Is it possible to find an econometric law that works well in explanation and prediction? The case of Australian money demand

Pratt and Schlaifer's (1984, 1988) research employed in efforts to produce laws in economics are considered and their use in predicting future data is described. Data for Australia are used to illustrate the approaches.     

Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype

Understanding the molecular underpinnings of cancer is of critical importance to the development of targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multifaceted cellular phenotype have therefore only been identified after signalling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signalling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state of murine and human colon cells. Notably, 14 out of 24 'cooperation response genes' were found to contribute to tumour formation in gene perturbation experiments. In contrast, only 1 in 14 perturbations of the genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy, and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain- and loss-of-function mutations.     

North Pacific seasonality and the glaciation of North America 2.7 million years ago

In the context of gradual Cenozoic cooling, the timing of the onset of significant Northern Hemisphere glaciation 2.7 million years ago is consistent with Milankovitch's orbital theory, which posited that ice sheets grow when polar summertime insolation and temperature are low. However, the role of moisture supply in the initiation of large Northern Hemisphere ice sheets has remained unclear. The subarctic Pacific Ocean represents a significant source of water vapour to boreal North America, but it has been largely overlooked in efforts to explain Northern Hemisphere glaciation. Here we present alkenone unsaturation ratios and diatom oxygen isotope ratios from a sediment core in the western subarctic Pacific Ocean, indicating that 2.7 million years ago late-summer sea surface temperatures in this ocean region rose in response to an increase in stratification. At the same time, winter sea surface temperatures cooled, winter floating ice became more abundant and global climate descended into glacial conditions. We suggest that the observed summer warming extended into the autumn, providing water vapour to northern North America, where it precipitated and accumulated as snow, and thus allowed the initiation of Northern Hemisphere glaciation.     

Distinguishing random environmental fluctuations from ecological catastrophes for the North Pacific Ocean

The prospect of rapid dynamic changes in the environment is a pressing concern that has profound management and public policy implications. Worries over sudden climate change and irreversible changes in ecosystems are rooted in the potential that nonlinear systems have for complex and 'pathological' behaviours. Nonlinear behaviours have been shown in model systems and in some natural systems, but their occurrence in large-scale marine environments remains controversial. Here we show that time series observations of key physical variables for the North Pacific Ocean that seem to show these behaviours are not deterministically nonlinear, and are best described as linear stochastic. In contrast, we find that time series for biological variables having similar properties exhibit a low-dimensional nonlinear signature. To our knowledge, this is the first direct test for nonlinearity in large-scale physical and biological data for the marine environment. These results address a continuing debate over the origin of rapid shifts in certain key marine observations as coming from essentially stochastic processes or from dominant nonlinear mechanisms. Our measurements suggest that large-scale marine ecosystems are dynamically nonlinear, and as such have the capacity for dramatic change in response to stochastic fluctuations in basin-scale physical states.     

Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis

Iron is required to produce haem and iron-sulphur (Fe-S) clusters, processes thought to occur independently. Here we show that the hypochromic anaemia in shiraz (sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5), a gene required in yeast for Fe-S cluster assembly. We found that grx5 was expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of grx5 yeast Fe-S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes. We found that loss of Fe-S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 5' iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2 including the iron response element did not. Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings uncover a connection between haem biosynthesis and Fe-S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe-S cluster assembly.