Epigenetic Signatures at AQP3 and SOCS3 Engage in Low-Grade Inflammation across Different Tissues

BackgroundElevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation.ResultsGenome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P ≤ 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels.ConclusionsEpigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus.     

Risikofaktoren für Krebs und MS in Kuhmilch und Rindfleisch?

Dairy cattle meat and milk factors contributing to the risk of cancers and multiple sclerosis A global epidemiological analysis of the incidence of colon and breast cancers suggests that consumption of meat and milk products of Eurasian dairy cattle contributes to the risk for these malignancies. Our group isolated a number of novel single‐stranded DNAs from serum and milk of dairy cattle. These are circular molecules (～1000–3000 nucleotides) of putative viral origin. Apparently this DNA does not integrate into chromosomal DNA of the animal hosts, but persists in a non‐integrated (episomal) state. Following transmission into human cells, this DNA is genetically active. Related isolates have been obtained from two lesions of patients with multiple sclerosis. Concepts have been developed to explain the potential etiological role of such agents for specific human diseases. Their involvement in human cancers and neurological diseases is presently subject of intensive investigations.     

Characterizing morphological (co)variation using structural equation models: Body size,allometric relationships and evolvability in a house sparrow metapopulation

Body size plays a key role in the ecology and evolution of all organisms. Therefore, quantifying the sources of morphological (co)variation, dependent and independent of body size, is of key importance when trying to understand and predict responses to selection. We combine structural equation modeling with quantitative genetics analyses to study morphological (co)variation in a meta‐population of house sparrows (Passer domesticus). As expected, we found evidence of a latent variable “body size,” causing genetic and environmental covariation between morphological traits. Estimates of conditional evolvability show that allometric relationships constrain the independent evolution of house sparrow morphology. We also found spatial differences in general body size and its allometric relationships. On islands where birds are more dispersive and mobile, individuals were smaller and had proportionally longer wings for their body size. Although on islands where sparrows are more sedentary and nest in dense colonies, individuals were larger and had proportionally longer tarsi for their body size. We corroborated these results using simulations and show that our analyses produce unbiased allometric slope estimates. This study highlights that in the short term allometric relationships may constrain phenotypic evolution, but that in the long term selection pressures can also shape allometric relationships.     

Measurement of 2J(H,C)- and 3J(H,C)-coupling constants by α/β selective HC(C)H-TOCSY

A new heteronuclear NMR pulse sequence for the measurement of ⁿJ(C,H) coupling constants, the /selective HC(C)H-TOCSY, is described. It is shown that the S³E element (Meissner et al., 1997a,b) can be used to obtain spin state selective coherence transfer in molecules, in which adjacent CH moieties are labeled with ¹³C. Application of the / selective HC(C)H-TOCSY to a 10nt RNA tetraloop 5-CGCUUUUGCG-3, in which the four uridine residues are ¹³C labeled in the sugar moiety, allowed measurement of two bond and three bond J(C,H) coupling constants, which provide additional restraints to characterize the sugar ring conformation of RNA in cases of conformational averaging.     

The dominating outer membrane protein of the hyperthermophilic Archaeum Ignicoccus hospitalis: a novel pore-forming complex

The membrane protein Imp1227 (Ignicoccus outer membrane protein; Imp1227) is the main protein constituent of the unique outer sheath of the hyperthermophilic, chemolithoautotrophic Archaeum Ignicoccus hospitalis. This outer sheath is the so far only known example for an asymmetric bilayer among the Archaea and is named 'outer membrane'. With its molecular mass of only 6.23 kDa, Imp1227 is found to be incorporated into the outer membrane in form of large, stable complexes. When separated by SDS-PAGE, they exhibit apparent masses of about 150, 50, 45 and 35 kDa. Dissociation into the monomeric form is achieved by treatment with SDS-containing solutions at temperatures at or above 113 degrees C. Electron micrographs of negatively stained samples confirm that isolated membranes are tightly packed with round complexes, about 7 nm in diameter, with a central, stain-filled 2 nm pore; a local two-dimensional crystalline arrangement in form of small patches can be detected by tomographic reconstruction. The comparison of the nucleotide and amino acid sequence of Imp1227 with public databases showed no reliable similarities with known proteins. Using secondary structure prediction and molecular modelling, an alpha-helical transmembrane domain is proposed; for the oligomer, a ring-shaped nonamer with a central 2 nm pore is a likely arrangement.     

Fibre types in locomotory muscles of the cartilaginous fish Chimaera monstrosa

The cartilaginous fish Chimaera monstrosa swims slowly by means of pectoral fin movements, and fast by undulations of the tail. In order to compare the fibres in the corresponding muscles, they were studied by histochemistry and electron microscopy. Three fibre types were identified by microphotometry and morphometry. Most of the axial muscles are white fibres, containing little mitochondria and glycogen. Red fibres, with glycogen and about 5 % mitochondria constitute a thin sheet in the axial muscles, composed of one fibre layer only. Pink fibres, with intermediate amounts of glycogen and mitochondria are situated between these two types, but are often not covered by red fibres. Pectoral muscles contain numerous red and intermediate fibres, partially mixed, superficially, and white fibres deeper. Pectoral muscle red fibres contain about 25 % mitochondria, half of which are situated in subsarcolemmal accummulations. The sarcotubular system has T-tubules at the Z discs, and the terminal cisternae are partially divided by regularly spaced clefts.     

Differential polypeptide display: the search for the elusive target

Proteomics, as a tool to identify proteins in biological samples, is gaining rapidly importance in the postgenomic era. Here we discuss the current and potential role of different techniques in the field of proteomics such as two-dimensional gel electrophoresis off-line coupled to MALDI-MS (2D-PAGE-MALDI-MS), high performance liquid chromatography mass spectrometry (HPLC-MS), surface enhanced laser desorption/ionization mass spectrometry (SELDI-MS) and a newly developed technique, capillary electrophoresis mass spectrometry (CE-MS). The developments of the last years are presented discussed.     

Overstorey–Understorey Interactions Intensify After Drought-Induced Forest Die-Off: Long-Term Effects for Forest Structure and Composition

Severe drought events increasingly affect forests worldwide, but little is known about their long-term effects at the ecosystem level. Competition between trees and herbs (‘overstorey–understorey competition’) for soil water can reduce tree growth and regeneration success and may thereby alter forest structure and composition. However, these effects are typically ignored in modelling studies. To test the long-term impact of water competition by the herbaceous understorey on forest dynamics, we incorporated this process in the dynamic forest landscape model LandClim. Simulations were performed both with and without understorey under current and future climate scenarios (RCP4.5 and RCP8.5) in a drought-prone inner-Alpine valley in Switzerland. Under current climate, herbaceous understorey reduced tree regeneration biomass by up to 51%, particularly in drought-prone landscape positions (i.e., south-facing, low-elevation slopes), where it also caused a shift in forest composition towards drought-tolerant tree species (for example, Quercus pubescens). For adult trees, the understorey had a minor effect on growth. Under future climate change scenarios, increasing drought frequency and intensity resulted in large-scale mortality of canopy trees, which intensified the competitive interaction between the understorey and tree regeneration. At the driest landscape positions, a complete exclusion of tree regeneration and a shift towards an open, savannah-like vegetation occurred. Overall, our results demonstrate that water competition by the herbaceous understorey can cause long-lasting legacy effects on forest structure and composition across drought-prone landscapes, by affecting the vulnerable recruitment phase. Ignoring herbaceous vegetation may thus lead to a strong underestimation of future drought impacts on forests.