The Developmental Chronnecto-Genomics (Dev-CoG) study: A multimodal study on the developing brain.

Brain development has largely been studied through unimodal analysis of neuroimaging data, providing independent results for structural and functional data. However, structure clearly impacts function and vice versa, pointing to the need for performing multimodal data collection and analysis to improve our understanding of brain development, and to further inform models of typical and atypical brain development across the lifespan. Ultimately, such models should also incorporate genetic and epigenetic mechanisms underlying brain structure and function, although currently this area is poorly specified. To this end, we are reporting here a multi-site, multi-modal dataset that captures cognitive function, brain structure and function, and genetic and epigenetic measures to better quantify the factors that influence brain development in children originally aged 9-14 years. Data collection for the Developmental Chronnecto-Genomics (Dev-CoG) study (http://devcog.mrn.org/) includes cognitive, emotional, and social performance scales, structural and functional MRI, diffusion MRI, magnetoencephalography (MEG), and saliva collection for DNA analysis of single nucleotide polymorphisms (SNPs) and DNA methylation patterns. Across two sites (The Mind Research Network and the University of Nebraska Medical Center), data from over 200 participants were collected and these children were re-tested annually for at least 3 years. The data collection protocol, sample demographics, and data quality measures for the dataset are presented here. The sample will be made freely available through the collaborative informatics and neuroimaging suite (COINS) database at the conclusion of the study.

From protons to OXPHOS supercomplexes and Alzheimer's disease: structure-dynamics-function relationships of energy-transducing membranes.

By the elucidation of high-resolution structures the view of the bioenergetic processes has become more precise. But in the face of these fundamental advances, many problems are still unresolved. We have examined a variety of aspects of energy-transducing membranes from large protein complexes down to the level of protons and functional relevant picosecond protein dynamics. Based on the central role of the ATP synthase for supplying the biological fuel ATP, one main emphasis was put on this protein complex from both chloroplast and mitochondria. In particular the stoichiometry of protons required for the synthesis of one ATP molecule and the supramolecular organisation of ATP synthases were examined. Since formation of supercomplexes also concerns other complexes of the respiratory chain, our work was directed to unravel this kind of organisation, e.g. of the OXPHOS supercomplex I(1)III(2)IV(1), in terms of structure and function. Not only the large protein complexes or supercomplexes work as key players for biological energy conversion, but also small components as quinones which facilitate the transfer of electrons and protons. Therefore, their location in the membrane profile was determined by neutron diffraction. Physico-chemical features of the path of protons from the generators of the electrochemical gradient to the ATP synthase, as well as of their interaction with the membrane surface, could be elucidated by time-resolved absorption spectroscopy in combination with optical pH indicators. Diseases such as Alzheimer's dementia (AD) are triggered by perturbation of membranes and bioenergetics as demonstrated by our neutron scattering studies.

Prediction uncertainty of environmental change effects on temperate European biodiversity.

Observed patterns of species richness at landscape scale (gamma diversity) cannot always be attributed to a specific set of explanatory variables, but rather different alternative explanatory statistical models of similar quality may exist. Therefore predictions of the effects of environmental change (such as in climate or land cover) on biodiversity may differ considerably, depending on the chosen set of explanatory variables. Here we use multimodel prediction to evaluate effects of climate, land-use intensity and landscape structure on species richness in each of seven groups of organisms (plants, birds, spiders, wild bees, ground beetles, true bugs and hoverflies) in temperate Europe. We contrast this approach with traditional best-model predictions, which we show, using cross-validation, to have inferior prediction accuracy. Multimodel inference changed the importance of some environmental variables in comparison with the best model, and accordingly gave deviating predictions for environmental change effects. Overall, prediction uncertainty for the multimodel approach was only slightly higher than that of the best model, and absolute changes in predicted species richness were also comparable. Richness predictions varied generally more for the impact of climate change than for land-use change at the coarse scale of our study. Overall, our study indicates that the uncertainty introduced to environmental change predictions through uncertainty in model selection both qualitatively and quantitatively affects species richness projections.

Vardenafil protects isolated rat hearts at reperfusion dependent on GC and PKG.

BACKGROUND AND PURPOSE: The type-5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell model of calcium stress. EXPERIMENTAL APPROACH: Infarct size in rat isolated hearts was measured after a 30 min regional ischemia and 120 min reperfusion. Vardenafil (1 nM-1 microM) was infused during reperfusion. HL-1 cardiomyocytes were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of mitochondrial membrane potential (psi m). KEY RESULTS: Vardenafil at reperfusion reduced infarct size as percentage of the ischemic zone from 45.8+/-2.0% in control hearts to 26.2+/-2.7% (P<0.001) only at 10 nM, whereas higher or lower dosages failed to protect. This protective effect was blocked by co-administration of either the GC inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or the PKG inhibitor, KT-5823. HL-1 cardiomyocytes, loaded with TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce calcium stress. This reduced the mean cell fluorescence to 63.3 +/- 3.8% of baseline values and vardenafil protected against this fall (78.6 +/- 3.6%, P<0.01). The vardenafil-induced protection of HL-1 cells was blocked by ODQ, KT-5823 or the PKG-inhibiting peptides DT-2 and DT-3, confirming a role for GC and PKG. CONCLUSIONS AND IMPLICATIONS: These results further support the hypothesis that PDE-5 inhibitors are protective in ischemic hearts, in addition to their known clinical effects in the treatment of erectile dysfunction in men.

Impact of quercetin and fish oil encapsulation on bilayer membrane and oxidation stability of liposomes.

Unsaturated soy phosphatidyl choline (PC) liposomes were systematically analyzed for chemical and physical stability and for influence on membrane fluidity, when quercetin and fish oil were encapsulated. The physical stability of liposomes was lowered with loading, which is mainly due to fish oil leakage. While fish oil did not induce oxidative acceleration, quercetin did not reduce lipid-derived radical formation but it did inhibit hexanal formation. It also showed no relevant effects on membrane fluidity, polarity or partitioning of the spin probe TEMPOL-benzoate (TB), as proved by EPR measurements and simulation. However, increasing concentration of fish oil in a membrane might increase the acyl chain dynamics and therefore apply a more attractive environment for TB. In contrast to the encapsulates increasing fluidity of saturated membranes by disturbing the lipid packing, membrane properties of unsaturated systems with a Tm below 0 °C were not influenced by encapsulation of quercetin or fish oil.

Telomere shortening: a new prognostic factor for cardiovascular disease post-radiation exposure.

Telomere length has been proposed as a marker of mitotic cell age and as a general index of human organism aging. Telomere shortening in peripheral blood lymphocytes has been linked to cardiovascular-related morbidity and mortality. The authors investigated the potential correlation of conventional risk factors, radiation dose and telomere shortening with the development of coronary artery disease (CAD) following radiation therapy in a large cohort of Hodgkin lymphoma (HL) patients. Multivariate analysis demonstrated that hypertension and telomere length were the only independent risk factors. This is the first study in a large cohort of patients that demonstrates significant telomere shortening in patients treated by radiation therapy who developed cardiovascular disease. Telomere length appears to be an independent prognostic factor that could help determine patients at high risk of developing CAD after exposure in order to implement early detection and prevention.

Diversity and composition of phytophagous insect guilds on Brassicaceae.

We investigated the guild structure of phytophagous insects on Brassicaceae in Poland and the influence of host-plant parameters (e.g. sampling effort, geographical distribution, taxonomic isolation, nitrogen indicator values) on the species richness of these guilds. The data were extracted from a study published by Lipa et al. The overall number of recorded ectophagous species is about twice the number of endophagous species. Irrespective of the feeding niche, species are predominantly oligophagous, feeding on more than two Brassicaceae genera. The relative importance of endophagous species within the fauna decreases with increasing host range. The sampling effort predicts a high proportion of the variance of alpha-diversity in oligo- and polyphagous insects, but only a low proportion in specialized species. After correction for sampling effort, most of the plant parameters do not explain an additional proportion of the variance in species richness. We hypothesize that the uniform chemical defence system across genera in Brassicaceae is an important factor triggering host range and diversity patterns in phytophagous insects on crucifers.

Quantification of cantharidin in canthariphilous ceratopogonidae (Diptera), anthomyiidae (Diptera) and cantharidin-producing oedemeridae (Coleoptera).

Cantharidin contents were determined in several canthariphilous insects by means of quantitative gas chromatography. Usually the ceratopogonidsAtrichopogon oedemerarum andA. trifasciatus caught in the field contained low concentrations of cantharidin, with concentrations in males, in most cases, being lower than in females. When fed in the laboratory with synthetic cantharidin, these species concentrated cantharidin by as much as 100-fold (males) and 40-fold (females). Accumulation in the different body tagmata (head, thorax, abdomen) of these species is similar. Maximal concentrations of cantharidin in tissues ofAtrichopogon are comparable to those known from oedemerid and meloid beetles. InA. trifasciatus about 90% of total cantharidin content is bound in tissues. Investigations using the canthariphilous anthomyiid flyAnthomyia pluvialis and three cantharidin-producing oedemerid species revealed the same pattern of distribution in different body tagmata as inAtrichopogon.

Spatial genetic structure in a metapopulation of the land snail Cepaea nemoralis (Gastropoda: Helicidae).

Habitat fragmentation is a major force affecting demography and genetic structure of wild populations, especially in agricultural landscapes. The land snail Cepaea nemoralis (L.) was selected to investigate the impact of habitat fragmentation on the spatial genetic structure of an organism with limited dispersal ability. Genetic and morphological patterns were investigated at a local scale of a 500 m transect and a mesoscale of 4 x 4 km in a fragmented agricultural landscape while accounting for variation in the landscape using least-cost models. Analysis of microsatellite loci using expected heterozygosity (HE), pairwise genetic distance (FST/1-FST) and spatial autocorrelograms (Moran's I) as well as shell characteristics revealed spatial structuring at both scales and provided evidence for a metapopulation structure. Genetic diversity was related to morphological diversity regardless of landscape properties. This pointed to bottlenecks caused by founder effects after (re)colonization. Our study suggests that metapopulation structure depended on both landscape features and the shape of the dispersal function. A range of genetic spatial autocorrelation up to 80 m at the local scale and up to 800 m at the mesoscale indicated leptokurtic dispersal patterns. The metapopulation dynamics of C. nemoralis resulted in a patchwork of interconnected, spatially structured subpopulations. They were shaped by gene flow which was affected by landscape features, the dispersal function and an increasing role of genetic drift with distance.

[Effectivity of intermittent treatment in patients with sputum-positive silico-tuberculosis (author's transl)]. / Effektivität der intermittierenden Behandlung bei Patienten mit BK-positiver Siliko-Tuberkulose)

89 patients with sputum-positive silico-tuberculosis got a fully supervised administered antituberculous treatment with intermittent regimens during the years 1969-1974. 65 of the patients had a history of former antituberculous treatment. In only 5 patients the treatment was unsuccessful. Four of the relapses were observed between the 6th and 11th month of treatment. One patient had a relapse 56 months after the onset of chemotherapy. The results indicate that only the quality of the anti-TB treatment is of importance for the course of the tuberculous component in silico-tuberculosis. The results are comparable with those of uncomplicated TB of the lungs.

[Surveillance of exposure in industrial styrene load]. / Zur Expositionsüberwachung bei beruflichen Styrenbelastungen.

Determinations of the styrene metabolites are reported with the high-performance liquid chromatography. The methodical investigations were used on a group of workers of the polyester processing. The establishment of the cumulation of metabolites and the appearance of pathological values of liver enzymes refer to the overcharge of biological regulations.