A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis

Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.     

The genome sequence of the rice blast fungus Magnaporthe grisea

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.     

Project knowledge and its resituation in the design of research projects: Seymour Benzer's behavioral genetics, 1965-1974

The article introduces a framework for analyzing the knowledge that researchers draw upon when designing a research project by distinguishing four types of “project knowledge”: goal knowledge, which concerns possible outcomes, and three forms of implementation knowledge that concern the realization of the project: 1) methodological knowledge that specifies possible experimental and non-experimental strategies to achieve the chosen goal; 2) representational knowledge that suggests ways to represent data, hypotheses, or outcomes; and 3) organizational knowledge that helps to build or navigate the material and social structures that enable a project. In the design of research projects such knowledge will be transferred from other successful projects and these processes will be analyzed in terms of modes of resituating knowledge. The account is developed by analyzing a case from the history of biology. In a reciprocal manner, it enables a better understanding of the historical episode in question: around 1970, several researchers who had made successful careers in the emerging field of molecular biology, working with bacterial model systems, attempted to create a molecular biology of the physiological processes in multicellular organisms. One of them was Seymour Benzer, who designed a research project addressing the physiological processes underlying behavior in Drosophila.     

Professional forecasters' expectations,consistency, and international spillovers

This paper focuses on the expectation formation process of professional forecasters by relying on survey data on forecasts regarding gross domestic product growth, consumer price index inflation and 3-month interest rates for a broad set of countries. We examine the interrelation between macroeconomic forecasts and also the impact of uncertainty on forecasts by allowing for cross-country interdependencies and time variation in the coefficients. We find that professional forecasts are often in line with the Taylor rule and identify significant expectation spillovers from monetary policy in the USA.     

Modeling expert forecasting knowledge for incorporation into expert systems

The use of continuous multivariate models to represent experts' knowledge of relations among a set of variables is reviewed. Such knowledge models can be incorporated into expert systems, complementing contingent rules, especially when representing experts' knowledge of functional relations among entities in noisy domains. Past work has most commonly involved linear averaging models in static domains, although nonlinear models and dynamic domains are also possible. Detecting errors in continuous multivariate models requires a different approach from detecting errors in collections of if-then rules. Methods for eliciting expert knowledge include modeling judgments made in real or hypothetical situations and using expert's self-insight directly to assist in construction of the model. Procedures for managing each of these methods have been computerized and could be included as elicitation tools in expert system building environments.     

Book review editorial

Book review editorial     

Plurality revisited: Diversity management and triple loop learning

This paper suggests one way of managing plurality of theories and methodologies and ways of operationalising them. It suggests that the management of options needs to be linked to a process of reflexive consciousness. Reflexive consciousness operates by recognising that choices of theoretical and methodological commitment have to be made for the purposes of action. Awareness of the provisional and partial nature of choices is key to the management of options. Choice-making is marked by an awareness of the way in which the facility for judgement has been exercised. This includes considering how judgements may be accounted for in the light of alternative choices. Informed awareness means taking into accounttheoretical debates that may be brought to bear in facilitating an appreciation of methodologies and possible operationalisations of them. It also means taking into account matters ofcontemporary concern (specialist or popular) raised in the process of social debate. Our argument is detailed through an explication of what we call diversity management and triple loop learning.