Kann man Bewusstsein neurobiologisch erfassen und erklären?

Kann die moderne Neurobiologie mit ihren Messdaten und Verfahren das Leib-Seele-Problem lösen? Diese Arbeit zeigt anhand der Thesen des deutschen Neurobiologen Wolf Singer die Schwierigkeit der Erfassung phänomenaler Zustände durch eine Beobachterperspektive. Aus philosophischer Sicht gelingt es der Neurobiologie nicht, den Übergang von Beobachtbarem zu subjektiv Erlebtem zu skizzieren

First-principles molecular-dynamics simulations for neutral p-chloranil and its radical anion

APS copyright is acknowledged url = {http://link.aps.org/doi/10.1103/PhysRevB.53.12112}International audienceThe neutral p -chloranil ~ 2,3,5,6-tetrachloro- p -benzoquinone ! and its radical anion have been extensively studied using the Car-Parrinello projector augmented wave method, which is an all-electron electronic structure method for first-principles molecular dynamics based on the local density approximation of density functional theory. Frequencies and eigenmodes are derived by fitting a system of harmonic oscillators to the molecular- dynamics trajectories. The dependence of the bond lengths and vibrational frequencies on the molecular ionicity is discussed, and the electron affinity, Coulomb repulsion, and the spin-splitting parameter of p -chloranil are also derived

metaP-Server: A Web-Based Metabolomics Data Analysis Tool

Metabolomics is an emerging field that is based on the quantitative measurement of as many small organic molecules occurring in a biological sample as possible. Due to recent technical advances, metabolomics can now be used widely as an analytical high-throughput technology in drug testing and epidemiological metabolome and genome wide association studies. Analogous to chip-based gene expression analyses, the enormous amount of data produced by modern kit-based metabolomics experiments poses new challenges regarding their biological interpretation in the context of various sample phenotypes. We developed metaP-server to facilitate data interpretation. metaP-server provides automated and standardized data analysis for quantitative metabolomics data, covering the following steps from data acquisition to biological interpretation: (i) data quality checks, (ii) estimation of reproducibility and batch effects, (iii) hypothesis tests for multiple categorical phenotypes, (iv) correlation tests for metric phenotypes, (v) optionally including all possible pairs of metabolite concentration ratios, (vi) principal component analysis (PCA), and (vii) mapping of metabolites onto colored KEGG pathway maps. Graphical output is clickable and cross-linked to sample and metabolite identifiers. Interactive coloring of PCA and bar plots by phenotype facilitates on-line data exploration. For users of commercial metabolomics kits, cross-references to the HMDB, LipidMaps, KEGG, PubChem, and CAS databases are provided. metaP-server is freely accessible at http://metabolomics.helmholtz-muenchen.de/metap2/

Water uptake by trees in a riparian hardwood forest (Rhine floodplain, France)

Water flow in the soil–root–stem system was studied in a flooded riparian hardwood forest in the upper Rhine floodplain. The study was undertaken to identify the vertical distribution of water uptake by trees in a system where the groundwater is at a depth of less than 1 m. The three dominant ligneous species (Quercus robur, Fraxinus excelsior and Populus alba) were investigated for root structure (vertical extension of root systems), leaf and soil water potential (m), isotopic signal (18O) of soil water and xylem sap. The root density of oak and poplar was maximal at a depth of 20 to 60 cm, whereas the roots of the ash explored the surface horizon between 0 and 30 cm, which suggests a complementary tree root distribution in the hardwood forest. The flow density of oak and poplar was much lower than that of the ash. However, in the three cases the depth of soil explored by the roots reached 1Ð2 m, i.e. just above a bed of gravel. The oak roots had a large lateral distribution up to a distance of 15 m from the trunk. The water potential of the soil measured at 1 m from the trunk showed a zone of strong water potential between 20 and 60 cm deep. The vertical profile of soil water content varied from 0Ð40 to 0Ð50 cm3 cm3 close to the water table, and 0Ð20 to 0Ð30 cm3 cm3 in the rooting zone. The isotopic signal of stem water was constant over the whole 24-h cycle, which suggested that the uptake of water by trees occurred at a relatively constant depth. By comparing the isotopic composition of water between soil and plant, it was concluded that the water uptake occurred at a depth of 20 to 60 cm, which was in good agreement with the root and soil water potential distributions. The riparian forest therefore did not take water directly from the water table but from the unsaturated zone through the effect of capillarit

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Chloroplast-localized 6-phosphogluconate dehydrogenase is critical for maize endosperm starch accumulation

Plants have duplicate versions of the oxidative pentose phosphate pathway (oxPPP) enzymes with a subset localized to the chloroplast. The chloroplast oxPPP provides NADPH and pentose sugars for multiple metabolic pathways. This study identified two loss-of-function alleles of the Zea mays (maize) chloroplast-localized oxPPP enzyme 6-phosphogluconate dehydrogenase (6PGDH). These mutations caused a rough endosperm seed phenotype with reduced embryo oil and endosperm starch. Genetic translocation experiments showed that pgd3 has separate, essential roles in both endosperm and embryo development. Endosperm metabolite profiling experiments indicated that pgd3 shifts redox-related metabolites and increases reducing sugars similar to starch-biosynthetis mutants. Heavy isotope-labelling experiments indicates that carbon flux into starch is altered in pgd3 mutants. Labelling experiments with a loss of cytosolic 6PGDH did not affect flux into starch. These results support the known role for plastid-localized oxPPP in oil synthesis and argue that amyloplast-localized oxPPP reactions are integral to endosperm starch accumulation in maize kernels

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism

The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs&#39; action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human serum from 1,762 participants of the KORA F4 (Cooperative Health Research in the Region of Augsburg) study population. Our intent was to find variations of metabolite concentrations related to the intake of various drug classes and-based on the associations found-to generate new hypotheses about on-target as well as off-target effects of these drugs. In total, we found 41 significant associations for the drug classes investigated: For beta-blockers (11 associations), angiotensin-converting enzyme (ACE) inhibitors (four assoc.), diuretics (seven assoc.), statins (ten assoc.), and fibrates (nine assoc.) the top hits were pyroglutamine, phenylalanylphenylalanine, pseudouridine, 1-arachidonoylglycerophosphocholine, and 2-hydroxyisobutyrate, respectively. For beta-blockers we observed significant associations with metabolite concentrations that are indicative of drug side-effects, such as increased serotonin and decreased free fatty acid levels. Intake of ACE inhibitors and statins associated with metabolites that provide insight into the action of the drug itself on its target, such as an association of ACE inhibitors with des-Arg(9)-bradykinin and aspartylphenylalanine, a substrate and a product of the drug-inhibited ACE. The intake of statins which reduce blood cholesterol levels, resulted in changes in the concentration of metabolites of the biosynthesis as well as of the degradation of cholesterol. Fibrates showed the strongest association with 2-hydroxyisobutyrate which might be a breakdown product of fenofibrate and, thus, a possible marker for the degradation of this drug in the human organism. The analysis of diuretics showed a heterogeneous picture that is difficult to interpret. Taken together, our results provide a basis for a deeper functional understanding of the action and side-effects of antihypertensive and lipid-lowering drugs in the general population

Dynamic patterns of postprandial metabolic responses to three dietary challenges

Food intake triggers extensive changes in the blood metabolome. The kinetics of these changes depend on meal composition and on intrinsic, health-related characteristics of each individual, making the assessment of changes in the postprandial metabolome an opportunity to assess someone's metabolic status. To enable the usage of dietary challenges as diagnostic tools, profound knowledge about changes that occur in the postprandial period in healthy individuals is needed. In this study, we characterize the time-resolved changes in plasma levels of 634 metabolites in response to an oral glucose tolerance test (OGTT), an oral lipid tolerance test (OLTT), and a mixed meal (SLD) in healthy young males (n = 15). Metabolite levels for samples taken at different time points (20 per individual) during the challenges were available from targeted (132 metabolites) and non-targeted (502 metabolites) metabolomics. Almost half of the profiled metabolites (n = 308) showed a significant change in at least one challenge, thereof 111 metabolites responded exclusively to one particular challenge. Examples include azelate, which is linked to ω-oxidation and increased only in OLTT, and a fibrinogen cleavage peptide that has been linked to a higher risk of cardiovascular events in diabetes patients and increased only in OGTT, making its postprandial dynamics a potential target for risk management. A pool of 89 metabolites changed their plasma levels during all three challenges and represents the core postprandial response to food intake regardless of macronutrient composition. We used fuzzy c-means clustering to group these metabolites into eight clusters based on commonalities of their dynamic response patterns, with each cluster following one of four primary response patterns: (i) “decrease-increase” (valley-like) with fatty acids and acylcarnitines indicating the suppression of lipolysis, (ii) “increase-decrease” (mountain-like) including a cluster of conjugated bile acids and the glucose/insulin cluster, (iii) “steady decrease” with metabolites reflecting a carryover from meals prior to the study, and (iv) “mixed” decreasing after the glucose challenge and increasing otherwise. Despite the small number of subjects, the diversity of the challenges and the wealth of metabolomic data make this study an important step toward the characterization of postprandial responses and the identification of markers of metabolic processes regulated by food intake

Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up

BACKGROUND: Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). AIM: We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. MATERIALS AND METHODS: We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia (defined as having a fasting triglyceride level above 1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses. RESULTS: Increased levels of leucine, arginine, valine, proline, phenylalanine, isoleucine and lysine were significantly associated with an increased risk of hypertriglyceridemia. These associations remained significant when restricting to those individuals who did not develop T2D in the 7-year follow-up. The increase per standard deviation of amino acid level was between 26 and 40 %. CONCLUSIONS: Seven amino acids were associated with an increased risk of developing hypertriglyceridemia after 7 years. Further studies are necessary to elucidate the complex role of these amino acids in the pathogenesis of metabolic disorders