Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Placentation defects are highly prevalent in embryonic lethal mouse mutants.

Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation

A Novel Mouse c-fos Intronic Promoter That Responds to CREB and AP-1 Is Developmentally Regulated In Vivo

BACKGROUND: The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene

The Development of Risk Politics in the UK: Thatcher’s ‘Remarkable’ but Forgotten ‘Don’t Die of Ignorance’ AIDS Campaign

Thirty years on from the dramatic and unprecedented AIDS advertising campaign organised by the Conservative administration of the late 1980s, this article reassesses the experience drawing upon subsequent memoirs and interviews. It does so in the context of an emergence of risk politics in the UK in the 1980s, situated within an historical perspective on the development of risk within modernity. Emphasis is placed upon the forgotten pragmatic, amoral core of the campaign which challenged the illiberal climate of the times, and how it was possible for an administration defined by high moralism to challenge it. The range of pressures that led to the campaign are outlined, including a conscious attempt to limit stigmatisation amidst the mood of wartime emergency that prevailed in late 1986/early 1987. Its emergency character meant little direct legacy of harm reduction has endured, but the article argues for a wider significance of the campaign as a key moment in the emergence of risk politics in the UK and beyond

A general refutation of Okishio’s theorem and a proof of the falling rate of profit

This is the first published general refutation of the Okishio theorem. An earlier refutation based on a specific example was published by Kliman and McGlone in 1988. Okishio’s theorem, published in 1961, asserts that if real wages stay constant, the rate of profit necessarily rises in consequence of any cost-reducing technical change. It proves this within a simultaneous equation (general equlibrium) framework. This paper establishes that this proposition is false within a differential equation (temporal) approach. In such a framework the denominator of the rate of profit rises continuously, regardless of whether or not there is technical change, unless capitalist consumption exceeds profit, as occurs in a slump. Okishio himself asserts that his theorem is ‘contrary to Marx’s Gesetz des Tendentiellen Falls der Profitrate’ – contrary to Marx’s law of the tendency of the rate of profit to fall. This assertion is, within the literature, universally taken to be the substantive content of the ‘Okishio Theorem’. Thus, if Marx’s approach to value is in fact temporal, and not simultaneist, this assertion by Okishio is false, since it applies not to Marx’s own theory, but to the interpretation of that theory subsequently attributed to Marx by a specific school of thought represented principally by Bortkiewicz, Sweezy, Morishima, Seton, and Steedman. The subsequent accumulation of hermeneutic evidence strongly supports the thesis that Marx’s theory is temporalist and not simultaneist. Since the Okishio theorem makes the general assertion that the rate of profit must necessarily rise if there are cost-saving technical changes, and since Kliman and McGlone demonstrate a particular case in which cost-saving technical change leads to a fall in the profit rate, the Kliman-McGlone paper is the first published refutation of the Okishio theorem. The present paper is a generalisation of this refutation which establishes the precise conditions under which the profit rate rise or falls, and establishes the general result that the profit rate necessarily falls as a consequence of capitalist accumulation with a constant real wage, until and unless accumulation ceases in value terms. Consequently the mathematical findings set out in this paper, refute the Okishio Theorem