John Campbell Brown OBE (1947–2019)

Obituary: John Campbell Brown OBE (1947–2019) - Astronomer Royal for Scotland and inspirational solar physicist, by Lyndsay Fletcher, Nicolas Labrosse and Alec MacKinnon

Stable Copper Isotope Incorporation Into Serum Caeruloplasmin in Human Health and Disease

Wilson's disease (WD) is a treatable inborn error of metabolism inherited in an autosomal recessive fashion (world-wide incidence 1:200,000). WD is a type of copper toxicity in which copper accumulation results from failure of normal liver transport into bile. The identification of affected individuals within a known family is important to prevent irreversible neurological and/or hepatic damage. The determination of serum and urine copper and of serum caeruloplasmin concentrations are usually but not always sufficient to make a diagnosis. A dynamic test to assay the incorporation of labelled Cu into serum caeruloplasmin may help diagnosis in equivocal cases. Tracer studies utilising the stable isotope 65Cu offers numerous practical advantages over the expensive and short-lived 64Cu (12hrs) and 67Cu (72hrs) radio-isotopes. A method for the determination of 65Cu in serum has been established using inductively coupled plasma mass spectrometry (ICP-MS). The pattern of 65Cu incorporation into the plasma protein pool of normals, heterozygotes for the WD gene and cases at timed intervals after oral dosage has now been documented. Can these measurements be improved by isolation from plasma of the main plasma Cu containing protein, caeruloplasmin? Fast protein liquid chromatography (FPLC; Pharmacia) was employed to separate the main 65Cu containing plasma protein caeruloplasmin. Albumin was separated by gel filtration and affinity chromatography to varying degrees, subsequent advances in affinity media for Cp gave superior results. Initially, four normal volunteers were given 65Cu orally, and had blood samples withdrawn at intervals up to one month. The fresh serum was prepared for ICP-MS analysis of total 65Cu and caeruloplasmin bound copper isolated. This thesis describes the development of methods to isolate the copper containing plasma protein caeruloplasmin labelled in vivo with 65Cu

Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children.

The development of executive function is linked to maturation of prefrontal cortex (PFC) in childhood. Childhood obesity has been associated with changes in brain structure, particularly in PFC, as well as deficits in executive functions. We aimed to determine whether differences in cortical structure mediate the relationship between executive function and childhood obesity. We analyzed MR-derived measures of cortical thickness for 2700 children between the ages of 9 and 11 years, recruited as part of the NIH Adolescent Brain and Cognitive Development (ABCD) study. We related our findings to measures of executive function and body mass index (BMI). In our analysis, increased BMI was associated with significantly reduced mean cortical thickness, as well as specific bilateral reduced cortical thickness in prefrontal cortical regions. This relationship remained after accounting for age, sex, race, parental education, household income, birth-weight, and in-scanner motion. Increased BMI was also associated with lower executive function. Reduced thickness in the rostral medial and superior frontal cortex, the inferior frontal gyrus, and the lateral orbitofrontal cortex partially accounted for reductions in executive function. These results suggest that childhood obesity is associated with compromised executive function. This relationship may be partly explained by BMI-associated reduced cortical thickness in the PFC.Wellcome Trust Bernard Wolfe Health Neuroscience Fun

Relations between concurrent hard X-ray sources in solar flares

Context: Solar flares release a large fraction of their energy into non-thermal electrons, but it is not clear where and how. Bremsstrahlung X-rays are observed from the corona and chromosphere. Aims: We aim to characterize the acceleration process by the coronal source and its leakage toward the footpoints in the chromosphere. The relations between the sources reflect the geometry and constrict the configuration of the flare. Methods: We studied solar flares of GOES class larger than M1 with three or more hard X-ray sources observed simultaneously in the course of the flare. The events were observed with the X-ray satellite RHESSI from February 2002 until July 2005. We used imaging spectroscopy methods to determine the spectral evolution of each source in each event. The images of all of the five events show two sources visible only at high energies (footpoints) and one source only visible at low energies (coronal or looptop source, in two cases situated over the limb). Results: We find soft-hard-soft behavior in both, coronal source and footpoints. The coronal source is nearly always softer than the footpoints. The footpoint spectra differ significantly only in one event out of five. Conclusions: The observations are consistent with acceleration in the coronal source and an intricate connection between the corona and chromosphere.Comment: accepted for publication in A&A, 11 pages, 9 figure

The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension.

In epithelia, tricellular vertices are emerging as important sites for the regulation of epithelial integrity and function. Compared to bicellular contacts, however, much less is known. In particular, resident proteins at tricellular vertices were identified only at occluding junctions, with none known at adherens junctions (AJs). In a previous study, we discovered that in Drosophila embryos, the adhesion molecule Sidekick (Sdk), well-known in invertebrates and vertebrates for its role in the visual system, localises at tricellular vertices at the level of AJs. Here, we survey a wide range of Drosophila epithelia and establish that Sdk is a resident protein at tricellular AJs (tAJs), the first of its kind. Clonal analysis showed that two cells, rather than three cells, contributing Sdk are sufficient for tAJ localisation. Super-resolution imaging using structured illumination reveals that Sdk proteins form string-like structures at vertices. Postulating that Sdk may have a role in epithelia where AJs are actively remodelled, we analysed the phenotype of sdk null mutant embryos during Drosophila axis extension using quantitative methods. We find that apical cell shapes are abnormal in sdk mutants, suggesting a defect in tissue remodelling during convergence and extension. Moreover, adhesion at apical vertices is compromised in rearranging cells, with apical tears in the cortex forming and persisting throughout axis extension, especially at the centres of rosettes. Finally, we show that polarised cell intercalation is decreased in sdk mutants. Mathematical modelling of the cell behaviours supports the notion that the T1 transitions of polarised cell intercalation are delayed in sdk mutants, in particular in rosettes. We propose that this delay, in combination with a change in the mechanical properties of the converging and extending tissue, causes the abnormal apical cell shapes in sdk mutant embryos