Simon Price

Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation.

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. Thus, any naturally occurring genetic variants that directly affect gene expression and/or protein function would be expected to impact on progression of pathological processes involving tissue remodeling. We scanned a 2-kilobase pair promoter region and all 13 exons of the humanMMP-2 gene, from a panel of 32 individuals, and we identified the position, nature, and relative allele frequencies of 15 variant loci as follows: 6 in the promoter, 1 in the 5′-untranslated region, 6 in the coding region, 1 in intronic sequence, and 1 in the 3′-untranslated region. The majority of coding region polymorphisms resulted in synonymous substitutions, whereas three promoter variants (at −1306, −790, and +220) mapped onto cis-acting elements. We functionally characterized all promoter variants by transient transfection experiments with 293, RAW264.7, and A10 cells. The common C → T transition at −1306 (allele frequency 0.26), which disrupts an Sp1-type promoter site (CCACC box), displayed a strikingly lower promoter activity with the T allele. Electrophoretic mobility shift assays confirmed that these differences in allelic expression were attributable to abolition of Sp1 binding. These data suggest that this common functional genetic variant influencesMMP-2 gene transcription in an allele-specific manner and is therefore an important candidate to test for association in a wide spectrum of pathologies for which a role for MMP-2 is implicated, including atherogenesis and tumor invasion and metastasis.

Relative sea-level changes in crete: reassessment of radiocarbon dates from Sphakia and west Crete

This article is concerned with the recognition and dating of Holocene relative sea-level changes along the coast of west Crete (an island located in the active Hellenic subduction arc of the southern Aegean) and in particular in Sphakia. Radiocarbon data for changes in sea levels collected and analysed previously must (a) be recorrected to take into account isotopic fractionation, and (b) recalibrated by using the new marine reservoir value. These new radiocarbon dates are analysed using Bayesian statistics. The resulting calendar dates for changes in sea level are younger than previously assumed. In particular the Great Uplift in western Crete in late antiquity must be dated to the fifth or sixth century AD, not to AD 365. Moreover, recent work on tectonics suggests that the Great Uplift need not have been accompanied by a catastrophic earthquake. Finally, we consider the consequences of the Great Uplift for some coastal sites in Sphakia.

The diachronic analysis of pastoralism through comparative variables

Diachronic analyses of pastoralism over the millennia pose a problem. Studies of one period can use models based on other periods as heuristic devices, to pose problems and questions for investigation. But survey archaeologists and others engaged in diachronic analysis cannot assume a period-specific model as a starting point. Instead, we propose that investigation begin from a set of seven variables, which constitute the elements for the formulation of comparative analyses: environment, location, scale, specialization, links with agriculture, gender/division of labour, and cultural integration. The first five have been discussed before in the literature, but the last two have not previously been given sufficient attention, because of the old dominance of environmental and economic preoccupations.

Agiasmatsi: a Greek cave sanctuary in Sphakia, SW Crete 1

The Agiasmati cave in SW Crete, investigated as part of the Sphakia Survey, served as a sanctuary in the Hellenistic-Early Roman period. It has four points of interest, (1) Two of its principal types of artefacts, ladles and multiple-nozzle lamps are rare or even unique to this site. (2) Fabric analysis has enabled significant progress to be made with the interpretation of the pottery. (3) Cave worship in this period is not well known on Crete. (4) Intensive exploration by the Sphakia Survey of the region in which the cave lies enables us to place the cave in the context of the contemporary settlement pattern and to reconfirm the value of archaeological survey.