Erfassung kognitiver Leistungspotentiale Erwachsener im Sozio-oekonomischen Panel (SOEP)

Im Erhebungsjahr 2006 wurden erstmals in einer Teilstichprobe des SOEP kognitive Kurztests durchgeführt. Ziel war es, ein robustes, von geschulten Interviewern leicht zu administrierendes Instrumentarium einzusetzen, das innerhalb weniger Minuten durchführbar ist. Annähernd 80 % aller zur Durchführung des Kognitionstests ausgewählten Befragungspersonen haben gültige Angeben gemacht. Somit stehen für mehr als 5.500 Personen erstmals neben vielfältigen zertifikatsbasierten Bildungsinformationen auch Indikatoren für kognitive Potentiale zur Verfügung. Neben der Dokumentation der Daten werden in diesem Bericht erste Verteilungen der Maße vorgestellt und Selektionsanalysen präsentiert. Die erste Wiederholungsmessung der Tests ist für das Erhebungsjahr 2010 vorgesehen

Erfassung kognitiver Leistungspotentiale Erwachsener im Sozio-oekonomischen Panel (SOEP)

Im Erhebungsjahr 2006 wurden erstmals in einer Teilstichprobe des SOEP kognitive Kurztests durchgeführt. Ziel war es, ein robustes, von geschulten Interviewern leicht zu administrierendes Instrumentarium einzusetzen, das innerhalb weniger Minuten durchführbar ist. Annähernd 80 % aller zur Durchführung des Kognitionstests ausgewählten Befragungspersonen haben gültige Angeben gemacht. Somit stehen für mehr als 5.500 Personen erstmals neben vielfältigen zertifikatsbasierten Bildungsinformationen auch Indikatoren für kognitive Potentiale zur Verfügung. Neben der Dokumentation der Daten werden in diesem Bericht erste Verteilungen der Maße vorgestellt und Selektionsanalysen präsentiert. Die erste Wiederholungsmessung der Tests ist für das Erhebungsjahr 2010 vorgesehen.

Laser Metal Deposition of AlSi10Mg with high build rates

Additive manufacturing with aluminum alloys is becoming increasingly important in the automotive industry to meet the growing demand for lightweight construction and flexibility. However, higher build rates and higher process efficiency are necessary for laser metal deposition (LMD) to be more economically competitive. The so called high-speed LMD allows high build rates by partial melting of the powder before it hits the melt pool but is currently limited to coatings of rotationally symmetrical parts. Our goal is to apply this process technology to the additive manufacturing of AlSi10Mg and thereby increase the build rate. In this work we demonstrate a successful build-up of cuboids manufactured with the alloy AlSi10Mg using feed rates ten times higher compared to state of the art. The tensile strength of these cuboids is in the range of 180 to 220 MPa

Implications for the Binding of the Protein G5P to DNA

Microorganisms accumulate molar concentrations of compatible solutes like ectoine to prevent proteins from denaturation. Direct structural or spectroscopic information on the mechanism and about the hydration shell around ectoine are scarce. We combined surface plasmon resonance (SPR), confocal Raman spectroscopy, molecular dynamics simulations, and density functional theory (DFT) calculations to study the local hydration shell around ectoine and its influence on the binding of a gene-S-protein (G5P) to a single-stranded DNA (dT(25)). Due to the very high hygroscopicity of ectoine, it was possible to analyze the highly stable hydration shell by confocal Raman spectroscopy. Corresponding molecular dynamics simulation results revealed a significant change of the water dielectric constant in the presence of a high molar ectoine concentration as compared to pure water. The SPR data showed that the amount of protein bound to DNA decreases in the presence of ectoine, and hence, the protein-DNA dissociation constant increases in a concentration- dependent manner. Concomitantly, the Raman spectra in terms of the amide I region revealed large changes in the protein secondary structure. Our results indicate that ectoine strongly affects the molecular recognition between the protein and the oligonudeotide, which has important consequences for osmotic regulation mechanisms

HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology

We present HepatoNet1, a manually curated large-scale metabolic network of the human hepatocyte that encompasses >2500 reactions in six intracellular and two extracellular compartments.Using constraint-based modeling techniques, the network has been validated to replicate numerous metabolic functions of hepatocytes corresponding to a reference set of diverse physiological liver functions.Taking the detoxification of ammonia and the formation of bile acids as examples, we show how these liver-specific metabolic objectives can be achieved by the variable interplay of various metabolic pathways under varying conditions of nutrients and oxygen availability

Transcription at the proximity of the nuclear pore: A role for the THP1-SAC3-SUS1-CDC31 (THSC) complex

4 páginas, 1 figura.A key aspect of eukaryotic gene expression is the coupling of transcription with RNA processing, polyadenylation and export. The use of new techniques based on tandem affinity purification (TAP) and chromatin immunoprecipitation (ChIP), and of genetic and cell biology approaches has contributed to the beginning of deciphering the network of protein-mRNA interactions accompanying this coupling. Although an extensive amount of work has shed light on this matter, the order of participation and precise role of the different proteins remain to be deciphered. It seems that different and sequential protein interactions must converge to finally promote the anchoring of genes to the nuclear periphery. Here we discuss the new data on the coupling of gene expression and RNA export, with emphasis on the THP1-SAC3-SUS1-CDC31 complex and the possible implications of these results on transcription at the nuclear pore.Research in A.A.’s lab is funded by grants from the Spanish Ministry of Science and Education and the Junta de Andalucía.Peer reviewe

Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1).

OBJECTIVE: To extend the phenotypic description of Charcot-Marie-Tooth disease (CMTX1) and to draw new genotype-phenotype relationships. METHODS: Mutations in GJB1 cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data from 160 patients (from 120 different families, with 89 different mutations) seen at the Inherited Neuropathies Consortium centers. RESULTS: We evaluated 87 males who had a mean age of 41 years (range 10-78 years) and 73 females who had a mean age of 46 years (range 15-84 years). Sensory-motor polyneuropathy affects both sexes, more severely in males than in females, and there was a strong correlation between age and disease burden in males but not in females. Compared with females, males had more severe reduction in motor and sensory neurophysiology parameters. In contrast to females, the radial nerve sensory response in older males tended to be more severely affected compared with younger males. Median and ulnar nerve motor amplitudes were also more severely affected in older males, whereas ulnar nerve motor potentials tended to be more affected in older females. Conversely, there were no statistical differences between the sexes in other features of the disease, such as problems with balance and hand dexterity. CONCLUSIONS: In the absence of a phenotypic correlation with specific GJB1 mutations, sex-specific distinctions and clinically relevant attributes need to be incorporated into the measurements for clinical trials in people with CMTX1. CLINICALTRIALSGOV IDENTIFIER: NCT01193075

The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance

The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (>95%) from heterozygous (t/+) males to their offspring. This phenotype is termed transmission ratio distortion (TRD) and is caused by the interaction of the t-complex responder (Tcr) with several quantitative trait loci (QTL), the t-complex distorters (Tcd1 to Tcd4), all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas +-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S) that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOKTcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and spermatozoa

allodb: An R package for biomass estimation at globally distributed extratropical forest plots

Allometric equations for calculation of tree above-ground biomass (AGB) form the basis for estimates of forest carbon storage and exchange with the atmosphere. While standard models exist to calculate forest biomass across the tropics, we lack a standardized tool for computing AGB across boreal and temperate regions that comprise the global extratropics. Here we present an integrated R package, allodb, containing systematically selected published allometric equations and proposed functions to compute AGB. The data component of the package is based on 701 woody species identified at 24 large Forest Global Earth Observatory (ForestGEO) forest dynamics plots representing a wide diversity of extratropical forests. A total of 570 parsed allometric equations to estimate individual tree biomass were retrieved, checked and combined using a weighting function designed to ensure optimal equation selection over the full tree size range with smooth transitions across equations. The equation dataset can be customized with built-in functions that subset the original dataset and add new equations. Although equations were curated based on a limited set of forest communities and number of species, this resource is appropriate for large portions of the global extratropics and can easily be expanded to cover novel forest types

Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants

Charcot-Marie-Tooth disease (CMT) due to GJB1 variants (CMTX1) is the second most common form of CMT. It is an X-linked disorder characterised by progressive sensory and motor neuropathy with males affected more severely than females. Many reported GJB1 variants remain classified as variants of uncertain significance (VUS). In this large, international, multicentre study we prospectively collected demographic, clinical and genetic data on patients with CMT associated with GJB1 variants. Pathogenicity for each variant was defined using adapted American College of Medical Genetics criteria. Baseline and longitudinal analyses were conducted to study genotype-phenotype correlations, to calculate longitudinal change using the CMT Examination Score (CMTES), to compare males versus females, and pathogenic/likely pathogenic (P/LP) variants versus VUS. We present 387 patients from 295 families harbouring 154 variants in GJB1. Of these, 319 patients (82.4%) were deemed to have P/LP variants, 65 had VUS (16.8%) and 3 benign variants (0.8%; excluded from analysis); an increased proportion of patients with P/LP variants compared with using ClinVar's classification (74.6%). Male patients (166/319, 52.0%, P/LP only) were more severely affected at baseline. Baseline measures in patients with P/LP variants and VUS showed no significant differences, and regression analysis suggested the disease groups were near identical at baseline. Genotype-phenotype analysis suggested c.-17G>A produces the most severe phenotype of the five most common variants, and missense variants in the intracellular domain are less severe than other domains. Progression of disease was seen with increasing CMTES over time up to 8 years follow-up. Standard response mean (SRM), a measure of outcome responsiveness, peaked at 3 years with moderate responsiveness (change in CMTES (ΔCMTES) = 1.3 ± 2.6, p = 0.00016, SRM = 0.50). Males and females progressed similarly up to 8 years, but baseline regression analysis suggested that over a longer period, females progress more slowly. Progression was most pronounced for mild phenotypes (CMTES = 0-7; 3-year ΔCMTES = 2.3 ± 2.5, p = 0.001, SRM = 0.90). Enhanced variant interpretation has yielded an increased proportion of GJB1 variants classified as P/LP and will aid future variant interpretation in this gene. Baseline and longitudinal analysis of this large cohort of CMTX1 patients describes the natural history of the disease including the rate of progression; CMTES showed moderate responsiveness for the whole group at 3 years and higher responsiveness for the mild group at 3, 4 and 5 years. These results have implications for patient selection for upcoming clinical trials