The role of ras and other low molecular weight guanine nucleotide (GTP)-binding proteins during hematopoietic cell differentiation

Recent progress in the understanding of signal transduction and gene regulation in hematopoietic cells has shown that many intracellular signalling pathways are modulated by low molecular weight guanine nucleotide (GTP)-binding proteins (LMWGs). LMWGs act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In hematopoietic cells, LMWGs have been shown to participate in essential functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signalling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, intracellular vesicle transport and secretion. In human leukemias, myelodysplastic syndromes and myeloproliferative disorders, Ras activation occurs by point mutations, overexpression or by alteration of NF-1 Ras-GTPase activating protein (GAP). These are postinitiation events in leukemia but may modulate growth-factor-dependent and independent leukemic growth. Two animal models of mutated N-ras expression resulting in myelodysplastic and myeloproliferative features are discussed. The role of Ras in organ development is discussed in the context of transgenic knockout mice. More LMWG functions will certainly be identified as we gain a better understanding of regulatory pathways modulating myeloid signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.     

Function and use of technical artefacts: social conditions of function ascription

It is argued that we cannot understand the notion of proper functions of artefacts independently of social notions. Functions of artefacts are related to social facts via the use of artefacts. The arguments in this article can be used to improve existing function theories that look to the causal history of artefacts to determine the function. A view that takes the intentions of designers into account to determine the proper function is both natural and often correct, but it is shown that there are exceptions to this. Taking a social constitutive element into account may amend these backwards looking theories. An improved theory may either have a disjunctive form—either the history or collective intentions determine the proper function—or, as is suggested in the article, be in the form of an encompassing account that views the designers’ intentions as social, in so far as they are accepted by the users. Designers have authority, which is a social fact. The views argued for here are applied to two existing theories of artefact functions, a causal historic approach and an action theoretic approach.