Excavations at the Viking Barrow Cemetery at Heath Wood, Ingleby, Derbyshire

The cemetery at Heath Wood, Ingleby, Derbyshire, is the only known Scandinavian cremation cemetery in the British Isles. It comprises fifty-nine barrows, of which about one-third have been excavated on previous occasions, although earlier excavators concluded that some were empty cenotaph mounds. From 1998 to 2000 three barrows were examined. Our investigations have suggested that each of the barrows contained a burial, although not all contain evidence of a pyre. A full report of the 1998-2000 excavations is provided, alongside a summary of the earlier finds. The relationship of Heath Wood to the neighbouring site at Repton is examined, in order to understand its significance for the Scandinavian settlement of the Danelaw. It is concluded that Heath Wood may have been a war cemetery of the Viking Great Army of AD 873-8

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

Expression of small heat shock proteins by the third-stage larva of Brugia pahangi

Changes in proteins synthesised by the infective third-stage larvae (L3) of the filarial nematode Brugia pahangi were examined with respect to the temperature shift encountered by the parasite as it migrates from insect to mammal, and the presence of serum in the culture medium. While the synthesis of a number of polypeptides is regulated by the temperature shift of the L3 from 28°C to 37°C in vitro, there is no evidence that serum has any significant effect on protein synthesis. Two complexes of small acidic polypeptides (22–24 kDa and 18 kDa) are synthesised for a limited period only by L3 transferred to 37°C. One component of each complex appears to be constitutively expressed at 28°C, but its synthesis is up-regulated at 37°C, while the remaining members of each complex are synthesised only at 37°C. Subjection of L3 and post-infective (p.i.) L3 to heat shock (41°C) also induces synthesis of both complexes, indicating that these heat-inducible polypeptides are related to the family of small heat shock proteins. The possible role of the heat shock-related proteins in this important environmental transition is considered

Roughton Gill Mine and Silver Gill Mine, Cumbria

Includes bibliographical references. Includes folded map in pocket inside back coverAvailable from British Library Document Supply Centre- DSC:1594. 7475(8/2001) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Identification and characterization of a DR4-restricted T cell epitope within chlamydia heat shock protein 60

An epitope within the 60 kD Chlamydia trachomatis heat shock protein (hsp) 60, recognized by a HLA-DRB1*0401-restricted T cell clone from a reactive arthritis patient, has been characterized. Stimulatory peptides contained a nine amino acid sequence (residues 38–46) predicted by algorithm to confer strong binding to DRB1*0401, with valine in the P1 position. The overall length of the peptide was critical for efficient recognition; peptides with at least one residue N-terminal to the putative P1 position were markedly more stimulatory than a peptide whose N-terminal is the P1 valine. Optimal responses were seen with 14mer peptides having two to three amino acids N- and C-terminal to the core 9mer. The sequence of the defined epitope is identical in hsp60 from both C. trachomatis and C. pneumoniae. Since the latter is a common respiratory pathogen, patients infected with C. trachomatis may already be primed for responses to hsp60 by prior infection with C. pneumoniae. Such secondary responses are important in the pathogenesis of chlamydia-induced inflammatory diseases such as trachoma. Priming by infection with enteric organisms was considered because of the similarity of the epitope sequence in Escherichia coli hsp60. However, although an E. coli-related peptide was recognized, intact E. coli hsp60 was not, suggesting that the epitope is cryptic in E. coli hsp60. Human hsp60 has six amino acid differences from chlamydial hsp60 in the epitope sequence and was not recognized. Thus cross-reactive recognition of self hsp60 could not be implicated in the pathogenesis of chlamydia-induced reactive arthritis in this patient

Stafford Castle, Staffordshire

Originally produced by the Royal Commission on the Historical Monuments of England. Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:1594. 7475(8/1997) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo