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Defects in podocyte signaling are the basis of many inherited glomerular diseases leading to glomerulosclerosis. CD2-associated protein (CD2AP) is highly expressed in podocytes and is considered to play an important role in the maintenance of the glomerular slit diaphragm. Mice deficient for CD2AP (CD2AP(-/-)) appear normal at birth but develop a rapid onset nephrotic syndrome at 3 weeks of age. We demonstrate that impaired intracellular signaling with subsequent podocyte damage is the reason for this delayed podocyte injury in CD2AP(-/-) mice. We document that CD2AP deficiency in podocytes leads to diminished signal initiation and termination of signaling pathways mediated by receptor tyrosine kinases (RTKs). In addition, we demonstrate that CIN85, a paralog of CD2AP, is involved in termination of RTK signaling in podocytes. CIN85 protein expression is increased in CD2AP(-/-) podocytes in vitro. Stimulation of CD2AP(-/-) podocytes with various growth factors, including insulin-like growth factor 1, vascular endothelial growth factor, and fibroblast growth factor, resulted in a significantly decreased phosphatidylinositol 3-kinase/AKT and ERK signaling response. Moreover, increased CIN85 protein is detectable in podocytes in diseased CD2AP(-/-) mice, leading to decreased base-line activation of ERK and decreased phosphorylation after growth factor stimulation in vivo. Because repression of CIN85 protein leads to a restored RTK signaling response, our results support an important role of CD2AP/CIN85 protein balance in the normal signaling response of podocytes.
Phosphodiesterase type 2A (PDE2A) hydrolyzes cyclic nucleotides cAMP and cGMP, thus efficiently controlling cNMP-dependent signaling pathways. PDE2A is composed of an amino-terminal region, two regulatory GAF domains, and a catalytic domain. Cyclic nucleotide hydrolysis is known to be activated by cGMP binding to GAF-B; however, other mechanisms may operate to fine-tune local cyclic nucleotide levels. In a yeast two-hybrid screening we identified XAP2, a crucial component of the aryl hydrocarbon receptor (AhR) complex, as a major PDE2A-interacting protein. We mapped the XAP2 binding site to the GAF-B domain of PDE2A. PDE assays with purified proteins showed that XAP2 binding does not change the enzymatic activity of PDE2A. To analyze whether PDE2A could affect the function of XAP2, we studied nuclear translocation of AhR, i.e. the master transcription factor controlling the expression of multiple detoxification genes. Notably, regulation of AhR target gene expression is initiated by tetrachlorodibenzodioxin (TCDD) binding to AhR and by a poorly understood cAMP-dependent pathway followed by the translocation of AhR from the cytosol into the nucleus. Binding of PDE2A to XAP2 inhibited TCDD- and cAMP-induced nuclear translocation of AhR in Hepa1c1c7 hepatocytes. Furthermore, PDE2A attenuated TCDD-induced transcription in reporter gene assays. We conclude that XAP2 targets PDE2A to the AhR complex, thereby restricting AhR mobility, possibly by a local reduction of cAMP levels. Our results provide first insights into the elusive cAMP-dependent regulation of AhR.
Identification of a lysosomal peptide transport system induced during dendritic cell development
(2007)
The delivery of protein fragments to major histocompatibility complex (MHC)-loading compartments of professional antigen-presenting cells is essential in the adaptive immune response against pathogens. Apart from the crucial role of the transporter associated with antigen processing (TAP) for peptide loading of MHC class I molecules in the endoplasmic reticulum, TAP-independent translocation pathways have been proposed but not identified so far. Based on its overlapping substrate specificity with TAP, we herein investigated the ABC transporter ABCB9, also named TAP-like (TAPL). Remarkably, TAPL expression is strongly induced during differentiation of monocytes to dendritic cells and to macrophages. TAPL does not, however, restore MHC class I surface expression in TAP-deficient cells, demonstrating that TAPL alone or in combination with single TAP subunits does not form a functional transport complex required for peptide loading of MHC I in the endoplasmic reticulum. In fact, by using quantitative immunofluorescence and subcellular fractionation, TAPL was detected in the lysosomal compartment co-localizing with the lysosome-associated membrane protein LAMP-2. By in vitro assays, we demonstrate a TAPL-specific translocation of peptides into isolated lysosomes, which strictly requires ATP hydrolysis. These results suggest a mechanism by which antigenic peptides have access to the lysosomal compartment in professional antigen-presenting cells.
The cytochrome bc1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr132 and Glu272, and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe129 and Tyr279. Substitution of Phe129 by lysine or arginine yielded a respiration-deficient phenotype and lipid-dependent catalytic activity. Increased bypass reactions were detectable for both variants, with F129K showing the more severe effects. Substitution with lysine leads to a disturbed coordination of a b heme as deduced from changes in the midpoint potential and the EPR signature. Removal of the aromatic side chain in position Tyr279 lowers the catalytic activity accompanied by a low level of bypass reactions. Pre-steady-state kinetics of the enzymes modified at Glu272 and Tyr132 confirmed the importance of their functional groups for electron transfer. Altered center N kinetics and activation of ubiquinol oxidation by binding of cytochrome c in the Y132F and E272D enzymes indicate long range effects of these mutations.
The cytochrome bc1 complex recycles one of the two electrons from quinol (QH2) oxidation at center P by reducing quinone (Q) at center N to semiquinone (SQ), which is bound tightly. We have analyzed the properties of SQ bound at center N of the yeast bc1 complex. The EPR-detectable signal, which reports SQ bound in the vicinity of reduced bH heme, was abolished by the center N inhibitors antimycin, funiculosin, and ilicicolin H, but was unchanged by the center P inhibitors myxothiazol and stigmatellin. After correcting for the EPR-silent SQ bound close to oxidized bH, we calculated a midpoint redox potential (Em) of approximately 90 mV for all bound SQ. Considering the Em values for bH and free Q, this result indicates that center N preferentially stabilizes SQ.bH(3+) complexes. This favors recycling of the electron coming from center P and also implies a >2.5-fold higher affinity for QH2 than for Q at center N, which would potentially inhibit bH oxidation by Q. Using pre-steady-state kinetics, we show that Q does not inhibit the initial rate of bH reduction by QH2 through center N, but does decrease the extent of reduction, indicating that Q binds only when bH is reduced, whereas QH2 binds when bH is oxidized. Kinetic modeling of these results suggests that formation of SQ at one center N in the dimer allows stabilization of SQ in the other monomer by Q reduction after intradimer electron transfer. This model allows maximum SQ.bH(3+) formation without inhibition of Q binding by QH2.
We have investigated the mechanism responsible for half-of-the-sites activity in the dimeric cytochrome bc(1) complex from Paracoccus denitrificans by characterizing the kinetics of inhibitor binding to the ubiquinol oxidation site at center P. Both myxothiazol and stigmatellin induced a 2-3 nm shift of the visible absorbance spectrum of the b(L) heme. The shift generated by myxothiazol was symmetric, with monophasic kinetics that indicate equal binding of this inhibitor to both center P sites. In contrast, stigmatellin generated an asymmetric shift in the b(L) spectrum, with biphasic kinetics in which each phase contributed approximately half of the total magnitude of the spectral change. The faster binding phase corresponded to a more symmetrical shift of the b(L) spectrum relative to the slower binding phase, indicating that approximately half of the center P sites bound stigmatellin more slowly and in a different position relative to the b(L) heme, generating a different effect on its electronic environment. Significantly, the slow stigmatellin binding phase was lost as the inhibitor concentration was increased. This implies that a conformational change is transmitted from one center P site in the dimer to the other upon stigmatellin binding to one monomer, rendering the second site less accessible to the inhibitor. Because the position that stigmatellin occupies at center P is considered to be analogous to that of the quinol substrate at the moment of electron transfer, these results indicate that the productive enzyme-substrate configuration is prevented from occurring in both monomers simultaneously.
Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1α
(2007)
Hypoxia inducible factor 1 (HIF-1), a key regulator for adaptation to hypoxia, is composed of HIF-1alpha and HIF-1beta. In this study, we present evidence that overexpression of mitochondria-located thioredoxin 2 (Trx2) attenuated hypoxia-evoked HIF-1alpha accumulation, whereas cytosolic thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount. Transactivation of HIF-1 is decreased by overexpression of Trx2 but stimulated by Trx1. Inhibition of proteasomal degradation of HIF-1alpha in Trx2-overexpressing cells did not fully restore HIF-1alpha protein levels, while HIF-1alpha accumulation was enhanced in Trx1-overexpressing cells. Reporter assays showed that cap-dependent translation is increased by Trx1 and decreased by Trx2, whereas HIF-1alpha mRNA levels remained unaltered. These data suggest that thioredoxins affect the synthesis of HIF-1alpha. Trx1 facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and eIF-4E, known to control cap-dependent translation. In contrast, Trx2 attenuated activities of Akt, p70S6K, and eIF-4E and provoked an increase in mitochondrial reactive oxygen species production. MitoQ, a mitochondria specific antioxidant, reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2 cells, supporting the notion of translation control mechanisms in affecting HIF-1alpha protein accumulation.
The catalytic mechanism, electron transfer coupled to proton pumping, of heme-copper oxidases is not yet fully understood. Microsecond freeze-hyperquenching single turnover experiments were carried out with fully reduced cytochrome aa(3) reacting with O(2) between 83 micros and 6 ms. Trapped intermediates were analyzed by low temperature UV-visible, X-band, and Q-band EPR spectroscopy, enabling determination of the oxidation-reduction kinetics of Cu(A), heme a, heme a(3), and of a recently detected tryptophan radical (Wiertz, F. G. M., Richter, O. M. H., Cherepanov, A. V., MacMillan, F., Ludwig, B., and de Vries, S. (2004) FEBS Lett. 575, 127-130). Cu(B) and heme a(3) were EPR silent during all stages of the reaction. Cu(A) and heme a are in electronic equilibrium acting as a redox pair. The reduction potential of Cu(A) is 4.5 mV lower than that of heme a. Both redox groups are oxidized in two phases with apparent half-lives of 57 micros and 1.2 ms together donating a single electron to the binuclear center in each phase. The formation of the heme a(3) oxoferryl species P(R) (maxima at 430 nm and 606 nm) was completed in approximately 130 micros, similar to the first oxidation phase of Cu(A) and heme a. The intermediate F (absorbance maximum at 571 nm) is formed from P(R) and decays to a hitherto undetected intermediate named F(W)(*). F(W)(*) harbors a tryptophan radical, identified by Q-band EPR spectroscopy as the tryptophan neutral radical of the strictly conserved Trp-272 (Trp-272(*)). The Trp-272(*) populates to 4-5% due to its relatively low rate of formation (t((1/2)) = 1.2 ms) and rapid rate of breakdown (t((1/2)) = 60 micros), which represents electron transfer from Cu(A)/heme a to Trp-272(*). The formation of the Trp-272(*) constitutes the major rate-determining step of the catalytic cycle. Our findings show that Trp-272 is a redox-active residue and is in this respect on an equal par to the metallocenters of the cytochrome c oxidase. Trp-272 is the direct reductant either to the heme a(3) oxoferryl species or to Cu (2+)(B). The potential role of Trp-272 in proton pumping is discussed.
In the diazotroph Klebsiella pneumoniae the flavoprotein NifL inhibits the activity of the nif-specific transcriptional activator NifA in response to molecular oxygen and combined nitrogen. Sequestration of reduced NifL to the cytoplasmic membrane under anaerobic and nitrogen-limited conditions impairs inhibition of cytoplasmic NifA by NifL. To analyze whether NifL is reduced by electrons directly derived from the reduced menaquinone pool, we studied NifL reduction using artificial membrane systems containing purified components of the anaerobic respiratory chain of Wolinella succinogenes. In this in vitro assay using proteoliposomes containing purified formate dehydrogenase and purified menaquinone (MK6) or 8-methylmenaquinone (MMK6) from W. succinogenes, reduction of purified NifL was achieved by formate oxidation. Furthermore, the respective reduction rates, which were determined using equal amounts of NifL, have been shown to be directly dependent on the concentration of both formate dehydrogenase and menaquinones incorporated into the proteoliposomes, demonstrating a direct electron transfer from menaquinone to NifL. When purified hydrogenase and MK6 from W. succinogenes were inserted into the proteoliposomes, NifL was reduced with nearly the same rate by hydrogen oxidation. In both cases reduced NifL was found to be highly associated to the proteoliposomes, which is in accordance with our previous findings in vivo. On the bases of these experiments, we propose that the redox state of the menaquinone pool is the redox signal for nif regulation in K. pneumoniae by directly transferring electrons onto NifL under anaerobic conditions.
By translocating proteasomal degradation products into the endoplasmic reticulum for loading of major histocompatibility complex I molecules, the ABC transporter TAP plays a focal role in the adaptive immunity against infected or malignantly transformed cells. A key question regarding the transport mechanism is how the quality of the incoming peptide is detected and how this information is transmitted to the ATPase domains. To identify residues involved in this process, we evolved a Trojan horse strategy in which a small artificial protease is inserted into antigenic epitopes. After binding, the TAP backbone in contact is cleaved, allowing the peptide sensor site to be mapped by mass spectrometry. Within this sensor site, we identified residues that are essential for tight coupling of peptide binding and transport. This sensor and transmission interface is restructured during the ATP hydrolysis cycle, emphasizing its important function in the cross-talk between the transmembrane and the nucleotide-binding domains. This allocrite sensor may be similarly positioned in other members of the ABC exporter family.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid that binds to G protein-coupled-receptors and activates various signaling cascades. Here, we show that in renal mesangial cells, SPC not only activates various protein kinase cascades but also activates Smad proteins, which are classical members of the transforming growth factor-β (TGFβ) signaling pathway. Consequently, SPC is able to mimic TGFβ-mediated cell responses, such as an anti-inflammatory and a profibrotic response. Interleukin-1β-stimulated prostaglandin E2 formation is dose-dependently suppressed by SPC, which is paralleled by reduced secretory phospholipase A2 (sPLA2) protein expression and activity. This effect is due to a reduction of sPLA2 mRNA expression caused by inhibited sPLA2 promoter activity. Furthermore, SPC upregulates the profibrotic connective tissue growth factor (CTGF) protein and mRNA expression. Blocking TGFβ signaling by a TGFβ receptor kinase inhibitor causes an inhibition of SPC-stimulated Smad activation and reverses both the negative effect of SPC on sPLA2 expression and the positive effect on CTGF expression. In summary, our data show that SPC, by mimicking TGFβ, leads to a suppression of proinflammatory mediator production and stimulates a profibrotic cell response that is often the end point of an anti-inflammatory reaction. Thus, targeting SPC receptors may represent a novel therapeutic strategy to cope with inflammatory diseases.
2,5-Diformylbenzene-1,4-diol (5) is a well-suited starting compound for the preparation of ditopic hydroquinone-based ligands. Here, we report an optimized synthesis of 5 which improves the overall yield from published 7% to 42 %. Three new ditopic Schiff base ligands, 2,5-[iPr2N(CH2)2N=CH]2 - 1,4-(OH)2-C6H2 (8), 2,5-(pyCH2N=CH)2-1,4-(OH)2-C6H2 (9), and 2,5-[py(CH2)2N=CH]2-1,4- (OH)2-C6H2 (10), have been synthesized from 5 and structurally characterized by X-ray crystal structure analysis (py = 2-pyridyl).
The ATP-binding cassette half-transporter Mdl1 from Saccharomyces cerevisiae has been proposed to be involved in the quality control of misassembled respiratory chain complexes by exporting degradation products generated by the m-AAA proteases from the matrix. Direct functional or structural data of the transport complex are, however, not known so far. After screening expression in various hosts, Mdl1 was overexpressed 100-fold to 1% of total mitochondrial membrane protein in S. cerevisiae. Based on detergent screens, Mdl1 was solubilized and purified to homogeneity. Mdl1 showed a high binding affinity for MgATP (Kd = 0.26 μm) and an ATPase activity with a Km of 0.86 mm (Hill coefficient of 0.98) and a turnover rate of 2.6 ATP/s. Mutagenesis of the conserved glutamate downstream of the Walker B motif (E599Q) or the conserved histidine of the H-loop (H631A) abolished ATP hydrolysis, whereas ATP binding was not affected. Mdl1 reconstituted into liposomes showed an ATPase activity similar to the solubilized complex. By single particle electron microscopy, a first three-dimensional structure of the mitochondrial ATP-binding cassette transporter was derived at 2.3-nm resolution, revealing a homodimeric complex in an open conformation.
Bovine mitochondrial ATP synthase commonly is isolated as a monomeric complex that contains 16 protein subunits and the natural IF1 inhibitor protein in substoichiometric amounts. Alternatively ATP synthase can be isolated in dimeric and higher oligomeric states using digitonin for membrane solubilization and blue native or clear native electrophoresis for separation of the native mitochondrial complexes. Using blue native electrophoresis we could identify two ATP synthase-associated membrane proteins with masses smaller than 7 kDa and isoelectric points close to 10 that previously had been removed during purification. We show that in the mitochondrial membrane both proteins are almost quantitatively bound to ATP synthase. Both proteins had been identified earlier in a different context, but their association with ATP synthase was unknown. The first one had been named 6.8-kDa mitochondrial proteolipid because it can be isolated by chloroform/methanol extraction from mitochondrial membranes. The second one had been denoted as diabetes-associated protein in insulin-sensitive tissue (DAPIT), which may provide a clue for further functional and clinical investigations.
We present predictions for the pseudorapidity dependence of the azimuthal anisotropy parameters v1 and v2 of baryons and inclusive charged hadrons in Pb + Pb collisions at a LHC energy of sNN=5.5 TeV applying a microscopic transport model, namely the quark–gluon string model (QGSM) which has been recently extended for parton rearrangement and fusion processes. Pb + Pb collisions with impact parameters b=2.3 fm and b=8 fm have been simulated in order to investigate additionally the difference between central and semiperipheral configurations. In contrast to v1ch(η) at RHIC, the directed flow of charged hadrons shows a small normal flow alignment. The elliptic flow v2ch(η) turns out to be rather similar in shape for RHIC and LHC conditions, the magnitude however increases about 10–20% at the LHC, leading to the conclusion that the hydrodynamical limit will be reached.
Within a dynamical quark recombination model, we explore various proposed event-by-event observables sensitive to the microscopic structure of the QCD-matter created at RHIC energies. Charge ratio fluctuations, charge transfer fluctuations and baryon-strangeness correlations are computed from a sample of central Au + Au events at the highest RHIC energy available (sNN=200 GeV). We find that for all explored observables, the calculations yield the values predicted for a quark–gluon plasma only at early times of the evolution, whereas the final state approaches the values expected for a hadronic gas. We argue that the recombination-like hadronization process itself is responsible for the disappearance of the predicted deconfinement signals. This might explain why no fluctuation signatures for the transition between quark and hadronic matter was ever observed in the experimental data up to now.
Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25–50 μg/ml inhibited staurosporine-induced apoptosis in THP-1 cells and mouse peritoneal macrophages, and it was cytoprotective in human primary monocytes upon serum withdrawal. Attenuated cell demise was reversed by blocking extracellular signal-regulated kinase (ERK) signaling. Translocation of cytochrome c to the cytosol was attenuated by OxLDL, which again demanded ERK signaling. Analysis of Bcl-2 family proteins revealed phosphorylation of Bad at serine 112 as well as ERK-dependent inhibition of Mcl-1 degradation. Although the formation of reactive oxygen species (ROS) is an established signal generated by OxLDL, ROS scavengers did not interfere with cell protection by OxLDL. Thus, activation of the ERK signaling pathway by OxLDL is important to protect phagocytes from apoptosis.
The nuclear stopping, the elliptic flow, and the HBT interferometry are calculated by the UrQMD transport model, in which potentials for “pre-formed” particles (string fragments) from color fluxtube fragmentation as well as for confined particles are considered. This description provides stronger pressure at the early stage and describes these observables better than the default cascade mode (where the “pre-formed” particles from string fragmentation are treated to be free-streaming). It should be stressed that the inclusion of potential interactions pushes down the calculated HBT radius RO and pulls up the RS so that the HBT time-related puzzle disappears throughout the energies from AGS, SPS, to RHIC.
Clear native electrophoresis and blue native electrophoresis are microscale techniques for the isolation of membrane protein complexes. The Coomassie Blue G-250 dye, used in blue native electrophoresis, interferes with in-gel fluorescence detection and in-gel catalytic activity assays. This problem can be overcome by omitting the dye in clear native electrophoresis. However, clear native electrophoresis suffers from enhanced protein aggregation and broadening of protein bands during electrophoresis and therefore has been used rarely. To preserve the advantages of both electrophoresis techniques we substituted Coomassie dye in the cathode buffer of blue native electrophoresis by non-colored mixtures of anionic and neutral detergents. Like Coomassie dye, these mixed micelles imposed a charge shift on the membrane proteins to enhance their anodic migration and improved membrane protein solubility during electrophoresis. This improved clear native electrophoresis offers a high resolution of membrane protein complexes comparable to that of blue native electrophoresis. We demonstrate the superiority of high resolution clear native electrophoresis for in-gel catalytic activity assays of mitochondrial complexes I–V. We present the first in-gel histochemical staining protocol for respiratory complex III. Moreover we demonstrate the special advantages of high resolution clear native electrophoresis for in-gel detection of fluorescent labeled proteins labeled by reactive fluorescent dyes and tagged by fluorescent proteins. The advantages of high resolution clear native electrophoresis make this technique superior for functional proteomics analyses.
Proton pumping respiratory complex I is a major player in mitochondrial energy conversion. Yet little is known about the molecular mechanism of this large membrane protein complex. Understanding the details of ubiquinone reduction will be prerequisite for elucidating this mechanism. Based on a recently published partial structure of the bacterial enzyme, we scanned the proposed ubiquinone binding cavity of complex I by site-directed mutagenesis in the strictly aerobic yeast Yarrowia lipolytica. The observed changes in catalytic activity and inhibitor sensitivity followed a consistent pattern and allowed us to define three functionally important regions near the ubiquinone-reducing iron-sulfur cluster N2. We identified a likely entry path for the substrate ubiquinone and defined a region involved in inhibitor binding within the cavity. Finally, we were able to highlight a functionally critical structural motif in the active site that consisted of Tyr-144 in the 49-kDa subunit, surrounded by three conserved hydrophobic residues.
This is the fourth in a series of publications on Zambian languages and grammar. The intention of the series is to boost the meagre scholarship and availability of educational materials on Zambian languages, which became particularly urgent in 1996, following the decision of the Zambian government to revert to the policy of using local languages as media of instruction. Kaonde (or more correctly Kikaonde) is spoken in the part of the North-Western Province of Zambia to the east of the Kabompo River, in adjacent parts of Mumbwa and Kaoma Districts to the south, and in the Katanga Province of the Democratic Republic of Congo to the North.
Captive of Fate
(2007)
Captive of Fate is the moving story of Ann, a victim of her own need for genuine love, and her gullibility in falling head over heels into the traps of lust set up by clever men. As Ann's biographic narrative unfolds, the reader is faced again and again with the haunting question: 'Do all men want only one thing from a woman?' Hidden between the lines and yet hammering constantly at the reader's conscience are issues pertaining to gender violence and the plight of women in Africa.
The Botsotso literary journal started in 1996 as a monthly 4 page insert in the New Nation, an independent anti-apartheid South African weekly and reached over 80,000 people at a time ? largely politisized black workers and youth ? with a selection of poems, short stories and short essays that reflected the deep changes taking place in the country at that time. Since the closure of the New Nation in 1999, the journal has evolved into a stand-alone compilation featuring the same mix of genres, and with the addition of photo essays and reviews. The Botsotso editorial policy remains committed to creating a mix of voices which highlight the diverse spectrum of South African identities and languages, particularly those that are dedicated to radical expression and examinations of South Africa's complex society.
The Millennium Development Goals address poverty, hunger, disease, illiteracy, environmental degradation, and discrimination against women, by the year 2015. In this volume scholars and policymakers in the fields of population and health reflect on the attainments of some of these goals, on the basis of empirical evidence in the Ghanaian context. The eight paper, with an introduction by the editors, synthesises papers presented at a seminar held in Ghana on ?Population, Health and Development in Relation to the Millennium Development Goals?, organised by the Population Association of Ghana.
From its modest beginnings in the mid-19th century, Dar es Salaam has grown to become one of sub-Saharan Africa?s most important urban centres. A major political, economic and cultural hub, the city stood at the cutting edge of trends that transformed twentieth-century East Africa. Dar es Salaam has recently attracted the attention of a diverse, multi-disciplinary, range of scholars, making it currently one of the continent?s most studied urban centres. This collection from eleven scholars from Africa, Europe, North America and Japan, draws on some of the best of this scholarship and offers a comprehensive, and accessible, survey of the city?s development. The perspectives include history, musicology, ethnomusicology, culture including popular culture, land and urban economics. The opening chapter offers a comprehensive overview of the history of the city. Subsequent chapters examine Dar es Salaam?s twentieth century experience through the prism of social change and the administrative repercussions of rapid urbanisation; and through popular culture and shifting social relations. The book will be of interest not only to the specialist in urban studies but also to the general reader with an interest in Dar es Salaam?s environmental, social and cultural history.
Songs and Politics in Eastern Africa brings together important essays on songs and politics in the region and beyond. Through an analysis of the voices from the margins, the authors (contributors) enter into the debate on cultural productions and political change. The theme that cuts across the contributions is that songs are, in addition to their aesthetic appeal, vital tools for exploring how political and social events are shaped and understood by citizens. Urbanization, commercialization and globalization contributed to the vibrancy of East African popular music of the 1990s which was marked by hybridity, syncretism and innovativeness. It was a product of social processes inseparable from society, politics, and other critical issues of the day. The lyrics explored socials cosmology, worldviews, class and gender relations, interpretations of value systems, and other political, social and cultural practices, even as they entertained and provided momentary escape for audience members. Frustration, disenchantments, and emotional fatigue resulting from corrupt and dictatorial political systems that stifle the potential of citizens drove and still drive popular music in Eastern Africa as in most of Africa. Songs and Politics in Eastern Africa is an important addition to the study of popular culture and its role in shaping society.
Lack of transparency and accountability in the planning practice allow for misuse and abuse of the planning system to serve the interests of the more powerful and influential groups, including those entrusted with the powers of planning. The outcomes of a non-inclusive, non-transparent and insensitive planning include: insecurity of land tenure rights and subsequently investments in land; poverty; informal land subdivision and building; unplanned spatial growth and endless conflicts in land development. These are detrimental to the residents and erode their trust and confidence in the government. It takes an organized, informed, confident and courageous group of residents or community to reject the non-inclusive form of planning and cause adoption of inclusive and collaborative planning that allows them space in the planning process. The achievement of such an organized group ? a turn towards democratic planning practice ? leads to a conclusion that informed, organized, confident and courageous civil society is a pillar of democracy. This book therefore argues that ineffective planning results, among other things, from defective land policy and legislation, and planning inability to recognize and make use of opportunities for shaping the built environment.
Paul E. Isert, a Dane, arrived in Ghana (then the Gold Coast) in 1783, taking advantage of an opening in the slave trade between Guinea and the West Indies. He was appointed as chief surgeon to the Danish establishments on the Guinea Coast. In 1786 he sailed to the West Indies with a cargo of slaves, who revolted. His experiences in Ghana and the West Indies resolved him to end the trans-Atlantic slave abuse. This book is written in the form of letters to his father. An elusive character, it is clear that he nonetheless had an unreservedly positive attitude towards Africa and its indigenous peoples, and an equally negative attitude towards the Europeans on the Guinea coast. An admirer of Rousseau?s philosophy, he was concerned about the corrupting influence of the European ?civilisation? on the ?Blacks?. His writing attempts at objectivity, seeking to find the common humanity. He claims that the ?Black? was, at least equal to that of the ?European?,which was not shared by his Danish predecessors. This is the first English language edition of his original Danish letters, previously published in German, Dutch, French, and Swedish.
The year-long celebration of Ghana's Golden Jubilee provides a fitting context for the republication of the book Kwame Nkrumah: Vision and Tragedy. In the lead-up to the celebration and over the course of the year, the life and times of Kwame Nkrumah will receive unprecedented public attention, official and unofficial. Kwame Nkrumah's very wide name-recognition is, paradoxically, accompanied by sketchy, often oversimplified knowledge about the events and processes of his life and times. For most of those born after independence in 1957, such knowledge does not extend much beyond who Kwame Nkrumah was and vague notions about he won us Independence. This book presents new material and new analysis, which helps to clarify aspects of the record, while advancing new perspectives. What comes across clearly throughout the book is the significant contribution of Nkrumah's vision and personality at a critical moment in the history of Africa and the Third World. He, perhaps more than any other, was able to identify, focus and catalyse the major factors and players driving the struggle for political independence in Ghana and liberation in other parts of Africa. In the process, he committed his life and work totally to a wide variety of activities and processes in Ghana, the continent and in the global Non-Aligned Movement.
It Happened in Ghana carries a positive message. Conceived as a literary work, it demonstrates that racial prejudice based on skin colour is not a pervasive and unalterable human condition. The principal characters who are both Black and White are embroiled in various encounters, notably wars, slave trade, colonialism and post colonial reconstruction. Regardless of their skin colour and cultural differences, they make friends or fall in love secretly during these encounters. When they are forced to part company by the cessation of hostilities or whatever brought them together, they serve in various capacities in new locations outside their original places of domicile. They are accepted or integrated into existing social structures because of the warmth oftheir personalities and the manner in which they are able to adjust themselves to the pressures and challenges of new environments. Changes in the circumstances of the principal characters or their descendants enable them not only to restore broken relationships but also to identify themselves with the cause of freedom and justice or to reconnect in various ways with the development aspirations of Ghana where it all started.
The religious life of the Tonga-speaking peoples of southern Zambia is examined over the last century, in the sense of how they have thought about the nature of their world, the meaning of their own lives, and the sources of good and evil in which their cosmology and society have been transformed. The twelve chapters cover Time, Space and Language; Basic Themes, Tonga Religious Vocabulary and its Referents; the Vocabulary of Shrines and Substance; Homestead and Bush; Ritual Communities and Actors; Rituals of the Life Course; Death and its Rituals; Evil and Witchcraft; and Christianity and Tonga Experience. The author has drawn on dairies by research assistants, and field notes and research of fellow anthropologists, but above all from her own interaction with Tonga people since 1946. The older people gave first hand memories of Ndebele and Lozi raids, David Linvingstone encamped near their villages in 1856 and 1862, the arrival of colonial administrators, traders, missionaries and European and Indian settlers, and in some cases, the end of colonial rule. Their experience and that of their children, grandchildren, and great grandchildren provides the basis for understanding Tonga religious experience. Elizabeth Colson is an American anthropologist who is widely published on the Tonga. Her research interests have particularly concentrated on the Gwembe Valley.
Art, Culture and Society Vol 1 is the first in a series of books to be published by Twaweza Communications on the relationship between art and society, with special reference to Kenya. It is part of a cultural leadership initiative being undertaken by the organization through a reexamination of the arts as they are produced and studied. This volume brings together important reflections on the arts and is a major step in encouraging dialogue on the relationship between creativity and the human condition in the region. Significantly, it creates a space for university-based academics to engage in dialogue with artists and writers based outside institutions of higher learning. The conversations will bridge the gap between the two domains for knowledge production and enrich creative enterprise in Kenya, in theory and practice. As the essays in this collection show, the present global situation demands a way to conceptualise and theorise an ever growing cultural interconnectedness, sometimes manifested in art; and interconnectedness that draws from a myriad of cultures and experiences. Through the bridges of contact and cultural exchange distant images are mediated and brought closer to us. They are reinterpreted and modified. In the final analysis, culture is shown to be an important aspect of human creativity but separateness and boundedness is contested. Instead, culture is shown to be malleable and fluid. The essays bring in a new freshness to our reading of the creative arts coming out of Kenya.
The Concept of Botho and HIV
(2007)
Ever since the publication of Placide Tempel's epoch-making work Bantu Philosophy, African philosophers have worked to dispel the myth that there is no metaphysics in Africa. In the East African context we remember the names of Joseph Nyasmi and Odera Oruka, and in the West African context, Pauline Hotoundji and Kwesi Wiredu have made monumental contributions to elucidate African metaphysics. This compendium, presented by a group of scholars from the University of Botswana, seeks to build bridges between the seemingly estranged disciplines of African metaphysics, existential philosophy, and economics in the contexts of HIV/AIDS.
The subject of human rights and its attendant these of access to justice have remained relevant areas to the legal fraternity. This relevance resonates well in the fields of teaching and learning the law, consultancy, legal practice and advocacy, law reform, and judicial decision making. In the East African region, however, the availability of research and reference material for these two areas of learning has remained low. It is against the backdrop of the foregoing that the publishing of the Digest on Human Rights and Access to Justice in East Africa is an important aspect of the development of the law in the region. Bringing together decisions of both municipal courts within the East Africa region beyond, the digest has breathed a totally new lease of life into the practice and comparative legal studies in the area of human rights and access to justice. To a large extent, the digest has robbed practitioners of law of the excuses attendant to poor advocacy in the arena of human rights. It has robbed judicial officer of the excuses attendant to shallow and poorly reasoned judgments. It has robbed students and teachers of law the excuses attendant to poorly researched theses in the area of human rights. Definitely, it has added immense value to the consumers of human rights and access to justice. This Digest is a product of the fruitful on-going collaboration between LawAfrica Publishing Ltd and East Africa Law Society. Both LawAfrica with its East Africa Law Reports, and EALS, with its ever-growing collaboration between East African lawyers, yearn for greater integration of legal practice in the three East African countries. This Digest is a contribution to that desire.
The Jurisprudence on Regional and International Tribunals Digest is borne out of the recent developments in the judicial arena of the East African Community and other inter-state arrangements where matters are increasingly getting litigated and determined at the international fora. With such a development, there is the more current need to document the reasoning, not just of judicial officers from the East African Court of Justice but also from other regional and international tribunals. This will help in consolidating knowledge on diverse aspects of substance and procedure from these tribunals for both academic and practice purposes. This digest no doubt adds value to practitioners in the East African region and beyond who are getting absorbed into legal practice before tribunals of an international law character. It is hoped that the digest will further be of great assistance to the community of the academia that is in need of material for the dispensation of knowledge in the area of international law.
No Turning Back relives the tumultuous beginnings of Africa's democratization experiment in the early 1990s. The main theme of the collection is an investment in hope and in the resilience of Africans. The poems are loud and clear in their castigation of dictatorship and its miseries. They celebrate the mass resolve and thirst for democracy by Africans for whom there is 'No turning back!' 'A lucid and truly memorable collection of poems. Dibussi forces us to turn back and look at the pivotal volcanic moments in Cameroon's history between 1990- 1993... As a student activist and budding journalist during this historic period, Dibussi captures cadences of this struggle eloquently.' Joyce Ashuntantang, Ph.D., Department of English, University of Connecticut, Greater Hartford, USA. 'This collection is an important document chronicling, through verse, the events of an era in a given space with unmitigated passion.' Kangsen Wakai, poet, Houston, Texas, USA '. a subtle yet unapologetic critique of Cameroon's chequered history of predatory governance. The poems provide succor to a people besieged first by the unrealised dreams of a political (mis)marriage and then a false promissory note on which their democratic development is written.' George Ngwane, Chair, National Book Development Council - Cameroon
Stories from Abakwa
(2007)
Childhood and growing up in Mimboland, Cameroon are infused with fascinating stories and adventures. Discover life in Abakwa with Tom and his friend, as they are chased through an orchard for secretly harvesting avocadoes and mangoes. Smile as Mathias Chi's overloaded canoe almost loses balance. Shiver as Roland runs through the dark streets and bleeding corridors of Mvog Mvog. And cry when Big Brother discovers how his siblings suffered when he was away at school. What happens to Esther when she finds the courage to make an announcement at the Abakwa Mountain Foot Radio Station about her husband's disappearance? Will Prudencia and Collette kill or give life? How does Prisca Lum deal with her dwarf husband? Some characters will remind you of people you know - or even of yourself. Drum beats and church bells, thunder and lightning, princes and princesses, visions and deceptions fill the pages. Discover your favorite stories waiting to be told and retold, again and again.
Not Yet Damascus
(2007)
The Convert : A Two-Act Play
(2007)
' ''This play tackles the theatrically attractive but ethically complex issue of Christian fundamentalism. Nyamnjoh, as a sociologist is well qualified to explore the social problems and psychological pressures which give rise to the born-again phenomenon, and the strong appeal of fundamentalist religion. The Convert, however is no schematic sociological tract. It deals with the conflicting imperatives in 21st century West Africa, which push ordinary people into extraordinary situations, and provides no easy solutions to the issues raised. Although the play revolves around the Ultimate Church of Christ and the four main characters affected by it, the audience is given a deftly sketched picture of a corrupt world beyond it, lacking in spiritual or community values. [..] The characterization. is remarkable for its avoidance of any obvious protagonist; the audience is allowed no clear character with whom to identify. The four main characters . have both virtues and flaws, each providing insights into ways the consumer-oriented materialism of modern life impacts upon African spirituality and community values. - David Kerr, Professor in Literature and Drama, University of Botswana ''''At the core of the implicit philosophy in Nyamnjoh's The Convert . is the theatrical manifesto that contemporary society has not only to liberate itself, and its productive powers from 'Pentecostal', freak religions and distortion, it also has to liberate these same productive capacities from their present prostration. There is a deep, engaging humanism that pervades The Convert, but it is a humanism emblematic, to speak analogously, of the Aeschylean variety.'''' - Bate Besong, Africa Review of Books.'''
Mind Searching
(2007)
In Mind Searching Nyamnjoh has attempted to do something rather clever - to expose, through the attitudes, feelings and thoughts of one man and a very simple story, the hypocrisy and corruption of Cameroon society and humanity in general, often using understatement and irony in good effect. The commentary is unremittingly cynical and returns again and again to corruption, callous squandering, exploitation, prostitution, and other fairly worn butts. The book depicts a society where basic freedoms are shackled, and thinking aloud treasonable. Hence the mental ramblings of the narrator and central character Judascious Fanda Yanda, in the form of an extended monologue full of observations, anecdotes and asides written from the point of view of an apparently insouciant naive. The basic method is to foreground the opinions and conversational elegance of the narrator, while having events going on as a background to his thoughts. We trace the narrator's progress from a disenchanted 'Damn? de la Terre' to a comfortably well off Private Secretary to a Vice Minister over a number of years. It is a clear illustration of how the system perpetuates its mediocrity and buys off any spark of initiative. Nyamnjoh has a good command of ironic tone and sound control over form and structure. He employs a very fluent style, and often has very urbane and neat turns of phrase. He captures the bored, superior, cynical and ultimately predatory tone of voice of his narrator extremely well.
The Disillusioned African
(2007)
This humorous tale of the na?ve and curious African student-cum-philosopher wandering between North and South, the rural and the urban, has been in gestation for a period of nearly two decades. With allusion to traditions of the philosophical novel and the picaresque, Nyamnjoh's protagonist travels from his African village to the sharply divided and socially cruel world of 1980s Britain. By casting aside his disillusion and the traps of servitude and victimhood, The Disillusioned African reveals his creative potential for curiosity and adventure. He brings a bird's eye view, always affectionate, gently mocking, to the cultural idiosyncrasies of the new world he encounters, which throws his own African culture, politics and socio-economic realities into light relief. Praise for The Disillusioned African 'Whatever the imagined future for Africa, this courageous book will certainly provide, for both its foreign readers and the young generation of Cameroonians, a provocative insight into the complex web of despair, frustration, paradox and hope . on the eve of the 21st century.' - Louise Cuming, Catholic University of Central Africa 'In his characteristically humorous style, Nyamnjoh portrays the various social ills in society and castigates the political elite he holds largely responsible.' - Piet Konings, African Studies Centre, Leiden, The Netherlands. 'Francis Nyamnjoh . has a particular way of saying very serious things in the most unserious manner. He entertains, and in the process he moralises, he teaches, he gives you lessons. learning experience and philosophy to give you a view of the dilemma of the African.' - Sammy Beban Chumbow, Professor of Linguistics, University of Yaounde I