Human foot bones from Klasies River main site, South Africa.

The caves at Klasies River contain abundant archaeological evidence relating to human evolution in the late Pleistocene of southern Africa. Along with Middle Stone Age artifacts, animal bones, and other food waste, there are hominin cranial fragments, mandibles with teeth, and a few postcranial remains. Three foot bones can now be added to this inventory. An adult first metatarsal is similar in size and discrete anatomical features to those from Holocene burials in the Cape Province. A complete and well-preserved second metatarsal is especially long and heavy at midshaft in comparison to all Holocene and more recent South African homologues. A large fifth metatarsal is highly distinctive in its morphology. In overall size, these pedal elements resemble specimens from late Pleistocene sites in western Asia, but there are some differences in proportions. The fossils support earlier suggestions concerning a relatively high level of sexual dimorphism in the African Middle Stone Age population. Squatting facets on the two lateral metatarsals appear to indicate a high frequency of kneeling among members of this group. The new postcranial material also underlines the fact that the morphology of particular skeletal elements of some of the 100,000-year-old Klasies River individuals falls outside the range of modern variation.

New human teeth from Middle Stone Age deposits at Klasies River, South Africa.

Since 1984, the main site at Klasies River has been re-investigated. Human remains, animal bones and stone artefacts have been collected from the LBS, SAS and other stratigraphic members, and these discoveries help to establish the antiquity of anatomically near-modern populations practicing a Middle Stone Age way of life on the southern coast of Africa. Several teeth found in the lower SAS levels in 1989-1991 can be matched in recent South African populations. Two complete upper molars representing one individual have crowns that are relatively short mesiodistally. These specimens are small in comparison to black South African homologues, but MD and BL dimensions fall close to the averages for San burials. This evidence confirms that several of the Klasies individuals have very small molars, while others have cheek teeth that are close to the upper limits for size variation in recent Africans. The new material is in keeping with the view that sex dimorphism within this Middle Stone Age population may be pronounced.

Racism and medical science in South Africa's Cape Colony in the mid- to late nineteenth century.

Racism has been a particular focus of the history of Western medicine in colonial South Africa. Much of the research to date has paradoxically interpreted Western medicine as both a handmaiden of colonialism and as a racist gatekeeper to the benefits of Western medical science. This essay suggests that while these conclusions have some validity, the framework in which they have been devised is problematic. Not only is that framework contradictory in nature, it underplays differences within Western medicine, privileges the history of explicit and intentional racial discrimination in medicine, and encourages a separate analysis of racism in law, in the medical profession, and in medical theory and practice. Using the example of the Cape Colony in South Africa, this paper shows how legislation, class, institutional setting, and popular stereotypes could influence the form, timing, and degree of racism in the medical professional, and in medical theory and practice. It also argues for an analytical distinction between 'racist medicine' and 'medical racism.'

Decreasing oncoprotein 18/stathmin levels reduces microtubule catastrophes and increases microtubule polymer in vivo.

Oncoprotein 18/stathmin (Op18) has been identified recently as a protein which destabilizes microtubules. To characterize the function of Op18 in living cells, we used microinjection of anti-Op18 antibodies or antisense oligonucleotides to block either Op18 activity or expression in interphase newt lung cells. Anti-tubulin staining of cells microinjected with anti-Op18 and fixed 1-2 hours after injection showed an increase in total microtubule polymer. In contrast, microinjection of either non-immune IgG or anti-Op18 preincubated with bacterially-expressed Op18 had little effect on microtubule polymer level. Cells treated with Op18 antisense oligonucleotides for 4 days had (greater than or equal to)50% reduced levels of Op18 with no change in the soluble tubulin level. Measurement of MT polymer level in untreated, antisense or nonsense oligonucleotide treated cells demonstrated that reduced Op18 levels resulted in a 2.5-fold increase in microtubule polymer. Next, the assembly dynamics of individual microtubules at the peripheral regions of living cells were examined using video-enhanced contrast DIC microscopy. Microinjection of antibodies against oncoprotein 18 resulted in a 2.2-fold reduction in catastrophe frequency and a slight reduction in plus end elongation velocity compared to uninjected cells or cells microinjected with non-immune IgG. Preincubation of anti-Op18 antibody with recombinant Op18 greatly diminished the effects of the antibody. Similarly, treatment of cells with antisense oligonucleotides reduced catastrophes 2.5- to 3-fold compared to nonsense oligonucleotide treated or untreated cells. The other parameters of dynamic instability were unchanged after reducing Op18 with antisense oligonucleotides. These studies are consistent with Op18 functioning to regulate microtubule catastrophes during interphase in vivo.

A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor.

A fundamental question in cell biology is how membrane proteins are sorted in the endocytic pathway. The sorting of internalized beta2-adrenergic receptors between recycling endosomes and lysosomes is responsible for opposite effects on signal transduction and is regulated by physiological stimuli. Here we describe a mechanism that controls this sorting operation, which is mediated by a family of conserved protein-interaction modules called PDZ domains. The phosphoprotein EBP50 (for ezrinradixin-moesin(ERM)-binding phosphoprotein-50) binds to the cytoplasmic tail of the beta2-adrenergic receptor through a PDZ domain and to the cortical actin cytoskeleton through an ERM-binding domain. Disrupting the interaction of EBP50 with either domain or depolymerization of the actin cytoskeleton itself causes missorting of endocytosed beta2-adrenergic receptors but does not affect the recycling of transferrin receptors. A serine residue at position 411 in the tail of the beta2-adrenergic receptor is a substrate for phosphorylation by GRK-5 (for G-protein-coupled-receptor kinase-5) and is required for interaction with EBP50 and for proper recycling of the receptor. Our results identify a new role for PDZ-domain-mediated protein interactions and for the actin cytoskeleton in endocytic sorting, and suggest a mechanism by which GRK-mediated phosphorylation could regulate membrane trafficking of G-protein-coupled receptors after endocytosis.

A method that allows the assembly of kinetochore components onto chromosomes condensed in clarified Xenopus egg extracts.

Kinetochores are complex macromolecular structures that link mitotic chromosomes to spindle microtubules. Although a small number of kinetochore components have been identified, including the kinesins CENP-E and XKCM1 as well as cytoplasmic dynein, neither how these and other proteins are organized to produce a kinetochore nor their exact functions within this structure are understood. For this reason, we have developed an assay that allows kinetochore components to assemble onto discrete foci on in vitro-condensed chromosomes. The source of the kinetochore components is a clarified cell extract from Xenopus eggs that can be fractionated or immunodepleted of individual proteins. Kinetochore assembly in these clarified extracts requires preincubating the substrate sperm nuclei in an extract under low ATP conditions. Immunodepletion of XKCM1 from the extracts prevents the localization of kinetochore-associated XKCM1 without affecting the targeting of CENP-E and cytoplasmic dynein or the binding of monomeric tubulin to the kinetochore. Extension of this assay for the analysis of other components should help to dissect the protein-protein interactions involved in kinetochore assembly and function.

Cape Town and 'country' doctors in the Cape Colony during the first half of the nineteenth century.

This paper argues that during the 'golden' age of medical reform in the first half of the nineteenth century in the Cape Colony there was significant differentiation within the medical profession which contributed to a slow and uneven process of professionalization in spite of comprehensive and early legal regulation under one licensing body. Differences in permitted practice, settlement patterns, economic and organizational opportunities gave doctors in Cape Town, the colony's biggest and most important city, greater incentives and more scope to develop professional regulation and organization than those in the rest of the colony. A government Ordinance passed in 1807 gave regularly-trained medical practitioners a legal monopoly over medical practice, but did not initially prevent those practising outside Cape Town from selling both medicines and medical advice. Cape Town doctors thus enjoyed greater social differentiation from tradesmen and better legal control over competition from druggists and 'irregulars' than country practitioners. The difference between practitioners in Cape Town and elsewhere remained important even after new regulations removed legal distinctions in 1830. While country practitioners now sought tighter regulation over permitted practice they could not easily make common cause with the more powerful professional medical élite in Cape Town. This élite group had vested social and economic interests in maintaining their privileged status within the Cape profession, especially when threatened by local recession and political and economic competition from Eastern Cape doctors in the 1850s.

Drug-resistant Plasmodium falciparum malaria in the eastern Transvaal.

In March 1993, a study was undertaken in the Komatipoort/Malelane area to monitor the in vitro sensitivity of Plasmodium falciparum to antimalarial drugs currently in use in South Africa. Of the 12 isolates collected, 7 were successfully tested for sensitivity to chloroquine and quinine, 6 for mefloquine susceptibility, and 5 for sensitivity to Fansidar. Four of the isolates were resistant to chloroquine at RIII level, 1 at RII level, and 2 were sensitive. All isolates were found to be sensitive to both quinine and mefloquine. Results suggested possible resistance to Fansidar. These findings have implications for tourists travelling to this area.

Southern Africa and modern human origins.

This paper argues that southern Africa was a remote part of the Old World in the late Pleistocene (125-10 ka ago). Because of this isolated position there was continuity without significant replacement in the resident population. Isolation and the relatively recent spread of agriculture to the region has allowed a section of this population to survive into the present. They are the Bushmen (San). Studies of geographic patterning in conventional genetic markers and mitochondrial DNA indicate that the Bushman clade has a long evolutionary history in southern Africa. Estimates of more than 100 ka for the continued presence of this population in the region are supported in archaeological investigations of sites with long sequences such as Klasies River main site and Border Cave. Human remains dating to the earlier part of the late Pleistocene have been recovered from these sites and the samples form a morphological series with the Klasies River remains possibly 20 ka older than those from Border Cave. There is no fossil record for the later Pleistocene, however, at a period when selection for a gracile morphology may have been pronounced. The cultural associations in the earlier late Pleistocene are with the Middle Stone Age. Expressions of cultural 'style' and the occurrence of similar artefact design types in the Middle and Later Stone Ages can be interpreted with reference to the ethnographic present. Temporal continuity can be shown in the geographical distribution of stylistic markers and this suggests participation in a shared cognitive system.(ABSTRACT TRUNCATED AT 250 WORDS)