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Concordant U-Pb dates of magmatic monazites in the dominant coarse-grained biotite (+muscovite) granites of the late Variscan Cornubian batholith demonstrate that the emplacement of the six main plutons~was diachronous, ranging from 293.1 + 1.3 Ma (Carnmenellis) to 274.5 ± 1.4 Ma (Land's End, southern lobe). 4°Ar-a9Ar age spectra for magmatic muscovites confirm that cooling to about 320 °C at the present level of exposure was accomplished within 4 to 5 Ma in each intrusion. Moreover, age spectra for hydrothermal muscovites show that development of the major Sn (-Cu) lodes of the South Crofty mine commenced before 286 Ma, only 2 to 3 Ma after cooling of the hosting Carn Brea granite, a satellite of the Carnmenellis pluton. The older plutons had therefore approached ambient temperatures, and had even experienced intense hydrothermal activity, before emplacement of the youngest.The richly-mineralized Cornubian batholith, exposed as a broadly linear array of plutons extending for over 220 km from the Isles of Scilly, Cornwall, to Dartmoor, Devon (Fig.

Teneurin C-terminal associated peptide (TCAP) is an ancient paracrine signalling agent that evolved via lateral gene transfer from prokaryotes into an early metazoan ancestor. Although it bears structural similarity to corticotrophin-releasing hormone (CRH), it inhibits the in vivo actions of CRH. The TCAPs are highly expressed in neurones, where they induce rapid cytoskeletal rearrangement and are neuroprotective. Because these processes are highly energy-dependent, this suggests that TCAP has the potential to regulate glucose uptake because glucose is the primary energy substrate in brain, and neurones require a steady supply to meet the high metabolic demands of neuronal communication. Therefore, the objective of the present study was to assess the effect of TCAP-mediated glucose uptake in the brain and in neuronal cell models. TCAP-mediated F-deoxyglucose (FDG) uptake into brain tissue was assessed in male wild-type Wistar rats by functional positron emission tomography. TCAP-1 increased FDG uptake by over 40% into cortical regions of the brain, demonstrating that TCAP-1 can significantly enhance glucose supply. Importantly, a single nanomolar injection of TCAP-1 increased brain glucose after 3 days and decreased blood glucose after 1 week. This is corroborated by a decreased serum concentration of insulin and an increased serum concentration of glucagon. In immortalised hypothalamic neurones, TCAP-1 increased ATP production and enhanced glucose uptake by increasing glucose transporter recruitment to the plasma membrane likely via AKT and mitogen-activated protein kinase/ERK phosphorylation events. Taken together, these data demonstrate that TCAP-1 increases glucose metabolism in neurones, and may represent a peptide signalling agent that regulated glucose uptake before insulin and related peptides.

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