"Je ne sais plus du tout qui je suis": The Phenomenology of Cancer in Anne Cuneo’s 'Une cuillerée de bleu'

Taking as its case study Anne Cuneo’s autopathography, Une cuillerée de bleu (1979), and supported by a phenomenological reading of the subjective realities of illness, including feelings of alienation, fragmentation, and passivity, this article considers how the experience of cancer affects the patient’s perception of her body, self, and world.

BRCA1 transcriptionally regulates genes associated with the basal breast cancer phenotype

Background Ten to twenty per cent of breast tumours exhibit a basallike genetic profile and these tumours carry a poor prognosis. Breast tumours which contain germline mutations for BRCA1 commonly exhibit a molecular profile similar to basal breast tumours. BRCA1 is a tumour suppressor gene which is mutated in up to 5–10% of breast cancer cases and is involved in multiple cellular processes including DNA damage control, cell cycle checkpoint control, apoptosis, ubiquitination and transcriptional regulation.

Methods Microarray-based profiling was carried out using the HCC1937EV and HCC1937BR breast cancer cell lines. Basal gene and protein expression levels were analysed by qRT-PCR and western blotting. ChIP analyses were performed and demonstrated that BRCA1 regulates basal gene expression through a transcriptional mechanism involving c-myc.

Results We have previously carried out microarray-based expression profiling to examine differences in gene expression when BRCA1 is reconstituted in BRCA1 mutated HCC1937 breast cancer cells. We observed that p-cadherin and the cytokeratin 5 and cytokeratin 17 genes, which are strongly correlated with the basal phenotype, are differentially expressed when BRCA1 is reconstituted. In addition, qRT-PCR and ChIP analysis of BRCA1 reconstituted cells show that BRCA1 represses the expression of these basal genes by a transcriptional mechanism. Furthermore, abrogation of endogenous BRCA1 protein in the T47D cell line using siRNA results in reexpression of these basal genes, suggesting that BRCA1 expression levels may be important in basal gene expression. We have also demonstrated that BRCA1 is physically associated with the promoter regions of basal genes through an association with c-myc. Consequently, we have confirmed that siRNA inhibition of c-myc in T47D cells results in re-expression of these genes.

Conclusions Our results suggest that BRCA1 is involved in the transcriptional regulation of genes associated with the basal phenotype and that BRCA1 controls basal gene expression through a transcriptional mechanism involving c-myc. Further work is now concentrating on defining the relationship between BRCA1 and basal gene expression and how this may affect clinical responses to breast cancer chemotherapy.

Climatic signals in the life histories of insects:the distribution and abundance of heather psyllids (Strophingia spp.) in the UK

1. The population density and age structure of two species of heather psyllid Strophingia ericae and Strophingia cinereae, feeding on Calluna vulgaris and Erica cinerea, respectively, were sampled using standardized methods at locations throughout Britain. Locations were chosen to represent the full latitudinal and altitudinal range of the host plants.

2. The paper explains how spatial variation in thermal environment, insect life-history characteristics and physiology, and plant distribution, interact to provide the mechanisms that determine the range and abundance of Strophingia spp.

3. Strophingia ericae and S. cinereae, despite the similarity in the spatial distribution patterns of their host plants within Britain, display strongly contrasting geographical ranges and corresponding life-history strategies. Strophingia ericae is found on its host plant throughout Britain but S. cinereae is restricted to low elevation sites south of the Mersey-Humber line and occupies only part of the latitudinal and altitudinal range of its host plant. There is no evidence to suggest that S. ericae has reached its potential altitudinal or latitudinal limit in the UK, even though its host plant appears to reach its altitudinal limit.

4. There was little difference in the ability of the two Strophingia spp. to survive shortterm exposure to temperatures as low as - 15 degrees C and low winter temperatures probably do not limit distribution in S. cinereae.

5. Population density of S. ericae was not related to altitude but showed a weak correlation with latitude. The spread of larval instars present at a site, measured as an index of instar homogeneity, was significantly correlated with a range of temperature related variables, of which May mean temperature and length of growing season above 3 degrees C (calculated using the Lennon and Turner climatic model) were the most significant. Factor analysis did not improve the level of correlation significantly above those obtained for single climatic variables. The data confirmed that S. ericae has a I year life cycle at the lowest elevations and a 2 year life cycle at the higher elevations. However, there was no evidence, as previously suggested, for an abrupt change from a one to a 2 year life cycle in S. ericae with increasing altitudes or latitudes.

6. By contrast with S. ericae, S. cinereae had an obligatory 1 year life cycle, its population decreased with altitude and the index of instar homogeneity showed little correlation with single temperature variables. Moreover, it occupied only part of the range of its host plant and its spatial distribution in the UK could be predicted with 96% accuracy using selected variables in discriminant analysis.

7. The life histories of the congeneric heather psyllids reflect adaptations that allow them to exploit host plants with different distributions in climatic and thereby geographical space. Strophingia ericae has the flexible life history that enables it to exploit C. vulgaris throughout its European boreal temperate range. Strophingia cinereae has a less flexible life history and is adapted for living on an oceanic temperate host. While the geographic ranges of the two Strophingia spp. overlap within the UK, the psyllids appear to respond differently to variation in their thermal environment.