The DUB/USP17 deubiquitinating enzymes, a multigene family within a tandemly repeated sequence

Here we report the identification of 10 human, 1 murine, and 2 rat ORFs, all of which represent additional members of the DUB/USP17 family of deubiquitinating enzymes. In addition, we demonstrate that this family constitutes part of a tandemly repeated sequence conserved throughout humans, mice, and rats. Furthermore, upon examination of the known family members we have found that the multiple genes observed, in contrast to other gene families, have arisen due to the independent expansion of an ancestral sequence within each species. This premise is further strengthened by the observation that the murine and rat genes span two exons while their human counterparts have one. These observations, in conjunction with previous work demonstrating that the DUB/USP17's are cytokine inducible and that they regulate both cell growth and survival, suggest that the DUB/USP17's are a large highly conserved family of genes that may play an important role in controlling cell fate.

James Anderson's Political Economy--His Influence on Smith and Malthus

James Anderson's powerful critique of Adam Smith's position on the corn export bounty was published in 1777. It focuse d on Smith's proposition that the bounty could not lead to increased corn production because it could not increase corn's real price. Smit h's response to the critique is traced in later editions of Wealth of Nations. While Anderson's critique of Smith influenced Thomas Malthu s's writings from 1803 onwards, his theory of differential rent did n ot influence Malthus at this stage. An examination of the evolution o f Malthus's ideas on rent between 1803 and 1815, however, indicates t hat Malthus knew and used Anderson's work on rent.

The DUB/USP17 deubiquitinating enzymes: A gene family within a tandemly repeated sequence, is also embedded within the copy number variable Beta-defensin cluste

Background: The DUB/USP17 subfamily of deubiquitinating enzymes were originally identified as immediate early genes induced in response to cytokine stimulation in mice (DUB-1, DUB-1A, DUB-2, DUB-2A). Subsequently we have identified a number of human family members and shown that one of these (DUB-3) is also cytokine inducible. We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the 'CAAX' box protease RCE1.

Results: Here we demonstrate that the human DUB/USP17 family members are found on both chromosome 4p16.1, within a block of tandem repeats, and on chromosome 8p23.1, embedded within the copy number variable betadefensin cluster. In addition, we show that the multiple genes observed in humans and other distantly related mammals have arisen due to the independent expansion of an ancestral sequence within each species. However, it is also apparent when sequences from humans and the more closely related chimpanzee are compared, that duplication events have taken place prior to these species separating.

Conclusions: The observation that the DUB/USP17 genes, which can influence cell growth and survival, have evolved from an unstable ancestral sequence which has undergone multiple and varied duplications in the species examined marks this as a unique family. In addition, their presence within the beta-defensin repeat raises the question whether they may contribute to the influence of this repeat on immune related conditions.

James Croll, metaphysical geologist

James Croll (1821–90) occupies a prominent position in the history of physical geology, and his pioneering work on the causes of long-term climate change has been widely discussed. During his life he benefited from the patronage of leading men of science; his participation in scientific debates was widely acknowledged, not least through his election as a Fellow of the Royal Society in 1876. For all that, the intellectual contribution that Croll himself considered to be of most significance—his articles and two books on metaphysics—has attracted very little attention. In addressing this neglect, it is argued here that Croll's interest in metaphysics, grounded in his commitment to a Calvinist form of Christianity, was central to his life and thought. Examining together Croll's geophysical and metaphysical writings offers a different and fruitful way of understanding his scientific career and points to the wider significance of metaphysics in late-Victorian scientific culture.