Isolation of fatty acids covalently bound to the gastric mucus glycoprotein of normal and cystic fibrosis patients

Covalently bound fatty acids were found in strictly purified and delipidated gastric mucus glycoprotein of normal and cystic fibrosis individuals. The susceptibility of this linkage to methanolic KOH and hydroxylamine treatment indicated the ester bond between fatty acids and glycoprotein. On the average, 2.9 nmol fatty acid/mg glycoprotein were found in normal samples, and 12.2 nmol/mg glycoprotein in samples derived from cystic fibrosis. In normal gastric mucus glycoprotein the covalently linked fatty acids consisted of hexadecanoate (47.0%), octadecanoate (22.0%), tetracosanoate (5.9%), octadecenoate (14.5%) and tetracosenoate (6.0%). In cystic fibrosis mucus glycoprotein the covalently bound fatty acids were comprised mainly of hexadecanoate (36.5%), octadecanoate (48.7%) and octadecenoate (8.6%). These data indicate that cystic fibrosis gastric mucus glycoprotein is highly acylated and perhaps this is the major defect of glycoproteins in this disease.     

Regulation of steroid sulphatase expression and activity in breast cancer

Steroid sulphatase (STS) catalyzes the conversion of oestrone sulphate (E1S) to oestrone (E1) and its action in breast tumours makes a major contribution to in situ oestrogen production in this tissue. Although expression of STS mRNA and STS activity are increased in malignant breast tissues compared with that in non-malignant tissues, little is known about the regulation of its expression or activity. In the present study we have used a RT-PCR technique to investigate the regulation of STS mRNA expression in cultured breast tissue fibroblasts and MCF-7 cells. STS mRNA expression was readily detectable in fibroblasts derived from breast tissue proximal to tumours, breast tumour tissue and reduction mammoplasty tissue. For two pre-menopausal subjects, STS mRNA expression was similar in proximal and tumour fibroblasts whereas for a third, post-menopausal subject, expression in breast tumour fibroblasts was 2.4-fold that in proximal fibroblasts. The cytokine tumour necrosis factor alpha (TNFalpha) or the STS inhibitor, 2-methoxyoestrone-3-O-sulphamate, had no effect on STS mRNA expression in fibroblasts. STS mRNA was detectable in MCF-7 cells but neither TNFalpha nor interleukin 6 (IL-6) affected its expression. Transient transfection of COS-1 and MCF-7 cells with a STS cDNA lacking STS 5' and 3' sequences increased activity 17-fold and 2-fold, respectively. TNFalpha plus IL-6 increased STS activity in mock transfected MCF-7 cells and further increased STS activity in transfected MCF-7 cells. This indicates that activation can occur independently of STS promoter and enhancer elements. In conjunction with the lack of regulation of STS mRNA it suggest that TNFalpha and IL-6 may increase STS activity via a post-translational modification of the enzyme or by increasing substrate availability.     

In situ adaptive response to climate and habitat quality variation: spatial and temporal variation in European badger (Meles meles) body weight

Variation in climatic and habitat conditions can affect populations through a variety of mechanisms, and these relationships can act at different temporal and spatial scales. Using post‐mortem badger body weight records from 15 878 individuals captured across the Republic of Ireland (7224 setts across ca. 15 000 km²; 2009–2012), we employed a hierarchical multilevel mixed model to evaluate the effects of climate (rainfall and temperature) and habitat quality (landscape suitability), while controlling for local abundance (unique badgers caught/sett/year). Body weight was affected strongly by temperature across a number of temporal scales (preceding month or season), with badgers being heavier if preceding temperatures (particularly during winter/spring) were warmer than the long‐term seasonal mean. There was less support for rainfall across different temporal scales, although badgers did exhibit heavier weights when greater rainfall occurred one or 2 months prior to capture. Badgers were also heavier in areas with higher landscape habitat quality, modulated by the number of individuals captured per sett, consistent with density‐dependent effects reducing weights. Overall, the mean badger body weight of culled individuals rose during the study period (2009–2012), more so for males than for females. With predicted increases in temperature, and rainfall, augmented by ongoing agricultural land conversion in this region, we project heavier individual badger body weights in the future. Increased body weight has been associated with higher fecundity, recruitment and survival rates in badgers, due to improved food availability and energetic budgets. We thus predict that climate change could increase the badger population across the Republic of Ireland. Nevertheless, we emphasize that, locally, populations could still be vulnerable to extreme weather variability coupled with detrimental agricultural practice, including population management.