The Wooden Structures

The final full text is available open access at https://universitypress.whiterose.ac.uk/site/chapters/10.22599/book1.f/The wooden structures at Star Car

A second timber circle, trackways, and coppicing at Holme-next-the-Sea beach, Norfolk: use of salt- and freshwater marshes in the Bronze Age

Since 1998 archaeological investigations on Holme-next-the-Sea beach have recorded the waterlogged remains of two Bronze Age timber circles, timber structures, coppiced trees, metal objects, and salt- and freshwater marshes. The second timber circle (Holme II) is only the third waterlogged structure of its type to be discovered in Britain and only the second to be dated by dendrochronology. The felling of timbers used in Holme II has been dated to the spring or summer of 2049 bc , exactly the time as the felling of the timbers used to build the first circle (Holme I). This shared date provides the only known example of two adjacent monuments constructed at precisely the same time in British prehistory. It also informs comparisons between Holme II and other British timber circles and therefore helps develop interpretations. This paper suggests Holme II was a mortuary monument directly related to the use of Holme I

Methods, Aims and Objectives

The final full text is available open access at https://universitypress.whiterose.ac.uk/site/chapters/10.22599/book2.a/The aims, objects and methods of the Star Carr projec

A kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signalling

Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (pGlu631Lys; E631K) in the mouse Csf1r locus. Homozygous mutation (Csf1rE631K/E631K) phenocopied the Csf1r knockout, with prenatal mortality or severe postnatal growth retardation and hydrocephalus. Heterozygous mutation delayed the postnatal expansion of tissue macrophage populations in most organs. Bone marrow cells from Csf1rE631K/+mice were resistant to CSF1 stimulation in vitro, and Csf1rE631K/+ mice were unresponsive to administration of a CSF1-Fc fusion protein, which expanded tissue macrophage populations in controls. In the brain, microglial cell numbers and dendritic arborisation were reduced in Csf1rE631K/+ mice, as in patients with ALSP. The microglial phenotype is the opposite of microgliosis observed in Csf1r+/- mice. However, we found no evidence of brain pathology or impacts on motor function in aged Csf1rE631K/+ mice. We conclude that heterozygous disease-associated CSF1R mutations compromise CSF1R signalling. We speculate that leukoencephalopathy associated with dominant human CSF1R mutations requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles