Leukotrienes B 4 , C 4 and D 4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Leukotrienes in psoriatic skin lesions are potent mediators of inflammation. We have studied the capacity of leukotrienes to stimulate the DNA synthesis of cultured human epidermal keratinocytes. At concentrations ranging from 10 −12 to 10 −8 M, LTB 4 produced a 100% increase of DNA synthesis determined both as the incorporation of [ 3 H] thymidine and as the labelling index. In comparison, LTB 4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S, 12S-LTB 4 and 5S, 12S-all-trans-LTB 4 did not change the DNA synthesis of keratinocytes, but the effect of LTB 4 was abolished in the presence of 5S, 12S-all- trans HLTB 4 . Being less potent than LTB 4 the peptidoleukotrienes (LTC 4 , LTD 4 ) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB 4 , was antagonized by EPL 55712. These results show that leukotrienes B 4 , C 4 and D 4 exert potent and stereospecific mitogenic effects on cultured human keratinocytes. The presence of these arachidonic acid metabolites in psoriatic skin lesions may be pertinent to both inflammation and aberrant epidermal growth in psoriasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74813/1/j.1365-2133.1985.tb02043.x.pd

Giving an Account of One’s Pain in the Anthropological Interview

In this paper, I analyze the illness stories narrated by a mother and her 13-year-old son as part of an ethnographic study of child chronic pain sufferers and their families. In examining some of the moral, relational and communicative challenges of giving an account of one’s pain, I focus on what is left out of some accounts of illness and suffering and explore some possible reasons for these elisions. Drawing on recent work by Judith Butler (Giving an Account of Oneself, 2005), I investigate how the pragmatic context of interviews can introduce a form of symbolic violence to narrative accounts. Specifically, I use the term “genre of complaint” to highlight how anthropological research interviews in biomedical settings invoke certain typified forms of suffering that call for the rectification of perceived injustices. Interview narratives articulated in the genre of complaint privilege specific types of pain and suffering and cast others into the background. Giving an account of one’s pain is thus a strategic and selective process, creating interruptions and silences as much as moments of clarity. Therefore, I argue that medical anthropologists ought to attend more closely to the institutional structures and relations that shape the production of illness narratives in interview encounters

Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances

We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif–function associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations

Engineering and design computational protein design - Editorial overview

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Long-Range Effects on Calcium Binding and Conformational Change in the N-Domain of Calmodulin†

Proteins within the EF-hand protein family exhibit different conformational responses to Ca2+ binding. Calmodulin and other members of the EF-hand protein family undergo major changes in conformation upon binding Ca2+. However, some EF-hand proteins, such as calbindin D9k (Clb), bind Ca2+ without a significant change in conformation. Here, we investigate the effects of replacement of a leucine at position 39 of the N-terminal domain of calmodulin (N-Cam) with a phenylalanine derived from Clb. This variant is studied alone and in the context of other mutations that affect the conformational properties of N-Cam. Strikingly, the introduction of Phe39, which is distant from the calcium binding sites, leads to a significant enhancement of Ca2+ binding affinity, even in the context of other mutations which trap the protein in the closed form. The results yield novel insights into the evolution of EF-hand proteins as calcium sensors versus calcium buffers