Scale change – Kingstons and royal power in the middle Anglo-Saxon England, c. AD 650–850

Several questions surrounding the origin and function of Husebyer are familiar to students of Anglo-Saxon England. Here too, there is evidence that the power of kings became, over the course of the early medieval period, increasingly territorial in character. Controls over movement, the diversification and extension of royal institutions, the tightening of systems of taxation and administration – all facets addressed by Huseby research – find parallels in England, particularly during the period c. AD 650-850. Some of these developments appear to be driven by kings, or the church; many others would seem to have emerged from the class of lesser nobles. Several recent works have addressed aspects of these processes at great length (e.g. Astill 2000; Hanson & Wickham 2000; Wickham 2005; Rippon 2010; Loveluck 2013), so they need not be given more than cursory treatment here. Instead, I would like to use this paper to discuss an interesting category of site in Anglo-Saxon England, places named Kingston that – though not identical to Husebyer – would seem similarly to encapsulate some of the broader processes of territorialisation

Signalling Intent: Beacons, Lookouts and Military Communications

Beacons and lookouts played a key role in the networks of local and regional communications of Anglo-Saxon England during the Viking Age (ninth to eleventh centuries). While the large fortified centres of the period are well known, the nature of interconnections between them and smaller-scale local arrangements have only recently received attention. Written evidence, place-names and landscape archaeology together allow for the reconstruction of elements of signalling and sighting systems. This contribution presents the historical evidence for beacons, discusses the context within which beacons and lookouts developed and draws upon a series of case studies to reveal local systems of communication in the landscape of Anglo-Saxon England

The Importance of Serine Phosphorylation of Ameloblastin on Enamel Formation

FAM20C is a newly identified kinase on the secretory pathway responsible for the phosphorylation of serine residues in the Ser-x-Glu/pSer motifs in several enamel matrix proteins. Fam20C-knockout mice showed severe enamel defects very similar to those in the ameloblastin (Ambn)–knockout mice, implying that phosphoserines may have a critical role in AMBN function. To test this hypothesis, we generated amelogenin (Amel) promoter-driven Ambn-transgenic mice, in which Ser⁴⁸, Ser²²⁶, and Ser²²⁷ were replaced by aspartic acid (designated as D-Tg) or alanines (designated as A-Tg). The negative charge of aspartic acid is believed to be able to mimic the phosphorylation state of serine, while alanine is a commonly used residue to substitute serine due to their similar structure. Using Western immunoblotting and quantitative polymerase chain reaction, the authors identified transgenic lines expressing transgenes somewhat higher (Tg+) or much higher (Tg++) than endogenous Ambn. The lower incisors collected from 7-d-old and 7-wk-old mice were analyzed by histology, scanning electron microscopy, immunohistochemistry, and Western immunoblotting to examine the morphology and microstructure changes in enamel, as well as the expression pattern of enamel matrix proteins. The A-Tg+ and A-Tg++ mice displayed severe enamel defects in spite of the expression level of transgenes, while the D-Tg+ and D-Tg++ mice showed minor to mild enamel defects, indicating that the D-Tg transgenes disturbed enamel formation less than the A-Tg transgenes did. Our results suggest that the phosphorylation state of serines is likely an essential component for the integrity of AMBN function

Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts.

Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-electrospray ionization-tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography-electrospray ionization-tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis

Synthetic collagen fascicles for the regeneration of tendon tissue.

The structure of an ideal scaffold for tendon regeneration must be designed to provide a mechanical, structural and chemotactic microenvironment for native cellular activity to synthesize functional (i.e. load bearing) tissue. Collagen fibre scaffolds for this application have shown some promise to date, although the microstructural control required to mimic the native tendon environment has yet to be achieved allowing for minimal control of critical in vivo properties such as degradation rate and mass transport. In this report we describe the fabrication of a novel multi-fibre collagen fascicle structure, based on type-I collagen with failure stress of 25-49 MPa, approximating the strength and structure of native tendon tissue. We demonstrate a microscopic fabrication process based on the automated assembly of type-I collagen fibres with the ability to produce a controllable fascicle-like, structural motif allowing variable numbers of fibres per fascicle. We have confirmed that the resulting post-fabrication type-I collagen structure retains the essential phase behaviour, alignment and spectral characteristics of aligned native type-I collagen. We have also shown that both ovine tendon fibroblasts and human white blood cells in whole blood readily infiltrate the matrix on a macroscopic scale and that these cells adhere to the fibre surface after seven days in culture. The study has indicated that the synthetic collagen fascicle system may be a suitable biomaterial scaffold to provide a rationally designed implantable matrix material to mediate tendon repair and regeneration

Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta

Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid

Ready Exerciser One: Effects of Music and Virtual Reality on Cycle Ergometer Exercise

© 2020 The Authors. Objectives Physical inactivity remains a major global health concern, and researchers have been encouraged to explore the role of technology in the promotion of physical activity. Technologies that deliver audio‐visual stimuli are frequently applied in the exercise domain. However, there is a paucity of research that examines the efficacy of modern virtual reality (VR) technology in this context. We investigated the effects of VR and music on affective, perceptual, enjoyment, and cardiac responses to aerobic‐type exercise. Design A fully counterbalanced, within‐subjects design was employed. Methods A convenience sample of recreationally active adult volunteers (N = 24) completed a 12‐min protocol during which they exercised under music, VR, VR‐with‐music, and control conditions. Results Analyses indicated a Condition × Time interaction for affective valence and perceived activation. Moreover, a main effect of condition emerged for state attention and perceived enjoyment. The VR and VR‐with‐music conditions elicited the most positive affective valence, highest levels of perceived activation, greatest number of dissociative thoughts, and most exercise enjoyment. Differences between these two conditions were negligible across the breadth of dependent variables. Conclusions The present findings illustrate the efficacy of modern VR technology in the exercise context, applied both with and without musical accompaniment. Additional research is required to assess the degree to which the findings are replicable among sedentary or ageing segments of the population. Given the emerging support pertaining to a positive relationship between affective responses and exercise adherence, VR technology should be considered as a means by which to promote an enjoyable exercise experience

New missense variants in RELT causing hypomineralised amelogenesis imperfecta

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic diseases characterised by dental enamel malformation. Pathogenic variants in at least 33 genes cause syndromic or non‐syndromic AI. Recently variants in RELT, encoding an orphan receptor in the tumour necrosis factor (TNF) superfamily, were found to cause recessive AI, as part of a syndrome encompassing small stature and severe childhood infections. Here we describe four additional families with autosomal recessive hypomineralised AI due to previously unreported homozygous mutations in RELT. Three families carried a homozygous missense variant in the fourth exon (c.164C > T, p.[T55I]) and a fourth family carried a homozygous missense variant in the 11th exon (c.1264C > T, p.[R422W]). We found no evidence of additional syndromic symptoms in affected individuals. Analyses of tooth microstructure with computerized tomography and scanning electron microscopy suggest a role for RELT in ameloblasts' coordination and interaction with the enamel matrix. Microsatellite genotyping in families segregating the T55I variant reveals a shared founder haplotype. These findings extend the RELT pathogenic variant spectrum, reveal a founder mutation in the UK Pakistani population and provide detailed analysis of human teeth affected by this hypomineralised phenotype, but do not support a possible syndromic presentation in all those with RELT‐variant associated AI