The natriuretic action of [4-Leucine]-arginine-vasotocin

Zusammenfassung [Leu⁴]-Arginin-vasotocin wirkt so wohl an Katzen (Chloralose-Narkose, Mannit-Diurese) als auch an wachen Ratten (mit 0.9%-iger NACl-Lösung belastet) und wachen nicht vorbehandelten Hunden natriuretisch und diuretisch.     

Unusual activity of the Sun during recent decades compared to the previous 11,000 years

Direct observations of sunspot numbers are available for the past four centuries, but longer time series are required, for example, for the identification of a possible solar influence on climate and for testing models of the solar dynamo. Here we report a reconstruction of the sunspot number covering the past 11,400 years, based on dendrochronologically dated radiocarbon concentrations. We combine physics-based models for each of the processes connecting the radiocarbon concentration with sunspot number. According to our reconstruction, the level of solar activity during the past 70 years is exceptional, and the previous period of equally high activity occurred more than 8,000 years ago. We find that during the past 11,400 years the Sun spent only of the order of 10% of the time at a similarly high level of magnetic activity and almost all of the earlier high-activity periods were shorter than the present episode. Although the rarity of the current episode of high average sunspot numbers may indicate that the Sun has contributed to the unusual climate change during the twentieth century, we point out that solar variability is unlikely to have been the dominant cause of the strong warming during the past three decades.     

The building blocks of planets within the 'terrestrial' region of protoplanetary disks

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.     

A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit

The hippocampus, a brain structure essential for memory and cognition, is classically represented as a trisynaptic excitatory circuit. Recent findings challenge this view, particularly with regard to the mossy fibre input to CA3, the second synapse in the trisynaptic pathway. Thus, the powerful mossy fibre input to CA3 pyramidal cells might mediate both synaptic excitation and inhibition. Here we show, by recording from connected cell pairs in rat entorhinal-hippocampal slice cultures, that single action potentials in a dentate granule cell evoke a net inhibitory signal in a pyramidal cell. The hyperpolarization is due to disynaptic feedforward inhibition, which overwhelms monosynaptic excitation. Interestingly, this net inhibitory synaptic response changes to an excitatory signal when the frequency of presynaptic action potentials increases. The process responsible for this switch involves the facilitation of monosynaptic excitatory transmission coupled with rapid depression of inhibitory circuits. This ability to immediately switch the polarity of synaptic responses constitutes a novel synaptic mechanism, which might be crucial to the state-dependent processing of information in associative hippocampal networks.     

Strategies for the design of inhibitors of aldose reductase, an enzyme showing pronounced induced-fit adaptations

Aldose reductase is involved in the polyol pathway, catalyzing the reduction of glucose to sorbitol. However, due to pronounced binding site adaptations, the enzyme can operate on a broad palette of structurally diverse substrates ranging from small aliphatic and aromatic aldehydes up to steroid-type ligands. A comparative analysis of the presently accessible crystal structures of aldose reductase complexes reveals four binding-competent protein conformations. Additional relevant conformers are detected through molecular dynamics simulations. They indicate an equilibrium of several conformers which is shifted towards the binding-competent geometries upon ligand binding. Such a manifold system with several alternative binding site conformers requires some tailored concepts in virtual screening. We followed two strategies, both successfully suggesting new micromolar inhibitors. In a first attempt, we concentrated on one preferred conformer and performed a virtual screening, assuming that the binding pocket of aldose reductase adopts only this conformation. In a second approach, we followed a ligand superpositioning method. Ligands were extracted in their bound conformations from three different crystal structures, all accommodating the ligands with different active site conformations. After merging these ligands into one supermolecule, mutual alignments were computed, taking candidate ligands from a screening database. The latter strategy also retrieved several structurally new inhibitors of micromolar potency.     

Mutations in SEC63 cause autosomal dominant polycystic liver disease

Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.     

The role of increasing temperature variability in European summer heatwaves

Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe.     

Increased seasonality in Middle East temperatures during the last interglacial period

The last interglacial period (about 125,000 years ago) is thought to have been at least as warm as the present climate. Owing to changes in the Earth's orbit around the Sun, it is thought that insolation in the Northern Hemisphere varied more strongly than today on seasonal timescales, which would have led to corresponding changes in the seasonal temperature cycle. Here we present seasonally resolved proxy records using corals from the northernmost Red Sea, which record climate during the last interglacial period, the late Holocene epoch and the present. We find an increased seasonality in the temperature recorded in the last interglacial coral. Today, climate in the northern Red Sea is sensitive to the North Atlantic Oscillation, a climate oscillation that strongly influences winter temperatures and precipitation in the North Atlantic region. From our coral records and simulations with a coupled atmosphere-ocean circulation model, we conclude that a tendency towards the high-index state of the North Atlantic Oscillation during the last interglacial period, which is consistent with European proxy records, contributed to the larger amplitude of the seasonal cycle in the Middle East.     

Licht- und elektronenmikroskopische Befunde an den Geschmacksknospen der Axolotlzunge

Summary The investigation of the taste buds in the tongue of the neotene Mexican axolotl (Siredon mexicanum) by light and electron microscopy demonstrates 4 different cell types: 1) R-cells, marginal cells of less differentiated character. 2) G-cells, granulated cells in basal position. 3) Cells of type A with fibrills, vesicular elements, and dark bodies, showing supporting and secretory function. 4) Cells of type B with an agranular endoplasmic reticulum in stripe like arrangement, supposed to be receptor cells.