The morphology of the Late Pleistocene hominin remains from the site of La Cotte de St Brelade, Jersey (Channel Islands).

Thirteen permanent fully erupted teeth were excavated at the Paleolithic site of La Cotte de St Brelade in Jersey in 1910 and 1911. These were all found in the same location, on a ledge behind a hearth in a Mousterian occupation level. They were originally identified as being Neanderthal. A fragment of occipital bone was found in a separate locality in a later season. Recent dating of adjacent sediments gives a probable age of <48 ka. The purpose of this article is to provide an updated description of the morphology of this material and consider its likely taxonomic assignment from comparison with Neanderthal and Homo sapiens samples. One of the original teeth has been lost, and we identify one as nonhominin. At least two adult individuals are represented. Cervix shape and the absence of common Neanderthal traits in several teeth suggest affinities with H. sapiens in both individuals, while crown and root dimensions and root morphology of all the teeth are entirely consistent with a Neanderthal attribution, pointing toward a possible shared Neanderthal and H. sapiens ancestry (the likely date of this material corresponds with the time in which both Neanderthals and H. sapiens were present in Europe). The occipital fragment is stratigraphically more recent and does not exhibit any diagnostic Neanderthal features.

The earliest evidence for anatomically modern humans in northwestern Europe.

The earliest anatomically modern humans in Europe are thought to have appeared around 43,000-42,000 calendar years before present (43-42 kyr cal BP), by association with Aurignacian sites and lithic assemblages assumed to have been made by modern humans rather than by Neanderthals. However, the actual physical evidence for modern humans is extremely rare, and direct dates reach no farther back than about 41-39 kyr cal BP, leaving a gap. Here we show, using stratigraphic, chronological and archaeological data, that a fragment of human maxilla from the Kent's Cavern site, UK, dates to the earlier period. The maxilla (KC4), which was excavated in 1927, was initially diagnosed as Upper Palaeolithic modern human. In 1989, it was directly radiocarbon dated by accelerator mass spectrometry to 36.4-34.7 kyr cal BP. Using a Bayesian analysis of new ultrafiltered bone collagen dates in an ordered stratigraphic sequence at the site, we show that this date is a considerable underestimate. Instead, KC4 dates to 44.2-41.5 kyr cal BP. This makes it older than any other equivalently dated modern human specimen and directly contemporary with the latest European Neanderthals, thus making its taxonomic attribution crucial. We also show that in 13 dental traits KC4 possesses modern human rather than Neanderthal characteristics; three other traits show Neanderthal affinities and a further seven are ambiguous. KC4 therefore represents the oldest known anatomically modern human fossil in northwestern Europe, fills a key gap between the earliest dated Aurignacian remains and the earliest human skeletal remains, and demonstrates the wide and rapid dispersal of early modern humans across Europe more than 40 kyr ago.

Nubian Levallois technology associated with southernmost Neanderthals.

Neanderthals occurred widely across north Eurasian landscapes, but between ~ 70 and 50 thousand years ago (ka) they expanded southwards into the Levant, which had previously been inhabited by Homo sapiens. Palaeoanthropological research in the first half of the twentieth century demonstrated alternate occupations of the Levant by Neanderthal and Homo sapiens populations, yet key early findings have largely been overlooked in later studies. Here, we present the results of new examinations of both the fossil and archaeological collections from Shukbah Cave, located in the Palestinian West Bank, presenting new quantitative analyses of a hominin lower first molar and associated stone tool assemblage. The hominin tooth shows clear Neanderthal affinities, making it the southernmost known fossil specimen of this population/species. The associated Middle Palaeolithic stone tool assemblage is dominated by Levallois reduction methods, including the presence of Nubian Levallois points and cores. This is the first direct association between Neanderthals and Nubian Levallois technology, demonstrating that this stone tool technology should not be considered an exclusive marker of Homo sapiens.

Middle Stone Age human teeth from Magubike rockshelter, Iringa Region, Tanzania.

In 2006, six isolated hominin teeth were excavated from Middle Stone Age (MSA) deposits at the Magubike rockshelter in southern Tanzania. They comprise two central incisors, one lateral incisor, one canine, one third premolar, and one fourth premolar. All are fully developed and come from the maxilla. None of the teeth are duplicated, so they may represent a single individual. While there is some evidence of post-depositional alteration, the morphology of these teeth clearly shares features with anatomically modern Homo sapiens. Both metric and non-metric traits are compared to those from other African and non-African dental remains. The degree of biological relatedness between eastern and southern African Stone Age hunter-gatherers has long been a subject of interest, and several characteristics of the Magubike teeth resemble those of the San of southern Africa. Another notable feature is that the three incisors are marked on the labial crown by scratches that are much coarser than microwear striations. These non-masticatory scratches on the Magubike teeth suggest that the use of the front teeth as tools included regularly repeated activities undertaken throughout the life of the individual. The exact age of these teeth is not clear as ESR and radiocarbon dates on associated snail shells give varying results, but a conservative estimate of their minimum age is 45,000 years.

Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer.

Lysophosphatidic acid (LPA), the simplest of all phospholipids, exhibits pleiomorphic functions in multiple cell lineages. The effects of LPA appear to be mediated by binding of LPA to specific members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors (GPCR). Edg 2, Edg4, and Edg7 are high affinity receptors for LPA, and Edg1 may be a low affinity receptor for LPA. PSP24 has been shown to be responsive to LPA in Xenopus oocytes, however, its role in mammalian cells is unclear. The specific biochemical events initiated by the different Edg receptors, as well as the biological outcomes of activation of the individual receptors, are only beginning to be determined. LPA levels are consistently elevated in the plasma and ascites of ovarian cancer patients, but not in most other epithelial tumors, with the exception of cervix and endometrium, suggesting that LPA may be of particular importance in the pathophysiology of ovarian cancer. In support of this concept, ovarian cancer cells constitutively and inducibly produce high levels of LPA and demonstrate markedly different responses to LPA than normal ovarian surface epithelium. Edg4 and Edg7 levels are consistently increased in malignant ovarian epithelial cells contributing to the aberrant response of ovarian cancer cells to LPA. Edg2 may represent a negative regulatory LPA receptor inducing apoptosis in ovarian cancer cells. Thus, increased levels of LPA, altered receptor expression and altered responses to LPA may contribute to the initiation, progression or outcome of ovarian cancer. Over 40% of known drugs target GPCR, making LPA receptors attractive targets for molecular therapeutics. Indeed, using the structure-function relationship of LPA in model systems, we have identified selective Edg2 anatgonists, as well as Edg4 and Edg7 agonists. These lead compounds are being assessed in preclinical model systems. Understanding the mechanisms regulating LPA production, metabolism and function could lead to improved methods for early detection and to new targets for therapy in ovarian cancer.