A simple system for mechanical and electrical recordings from frog nerve-muscle preparation

Summary A device is described which can be used for simultaneous measurement of the muscle action potential and the contraction of the frog gastrocnemius nerve-muscle preparation. The apparatus is characterized by ease of construction, good accuracy and reliability.We thank Ms.C. Friedemann for preparation of the drawings; Ms.A. Middelmann for technical assistance.     

Discovery of a flank caldera and very young glacial activity at Hecates Tholus, Mars

The majority of volcanic products on Mars are thought to be mafic and effusive. Explosive eruptions of basic to ultrabasic chemistry are expected to be common, but evidence for them is rare and mostly confined to very old surface features. Here we present new image and topographic data from the High Resolution Stereo Camera that reveal previously unknown traces of an explosive eruption at 30 degrees N and 149 degrees E on the northwestern flank of the shield volcano Hecates Tholus. The eruption created a large, 10-km-diameter caldera approximately 350 million years ago. We interpret these observations to mean that large-scale explosive volcanism on Mars was not confined to the planet's early evolution. We also show that glacial deposits partly fill the caldera and an adjacent depression. Their age, derived from crater counts, is about 5 to 24 million years. Climate models predict that near-surface ice is not stable at mid-latitudes today, assuming a thermo-dynamic steady state. Therefore, the discovery of very young glacial features at Hecates Tholus suggests recent climate changes. We show that the absolute ages of these very recent glacial deposits correspond very well to a period of increased obliquity of the planet's rotational axis.     

Evidence from the Mars Express High Resolution Stereo Camera for a frozen sea close to Mars' equator

It is thought that the Cerberus Fossae fissures on Mars were the source of both lava and water floods two to ten million years ago. Evidence for the resulting lava plains has been identified in eastern Elysium, but seas and lakes from these fissures and previous water flooding events were presumed to have evaporated and sublimed away. Here we present High Resolution Stereo Camera images from the European Space Agency Mars Express spacecraft that indicate that such lakes may still exist. We infer that the evidence is consistent with a frozen body of water, with surface pack-ice, around 5 degrees north latitude and 150 degrees east longitude in southern Elysium. The frozen lake measures about 800 x 900 km in lateral extent and may be up to 45 metres deep--similar in size and depth to the North Sea. From crater counts, we determined its age to be 5 +/- 2 million years old. If our interpretation is confirmed, this is a place that might preserve evidence of primitive life, if it has ever developed on Mars.     

Chromosomenaberrationen in Tumorasziteszellen des Ehrlich-Karzinoms der Maus nach Röntgenbestrahlungin vivo bei verschiedenen Sauerstoffpartialdrucken

Summary The frequency of radio-induced fragments of chromosomes increases in ascites-cells of the Ehrlich-carcinoma at higher oxygen partial pressure, to which test animals are exposed during irradiation.     

De novo mutations revealed by whole-exome sequencing are strongly associated with autism

Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders. But whereas de novo single nucleotide variants have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, α subunit), a result that is highly unlikely by chance.     

Atomic model of the type III secretion system needle

Pathogenic bacteria using a type III secretion system (T3SS) to manipulate host cells cause many different infections including Shigella dysentery, typhoid fever, enterohaemorrhagic colitis and bubonic plague. An essential part of the T3SS is a hollow needle-like protein filament through which effector proteins are injected into eukaryotic host cells. Currently, the three-dimensional structure of the needle is unknown because it is not amenable to X-ray crystallography and solution NMR, as a result of its inherent non-crystallinity and insolubility. Cryo-electron microscopy combined with crystal or solution NMR subunit structures has recently provided a powerful hybrid approach for studying supramolecular assemblies, resulting in low-resolution and medium-resolution models. However, such approaches cannot deliver atomic details, especially of the crucial subunit-subunit interfaces, because of the limited cryo-electron microscopic resolution obtained in these studies. Here we report an alternative approach combining recombinant wild-type needle production, solid-state NMR, electron microscopy and Rosetta modelling to reveal the supramolecular interfaces and ultimately the complete atomic structure of the Salmonella typhimurium T3SS needle. We show that the 80-residue subunits form a right-handed helical assembly with roughly 11 subunits per two turns, similar to that of the flagellar filament of S. typhimurium. In contrast to established models of the needle in which the amino terminus of the protein subunit was assumed to be α-helical and positioned inside the needle, our model reveals an extended amino-terminal domain that is positioned on the surface of the needle, while the highly conserved carboxy terminus points towards the lumen.