A hypersensitive site in hsp70 chromatin requires adjacent not internal DNA sequence

Nuclease-hypersensitive sites in chromatin exist at the 5' side of many eukaryotic genes. To gain some understanding of the molecular basis of these hypersensitive sites, we have now examined the pair of sites upstream of the Drosophila hsp70 gene in a series of plasmids that contain deletions in the hypersensitive region and have been transformed into yeast cells. Hypersensitive sites 5' to a Drosophila hsp70 gene are preserved when this gene is introduced into yeast by transformation. We find that a yeast strain containing a plasmid in which the deletion extends through the first hypersensitive site still displays the normal pair of hypersensitive sites, so DNA sequences over which the first hypersensitive site is centred are not required for hypersensitivity at this position and the site can form over a foreign DNA sequence juxtaposed against this deletion end point. Deletions progressing further into the region bracketed by the pair of 5' hypersensitive sites eliminate the first hypersensitive site and alter the downstream site. We propose that the hypersensitive sites are generated through the binding of a protein that renders flanking sequences more accessible to nucleases, perhaps by preventing normal chromatin packaging.     

Pressure acclimation of the eel and liver membrane composition

Homeoviscous adaptation of membrane fluidity is known to exist in fish living at great depths. Is this adaptation also present in fish living near the surface but experimentally acclimated to high pressure? The composition of mitochondria-rich fractions extracted from the livers of eels acclimated for 15 days at 101 ATA was determined. The results show that pressure induced a significant increase (+100%) of total phospholipids (PL) and cholesterol without a change in their ratio. The increase of PL content was accompanied by a decrease in phosphatidylcholine in favour of phosphatidyl ethanolamine which, due to its preference for the H₁₁ form, is able to compensate for the loss in fluidity induced by pressure.     

Minds, machines and economic agents: Cambridge receptions of Boole and Babbage

In the 1860s and 1870s the logic of Boole and the calculating machines of Babbage were key resources in W. S. Jevons’s attempt to construct a mechanical model of the mind, and both therefore played an important role in Jevons’s attempted revolution in economic theory. In this same period both Boole and Babbage were studied within the Cambridge Moral Sciences Tripos, but the Cambridge reading of Boole and Babbage was much more circumspect. Implicitly following the division of the moral sciences into material and ‘real’ as established by the Rev. Grote, John Venn treated Boole’s logic as a purely formal science, while Alfred Marshall based his psychological model of the mechanical part of the human mind upon Babbage’s two-level machine. From the different perspectives of logic and psychology, Venn and Marshall did not simply incorporate their readings of Boole and Babbage, but also attempted to establish the limits to any mechanical explanation of the mind. This comparison of the attitudes to mental science of Jevons and Marshall provides a foundation from which the differing conceptions of economic theory of the two men can be established.     

A family study of endophenotypes for psychosis within an early intervention programme in Hong Kong: Rationale and preliminary findings

The study of endophenotypes may be a viable strategy to tackle the genetic complexity and phenotypic heterogeneity of psychosis, but this research direction is relatively under-developed in China as compared to Western countries. We have recently initiated one of the first family studies of endophenotypes for psychosis in China. Patients entering an established early psychosis intervention service are recruited into this research project for phenotyping, endophenotyping and genotyping. At the endophenotypic...     

The Remote Academic

Systemic Practice and Action Research -     

PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR

Loss of the promyelocytic leukaemia (PML) tumour suppressor has been observed in several human cancers. The tumour-suppressive function of PML has been attributed to its ability to induce growth arrest, cellular senescence and apoptosis. Here we identify PML as a critical inhibitor of neoangiogenesis (the formation of new blood vessels) in vivo, in both ischaemic and neoplastic conditions, through the control of protein translation. We demonstrate that in hypoxic conditions PML acts as a negative regulator of the synthesis rate of hypoxia-inducible factor 1alpha (HIF-1alpha) by repressing mammalian target of rapamycin (mTOR). PML physically interacts with mTOR and negatively regulates its association with the small GTPase Rheb by favouring mTOR nuclear accumulation. Notably, Pml-/- cells and tumours display higher sensitivity both in vitro and in vivo to growth inhibition by rapamycin, and lack of PML inversely correlates with phosphorylation of ribosomal protein S6 and tumour angiogenesis in mouse and human tumours. Thus, our findings identify PML as a novel suppressor of mTOR and neoangiogenesis.     

Evolutionary genetics: evolution of mate choice in the wild

Qvarnstr?m et al. test whether the preference of female collared flycatchers (Ficedula albicollis) for males with large forehead patches could have evolved as a by-product of selection acting on male patch size. They find that the crucial genetic correlation between female choice and male patch size is not significant, and conclude that preference for large patches must have been shaped directly by selection. However, their use of the patch size of a female's social partner as a measure of choice is incomplete, and will result in low estimates of the potential for direct selection to shape female preference. Their study is therefore unable to resolve the question of how female preference for large forehead patches has evolved.     

Plant genetics: increased outcrossing in hothead mutants

Arising from: S. J. Lolle, J. L. Victor, J. M. Young & R. E. Pruitt 434, 505-509 (2005); Lolle et al. reply. Lolle et al. report that loss-of-function alleles of the HOTHEAD (HTH) gene in Arabidopsis thaliana are genetically unstable, giving rise to wild-type revertants. On the basis of the reversion of many other genetic markers in hth plants, they suggested a model in which a cache of extragenomic information could cause genes to revert to the genotype of previous generations. In our attempts to reproduce this phenomenon, we discovered that hth mutants show a marked tendency to outcross (unlike wild-type A. thaliana, which is almost exclusively self-fertilizing). Moreover, when hth plants are grown in isolation, their genetic inheritance is completely stable. These results may provide an alternative explanation for the genome wide non-mendelian inheritance reported by Lolle et al.     

Insights into the dynamics of mantle plumes from uranium-series geochemistry

The long-standing paradigm that hotspot volcanoes such as Hawaii or Iceland represent the surface expression of mantle plumes--hot, buoyant upwelling regions beneath the Earth's lithosphere--has recently been the focus of controversy. Whether mantle plumes exist or not is pivotal for our understanding of the thermal, dynamic and compositional evolution of the Earth's mantle. Here we show that uranium-series disequilibria measured in hotspot lavas indicate that hotspots are indeed associated with hot and buoyant upwellings and that weaker (low buoyancy flux) hotspots such as Iceland and the Azores are characterized by lower excess temperatures than stronger hotspots such as Hawaii. This direct link between buoyancy flux and mantle temperature is evidence for the existence of mantle plumes.