Über die Rolle der Stabilitätsbetrachtungen in der Entwicklung der Bohrschen Atomtheorie

Ohne Zusammenfassung Vorgelegt von L. Rosenfeld     

Real-time observation of trigger factor function on translating ribosomes

The contribution of co-translational chaperone functions to protein folding is poorly understood. Ribosome-associated trigger factor (TF) is the first molecular chaperone encountered by nascent polypeptides in bacteria. Here we show, using fluorescence spectroscopy to monitor TF function and structural rearrangements in real time, that TF interacts with ribosomes and translating polypeptides in a dynamic reaction cycle. Ribosome binding stabilizes TF in an open, activated conformation. Activated TF departs from the ribosome after a mean residence time of approximately 10 s, but may remain associated with the elongating nascent chain for up to 35 s, allowing entry of a new TF molecule at the ribosome docking site. The duration of nascent-chain interaction correlates with the occurrence of hydrophobic motifs in translating polypeptides, reflecting a high aggregation propensity. These findings can explain how TF prevents misfolding events during translation and may provide a paradigm for the regulation of nucleotide-independent chaperones.     

An amorphous solid state of biogenic secondary organic aerosol particles

Secondary organic aerosol (SOA) particles are formed in the atmosphere from condensable oxidation products of anthropogenic and biogenic volatile organic compounds (VOCs). On a global scale, biogenic VOCs account for about 90% of VOC emissions and of SOA formation (90?billion kilograms of carbon per year). SOA particles can scatter radiation and act as cloud condensation or ice nuclei, and thereby influence the Earth's radiation balance and climate. They consist of a myriad of different compounds with varying physicochemical properties, and little information is available on the phase state of SOA particles. Gas-particle partitioning models usually assume that SOA particles are liquid, but here we present experimental evidence that they can be solid under ambient conditions. We investigated biogenic SOA particles formed from oxidation products of VOCs in plant chamber experiments and in boreal forests within a few hours after atmospheric nucleation events. On the basis of observed particle bouncing in an aerosol impactor and of electron microscopy we conclude that biogenic SOA particles can adopt an amorphous solid-most probably glassy-state. This amorphous solid state should provoke a rethinking of SOA processes because it may influence the partitioning of semi-volatile compounds, reduce the rate of heterogeneous chemical reactions, affect the particles' ability to accommodate water and act as cloud condensation or ice nuclei, and change the atmospheric lifetime of the particles. Thus, the results of this study challenge traditional views of the kinetics and thermodynamics of SOA formation and transformation in the atmosphere and their implications for air quality and climate.     

A comprehensive linkage analysis for myocardial infarction and its related risk factors

Coronary artery disease and myocardial infarction (MI) are leading causes of death in the western world. Numerous studies have shown that risk factors such as diabetes mellitus, arterial hypertension and hypercholesterolemia contribute to the development of the disease. Although each risk factor by itself is partly under genetic control, a positive family history is an independent predictor, which suggests that there are additional susceptibility genes. We have scanned the whole genome in 513 families to identify chromosomal regions linked to myocardial infarction and related risk factors that are known to be under genetic control. Here we show, by using variance component analysis and incorporating risk factors, that risk of myocardial infarction maps to a single region on chromosome 14 with a significant lod score of 3.9 (pointwise P=0.00015, genome-wide P<0.05), providing evidence of a principal MI locus. To characterize this locus we analyzed each risk factor by itself. Serum concentrations of lipoprotein (a) show linkage to both the apolipoprotein (a) locus (lod score 26.99) and a new locus on chromosome 1 (lod score 3.8). There is suggestive linkage for diabetes mellitus on chromosome 6 (lod score 2.96), for hypertension on chromosomes 1 and 6, for high-density and low-density lipoprotein cholesterol on chromosomes 1 and 17, and for triglyceride concentrations on chromosome 9. Although some of these risk factors overlap with previously identified loci, none overlaps with the newly identified susceptibility locus for myocardial infarction and coronary artery disease.     

Functional profiling of the Saccharomyces cerevisiae genome

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.     

T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases

Primary T-cell responses in lymph nodes (LNs) require contact-dependent information exchange between T cells and dendritic cells (DCs). Because lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool is composed of non-synchronized cells with different dwell times that display heterogeneous behaviour in mouse LNs in vitro. Here we employ two-photon microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell time in LNs was synchronized. During the first 8 h after entering from the blood, T cells underwent multiple short encounters with DCs, progressively decreased their motility, and upregulated activation markers. During the subsequent 12 h T cells formed long-lasting stable conjugates with DCs and began to secrete interleukin-2 and interferon-gamma. On the second day, coinciding with the onset of proliferation, T cells resumed their rapid migration and short DC contacts. Thus, T-cell priming by DCs occurs in three successive stages: transient serial encounters during the first activation phase are followed by a second phase of stable contacts culminating in cytokine production, which makes a transition into a third phase of high motility and rapid proliferation.     

Power requirement of the geodynamo from ohmic losses in numerical and laboratory dynamos

In the Earth's fluid outer core, a dynamo process converts thermal and gravitational energy into magnetic energy. The power needed to sustain the geomagnetic field is set by the ohmic losses (dissipation due to electrical resistance). Recent estimates of ohmic losses cover a wide range, from 0.1 to 3.5 TW, or roughly 0.3-10% of the Earth's surface heat flow. The energy requirement of the dynamo puts constraints on the thermal budget and evolution of the core through Earth's history. Here we use a set of numerical dynamo models to derive scaling relations between the core's characteristic dissipation time and the core's magnetic and hydrodynamic Reynolds numbers--dimensionless numbers that measure the ratio of advective transport to magnetic and viscous diffusion, respectively. The ohmic dissipation of the Karlsruhe dynamo experiment supports a simple dependence on the magnetic Reynolds number alone, indicating that flow turbulence in the experiment and in the Earth's core has little influence on its characteristic dissipation time. We use these results to predict moderate ohmic dissipation in the range of 0.2-0.5 TW, which removes the need for strong radioactive heating in the core and allows the age of the solid inner core to exceed 2.5 billion years.     

No cold dust within the supernova remnant Cassiopeia A

A large amount (about three solar masses) of cold (18 K) dust in the prototypical type II supernova remnant Cassiopeia A was recently reported. It was concluded that dust production in type II supernovae can explain how the large quantities (approximately 10(8) solar masses) of dust observed in the most distant quasars could have been produced within only 700 million years after the Big Bang. Foreground clouds of interstellar material, however, complicate the interpretation of the earlier submillimetre observations of Cas A. Here we report far-infrared and molecular line observations that demonstrate that most of the detected submillimetre emission originates from interstellar dust in a molecular cloud complex located in the line of sight between the Earth and Cas A, and is therefore not associated with the remnant. The argument that type II supernovae produce copious amounts of dust is not supported by the case of Cas A, which previously appeared to provide the best evidence for this possibility.     

Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation

Protein modification by ubiquitin is emerging as a signal for various biological processes in eukaryotes, including regulated proteolysis, but also for non-degradative functions such as protein localization, DNA repair and regulation of chromatin structure. A small ubiquitin-related modifier (SUMO) uses a similar conjugation system that sometimes counteracts the effects of ubiquitination. Ubiquitin and SUMO compete for modification of proliferating cell nuclear antigen (PCNA), an essential processivity factor for DNA replication and repair. Whereas multi-ubiquitination is mediated by components of the RAD6 pathway and promotes error-free repair, SUMO modification is associated with replication. Here we show that RAD6-mediated mono-ubiquitination of PCNA activates translesion DNA synthesis by the damage-tolerant polymerases eta and zeta in yeast. Moreover, polymerase zeta is differentially affected by mono-ubiquitin and SUMO modification of PCNA. Whereas ubiquitination is required for damage-induced mutagenesis, both SUMO and mono-ubiquitin contribute to spontaneous mutagenesis in the absence of DNA damage. Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability.     

Orientierende netzhautnahe pH-Messung im Glaskörper des Kaninchens bei intravenöser Glukose-infusion

Summary After i.v. infusion of glucose a decrease of pH to 6,85±0,12 measured in the vitreous body of the rabbit eye near the retina can be recorded.