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The significance of morphological variation in Acheulean bifaces has been a central issue in Palaeolithic research for well over a century. For much of that period interpretation has been dominated by culturehistorical models and it is only in the past 20 years that other explanatory factors have received adequate attention. This paper examines the combined role of several of these factors -namely raw materials, reduction intensity, and function -on biface variability in the British Isles, with special reference to the two major shapedbased 'tradition' devised by Roe (1967;. First-hand examination of bifaces from 19 assemblages suggests that final biface shape depends largely on the dimensions of the original raw materials and the technofunctional strategies designed to deal with them. Through these observations a new model is generated and tested. This suggests that the patterning in the British Acheulean simply reflects the nature of the resources available at a site and the hominid procurement and technological strategies used to exploit them. According to this model, well-worked ovates with all-round edges were preferentially produced wherever raw materials were large and robust enough to frequently support intensive reduction procedures, usually when obtained from primary flint sources. Assemblages characterised by partially-edged, moderately-reduced pointed forms were only manufactured when smaller, narrower blanks, that imposed restrictions on human technological actions regarding the location and extent of working, were exploited. Such blanks were usually obtained from a secondary flint source, such as river gravel. Thus, Roe's pointed and ovate 'traditions' are seen not as the products of different biface making populations, but as the same broad populations coping with the exigencies of a heterogeneous environment, using different resources in an adaptive, flexible manner.Sample size Foints-.Ovates (remaindercleavers)

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No abstract

Currently, one-third of the world's population is believed to be latently infected with Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis establishes latent infection remain largely undefined. mprAB encodes a two-component signal transduction system required by M. tuberculosis for aspects of persistent infection. MprAB regulates a large and diverse group of genetic determinants in response to membrane stress, including the extracytoplasmic function (ECF) sigma factor sigE and the HtrA-like serine protease pepD. Recent studies have demonstrated that PepD functions as both a protease and chaperone in vitro. In addition, inactivation of pepD alters the virulence of M. tuberculosis in a mouse model system of infection. Here, we demonstrate that PepD plays an important role in the stress response network of Mycobacterium mediated through MprAB and SigE. In particular, we demonstrate that the protease activity of PepD requires the PDZ domain, in addition to the catalytic serine at position 317. pepD expression initiates from at least three promoters in M. tuberculosis, including one that is regulated by SigE and is located upstream of the mprA coding sequence. Deletion of pepD or mprAB in Mycobacterium smegmatis and M. tuberculosis alters the stress response phenotypes of these strains, including increasing sensitivity to SDS and cell wall antibiotics and upregulating the expression of stress-responsive determinants, including sigE. Taking these data together, we hypothesize that PepD utilizes its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation.Currently, one-third of the world's population is believed to be latently infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. There are an estimated 9 million new cases of infection caused by this organism each year, accounting for more than 2 million deaths annually (3). This makes M. tuberculosis one of the leading causes of death due to a single infectious agent. Humans are the only known reservoir of M. tuberculosis, and as such, part of its success as a pathogen lies in its ability to maintain a significant persistent reservoir within the population. Latently infected individuals are asymptomatic and are harder to treat, thereby complicating measures to control the spread of disease (27). In addition, the emergence of multi-and extensively drug-resistant strains has further compromised established strategies for treatment. A better understanding of the mechanisms by which M. tuberculosis establishes persistent infection is urgently needed so that better therapeutics for the latently infected population can be developed.M. tuberculosis is a facultative intracellular pathogen that primarily infects alveolar macrophages. The organism survives within these cells by blocking key steps in the phagosome maturation process (38). Infection by M. tubercul...