The retinoic acid receptor (RARot) is expressed in virtually all hematopoietic lineages, but the role of this transcription factor in regulating the growth and differentiation of hematopoietic progenitors is unknown. We have constructed a mutant RARer that both exhibits dominant-negative activity against the normal RARer in transient expression assays in mouse fibroblasts and inhibits retinoic acid-induced neutrophilic differentiation of the HL-60 human promyelocytic leukemia cell line. When this dominant-negative RARa construct is introduced into the multipotent intedeukin-3-dependent FDCP mix A4 murine hematopoietic cell line, there is a rapid switch from spontaneous neutrophil/monocyte differentiation to basophil/mast cell development. Thus, in this multipotent hemopoietic cell line the normal RARa transcription factor and/or related molecules appear to promote the differentiation of neutrophils and monocytes but suppress the development of basophils/mast cells.

T-cell hybridomas, thymocytes, and T cells can be induced to undergo apoptotic cell death by activation through the T-cell receptor. This process requires macromolecular synthesis and thus gene expression, and it has been shown to be influenced by factors regulating transcription. Recently, activation, T-cell hybridomas rapidly express the Fas/CD95 receptor and its ligand, Fas ligand (FasL), which interact to transduce the death signal in the activated cell. Retinoids, the active metabolites of vitamin A, modulate expression of specific target genes by binding to two classes of intracellular receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). They are potent modulators of apoptosis in a number of experimental models, and they have been shown to inhibit activation-induced apoptosis in T-cell hybridomas and thymocytes. Particularly effective is the prototypic pan-agonist 9-cis retinoic acid (9-cis RA), which has high affinity for both RARs and RXRs. We report here that 9-cis RA inhibits T-cell receptor-mediated apoptosis in T-cell hybridomas by blocking the expression of Fas ligand following activation. This inhibition appears to be at the level of FasL mRNA, with the subsequent failure to express cell surface FasL. RAR-selective (TTNPB) or RXR-selective (LG100268) ligands alone were considerably less potent than RAR-RXR pan-agonists. However, the addition of both RAR- and RXR-selective ligands was as effective as the addition of 9-cis RA alone. The demonstrates that the inhibitory effect requires the ligand-mediated activation of both retinoid receptor signaling pathways.

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Pedagogy and the`cultural turn' in geography Clive Barnett's (1998) and Noel Castree's (1999) recent editorials in Society and Space take the debate over geography's`cultural turn' into new territory: the classroom. Moving the discussion from the high ground of theory into the lowly realm of teaching, Barnett and Castree find at the heart of cultural studies approaches in geography a pedagogy that is``part of efforts to manage social life and render individuals and groups self-regulating in accordance with the norms of neoliberal economics and social conservatism'' (Barnett, 1998, page 634). Although Castree warns against concluding that the cultural turn is``no more than academic neoconservatism in a particularly cunning guise'' (1999, page 260), he asks whether the``new modalities of knowledge'' introduced by the cultural turn into geography are``being merely coopted into a wellestablished pedagogic model in which teachers`instruct' students in what, for the state and business, are the desirable arts of clear thinking, problem solving, clear speaking, coherent writing, and other CTSs [core transferable skills]?'' (page 260). While Barnett and Castree rightly raise the question of pedagogy in attempting to come to terms with`m ore mundane estimations of the political purchase of academic work'' (Barnett, 1998, page 634), they too hastily equate the cultural turn with conservative teaching practices, thus ignoring the increasing engagement of left geographers with theories of critical pedagogy' that have come out of the cultural studies tradition. I want to suggest that a better understanding of the political relevance of academic work in the wake of the`new modalities of knowledge' introduced by cultural studies ö one that takes seriously Barnett's and Castree's calls for institutionally situating geography's cultural turn in the academyöwould engage with the growing body of work in`critical pedagogy' that seeks to understand the pedagogic implications of the cultural turn. By so doing, left geographers would be in a better position to realize the radical possibilities for classroom practice opened up by`new modalities of knowledge', rather than seeing them squandered or co-opted through traditional pedagogic approaches. Instead of dismissing cultural studies approaches on unsupportable assumptions that they necessarily implicate a reactionary pedagogy, as Barnett and Castree seem to do, I would point out that pedagogic theory coming out of the cultural turn, under the rubric of`critical pedagogy', has important lessons for left geographers who seek to avoid the very scenario of cooptation that Castree envisions. In other words, the`new modalities of knowledge' introduced by the cultural turn are not to blame for pedagogies that play into neoliberal hands, just the opposite: when taken to implicate knowledge produced inside the classroom, those new modalities imply a new pedagogy that holds radical possibilities for promoting more inclusive, emancipatory, and democratic practices, inside and outside the classroo...

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