A survey of trainee specialists experiences at the University of Cape Town (UCT): Impacts of race and gender

<p>Abstract</p> <p>Background</p> <p>Efforts to redress racial and gender inequalities in the training of medical specialists has been a central part of a dedicated programme in the Faculty of Health Sciences at the University of Cape Town (UCT). This study aimed to describe trends in race and gender profiles of postgraduate students in medical specialties (registrars) from 1999 to 2006 and to identify factors affecting recruitment and retention of black and female trainees.</p> <p>Method</p> <p>Review of faculty databases for race and gender data from 1999 to 2006. Distribution of an anonymous self-administered questionnaire to all registrars in 2005/2006.</p> <p>Results</p> <p>The percentage of African registrars doubled from 10% to 19% from 1999 to beyond 2002. The percentages of Africans, Coloureds and Indians rose steadily from 26% to 46% from 1999 to 2005, as did that of women from 27% to 44%. The institution's perceived good reputation, being an alumnus and originating from Cape Town were common reasons for choosing UCT for training. A quarter of respondents reported knowledge of a friend who decided against studying at UCT for reasons which included anticipated racial discrimination. Black respondents (23%), particularly African (50%), were more likely to describe registrarship at UCT as unwelcoming than white respondents (12%). Specific instances of personal experience of discrimination were uncommon and not associated with respondents' race or gender. Registrars who had had a child during registrarship and those reporting discrimination were more likely to rate the learning and research environment as poor (Odds Ratio, 4.01; 95% CI 0.98 – 16.47 and 1.99 95% CI 0.57 – 6.97, respectively).</p> <p>Conclusion</p> <p>The proportion of black and female registrars at the University of Cape Town has increased steadily from 1999 to 2006, most likely a result of systematic equity policies and procedures adopted in the faculty during this period. The data point to a need for policies to make the institution more welcoming to diversity and for strategies to address institutional culture and mentorship, with an aim to develop examples of best practices to share within and between institutions.</p

Interactions between growth-dependent changes in cell size, nutrient supply and cellular elemental stoichiometry of marine Synechococcus

The factors that control elemental ratios within phytoplankton, like carbon:nitrogen:phosphorus (C:N:P), are key to biogeochemical cycles. Previous studies have identified relationships between nutrient-limited growth and elemental ratios in large eukaryotes, but little is known about these interactions in small marine phytoplankton like the globally important Cyanobacteria. To improve our understanding of these interactions in picophytoplankton, we asked how cellular elemental stoichiometry varies as a function of steady-state, N- and P-limited growth in laboratory chemostat cultures of Synechococcus WH8102. By combining empirical data and theoretical modeling, we identified a previously unrecognized factor (growth-dependent variability in cell size) that controls the relationship between nutrient-limited growth and cellular elemental stoichiometry. To predict the cellular elemental stoichiometry of phytoplankton, previous theoretical models rely on the traditional Droop model, which purports that the acquisition of a single limiting nutrient suffices to explain the relationship between a cellular nutrient quota and growth rate. Our study, however, indicates that growth-dependent changes in cell size have an important role in regulating cell nutrient quotas. This key ingredient, along with nutrient-uptake protein regulation, enables our model to predict the cellular elemental stoichiometry of Synechococcus across a range of nutrient-limited conditions. Our analysis also adds to the growth rate hypothesis, suggesting that P-rich biomolecules other than nucleic acids are important drivers of stoichiometric variability in Synechococcus. Lastly, by comparing our data with field observations, our study has important ecological relevance as it provides a framework for understanding and predicting elemental ratios in ocean regions where small phytoplankton like Synechococcus dominates

The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell

Uji Aktivitas Tonikum Ekstrak Etanol Daun Seledri (Apium graveolens L.) Metode Natatory Exhaustion

Fatigue syndrome menunjukkan karakter kelelahan yang intens dengan durasi lebih dari enam bulan dan berhubungan dengan berbagai gejala pada pasien. Kelelahan ini tidak pulih setelah tidur malam dan dapat mengganggu aktivitas sehari-hari sebanyak 50% (Fernández et al., 2009). Penggunaan tonikum untuk mengurangi gejala sindrom ini menjadi salah satu pilihan masyarakat. Tujuan penelitian ini adalah untuk mengetahui adanya aktivitas tonikum beserta dosis optimum ekstrak etanol Daun Seledri (Apium graveolens L.) secara in vivo. Metode penelitian yaitu dengan mengujikan ekstrak etanol 96% pada 25 ekor mencit yang terbagi dalam 5 kelompok. Kelompok kontrol negatif CMC Na 0,5%, kontrol positif kafein 100 mg/KgBB, kelompok ekstrak daun seledri 100 mg/KgBB, 200 mg/KgBB dan 400 mg/KgBB diberikan secara peroral. Pengujian dilakukan dengan metode natatory exhaustion. Analisis data dilakukan dengan cara membandingkan waktu berenang sebelum dan sesudah perlakuan dan disajikan dalam presentase. Hasil penelitian menunjukkan ekstrak etanol daun seledri dosis 400 mg/KgBB memiliki aktivitas tonikum paling tinggi sebesar 30,35% sedangkan kontrol positif kafein menunjukkan aktivitas tonikum sebesar 23,44%. Hal ini diduga kerena adanya berbagai senyawa yang dapat bersinergi meningkatkan aktivitas tonikum

Direct transmembrane interaction between actin and the pore-competent, cholesterol-dependent cytolysin pneumolysin

The eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells. These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover. Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro. In cells, the toxin co-localised with F-actin shortly after exposure, and this direct interaction was verified by Förster resonance energy transfer. PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved. The dissociation constant of G-actin binding to PLY in a biochemical environment was 170–190 nM, which is indicative of a high-affinity interaction, comparable to the affinity of other intracellular actin-binding factors. Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought

YvcK, a protein required for cell wall integrity and optimal carbon source utilization, binds uridine diphosphate-sugars

International audienceIn Bacillus subtilis, Listeria monocytogenes and in two Mycobacteria, it was previously shown that yvcK is a gene required for normal cell shape, for optimal carbon source utilization and for virulence of pathogenic bacteria. Here we report that the B. subtilis protein YvcK binds to Uridine diphosphate-sugars like Uridine diphosphate-Glucose (UDP-Glc) and Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) in vitro. Using the crystal structure of Bacillus halodurans YvcK, we identified residues involved in this interaction. We tested the effect of point mutations affecting the ability of YvcK to bind UDP-sugars on B. subtilis physiology and on cell size. Indeed, it was shown that UDP-Glc serves as a metabolic signal to regulate B. subtilis cell size. Interestingly, we observed that, whereas a yvcK deletion results in the formation of unusually large cells, inactivation of YvcK UDP-sugar binding site does not affect cell length. However, these point mutations result in an increased sensitivity to bacitracin, an antibiotic which targets peptidoglycan synthesis. We thus propose that UDP-GlcNAc, a precursor of peptidoglycan, could be a good physiological ligand candidate of YvcK