species: <Emphasis Type="Italic">Albugo amaranthi,A. candida and A. tragopogonis</Emphasis> (Peronosporales,Albuginaceae)

The fatty acid composition of the biotrophic white rust species A. amaranthi, A. candida and A. tragopogonis was identified by means of GC and GC/MS analysis. Besides the common saturated fatty acids of C14 to C22 chain length, several unusual monounsaturated and polyunsaturated fatty acids were present in significant amounts in the lipid profiles of the three species. Each taxon revealed its own characteristic pattern which was uniform among populations of different geographic origin and independent from the host species. Fatty acids were obtained from minute amounts of sporangia collected from the surface of desiccated host plants. Comparison of herbarium specimens revealed a decrease of polyunsaturated compounds after storage for 30 months at room temperature, but still allowed unquestionable species differentiation.     

Mustering Fortune: Attraction and Multiplication in the Echoes of the Boom

Since the end of the socialist period, Mongolia has experienced economic instabilities, growing inequalities, and increasing urbanisation. Prosperity (dallaga) rituals, once predominantly carried out by nomadic herders at specific times of the year, are now also held regularly within Ulaanbaatar’s Buddhist temples. In these ceremonies, Buddhist lamas and lay participants attempt to ‘call’ or ‘pull’ wealth to the household. In this urban context, prosperity rituals are overtly about money, combining nomadic notions of wealth, sedentary ideas of growth and multiplication, and contemporary anxieties regarding growing corruption and inequality. Following from nomadic ideas that link prosperity with movement, dallaga rituals attempt to influence the ways that money travels around the economy. As money has seed like qualities, one must be careful to ensure that the right kind of money is attracted to the household so that it does not multiply the misfortunes that are thought to characterise money made through ill-gotten means.     

Epithelial-to-mesenchymal transition in fibrosis: Collagen type I expression is highly upregulated after EMT,but does not contribute to collagen deposition

The hallmark of fibrosis is an accumulation of fibrillar collagens, especially of collagen type I. There is considerable debate whether in vivo type II epithelial-to-mesenchymal transition (EMT) is involved in organ fibrosis. Lineage tracing experiments by various groups show opposing data concerning the relative contribution of epithelial cells to the pool of myofibroblasts. We hypothesized that EMT-derived cells might directly contribute to collagen deposition. To study this, EMT was induced in human epithelial lung and renal cell lines in vitro by means of TGF-β1 stimulation, and we compared the collagen type I (COL1A1) expression levels of transdifferentiated cells with that of myofibroblasts obtained by TGF-β1 stimulation of human dermal and lung fibroblasts. COL1A1 expression levels of transdifferentiated epithelial cells appeared to be at least one to two orders of magnitude lower than that of myofibroblasts. This was confirmed at immunohistochemical level: in contrast to myofibroblasts, collagen type I deposition by EMT-derived cells was not or hardly detectable. We postulate that, even when type II EMT occurs in vivo, the direct contribution of EMT-derived cells to collagen accumulation is rather limited.     

Long-Term Trends in Tree-Ring Width and Isotope Signatures (δ13C, δ15N) of Fagus sylvatica L. on Soils with Contrasting Water Supply

We investigated long-term responses (since 1850) of Fagus sylvatica (Luxembourg; central Europe) to shifts in temperature, precipitation, and nitrogen deposition by analyzing diameter at breast height (DBH) increment, basal area increment (BAI), and tree-ring stable isotopes (δ¹³C, δ¹⁵N). We compared stands on soils with contrasting water supply (Regosols and Cambisols with an available water capacity of ca. 40 and 170 mm, respectively) and of two different age classes (ca. 60 vs. 200 years). All stands showed a peak in DBH increment in the decade 1978–1987, but a decline in increment growth in subsequent decades. In addition, BAI declined in mature stands in the last two decades. Decreasing increment rates were attributable to an increasing drought limitation of stands, mainly induced by increasing temperatures in the last two decades. Contrary to our expectations, stands on Cambisols showed a similar susceptibility to shifts in temperature and precipitation as stands on Regosols, suggesting a strong adaptation of the respective ecotypes grown at dryer sites. This result was in line with long-term trends for tree-ring δ¹³C signatures, which did not differ significantly between stands on Cambisols and Regosols. Climate impacts on tree-ring δ¹⁵N signatures were low. High spring precipitation and temperatures caused increasing and decreasing δ¹⁵N values, respectively, but only in mature stands on Cambisols. Stands on Regosols tended to have lower δ¹⁵N values than stands on Cambisols. Decreasing δ¹⁵N values in recent decades suggest an increasing impact of allochthonous N loads with isotopically lighter N.     

New insights into DNA barcoding of seagrasses

Taxonomists find some plant genera challenging because of the few morphological differences or unclear characters among closely related species, which leads to the misidentification of taxa. DNA barcoding is an approach to identify species by using short orthologous DNA sequences, known as ‘DNA barcodes’. Concatenated rbcL and matK sequences are considered DNA barcodes for seagrasses. However, these markers are not applicable to all members of seagrasses at the species level, especially within the genus Halophila. Our previous studies indicated that the internal transcribed spacer (ITS) showed higher species resolution than the concatenated rbcL and matK sequences in the case of Halophila ovalis and closely related species. In this study, 26 ITS, two rbcL and two matK consensus sequences from 18 seagrass taxa belonging to four families collected in India, Vietnam, Germany, Croatia and Egypt were processed. Molecular ITS analysis resolved five clades. The results also indicate that the Cymodoceaceae family might be a non-monophyletic group. In conclusion, ITS could be applied as a DNA barcode for seagrasses instead of the rbcL/matK system previously proposed.     

Immune responses to stress after stress management training in patients with rheumatoid arthritis

Introduction

Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA.

Methods

In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.

Results

Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment.

Conclusions

In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease.

Trial registration

The Netherlands National Trial Register (NTR1193)