Out of the meridian: John Bird's equatorial sector and the new technology of astronomical measurement

When Thomas Hornsby commissioned John Bird to build a set of five major astronomical instruments for the new Radcliffe Observatory, Oxford, the order included an Equatorial Sector. This was an instrument of experimental design, intended to measure angles out of the meridian. Although in itself a transitional instrument, the Equatorial Sector's capacity for extra-meridional measurement, especially for the observation of comets, encouraged craftsmen to develop the design first into the Equatorial Circle, and then into the large equatorially mounted refracting telescope used in conjunction with micrometers. Although other Equatorial Sectors were made, Bird's instrument for Oxford is the only one that survives intact. The present study examines this unique artefact within the context of changing astronomical demands between the 1770s and the 1820s.     

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.     

Insect behavior at the leaf surface and learning as aspects of host plant selection

Summary Direct observations on the feeding behavior of insect herbivores are uncommon, but important. The important aspects of host-plant selection by phytophagous insects that have been revealed by such observations are the role of chemicals in the leaf surface, and learning. There are few detailed reports of behavior at the leaf surface, but these indicate that many, if not all, insects exhibit behavior pattenrs that can be interpreted as an examination of the quality of the surface and acceptance or rejection may follow without further testing. A number of experiments show that chemicals from the leaf surface commonly contribute to the acceptability or otherwise of a plant and in most cases so far the active chemicals are of widespread occurrence, not having a specific association with the host plant. Some experiments show that the association between surface chemicals and plant palatability is learned, but in other cases there is evidence of an innate response. Habituation to deterrent chemicals has been demonstrated in the laboratory, but not in the field. Food aversion learning also occurs and may be important in dietary switching by polyphagous insects.