Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.

Abstract

After training as a gastroenterologist in the UK the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant he introduced the use of plasma exchange to treat FH homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway.

Management of heterozygous FH has been greatly facilitated by statins and PCSK9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH whereas in heterozygotes the current need is better detection.

Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD). More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for lutein and zeaxanthin supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with lutein and zeaxanthin might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves  are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as  prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using -3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2) that releases the incorporated DHA from phospholipids and enhances the synthesis of docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer  RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A).  RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.

Genetic variants that increase the risk of fatty liver disease (FLD) and cirrhosis have recently been identified in the proximity of membrane bound O-acyltransferase domain-containing 7 (MBOAT7).  To elucidate the link between these variants and FLD we characterized Mboat7 liver-specific knock-out mice (Mboat7-LSKO).  Chow-fed Mboat7-LSKO mice developed fatty livers and associated liver injury.  Lipidomic analysis of liver using mass spectrometry revealed a pronounced reduction in 20-carbon polyunsaturated fatty acid content in phosphatidylinositols (PIs), but not in other phospholipids. The change in fatty acid composition of PIs in these mice was associated with a marked increase in de novo lipogenesis due to activation of SREBP-1c, a transcription factor that coordinates the activation of genes encoding enzymes in the fatty acid biosynthesis pathway. Hepatic removal of both SREBP cleavage activating protein (Scap) and Mboat7 normalized hepatic triglycerides relative to Scap only hepatic knock-out showing increased SREBP-1c processing is required for Mboat7 induced steatosis.  This study reveals a clear relationship between PI fatty acid composition and regulation of hepatic fat synthesis and delineates the mechanism by which mutations in MBOAT7 cause hepatic steatosis.

Mendelian randomization (MR) of lipid traits in coronary artery disease (CAD) has provided evidence for causal associations of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid trait genetic variants and to account for these effects in MR of lipid traits in CAD. We performed multivariable MR using inverse variance-weighted (IVW) and MR-Egger methods in large (n ≥ 300,000) GWAS datasets. We found that 30% of lipid trait genetic variants have effects on metabolic syndrome traits, including body mass index (BMI), type 2 diabetes (T2D), and systolic blood pressure (SBP). Nonetheless, in multivariable MR analysis, LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, BMI, T2D, and SBP are independently associated with CAD, and each of these associations is robust to adjustment for directional pleiotropy. MR at loci linked to direct effects on HDL-C and TG suggests locus- and mechanism-specific causal effects of these factors on CAD.

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (VLC-PUFAs,n-3, ≥ 28 carbons) are at the sn-1 of this PC molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes. Here, we review the structures and stereochemistry of novel elovanoid (ELV)-N32 and ELV-N34 to be ELV-N32: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydo-triaconta-14,17,21,23,25,29-hexaenoic acid; ELV-N34: (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetra-triaconta-16,19,23,25,27,31-hexaenoic acid. ELVs are low-abundance, high-potency, protective mediators. Their bioactivity includes enhancing of anti-apoptotic and pro-survival protein expression with concomitant downregulation of pro-apoptotic proteins when RPE is confronted with uncompensated oxidative stress (UOS). ELVs also target PRC/RPE senescence gene programming, the senescence secretory phenotype in the interphotoreceptor matrix (IPM), as well as inflammaging (chronic, sterile, low-grade inflammation). An important lesson on neuroprotection is highlighted by the ELV mediators that target the terminally differentiated PRC and RPE, sustaining a beautifully synchronized renewal process. The role of ELVs in PRC and RPE viability and function uncovers insights on disease mechanisms and the development of therapeutics for age-related macular degeneration (AMD), Alzheimer’s disease (AD), and other pathologies.

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.

Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of patients carrying either L75P or L174S ApoA-I amyloidogenic variants a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by inducing the degradation of hepatic low-density lipoprotein receptor (LDLR). Plasma PCSK9 has two main molecular forms: a 62-kDa mature form (PCSK9_62) and a 55-kDa, furin-cleaved form (PCSK9_55). PCSK9_55 is considered less active than PCSK9_62 in degrading LDLR. We aimed to identify the site of PCSK9_55 formation (intra- vs. extracellular) and to further characterize the LDLR-degradative function of PCSK9_55 relative to PCSK9_62. Co-expressing PCSK9_62 with furin in cell culture induced formation of PCSK9_55, most of which was found in the extracellular space. Under the same conditions we found that: i) adding a cell-permeable furin inhibitor preferentially decreased the formation of PCSK9_55 extracellularly; ii) using pulse-chase, we observed the formation of PCSK9_55 exclusively extracellularly in a time-dependent manner. A recombinant form of PCSK9_55 was efficiently produced but displayed impaired secretion that resulted in its intracellular trapping. However, the non-secreted PCSK9_55 was able to induce degradation of LDLR, though with 50% lower efficiency compared with PCSK9_62. Collectively, our data show that PCSK9_55 is generated in the extracellular space, and that intracellular PCSK9_55 is not secreted but retains the ability to degrade the LDLR through an intracellular pathway.

Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically elevated levels of 7-dehydrocholesterol (7-DHC) in all bodily tissues and fluids. Previous mouse models of SLOS have been hampered by postnatal lethality when Dhcr7 is knocked out globally, while a hypomorphic mouse model showed improvement in the biochemical phenotype with ageing, and did not manifest most other characteristic features of SLOS. We report the generation of a conditional knockout of Dhcr7 (Dhcr7flx/flx), validated by generating a mouse with a liver-specific deletion (Dhcr7L-KO). Phenotypic characterization of liver-specific knockout mice revealed no significant changes in viability, fertility, growth curves, liver architecture, hepatic triglyceride secretion, or parameters of systemic glucose homeostasis. Furthermore, qPCR and RNA-Seq analyses of livers revealed no perturbations in pathways responsible for cholesterol synthesis, either in male or female Dhcr7L-KO mice, suggesting hepatic disruption of post-squalene cholesterol synthesis leads to minimal impact on sterol metabolism in the liver. This validated conditional Dhcr7 knockout model may now allow us to systematically explore the pathophysiology of SLOS, by allowing for temporal, cell and tissue-specific loss of DHCR7.

Lecithin:cholesterol-acyl-transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodelling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT func- tionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences. Although several hypotheses were formulated, the exact molecular recognition mechanism between LCAT and HDLs is still unknown. We employed a combination of structural bioinformatics procedures to deepen the insights into the HDL-LCAT interplay that promotes LCAT activation and cholesterol esterification. We have generated a data-driven model of reconstituted HDL (rHDL) and studied the dynamics of an assembled rHDL::LCAT supramolecular complex, pinpointing the conformational changes originating from the interaction between LCAT and apolipoprotein A-I (apoA-I) that are necessary for LCAT activation. Specifically, we propose a mechanism in which the anchoring of LCAT lid to apoA-I helices allows the formation of a hydrophobic hood that expands LCAT active site and shields it from the solvent, allowing the enzyme to process large hydrophobic substrates.

Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.

The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low fat (LF) diet or high fat diets with (HFHC) or without (HF) cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as increased adiposity with adipose tissue inflammation and liver steatosis. However, when animals were fed the HF diet supplemented with cholesterol, the LRP1 NPxY mutation prevents hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, insulin signaling is impaired in LRP1 NPxY mutant hepatocytes and this mutation does not protect against HFHC-induced insulin resistance. The selective metabolic improvement observed in HFHC-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lowering of plasma and hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice in response to HF or HFHC diet feeding indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.

Apolipoproteins C-I, C-II and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer’s disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1. delineate apoC-I, C-II and C-III isoform profiles in CSF and plasma in a cohort of non-demented older individuals (n = 61), and 2. examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared to matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two non-sialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF, and apoC-II in plasma and CSF, was observed in individuals carrying at least one apoE E4 allele. Increased apoC-I and apoC-II truncations were  associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of E4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE E4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer’s disease pathology with apoCs processing and function in the brain.

Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3’s role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approx. 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, α-β hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism, such as fatty acid oxidation, de novo lipogenesis and triglyceride secretion. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism

Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of > 90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, while diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear co-localization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

Deficiency of glucocerebrosidase (GBA), a lysosomal β-glucosidase, causes Gaucher disease. The enzyme hydrolyzes β-glucosidic substrates and transglucosylates cholesterol to cholesterol-β-glucoside. Here we show that recombinant human GBA also cleaves β-xylosides and transxylosylates cholesterol. The xylosyl-cholesterol formed acts as acceptor for subsequent formation of di-xylosyl-cholesterol. Common mutant forms of GBA from patients with Gaucher disease with reduced β-glucosidase activity were similarly impaired in β-xylosidase, transglucosidase and transxylosidase activities, except for a slightly reduced xylosidase/glucosidase activity ratio of N370S GBA and a slightly reduced transglucosylation/glucosidase activity ratio of D409H GBA. XylChol was found to be reduced in spleen from Gaucher disease patients. The origin of newly identified XylChol in mouse and human tissues was investigated. Cultured human cells exposed to exogenous β-xylosides generated XylChol in a manner dependent on active lysosomal GBA but not the cytosol-facing β-glucosidase GBA2. We later sought an endogenous β-xyloside acting as donor in transxylosylation reactions, identifying xylosylated ceramide (XylCer) in cells and tissues that serve as donor in the formation of XylChol. UDP-glucosylceramide synthase (GCS) was unable to synthesize XylChol but could catalyse formation of XylCer. Thus, food-derived β-D-xyloside and XylCer are potential donors for the GBA-mediated formation of XylChol in cells. The enzyme GCS produces XylCer at a low rate. Our findings point to further catalytic versatility of GBA and prompt a systematic exploration of the distribution and role of xylosylated lipids.

Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR).  This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid lowering drugs, such as fibrates, omega 3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol or HDL/LDL cholesterol ratio. Guided by these findings, plasma lipid and lipoprotein-independent mechanisms are addressed based on clinical, cell culture and animal model studies. Potential retinal-specific effects of fatty acids oxidation products, cholesterol, and ceramide, as well as lipid independent effects of PPAR alpha activation are summarized based on current literature. Overall, this review highlights promising potential of lipid-based treatment strategies further enhanced by the new knowledge of intra-retinal lipids and lipoproteins in DR.

Microtubules are polymers composed of αβ-tubulin subunits that provide structure to cells and play a crucial role in in the development and function of neuronal processes and cilia, microtubule-driven extensions of the plasma membrane that have sensory (primary cilia) or motor (motile cilia) functions. To stabilize microtubules in neuronal processes and cilia, α tubulin is modified by the posttranslational addition of an acetyl group, or acetylation. We discovered that acetylated tubulin in microtubules interacts with the membrane sphingolipid, ceramide. However, the molecular mechanism and function of this interaction are not understood. Here, we show that in human iPS cell-derived neurons, ceramide stabilizes microtubules, which indicates a similar function in cilia. Using proximity ligation assays, we detected complex formation of ceramide with acetylated tubulin in C. reinhardtii flagella and cilia of human embryonic kidney (HEK293T) cells, primary cultured mouse astrocytes, and ependymal cells. Using incorporation of palmitic azide and click chemistry-mediated addition of fluorophores, we show that a portion of acetylated tubulin is S-palmitoylated. S-palmitoylated acetylated tubulin is colocalized with ceramide-rich platforms (CRPs) in the ciliary membrane, and it is coimmunoprecipitated with Arl13b, a GTPase that mediates transport of proteins into cilia. Inhibition of S-palmitoylation with 2-bromo palmitic acid or inhibition of ceramide biosynthesis with fumonisin B1 reduces formation of the Arl13b-acetylated tubulin complex and its transport into cilia, concurrent with impairment of ciliogenesis. Together, these data show, for the first time, that CRPs mediate membrane anchoring and interaction of S-palmitoylated proteins that are critical for cilium formation, stabilization, and function. 

Middle East and North Africa

Research on the Middle East and North Africa region focuses on changes to politics and society, economics, and security issues.

This is a turbulent period for the region following the Arab Spring, with conflict in Syria continuing to impact its neighbours, governance in Libya under scrutiny, and increasing pressures on the Gulf monarchies, especially around human rights.   

Key research areas include the Gulf States and the Gulf Cooperation Council (GCC), the future of the state, mapping the region’s war economies, the Yemen conflict, Iraq’s reconstruction, and the influence of Saudi Arabia and Iran.

Political Opposition and Policy Alternatives in Zambia 31 October 2017 — 10:30AM TO 11:30AM Anonymous (not verified) 19 October 2017 Chatham House, London

In Zambia’s 2016 national election, the Patriotic Front (PF) was re-elected by a narrow margin. The PF’s Edgar Lungu secured 50.35 per cent of the vote according to the Electoral Commission of Zambia, narrowly avoiding a second round, while his main rival, Hakainde Hichilema, won 47.67 per cent. The UPND, led by Mr Hichilema, alleges electoral fraud and has challenged the result in the courts and through direct protests. Mr Hichilema was imprisoned for 100 days.

At this meeting, Hakainde Hichilema will discuss his UPND priorities, how to strengthen opposition parties and their role in Zambia’s democratic future.

Read transcript

POSTPONED: Zimbabwe Futures 2025: Financial Sector Expansion and Policy Priorities 15 November 2017 — 9:00AM TO 11:30AM Anonymous (not verified) 6 November 2017 Harare, Zimbabwe 

This roundtable will draw on current best practice and senior level expertise to identify policy options for financial stability and sector growth. A depoliticized analysis of the development agenda will highlight requisite conditions and prospective policies for a business-driven roadmap to the economic recovery of Zimbabwe, with a specific focus on the financial sector.

Participants will discuss macro-economic policy and stability, retail banking products and services, fintech, mobilizing domestic finance for national infrastructure and balancing consumer price index and inflation.

This event is being held in partnership with the Zimbabwe Business Club.

PLEASE NOTE, THIS EVENT HAS BEEN POSTPONED UNTIL FURTHER NOTICE.

Business Development in Madagascar: How to Enable Entrepreneurialism 15 November 2017 — 12:00PM TO 1:00PM Anonymous (not verified) 9 November 2017 Chatham House, London

How Influential Is China in Zimbabwe? Expert comment sysadmin 20 November 2017

A trip to Beijing by Zimbabwe’s military chief was a ‘normal military exchange’, China’s foreign ministry said after the army seized power in Harare. Alex Vines examines the extent of China’s influence in Zimbabwe.

The news that General Constantino Chiwenga had visited China only a few days before the military takeover in Zimbabwe was a coincidence that did not go unnoticed. There was also speculation after China said it was closely watching developments, but stopped short of condemning President Robert Mugabe’s apparent removal from power.

China is Zimbabwe’s fourth-largest trading partner and its largest source of investment - with stakes worth many billions of pounds in everything from agriculture to construction. Zimbabwe is the dependent partner - with China providing the largest market for its exports and much needed support to its fragile economy.

China’s relations with Zimbabwe are deep, starting during the Rhodesian Bush War. Robert Mugabe failed in 1979 to get Soviet backing, so turned to China, which provided his guerrilla fighters with weapons and training. Both countries formally established diplomatic relations at Zimbabwean independence in 1980 and Mugabe visited Beijing as prime minister the following year. He has been a regular visitor since.

For years, Zimbabwe’s officials have tried to play off China against the West, advocating the country’s ‘Look East’ strategy, particularly following the introduction of EU sanctions in 2002. Indeed, a decade ago, Mugabe told a packed rally at the Chinese-built national sports stadium in Harare: ‘We have turned east, where the sun rises, and given our back to the west, where the sun sets.’

China’s military engagement also deepened during Zimbabwe’s ‘Look East’ era. Significant purchases were made, including Hongdu JL-8 jet aircraft, JF-17 Thunder fighter aircraft, vehicles, radar and weapons. However, following a controversy about a shipment of arms in 2008, Beijing decided to list Zimbabwe for ‘limited level’ military trading.

Despite Zimbabwe’s efforts, the ‘Look East’ strategy did not bring the investment flood hoped for and a decade later, in August 2015, Mugabe openly asked for Western re-engagement in his ‘state of the nation’ address.

Now, the reality is that increasingly Chinese and Western interests - particularly those of the UK - have become aligned. Not far from each other in the outer suburbs of Harare, two of the biggest embassies in Zimbabwe are the British and the Chinese. As other embassies scaled down or closed, Beijing’s expanded. Whereas British diplomats were well connected with business, civil society and opposition figures, the Chinese invested in ‘technical support’ of the party of government Zanu-PF, including state security and the presidency. When it came to Zanu-PF politics and factionalism, Chinese diplomats were well connected and insightful and, like their Western colleagues, concerned about stability, a better investment climate and adherence to the rule of law.

President Xi Jinping visited Zimbabwe in 2015 and President Mugabe visited Beijing in January 2017. In public, the Chinese leader said his country is willing to encourage capable companies to invest in Zimbabwe. But in private, the message was that there would be no more loans until Zimbabwe stabilized its economy.

In 2016 trade between the two countries amounted to $1.1 billion, with China the biggest buyer of Zimbabwean tobacco and also importing cotton and various minerals. In return Zimbabwe imported electronics, clothing and other finished products. Chinese state construction firms have also been active, building infrastructure including Zimbabwe’s $100 million National Defence College. And last year China agreed to finance a new 650-seat parliament in Harare.

But Chinese diplomats and many businesses are waiting for better days in Zimbabwe. Some companies have found the investment climate challenging - being burned on diamonds, for example - and have looked for alternative markets. A couple of weeks ago I was in China, attending a meeting on China-Africa relations and Zimbabwe was not mentioned once. Unlike Ethiopia, Sudan, or Angola that are strategic partners, or big markets like Nigeria, Kenya and South Africa, Zimbabwe is far from being Beijing’s new priority.

So, Beijing’s interest is in a better investment climate in Zimbabwe. A clear transitional arrangement resulting in elections for a legitimate government in Harare is as much in Beijing’s interest as London’s.

The ‘Look East’ and the ‘Re-engagement with the West’ strategies have not brought about the confidence and investment that Zimbabwe needs. What Zimbabwe requires is stable and accountable government - then investors from Asia, America and Europe will seriously consider that Zimbabwe has an investment future. This was the message that Mugabe received in Beijing in January. And the one which Zimbabwe’s military chief also was given last week.

This article was originally published by BBC News.

Mugabe’s Departure Ushers in a Heady New Era for Zimbabwe Expert comment sysadmin 23 November 2017

The country is experiencing an almost unprecedented convergence, with traditional political, economic and social fault lines bridged as Zimbabweans make common cause for change.

The ecstatic scenes said it all – Zimbabweans around the world are celebrating the resignation of Robert Mugabe as president. In January 1980, hundreds of thousands of Zimbabweans thronged Zimbabwe Grounds stadium in Highfields township, Harare, to welcome Mugabe back from exile. In March 1980, with reggae icon Bob Marley and Britain’s Prince Charles in attendance, thousands filled Rufaro Stadium to witness the handover from Rhodesia to the new nation of Zimbabwe. Thirty-seven years later, the largest crowds Harare has ever witnessed flooded the streets once again; not to welcome Mugabe in, but to see him out. One simple, taut phrase summed up the day’s events: ‘This is our second independence day.’

How did it come to this?

History has been put on fast-forward, and left Zimbabwe – and the world – shaken. Just two weeks ago, it seemed to be the height of folly to think that Mugabe would leave office on any but his own terms. Emmerson Mnangagwa had been sacked as vice president, and his followers had been purged. Grace Mugabe, with ringing endorsements from the women’s and youth leagues, looked set to be elevated to the vice presidency at the ZANU-PF congress in less than a month’s time.

Mugabe was expected to stay until the 2018 elections, after which he would hand over the presidency to his wife. It was the prospect of Grace Mugabe becoming Zimbabwe’s next president which brought in the military. Aware that they had three weeks or less to prevent a dynastic succession and a looming purge of the military itself, Zimbabwe’s military chose, not the audacity of hope, but the hope of audacity, and launched Operation Restore Legacy to stop the rot.

What has happened in Zimbabwe is not a people’s revolution in the traditional sense. The Bourbons in France, the Romanov dynasty in Russia, the Shah of Iran, and the autocrats of north Africa’s Arab Spring were all felled by continuous street protests which ultimately received the support of the military.

In Zimbabwe it has been the military who have been the drivers of revolutionary change. What has happened is that an internal party-factional power struggle has inadvertently led to a military-guided popular revolution and the ousting of the Mugabes. Zimbabwe’s military, often seen as the guardians of the state, became instead the guardians of the people. They are seen, for now at least, as liberators, and national heroes. This has been a very Zimbabwean revolution.

So what next?

These are heady days. Zimbabwe is experiencing an almost unprecedented national convergence, with traditional political, economic and social fault lines bridged as Zimbabweans make common cause for change. It is not quite a ‘Zimbabwe Spring’, but it is perhaps a ‘Zimbabwe Sunrise’.

Parliament, which on Tuesday had met to impeach Robert Mugabe, is now installing, through constitutional procedures, Emmerson Mnangagwa as president, who will be given the mandate to form an interim government. Mnangagwa will be further ratified at the ZANU-PF Congress in December where he will be named and acclaimed as ZANU-PF’s candidate for the next general elections, which constitutionally are due by mid-2018 (although it is unclear whether this will indeed be the case).

Mnangagwa has a full in-tray. He needs to form a government quickly and has to balance the need for inclusivity and consultation, with the undoubted pressure to reward his followers. With Zimbabwe’s economy nearing paralysis, Zimbabwe’s new president will be under pressure to deliver. Although many are nervous about his history as Mugabe’s ally and his reputation for toughness, Mnangagwa is also an astute political survivor, and has been pro-business and supportive of Zimbabwe’s ongoing re-engagement with the global community.

Zimbabwe has become a cashless society not by design, but by default; with formal unemployment at 80 per cent and with a largely informalized economy in which much of Zimbabwe’s citizenry have been reduced to penury and classic short-termism, there is plenty for Zimbabwe’s next president to think about. Activists wonder whether he will try to introduce systemic change, or merely go through the motions. He may well face a binary choice between government or governance.

And yet there are also positives. Zimbabwe’s institutions have proven to be resilient, and there is still a reservoir of dedicated and competent professionals in both public and private sectors. Although still laggardly, Zimbabwe had begun to progress in ‘ease of doing business’ indices. There is a large diaspora who have continued to engage with Zimbabwe; and Zimbabwe’s recent ‘Look East’ and de facto ‘Look West’ re-engagement policies can be built upon.

Many are urging caution and saying that Zimbabwe needs a second, truly democratic revolution. Perhaps. But right now, Mnangagwa should be given a chance. Farai, a friend of mine in Harare, said this: ‘Yes we know this euphoria may be short-lived. But even if it turns out that we were only happy for a day, let’s make it a brilliant day. Rega tifare nhasi (Let us be happy today).’

A version of this article was first published by the Guardian.

South Africa Needs a Strategic Vision for Its Continent Expert comment sysadmin 24 November 2017

South Africa has the potential to catalyse growth across its sub-region and the continent, but the government must develop a comprehensive strategy that aligns political, ideological and commercial interests.

South Africa’s status as the ‘gateway to Africa’ is under serious threat. Its companies continue to flourish, but complex relationships at home and abroad constrain government capacity to match its economic dominance with political reach and influence.

South Africa’s policies towards the rest of the continent are often accused of being inconsistent and incoherent. It has been a development partner to the region and to international donors; a moral leader, championing human rights and exporting its own model of transition; and an advocate and representative for the continent in international forums. However, it has simultaneously been accused of exploiting its economic dominance at the expense of its neighbours; handicapped by the political debts owed by the ANC to other liberation movements for their assistance in the struggle; and criticized for its arrogance in seeking to position itself as the ‘legitimate’ voice of Africa.

At the same time, reputational risks, a weakened policy environment and poor growth have taken the shine off South Africa’s ‘Gateway to Africa’ rhetoric. South Africa faces considerable domestic economic issues. Growth forecasts have fallen from 1.3 to 0.7 per cent, State owned enterprises are a huge burden on the treasury, and the forecast budget deficit is R50.8 billion (£2.7 billion), at a time when the cost of borrowing is increasing following downgrades of the country’s credit ratings.

Political risk is high, lowering investor confidence. Corruption, poor service delivery and the government’s under-delivery on citizen’s expectations are exacerbating social tensions in a country with expanded unemployment at 36.4 per cent, and one of the highest rates of inequality in the world. McKinsey, KPMG and HSBC have all become entangled in scandal relating to their dealings with government entities that have become ‘captured’ by private interests.

Despite these concerns, South Africa nonetheless remains the backbone of the regional economy, and its firms are key players across the continent. Johannesburg hosts the deepest and most sophisticated capital market on the continent, and Pretoria has one of the highest numbers of diplomatic missions in the world. ESKOM provides around 75 per cent of the electricity contribution to the Southern Africa SADC Power pool – comprising 12 countries, including those as far north as DRC and Tanzania – and South African ports facilitate over half of sub-Saharan Africa’s non-commodity trade with the rest of the world.

Post-apartheid expansion across the continent by South African companies was initially met with resistance, but these relationships have improved significantly – and South African firms retain significant advantages. South African retailers have the scale to incorporate regional producers into continental supply chains, purchasing fresh produce at a competitive price from regional agri-businesses, then re-selling further afield. For example, Zambeef supplies meat from Zambia to Shoprite stores in west Africa.

African companies in turn rely on South Africa as a significant consumer of goods, services and primary commodities. A South African government agreement with the DRC to import about half of the electricity that will be produced by a new grand-scale hydro-power project guaranteed its bankability. Mozambique is looking to maximize the potential of its world-class natural gas reserves by building a pipeline into South Africa, thus benefitting from the purchasing power of South African parastatal electricity utility firm ESKOM.

But South Africa’s status as an economic hegemon is not mirrored in its political relationships. South Africa’s GDP is five times higher than the six countries with which it shares a border, combined. But successive ANC governments have been unable to fully flex this economic muscle. Partly this is a legacy of history. It is not forgotten that the regional economic body, the Southern African Development Community, originated as the organization of Front Line States coordinating efforts to end apartheid, and ZANU-PF officials in Zimbabwe lecture their ANC counterparts on liberation.

The pan-African vision of former president Thabo Mbeki, and promotion of South Africa’s transition as a model for the continent, reflected the values that have driven ANC policy since the end of apartheid. But the coherence of South Africa’s foreign policy has been undermined by conflict and contradiction within the government. Appetite for engagement in Africa is dwindling. The country’s ability to project military influence across the continent is in critical decline. Jacob Zuma’s use of regional political bodies as a means of removing political rivals from domestic politics has corroded goodwill.

A new Africa Programme research paper argues that a fresh approach to South African engagement on the continent is both possible and necessary. South Africa can use its relative economic weight to play a stronger developmental role, leveraging the strengths of its business sector and its financial agencies. But it must match this with stronger and more cooperative political engagement, particularly through cultivating relationships with pivotal states such as Nigeria, Kenya, Ethiopia and Angola.

In December, the ANC will elect a new leader to take the party into elections in 2019. Both leading candidates have international experience – Nkosazana Dlamini-Zuma was the chair of the African Union, and Cyril Ramaphosa has led regional responses to crises in South Sudan, Lesotho and Burundi. South Africa still has considerable foreign policy resources at its disposal. A new strategic vision for Africa that unites the interests of government and business, both domestically and in partner states, can deliver prosperity for both South Africa and the region – and need not contradict the values that have shaped South Africa’s aspirations for the continent in the post-apartheid era.

Mugabe’s Fall Is a Wake-Up Call for Africa’s Leaders Expert comment sysadmin 27 November 2017

The continent’s long-standing leaders will come under increasing pressure to demonstrate their societal value. Some will become more oppressive; others may conclude that their time has expired.

The end of the Mugabe presidency in Zimbabwe – with the swearing in of Emmerson Mnangagwa in Harare on Friday – is being watched closely across Africa, and especially by its long-standing leaders.

Currently, 30 per cent of African countries are ruled by long-standing rulers, defined as heads of state that have ruled for more than 10 years. Africa is not unique in this respect (Central Asia also has its share of ageing leaders), but Africa has a long tradition, and about a fifth of all African heads of state since independence can be classified as long-standing.

A recent study, African Futures: Horizon 2025, by the European Union Institute of Security Studies (and which this writer contributed to), shows that long-standing rulers in Africa are reducing in number. President José Eduardo dos Santos of Angola stepped down voluntarily in September after almost 38 years in office, and Yahya Jammeh of Gambia was forced out after 23 years in office in early 2017. Robert Mugabe was forced out as leader earlier this week after 37 years.

This still leaves a cluster of other ageing leaders: Teodoro Obiang Nguema Mbasogo of Equatorial Guinea (38 years); Paul Biya of Cameroon (35 years); Yoweri Museveni of Uganda (31 years); Omar al-Bashir of Sudan (28 years); and eight others.

Many of them are coming under increased internal pressure. Demonstrations against Togo’s Faure Gnassingbé in Lome over the summer resulted in him agreeing that any future president could stand for only two terms. In the Democratic Republic of the Congo, Joseph Kabila is also under increased pressure to agree to elections, after 16 years in power.

Within all of this, there is a pattern of leaders in west and southern Africa adopting the principle of only serving two terms.

De-facto monarchies

Long-standing rulers still thrive in central Africa and its Great Lakes region. Presidents here have successfully changed constitutions to remain in office. They include Denis Sassou Nguesso of the Republic of the Congo and Yoweri Museveni of Uganda. Zimbabwe will be a warning to them that they should not assume that they will be able to behave as de-facto monarchies, leaving office only after dying of natural causes and handing power over to their family.

Robert Mugabe’s intention to hand power to his wife, Grace, spectacularly backfired. As a couple of Zimbabwe military officials dryly commented: ‘Leadership is not sexually transmitted.’ Former president Hosni Mubarak in Egypt also miscalculated by trying to groom his son, although Ali Bongo Ondimba succeeded his father as president of Gabon after his father died. Equatorial Guinea is still heading for a crisis as President Obiang is grooming his deeply unpopular playboy son, Teodorin, to succeed him.

What Zimbabwe reminds us is that, with the exception of central Africa, there will be more long-standing leaders in Africa disappearing over the coming decade. This is due partly to pressure and partly to their ageing: 13 current long-standing rulers are aged between 65 and 84 years old. This means there will be more transitions taking place such as the one that occurred in Zimbabwe on Friday or the smooth one in Angola in September, when president dos Santos stepped down and handed power to João Lourenço.

This is good news for Africa, which has the most youthful and fastest-growing population in the world. It is the second-largest and second-most populated continent. More than 40 per cent of Africans are under 15, and 20 per cent are between 15 and 24. By 2050, one third of the world’s youth population will live in Africa, up from one fifth in 2012. This means a dramatic disconnect is developing between long-standing leaders and their population.

Generational politics was visible over the past week in Zimbabwe and in the end the older generation prevailed through military intervention. This is transitional politics, and there is likely to be more of it.

Increasing pressure

Other long-serving leaders like Museveni have watched closely. Museveni has already responded to shore up support of his military by giving them a significant pay rise. There is likely to be more investment in the military by Africa’s long-standing leaders in the coming months.

Change in Africa comes in fits and starts. The fall of Mugabe is a reminder that Africa is dynamic and change is occurring all the time. Africa’s long-standing leaders will come under increasing pressure to demonstrate their societal value. Some will become more oppressive; others may conclude that their time has expired and that they should welcome a transition.

This is the key lesson of Angola – where president dos Santos willingly retired after 37 years in power. Mugabe dreamed of dying in office and being succeeded by his wife – and was forced out by the military. I predict both models will be repeated in Africa in coming years.

This article was originally published in the Irish Times.

Rebuilding Zimbabwe's Economy: Emmerson Mnangagwa’s Immediate Priorities Expert comment sysadmin 13 December 2017

Zimbabwe cannot expect to rebuild in the same economic model that brought previous prosperity.

Returning to Harare as Zimbabwe’s president-designate Emmerson Mnangagwa declared, ‘We want to grow our economy, we want peace, we want jobs, jobs, jobs.’

Robert Mugabe leaves a legacy of an independent Zimbabwe in a deep economic crisis. Much remains uncertain as to what a new government in Zimbabwe will look like, and there is sure to be continuity as well as considerable change.

What is clear is that a new administration under Mnangagwa will need to turn the economy around to garner support and legitimacy from the Zimbabwean people. Zimbabwe’s economic output halved over the period 1997–2008, and it has not recovered. With more than 80 per cent of Zimbabweans in the informal economy, and with social and economic resilience undermined by previous crises and decades of mismanagement, the stakes for the new leader are very high.

Reform will be difficult particularly because politically connected elites have acquired businesses through uncompetitive means. They will be reluctant to see significantly more competition. But they will also want an improved economic environment. And there is scope for the people of Zimbabwe to benefit from this.

An important change will be in the prioritization of economic stability. Mugabe demonstrated that he was willing to make political decisions irrespective of the economic consequences. Mnangagwa is thought to be less ideological and more of a pragmatist. For him, delivering economic recovery will be crucial to building political support.

The most pressing fiscal priority is the public wage bill. Employment costs account for over 80 per cent of government expenditure, crowding out spending on social programmes, health and education. But the fragility of the economy means that reform cannot be fast-tracked. The public wage bill accounts for over 20 per cent of GDP and is an essential driver of demand. Public sector workers are also politically influential. Another further priority is the reform of state-owned enterprises that are pressuring the fiscus.

A new administration will need to rebuild confidence. Policymakers have been operating in a low-confidence environment for a long time, but for any meaningful change to take root there has to be trust between the government, businesses and the people of Zimbabwe. Businesses and citizens will want to see a plan of action for remonetizing the economy. Zimbabwe faces an acute liquidity crisis. A shortage of US dollars and a lack of confidence in government-issued bond notes are testing resilience.

The financial system has recovered from a crisis of nonperforming loans – triggered by high debt amassed during the post-dollarization boom, and weak corporate governance. But the system remains highly fragile and swamped with government debt. Hard cash US dollar deposits fell from 49 per cent ($582 million) in 2009 to just six per cent ($269 million) in 2016. In 2015, industrial utilization stood at just 34.3 per cent of installed capacity, and it was estimated that just five per cent of the country’s businesses were viable.

The crux of the Zimbabwean economy is the linkage between agriculture and manufacturing. Commercial agriculture contributes approximately 12 per cent of the country’s GDP, and more than 60 per cent of inputs into the manufacturing sector. Tobacco in particular is a vital earner of much needed foreign exchange. Policies to support mid-scale farmers will have multiplier effects. They drive agricultural growth and generate jobs throughout the supply chain.

Zimbabwe also has world-class natural resource endowments including ferrochrome, gold, copper, iron ore, lithium, diamonds and platinum group metals. But longer investment-gestation periods and industry risk adversity will mean that payoffs from fresh investments in this sector will take longer to materialize.

Domestic finance will need to be mobilized to generate recovery, and this will need to be supported by international investment. But international investors entering the country must be cognizant of Zimbabwean’s expectations and also historical perceptions – especially around the scepticism of neoliberal economics as a result of failed structural adjustment programmes in the 1990s.

Zimbabweans have high social expectations for international investors. Educated, tech-savvy, internationally connected youth are at the core of the consumer class that investors will be targeting, to both sell products to but also to staff offices in country. But this cohort also has a greater expectation of international companies to adhere to the norms and standards that they abide by at home and not take advantage of weak governance or poor regulation to exploit citizens.

Investors in Zimbabwe must also recognize that behind the controversial Mugabe policies of land reform and indigenization – the empowerment of local citizens through shared ownership – was a popular desire for postcolonial economic transformation. This sentiment remains. Working in partnership with local entities and communicating the economic contribution made to society will be necessary to build a long-term presence in Zimbabwe, and reap the dividend of what many hope to be a new start for the country.

Fresh thinking is required from domestic policymakers and international partners. A skilled population and estimated 3-5 million-strong diaspora will bring international experience and make a considerable contribution to this process. Some of this thinking has been done. The Lima process of re-engagement with international financial institutions that was agreed at the end of 2015 has laid some of the groundwork, especially around international expectations regarding both economic and governance reform – the substance of which was analysed in a 2016 Chatham House paper. The implementation of recommendations of the well-regarded auditor-general’s report on SOE reform will also be a key prerequisite for long-term reform.

Zimbabweans are not alone in processing what has happened and how to react. Investors have long been poised to capitalize on what is perceived to be one of the continent’s best long-term prospects. A lot will remain unchanged following the transition. But significantly, for the first time in decades, there is a real opportunity to effect positive change and improve the livelihoods of millions of Zimbabweans.

This article was originally published at the Huffington Post.

Ramaphosa Has Won the Battle. But Can He Win the War? Expert comment sysadmin 21 December 2017

Cyril Ramaphosa is taking charge of South Africa’s ruling party, the ANC, at its weakest point in post-apartheid history. Expectations couldn’t be higher.

Ramaphosa ran for the leadership of the ANC on a platform of party renewal, economic recovery, and building the capacity of the state. But Jacob Zuma remains the President of South Africa and, under the constitution, can stay in office until elections in 2019. Therefore, meeting expectations on economic recovery will depend on Ramaphosa taking the presidency – and he has a number of political battles to face before that becomes reality.

To begin with, Ramaphosa and his supporters did not win a total victory at the elective conference. The presidency was only one position in the senior cadre – the co-called ‘top six’ – that was elected. This body is now split evenly between Ramaphosa and his allies, and those that supported his opponent Dr Nkosazana Dlamini-Zuma - Jacob Zuma’s preferred successor. This creates two centres of power in the ANC, limiting what Ramaphosa will be able to achieve from within the party.

Although there is significant pressure from the electorate to remove Zuma from national office, actually doing so will be difficult. Zuma’s predecessor Thabo Mbeki was removed from the national presidency before his term was up when the National Executive Committee (NEC) of the party recalled him from office following Zuma’s assumption of party leadership. But this option may not be available to Ramaphosa. The split within the ‘top six’ and new NEC will make it difficult to present an ultimatum to Zuma. His loyalists will not want a witch hunt within the party.

Corruption and elitism within the party

Much of the tension centres on questions of corruption, the dominant political issue in South Africa at the moment. In the build up to the elective conference Gwede Mantashe - now national chairperson - admitted that “The biggest challenge from where we’re sitting is the image and the reputation of the ANC. The ANC is seen as equal to corruption and looting.” Ramaphosa made anti-corruption initiatives a centrepiece of his campaign, including the establishment of a judicial commission and rapid action to investigate and prosecute the guilty.

But the split within the party may undermine the credibility of these promises. Ramaphosa’s problem is that some of the new ‘top six’ - including Deputy President David Mabuza, and Secretary General Ace Magashule – would be high on the list of those the electorate want to see investigated. Party resistance may restrict the extent to which Ramaphosa can demonstrate a comprehensive break from the past.

Corruption within the party goes far deeper than the headline cases of ‘state capture’ and expropriation. At a branch level, access to political power has become the primary means of access to economic resource. It is a process of selective patronage that differentiates between those who are ‘in’ from those who aren’t. At its broadest, this type of corruption has created a mistrust of the ANC and the new economic elite that the party has created around it – including Ramaphosa himself.

Having lost out to Mbeki in the fight to succeed Mandela despite being the favourite for the job, Ramaphosa spearheaded the ANC’s deployment of cadres in business. He has become one of the country’s richest men, and a highly sought after board member by South Africa’s largest companies across mining, telecoms, and logistics.

One of his biggest challenges will be to remove the perception of elitism as his senior position within the party and economy has given rise to mistrust from a grass roots level. The political tussle at the conference was also largely driven by a small number of the party elite being able to control large groups of delegate votes. The nature of political competition within the party is symptomatic of the ANCs electoral dominance in the early days of the nation’s democracy. But this support is now far less certain, and the party cannot afford to become complacent.

Resetting the relationship with business

Ramaphosa’s business dealings may mean he has to walk a fine line in censuring his colleagues for making money from politics. But it may also be a significant opportunity for the party to reset its relationship with the private sector. Under Mbeki, relations between the ANC and business were distant, but characterized by recognition of mutual dependence.

Under Zuma this relationship deteriorated, and the President demonstrated he was willing to make decisions to boost his political power irrespective of economic consequences. Ramaphosa could, for the first time, truly align the interests of business and government, without abandoning his transformative policy agenda.

At an ANC regional economic colloquium in Johannesburg in November Ramaphosa outlined his ten-point economic plan. It would deliver the party’s adopted mantra of ‘radical economic transformation’, but through broadly neo-liberal policies on private business development and state-owned enterprise reform to allow private capital to co-invest.

He took the ethos and principles of the Freedom Charter – the 1955 statement of core ANC principles – and applied them to a modernising economy. Talk of a ‘new deal’, productive partnerships in the mining sector, and an emphasis on job creation in manufacturing will woo investors. The rand surged upon his election.

But Ramaphosa will not be able to deliver on the economic demands of the country until he is in the office of the presidency - and Zuma still holds many of the cards. Ramaphosa can promise his followers potential power and government positions in future, but Zuma can still offer them now.

Removing Zuma will require skilful internal party politicking, and Ramaphosa will need to limit the fallout – he cannot afford to further damage the credibility of the party before it faces the electorate in 2019. He has won the battle, but the outcome of the war is far from certain.

Tsvangirai Leaves an Important Political Legacy in Southern Africa Expert comment sysadmin 21 February 2018

The story of Zimbabwe’s ‘people’s champion’ offers a powerful example to a region in need of new political compromises.

The death of Movement for Democratic Change (MDC) leader Morgan Tsvangirai is a loss for Zimbabwe. In nearly three decades of speaking truth to power, Tsvangirai helped to change his nation and the region.

Southern Africa’s new politics

His death marks a period of transition for regional governments and opposition parties alike. The Zuma era has ended in South Africa while Mozambique, Namibia and Angola have also seen political transitions, pushing modernization agendas to appeal to young citizenries that increasingly see politics in separate terms from the liberationist struggles of the previous generation.

Regional opposition movements also face winds of change: the longstanding opposition leader in the Democratic Republic of the Congo, Etienne Tshekedi, passed away in 2017, and Mozambique’s Afonso Dhlakama and Kenya’s Raila Odinga are both aging. These movements similarly need to appeal to a younger audience or risk losing relevance.

From trade unionist to opposition leader

Tsvangirai’s career is an eloquent illustration of these challenges. Born in Buhera in rural eastern Zimbabwe, Tsvangirai worked in textiles and mining before politics – diverse experience which gave him crucial exposure to the lives of ordinary people across the country. In his early years, he also worked for ZANU-PF, before leaving to forge his own political path. He became increasingly active in mining politics, rising to the executive of the National Mineworker’s Union and, in 1989, to secretary-general of the powerful Zimbabwe Congress of Trade Unions.

In the late 1990’s, Zimbabwe was riven by questions over land, war veterans, the Congo conflict, a shrinking economy and growing doubts about ZANU-PF itself. Opposition leaders of the time could not answer them; those such as Edgar Tekere and Margaret Dongo struggled to win support beyond their local constituencies, and liberation leader Joshua Nkomo’s ZAPU had been merged with ZANU-PF in the 1987 Unity Accord.

But in 2000, Zimbabwe’s ‘perfect storm’ of a divisive constitutional referendum, land redistribution and a June election made Tsvangirai and the newly minted MDC, formed in 1999, a national rival to ZANU-PF. Through subsequent national elections in 2002, 2005, 2008 and 2013, Zimbabwe remained polarized between competing visions of Zimbabwe future: ZANU-PF’s powerful black liberationist politics of identity and the opposition’s equally compelling liberal democracy agenda.

Tsvangirai’s achievement was to provide a credible alternative to liberation icon Robert Mugabe. Tsvangirai also resuscitated Zimbabwe’s tradition of urban nationalism, and was a successor to Benjamin Burombo and other mid-century Zimbabwean urban leaders. Tsvangirai would in turn be a touchstone for contemporary urban activists Evans Mawarire, Linda Masarira and others.

From opposition to coalition

The political struggle for Zimbabwe became global, with Mugabe and Tsvangirai both winning support from rival international power blocs. In March 2007, pictures of a beaten and bloodied Tsvangirai helped to galvanize support for the MDC in the 2008 elections. But the disputed result and violent subsequent run-off between Tsvangirai and Mugabe led the regional community to push both men into a coalition government, with Tsvangirai as prime minister.

Despite continuous ructions, the Government of National Unity (GNU) held, and stabilized Zimbabwe’s collapsed economy, until 2013. Although often politically out-manoeuvred by Mugabe, Tsvangirai deserves credit for getting the opposition a share of political power and for holding his nerve against many who wanted to collapse the GNU.

Tsvangirai was no saint; his complicated love life, and tacit approval of violent attacks on party dissenters, do him no credit. More importantly, the MDC neglected its grassroots supporters during the GNU, and paid the price in its comprehensive 2013 electoral defeat. But although diminished, Tsvangirai remained Zimbabwe’s most popular opposition politician, and the MDC’s new leaders will have quite a task ahead of them, even if they have been planning since his courageous 2016 public admission of colon cancer.

The MDC after Tsvangirai

Nelson Chamisa, one of the three MDC vice presidents, has now been appointed as acting president by the party’s national committee. Chamisa inherits a fractured and fractious party, and one which has also fallen out with the Tsvangirai family. The other two vice presidents, Thokozani Khupe and Elias Mudzuri, have also set their sights on party leadership.

At 40, Chamisa, an orator with grassroots appeal, has a huge task. With general elections due by July, he has to unite the party, counter Zimbabwe’s rising ethno-politics, prove himself as leader of a broader opposition coalition and take on a resurgent President Emmerson Mnangagwa and ZANU-PF.

Electorally, the opposition’s strongest card has always been the urban vote and the economy. But Mnangagwa has fast forwarded a comprehensive economic reform and internationalist agenda. This, and Mugabe’s exit, have forced Chamisa, Joice Mujuru and other opposition leaders to play catch-up. Zimbabwe’s elections, the first since 2000 without Mugabe and Tsvangirai as contenders, will be of global interest as the country navigates the new political dynamics.

The people’s champion

Morgan Tsvangirai’s resilience earned him respect from friends and foes alike, with Zimbabwe’s President Mnangagwa and Vice President Constantino Chiwenga visiting him at home a few weeks ago. A former nominee for the Nobel Peace Prize, Tsvangirai, popularly known by his totem of ‘Save’ and also called mudhara [the old man] deserves national hero status. He will certainly be remembered as the ‘people’s champion’, and a pioneer in bridging the generational and ideological fissures that have shaped Southern Africa’s politics.

With their leader now gone, the turbulent MDC will undoubtedly be hoping for a ‘remembrance vote’ in his memory to carry them through the elections. But beyond that, his story offers a powerful example to a region in need of new political compromises.

Angola Forum 2018: 30th Anniversary of the Battle of Cuito Cuanavale 23 March 2018 — 10:00AM TO 2:30PM Anonymous (not verified) 8 March 2018 Chatham House, London

Reflections on Southern Africa’s Turning Point

23 March 2018 marks the 30th anniversary of the final assault of what became known as the Battle of Cuito Cuanavale.

The confrontation between the Angolan army, supported by Cuba and the Soviet Union, and the armed opposition UNITA, supported by the South African Defence Force, is the largest land battle to have taken place in Africa since World War Two.

The battle was a watershed in Angolan and southern African history, but its significance continues to be contested. Today, although the battlefield has a monument and museum, it remains one of the most landmine-contaminated parts of Angola and this hinders development plans for international tourism.

This event brings together veterans and experts to contribute towards developing a deeper understanding of the battle. Discussions will further focus on the significance of the wider events around the battle, its regional implications, as well as the legacy of the battlefield.

Zimbabwe Ahead of the Elections: Political and Economic Challenges 8 May 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 3 May 2018 Chatham House, London

The upcoming elections in Zimbabwe will be the first since 2000 in which former president Robert Mugabe and long-time opposition leader Morgan Tsvangirai are not on the ballot paper. A key electoral issue for many voters will be the economy: recent years have been marked by high unemployment rates, chronic cash shortages and mounting public debt. Although this has traditionally been a strong campaigning issue for the opposition, President Emmerson Mnangagwa has fast-tracked comprehensive economic reforms.

At this event, Nelson Chamisa, MDC Alliance presidential candidate, will discuss his efforts to build a united opposition coalition with a strong message, the steps needed to ensure a free and fair election can take place, and the role that international partners can play in Zimbabwe’s democratic process.

Afonso Dhlakama’s Death Changes the Calculation for Peace Prospects in Mozambique Expert comment sysadmin 4 May 2018

If politicians continue to act in good faith, the death of the opposition leader may be a significant opportunity to finally draw a line under Mozambique’s long war.

The unexpected death of opposition and ex-rebel leader Afonso Dhlakama on 3 May is a game changer for Mozambique’s politics and an almost-completed peace process. The 65-year old Dhlakama, who died of a heart attack, had led Renamo for 38 years and had totally dominated his party. Dhlakama regularly boasted that he was Mozambique’s ‘father of democracy’, despite not allowing competition within his own party, and he leaves a legacy of more than 30 years of struggle, through both armed action and peaceful politics.

A long war

Originally Renamo had been a tool for the white minority regimes of Rhodesia and apartheid South Africa to challenge the socialist Frelimo political party that took power in Mozambique in 1975. But under Dhlakama’s command, by the late 1980s Renamo had become increasingly independent and rooted in Mozambique. After Renamo’s long war with Frelimo ground to a hurting stalemate, a transition led to Mozambique’s first multiparty elections in 1994, and the creation of a new joint army. A ‘pay and scatter’ programme successfully dispersed and reintegrated many thousands of ex-combatants.

But early post-election gains did not translate to lasting peace. Disarmament was a time-limited, technical process, and devoted declining resources and attention to clusters of ex-combatants that failed to disperse. In addition, Dhlakama was allowed to maintain an armed militia under the guise of a presidential guard.

Mounting economic inequality, notably in opposition strongholds such as central Mozambique, saw Renamo made political gains and Dhlakama nearly won the 1999 presidential elections. (Some believe he did.) The result focused Frelimo’s attention on the threat that Renamo posed and, ultimately, a strategy of pursuing total Frelimo domination across the country, culminating in a crushing Frelimo victory at the 2009 elections.

This humiliated and marginalized former Renamo rebels, resulting in Dhlakama ordering their return to targeted armed violence in 2013. Frelimo’s new leader, President Filipe Nyusi, took power in 2015 and sought direct dialogue with Dhlakama. Five rounds of internationally mediated peace talks took place from July to December. Finally, in late December 2016, Dhlakama announced a unilateral truce, which was extended twice and subsequently made indefinite.

New peace talks also started and, in August 2017 and February 2018, President Nyusi and Dhlakama showed the courage to meet in person, near Renamo’s base in central Mozambique, to build up mutual trust and discuss the details of the emerging peace deal – including the demobilization or integration into government security forces for Renamo’s now mostly middle-aged gunmen.

Dhlakama the ‘Big Man’

Dhlakama’s sudden death has fundamentally changed the negotiation dynamics. He never allowed for any serious succession planning, and ensured all key decisions were his and his alone. Renamo had already decided that he would be its presidential candidate for the 2019 national elections.

His party is significantly weakened by his death and unlikely able to fully recover – but needs to try and reach consensus quickly on a successor, as it will also compete in municipal elections in October and was expecting significant gains. There will be a number of contenders to succeed him including from the parliamentary wing, led by his niece Ivone Soares, its secretary general, Manuel Bissopo, and a few others.

But Renamo’s key leverage for now remains some 1,000 middle-aged gunmen in central Mozambique who have been stoically loyal to Dhlakama since the 1980s and who have little respect for the younger generation of professional politicians based in Maputo. Some may be bought off by government offers, others integrated into localised organized crime groups and others into internal Renamo sectarianism. The risk of fragmentation is real.

Renamo’s weakness could also embolden Frelimo hardliners to seek a return to unilateral domination of Mozambique’s political landscape, and to undermine the peace process. That would be a serious tactical mistake by Frelimo, as a lasting deal is close and the death of Dhlakama could actually assist in making this settlement lasting. Dhlakama was quixotic and prone to changing his mind, often influenced by the last person he spoke to – his death potentially introduces greater predictability in negotiations and in any post-deal implementation.

President Nyusi is clearly aware of this as he hailed on state television TVM that Dhlakama was ‘a citizen who has always worked for Mozambique’ and said he was distraught at the news of his death. He stated, ‘I hope that we as Mozambicans can continue to do everything so things do not go down.’ He also addressed Renamo’s support base by saying that ‘[Dhlakama] did everything so that there would be peace. The last time he spoke to me, he said he was not going to miss out anything in peace negotiations.’

Renamo’s gunmen are fatigued and want to retire with dignity but are vulnerable to manipulation and political miscalculation by Mozambican’s positioning politicians. International partners and investors can engage, by emphasizing that sustainable peace is the only pathway to poverty reduction and inclusive economic development.

This includes assisting development and reconciliation projects in areas impacted by the renewed conflict since 2013. Long-term investment for development in Renamo’s key constituencies could help avoid fragmentation at a critical time – faith groups and NGOs may also have a key role to play.

If Mozambique’s politicians continue to act in good faith, the death of Dhlakama may constitute a significant opportunity to finally draw a line under Mozambique’s long war.

South Africa's Land Reform Quandary: Scenarios and Policy 10 July 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 13 June 2018 Chatham House, London

Slow delivery on expectations of land redistribution in South Africa has once again put the issue at the forefront of political debate in the country. A parliamentary public consultation process will consider whether constitutional change is required to accelerate expropriation without compensation. Policymakers face dual - often opposing - pressures due to investors’ fears of negative economic impacts as well as citizens’ frustrations over persistent inequality and hardship. State land and tribal trust land remain contentious issues for rural economic development, but with two thirds of the population now living in urban areas policy responses must be as cognizant of the country’s future as it is of its past.

At this meeting, Terence Corrigan, project manager at the South African Institute of Race Relations, will discuss the current debates on expropriation and present the institute’s latest research on future scenarios of land reform in South Africa.

Attendance at this event is by invitation only.

Improving Economic Management for Sustainable Growth in Zambia 13 July 2018 — 9:00AM TO 10:00AM Anonymous (not verified) 19 June 2018 Chatham House, London

THIS EVENT IS POSTPONED.

High levels of infrastructure investment funded by commercial loans, against a backdrop of subdued economic growth, resulted in an increase in Zambia’s public external debt from $8.7 billion in 2017 to $9.3 billion in March 2018.

In June 2018 Zambia’s Ministry of Finance announced new austerity measures aimed at reducing the country’s debt burden, as part of an ongoing reform agenda that is hoped to stabilise the economy.

In the meantime Zambia grapples with severe social and development challenges. Decreased spending in health, education and social protection, and poor access in rural areas, have already left Zambia ranked 139th out of 188 countries in the UNDP’s 2016 human development index.

At this meeting Margaret Mwanakatwe, minister of finance, discusses the government’s financial reform agenda, its engagement with creditors and IFIs, and plans for generating sustainable growth and job creation.

Zimbabwe's Elections Were Meant to Start a New Era Expert comment sysadmin 14 August 2018

Emmerson Mnangagwa has been declared president of Zimbabwe amid protests and violence but Zimbabweans are now in a post-political, economy-first mood, writes Knox Chitiyo.

Before Zimbabwe’s general election on 30 July, there was a lot of talk about there being ‘landmark change’ and ‘credibility.’ But in many ways it was déjà vu. President Emmerson Mnangagwa’s ruling ZANU-PF party won the parliamentary vote, taking a majority 144 seats out of 210. The opposition MDC Alliance, a seven-party coalition led by Nelson Chamisa, won 64 seats—an improvement on their 2013 showing of 44 seats, but still falling far short of expectations.

The presidential results were much closer. After clashes on Wednesday, the incumbent Mnangagwa was declared winner early Friday morning, taking 50.8 per cent of the vote against Chamisa’s 44.3 per cent. The 21 other independent presidential candidates polled less than 5 per cent between them.

The polls didn’t quite live up to the hype. There was much that was positive: the prelude and election day were peaceful, with a minimal military presence. Opposition candidates were able to hold nationwide rallies (including in ZANU-PF’s rural heartland) without interference—an electoral first. ZANU-PF leaders and the military called for a peaceful process. Four women candidates contested the presidential vote, another first. More than 5 million Zimbabweans registered out of an eligible voting population of 7.2 million, and there was a near record 75 per cent turnout on voting day. Zimbabwe invited official observers from 46 countries and 15 international organizations, and, for the first time since 2002, observers from the EU, the Commonwealth and the US were present.

But shortcomings included late public access to the imperfect biometric voters roll and controversies about the ballot papers. There were also misogynistic social media attacks and threats against female candidates and the Zimbabwe Electoral Commission (ZEC) chair Justice Priscilla Chigumba.

The three-day wait for presidential results saw a further decline in public trust in the ZEC, and the opposition’s premature announcement of a Chamisa victory only fanned the political flames.

On Wednesday, six unarmed civilians were shot dead by soldiers in Harare, with dozens more assaulted. A Joint International Observer Mission statement promptly condemned the violence and called for restraint.

The election process was a boon for democracy, but ironically the result has entrenched the two-party parliamentary system and marginalized alternative voices. Mnangagwa has been conciliatory in his post-election statements, saying that Nelson Chamisa has a ‘crucial role to play’ and calling for unity to ‘build a new Zimbabwe for all.’

But Chamisa’s MDC Alliance has refused to accept the results, calling them ‘fake’ and a ‘scandal.’ The MDC has raised genuine transparency concerns and will likely challenge the results in court, but much of this may be cosmetic—with little chance of a 2017 Kenya-style presidential re-run. There is no critical mass of opposition parties to sustain a challenge, nor is there a popular appetite for a protracted political feud.

Zimbabwe’s democracy agenda may be heading into the slow lane, and Chamisa may be pressured by his coalition partners to make a political accommodation with Mnangagwa. Nevertheless, despite setbacks, Zimbabwe’s opposition and civil society has a long history of resilience under pressure and the struggle for democracy will continue.

Mnangagwa has a full in-tray. He has to unite a fractious ZANU-PF and manage internal civil-military and generational faultlines. Beyond that, he may need a public reconciliation with Chamisa—similar to how in Kenya and Mozambique, similar incumbent-opposition quarrels were mended by public rapprochements.

But Zimbabweans are now in a post-political, economy-first mood. Resolving the cash crisis is crucial. Few Zimbabweans can withdraw more than $50 a day from banks or ATMs—and much of this is paid out in unpopular ‘bond coins.’ The formal sector has contracted to only 20 per cent of the economy, and the informal sector lacks the capacity to push an economic renewal.

Zimbabwe’s new internationalism is premised upon the 2015 Lima process economic reform pathway for debt arrears clearance. (The country has a $10 billion foreign debt.) There has been a modest increase in foreign and diaspora investment, but the big-money Chinese, Russian and other pledges are long-horizon projects. What Zimbabwe needs is a short-term economic stimulus—to support small and medium-sized businesses.

For this to happen, Mnangagwa has to stay the course on economic reform, ease of doing business and the anti-corruption agenda. The pivot from reform to transformation in Zimbabwe will require all hands on deck, including civil society, the opposition, Zimbabwe diaspora and foreign investors, in a partnership for development.

A positive global verdict on the elections could supercharge investment, but time will tell whether these polls have been a deal-maker or a deal-breaker.

Zimbabwe’s elections often split the global south and the global north, and this could be the case again. The EU will have to decide whether to continue their incremental rapprochement with Zimbabwe, or accelerate to the reciprocity-based, ‘Re-Engagement 2.0’ approach currently favoured by the UK although the US is unlikely to lift statutory sanctions anytime soon.

Zimbabwe’s possible return to the Commonwealth could also be divisive, given the broader global context of the perceived existential clash between beleaguered liberal democracy and the rise of populist—and popular—autocracies across the globe.

President Mnangagwa—along with South Africa’s President Cyril Ramaphosa, Mozambique’s Filipe Nyusi and others—belong to a pragmatic new wave of regional economic reformers nudging liberationism away from ideology. He now has an electoral mandate to lead a divided country. For sisters Chipo and Tendai, both businesswomen based in Harare who voted for Mnangagwa and Chamisa respectively, the future needs to come now. ‘There is too much talk,’ they said, ‘we live every day between hope and despair. We need cash and jobs. We are tired of being tired.’

This was originally published in TIME.

Higher Education in South Africa: Demands for Inclusion and the Challenges of Reform 17 October 2018 — 5:00PM TO 6:00PM Anonymous (not verified) 18 September 2018 Chatham House, London

Economic Reform and Recovery in Zimbabwe 8 October 2018 — 2:30PM TO 3:30PM Anonymous (not verified) 4 October 2018 Chatham House, London

Public Service, Accountability and Delivery in Malawi 17 October 2018 — 12:00PM TO 1:00PM Anonymous (not verified) 11 October 2018 Chatham House, London

Political Reform in Angola: Challenges and Priorities for Elected Officials 31 October 2018 — 4:00PM TO 5:00PM Anonymous (not verified) 26 October 2018 Chatham House, London

Angola’s reformulated National Assembly has passed a series of legislative reforms since elections in August 2017, in which the ruling MPLA won a majority of 150 seats to the 51 held by the UNITA leading opposition party.

Many of the changes have targeted the revitalization of an underperforming economy and improved governance: in June 2018 parliament approved a new private investment law aimed at diversifying Angola’s fiscal base beyond oil revenues while new legislation in May mandated the return of illicitly exported capital of over $100,000.

As the appetite for measurable progress across all sectors of society remains high, and with newly constituted municipal elections scheduled for 2020, inclusive and accountable political debate will remain critical to Angola’s future.

At the event, a cross-party delegation discuss the role of the National Assembly in affecting political change and the importance of maintaining open dialogue among opposing voices to address the challenges facing Angola.

Water, Energy and Development in Angola: From Ambition to Actuality 13 December 2018 — 5:00PM TO 6:00PM Anonymous (not verified) 28 November 2018 Chatham House, London

Zimbabwe Futures 2030: Policy Priorities for Economic Expansion 28 February 2019 — 9:00AM TO 1:00PM Anonymous (not verified) 7 February 2019 Harare, Zimbabwe

This roundtable draws on current best practice and senior level expertise to identify policy options for long term economic expansion in Zimbabwe and pathways for inclusive development.

Participants discuss the necessary policies and business strategies to enable and support the effective implementation of the Transitional Stabilization Programme and longer term national development plans.

The discussions highlight requisite conditions for a business-driven and inclusive process towards Zimbabwe’s long-term economic recovery.

This event was held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung.