Uptake of bacterial H3-DNA into fish embryos

Zusammenfassung H³-DNA vonSalmonella typhimurium wurde in den Dotter vonPlatypoecilus maculatus-Embryonen injiziert und ihr Verbleib untersucht. Nach 45 Stunden findet man 45% der injizierten H³-DNA-Radioaktivität in der säurelöslichen Fraktion des Dotters. Von diesem Zeitpunkt an nimmt die Radioaktivität in der säureunlöslichen Fraktion der Embryonen ständig zu, bis nach 140 Stunden ein Wert von 50% erreicht ist. Der hohe Anteil an radioaktivem säurenunlöslichem Material im Dotter, der 140 Stunden nach der Injektion noch ca. 35% beträgt, lässt vermuten, dass hier noch hochmolekulare Bakterien-DNA vorhanden ist. Somit erscheint die Möglichkeit einer Aufnahme dieser hochmolekularen DNA in die Embryozellen nicht ausgeschlossen.     

Regulation of Lethal giant larvae by Dishevelled

The establishment of polarity in many cell types depends on Lgl, the tumour suppressor product of lethal giant larvae, which is involved in basolateral protein targeting. The conserved complex of Par3, Par6 and atypical protein kinase C phosphorylates and inactivates Lgl at the apical surface; however, the signalling mechanisms that coordinate cell polarization in development are not well defined. Here we show that a vertebrate homologue of Lgl associates with Dishevelled, an essential mediator of Wnt signalling, and that Dishevelled regulates the localization of Lgl in Xenopus ectoderm and Drosophila follicular epithelium. We show that both Lgl and Dsh are required for normal apical-basal polarity of Xenopus ectodermal cells. In addition, we show that the Wnt receptor Frizzled 8, but not Frizzled 7, causes Lgl to dissociate from the cortex with the concomitant loss of its activity in vivo. These findings suggest a molecular basis for the regulation of cell polarity by Frizzled and Dishevelled.     

Chicken gizzard,a myoglobin containing smooth muscle

Zusammenfassung In der glatten Muskulatur des Hühnermuskelmagens konnte ein wasserlösliches Hämoprotein nachgewiesen werden, das sich chromatographisch und spektrophotometrisch wie Myoglobin verhält.

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This work is supported by a grant from the Deutsche Forschungsgemeinschaft.     

Quantum states of neutrons in the Earth's gravitational field.

The discrete quantum properties of matter are manifest in a variety of phenomena. Any particle that is trapped in a sufficiently deep and wide potential well is settled in quantum bound states. For example, the existence of quantum states of electrons in an electromagnetic field is responsible for the structure of atoms, and quantum states of nucleons in a strong nuclear field give rise to the structure of atomic nuclei. In an analogous way, the gravitational field should lead to the formation of quantum states. But the gravitational force is extremely weak compared to the electromagnetic and nuclear force, so the observation of quantum states of matter in a gravitational field is extremely challenging. Because of their charge neutrality and long lifetime, neutrons are promising candidates with which to observe such an effect. Here we report experimental evidence for gravitational quantum bound states of neutrons. The particles are allowed to fall towards a horizontal mirror which, together with the Earth's gravitational field, provides the necessary confining potential well. Under such conditions, the falling neutrons do not move continuously along the vertical direction, but rather jump from one height to another, as predicted by quantum theory.     

Site-independent expression of the chicken beta A-globin gene in transgenic mice

The level of expression of exogenous genes carried by transgenic mice typically varies from mouse to mouse and can be quite low. This behaviour is attributed to the influence of the mouse chromatin near the site of transgene integration. This 'position effect' has been seen in transgenic mice carrying the human beta-globin gene. It was however, abolished when DNase I hypersensitive sites (normally found 65 to 44 kilobases (kb) upstream) were linked to the human beta-globin transgene. Thus, the upstream DNA (previously named a dominant control or locus activation region, now denoted a locus control region) conferred the ability to express human beta-globin at high levels dependent on copy number on every mouse carrying the construct. We report here an investigation of chicken beta A-globin gene expression in transgenic mice. A 4.5-kb fragment carrying the beta A-globin gene and its downstream enhancer, without any far upstream elements, is sufficient to ensure that every transgenic mouse expresses chicken globin messenger RNA at levels proportional to the transgene copy number. Thus the chicken DNA elements that allow position-independent expression can function in mice. In marked contrast to the human beta cluster, these elements are no farther than 2 kb from the gene. The location of the elements within the cluster demonstrates that position independence can be mediated by DNA that does not define a gene cluster boundary.     

Configuration of the magnetic field and reconstruction of Pangaea in the Permian period

The virtual geomagnetic poles of Laurasia and Gondwanaland in the Carboniferous and Permian periods diverge significantly when these continents are reassembled according to the fit calculated by Bullard et al. Two interpretations have been offered: Briden et al. explain these divergences by a magnetic field configuration very different from that of a geocentric axial dipole; Irving (and private communication), Van der Voo and French(4) suggest a different reconstruction and it is shown here that these two interpretations are not incompatible and that the first may help the second.     

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.     

Shifting ontologies, changing classifications: plant materials from 1700 to 1830

This paper studies European chemists’ shifting ontologies of materials by comparing the ways in which they classified materials. The focus is on plant materials, their different identities, and the changing ways chemists sorted out and ordered plant materials in the eighteenth and early nineteenth centuries. The main goals of the paper are to follow the development of plant materials from ordinary, everyday materials and commodities in the early eighteenth century to purified carbon compounds and organic substances familiar only to experts in the 1830s, and to reconstruct chemists’ ways of classifying these objects in different practical and intellectual contexts.The study of changes in European chemists’ ways of classifying plant materials over more than a century brings to the foreground a trajectory of ontological shifts that is ‘punctuated’ in the 1750s, the 1790s, and the 1830s. Early eighteenth-century plant materials, which were commodities of the apothecary trade and other arts and crafts, were elevated epistemically as compound components or ‘proximate principles’ of plants in the 1750s, reduced to organic compounds in the 1790s, and replaced by carbon compounds in the 1830s. The last, third transformation of the epistemic constitution of materials and the mode of their classification was accompanied by a deep transformation of the material culture of plant chemistry. After the late 1830s, many of the eighteenth-century vegetable commodities disappeared from chemists’ agenda or were split into different substances individuated and identified in new ways. Coal tar products, and new organic artefacts containing chlorine or bromine, entered the chemical laboratory in the 1820s and became fused with the purified rest of the previous plant and animal substances. The material objects of the new culture of organic chemistry became detached from the materials applied in the extant arts and crafts. It was only in the late 1850s, with the rise of the synthetic dye industry, that a great number of these laboratory substances became involved in industrial production.