Critical orientations for humanising health sciences education in South Africa

In this article, the authors make a case for the ’humanisation' and ’decolonisation' of health sciences curricula in South Africa, using integration as a guiding framework. Integration refers to an education that is built on a consolidated conceptual framework that includes and equally values the natural or biomedical sciences as well as the humanities, arts and social sciences, respecting that all of this knowledge has value for the practice of healthcare. An integrated curriculum goes beyond add-on or elective courses in the humanities and social sciences. It is a curriculum that includes previously marginalised sources of knowledge (challenging knowledge hierarchies and decolonising curricula); addresses an appropriate intellectual self-image in health sciences education (challenging the image of the health professional); promotes understanding of history and social context, centring issues of inclusion, access and social justice (cultivating a social ethic) and finally, focuses on care and relatedness as an essential aspect of clinical work (embedding relatedness in practice). The article offers a brief historical overview of challenges in health and health sciences education in South Africa since 1994, followed by a discussion of contemporary developments in critical health sciences pedagogies and the medical and health humanities in South Africa. It then draws on examples from South Africa to outline how these four critical orientations or competencies might be applied in practice, to educate health professionals that can meet the challenges of health and healthcare in contemporary South Africa

The determinants of vulnerability to currency crises: country-specific factors versus regional factors

We investigate the determinants of exchange market pressures (EMP) for some new EU member states at both the national and regional levels, where macroeconomic and financial variables are considered as potential sources. The regional common factors are extracted from these variables by using dynamic factor analysis. The linear empirical analysis, in general, highlights the importance of country-specific factors to defend themselves against vulnerability in their external sectors. Yet, given a significant impact of the common component in credit on EMP, a contagion effect is apparent through the conduit of credit market integration across these countries under investigation

PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas

We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT–PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

Carbonates from the ancient world's longest aqueduct:A testament of Byzantine water management

The fourth‐ and fifth‐century aqueduct system of Constantinople is, at 426 km, the longest water supply line of the ancient world. Carbonate deposits in the aqueduct system provide an archive of both archaeological developments and palaeo‐environmental conditions during the depositional period. The 246‐km‐long aqueduct line from the fourth century used springs from a small aquifer, whereas a 180‐km‐long fifth‐century extension to the west tapped a larger aquifer. Although historical records testify at least 700 years of aqueduct activity, carbonate deposits in the aqueduct system display less than 27 years of operation. This implies that the entire system must have been cleaned of carbonate, presumably during regular campaigns. A 50‐km‐long double‐aqueduct section in the central part of the system may have been a costly but practical solution to allow repairs and cleaning of the aqueducts of carbonate to ascertain a continuous water supply to the city. The fifth‐century channel was commonly contaminated with clay, caused by the nature of the aqueduct system and possible local damage to the channel. This clay‐rich water could have been one of the reasons for the construction of large reservoirs in Constantinople. imageLeverhulme Trust http://dx.doi.org/10.13039/501100000275Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/50110000165

Role of thrombin receptor in breast cancer invasiveness

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism. © 1999 Cancer Research Campaig

Ion-Mobility Mass Spectrometry for the Rapid Determination of the Topology of Interlocked and Knotted Molecules.

A rapid screening method based on traveling-wave ion-mobility spectrometry (TWIMS) combined with tandem mass spectrometry provides insight into the topology of interlocked and knotted molecules, even when they exist in complex mixtures, such as interconverting dynamic combinatorial libraries. A TWIMS characterization of structure-indicative fragments generated by collision-induced dissociation (CID) together with a floppiness parameter defined based on parent- and fragment-ion arrival times provide a straightforward topology identification. To demonstrate its broad applicability, this approach is applied here to six Hopf and two Solomon links, a trefoil knot, and a [3]catenate.Deutsche Forschungsgemeinschaft (CRC 765 “Multivalency”). Alexander von Humboldt Foundation. Swiss National Science Foundation (PZ00P2_161270). Fondation Wiener-Anspach

Organization of multiprotein complexes at cell–cell junctions

The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance