v Mouse Ifit1b is a cap1-RNA-binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c [RNA] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of “self” in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess “nonself” cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA–binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family. Full Article
v Development of a novel mammalian display system for selection of antibodies against membrane proteins [Immunology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies. Full Article
v Quantitative phosphoproteomic analysis reveals involvement of PD-1 in multiple T cell functions [Signal Transduction] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Programmed cell death protein 1 (PD-1) is a critical inhibitory receptor that limits excessive T cell responses. Cancer cells have evolved to evade these immunoregulatory mechanisms by upregulating PD-1 ligands and preventing T cell–mediated anti-tumor responses. Consequently, therapeutic blockade of PD-1 enhances T cell–mediated anti-tumor immunity, but many patients do not respond and a significant proportion develop inflammatory toxicities. To improve anti-cancer therapy, it is critical to reveal the mechanisms by which PD-1 regulates T cell responses. We performed global quantitative phosphoproteomic interrogation of PD-1 signaling in T cells. By complementing our analysis with functional validation assays, we show that PD-1 targets tyrosine phosphosites that mediate proximal T cell receptor signaling, cytoskeletal organization, and immune synapse formation. PD-1 ligation also led to differential phosphorylation of serine and threonine sites within proteins regulating T cell activation, gene expression, and protein translation. In silico predictions revealed that kinase/substrate relationships engaged downstream of PD-1 ligation. These insights uncover the phosphoproteomic landscape of PD-1–triggered pathways and reveal novel PD-1 substrates that modulate diverse T cell functions and may serve as future therapeutic targets. These data are a useful resource in the design of future PD-1–targeting therapeutic approaches. Full Article
v Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice [Developmental Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity. Full Article
v ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit [Developmental Biology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit. Full Article
v Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription [Gene Regulation] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation. Full Article
v Peptidoglycan analysis reveals that synergistic deacetylase activity in vegetative Clostridium difficile impacts the host response [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15–25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host–pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence. Full Article
v Fluctuation in O-GlcNAcylation inactivates STIM1 to reduce store-operated calcium ion entry via down-regulation of Ser621 phosphorylation [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Stromal interaction molecule 1 (STIM1) plays a pivotal role in store-operated Ca2+ entry (SOCE), an essential mechanism in cellular calcium signaling and in maintaining cellular calcium balance. Because O-GlcNAcylation plays pivotal roles in various cellular function, we examined the effect of fluctuation in STIM1 O-GlcNAcylation on SOCE activity. We found that both increase and decrease in STIM1 O-GlcNAcylation impaired SOCE activity. To determine the molecular basis, we established STIM1-knockout HEK293 (STIM1-KO-HEK) cells using the CRISPR/Cas9 system and transfected STIM1 WT (STIM1-KO-WT-HEK), S621A (STIM1-KO-S621A-HEK), or T626A (STIM1-KO-T626A-HEK) cells. Using these cells, we examined the possible O-GlcNAcylation sites of STIM1 to determine whether the sites were O-GlcNAcylated. Co-immunoprecipitation analysis revealed that Ser621 and Thr626 were O-GlcNAcylated and that Thr626 was O-GlcNAcylated in the steady state but Ser621 was not. The SOCE activity in STIM1-KO-S621A-HEK and STIM1-KO-T626A-HEK cells was lower than that in STIM1-KO-WT-HEK cells because of reduced phosphorylation at Ser621. Treatment with the O-GlcNAcase inhibitor Thiamet G or O-GlcNAc transferase (OGT) transfection, which increases O-GlcNAcylation, reduced SOCE activity, whereas treatment with the OGT inhibitor ST045849 or siOGT transfection, which decreases O-GlcNAcylation, also reduced SOCE activity. Decrease in SOCE activity due to increase and decrease in O-GlcNAcylation was attributable to reduced phosphorylation at Ser621. These data suggest that both decrease in O-GlcNAcylation at Thr626 and increase in O-GlcNAcylation at Ser621 in STIM1 lead to impairment of SOCE activity through decrease in Ser621 phosphorylation. Targeting STIM1 O-GlcNAcylation could provide a promising treatment option for the related diseases, such as neurodegenerative diseases. Full Article
v N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis. GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage. Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS. Full Article
v Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Infiltration of peripheral immune cells after blood-brain barrier dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx, a network of membrane-bound glycoproteins and proteoglycans that covers the lumen of endothelial cells, functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans, a component of the endothelial glycocalyx, were studied in the context of ischemic stroke using a photochemically induced thrombosis mouse model. Decreased levels of heparan sulfate and chondroitin sulfate and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine + glycosaminoglycan oligosaccharides as compared with N-acetylcysteine administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by immortalized endothelial cells and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein (ACR) exposure. We identified the ACR-modified amino acid residues of proHPSE using nano LC–MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), Lys107, and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part is attributed to the activation of proHPSE. Because proHPSE, but not HPSE, localizes outside cells by binding with heparan sulfate proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx. Full Article
v Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria. Full Article
v The structure of a family 110 glycoside hydrolase provides insight into the hydrolysis of {alpha}-1,3-galactosidic linkages in {lambda}-carrageenan and blood group antigens [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 α-Linked galactose is a common carbohydrate motif in nature that is processed by a variety of glycoside hydrolases from different families. Terminal Galα1–3Gal motifs are found as a defining feature of different blood group and tissue antigens, as well as the building block of the marine algal galactan λ-carrageenan. The blood group B antigen and linear α-Gal epitope can be processed by glycoside hydrolases in family GH110, whereas the presence of genes encoding GH110 enzymes in polysaccharide utilization loci from marine bacteria suggests a role in processing λ-carrageenan. However, the structure–function relationships underpinning the α-1,3-galactosidase activity within family GH110 remain unknown. Here we focus on a GH110 enzyme (PdGH110B) from the carrageenolytic marine bacterium Pseudoalteromonas distincta U2A. We showed that the enzyme was active on Galα1–3Gal but not the blood group B antigen. X-ray crystal structures in complex with galactose and unhydrolyzed Galα1–3Gal revealed the parallel β-helix fold of the enzyme and the structural basis of its inverting catalytic mechanism. Moreover, an examination of the active site reveals likely adaptations that allow accommodation of fucose in blood group B active GH110 enzymes or, in the case of PdGH110, accommodation of the sulfate groups found on λ-carrageenan. Overall, this work provides insight into the first member of a predominantly marine clade of GH110 enzymes while also illuminating the structural basis of α-1,3-galactoside processing by the family as a whole. Full Article
v {alpha}2-Macroglobulin-like protein 1 can conȷugate and inhibit proteases through their hydroxyl groups, because of an enhanced reactivity of its thiol ester [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment. Full Article
v Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform. Although homomeric Cxs forms have been largely described functionally and structurally, the stoichiometry and arrangement of heteromeric Cx channels remain unknown. The latter, however, are widely expressed in human tissues and variation might have important implications on channel function. Investigating properties of heteromeric Cx channels is challenging considering the high number of potential subunit arrangements and stoichiometries, even when only combining two Cx isoforms. To tackle this problem, we engineered an HA tag onto Cx26 or Cx30 subunits and imaged hemichannels that were liganded by Fab-epitope antibody fragments via atomic force microscopy. For Cx26-HA/Cx30 or Cx30-HA/Cx26 heteromeric channels, the Fab-HA binding distribution was binomial with a maximum of three Fab-HA bound. Furthermore, imaged Cx26/Cx30-HA triple liganded by Fab-HA showed multiple arrangements that can be derived from the law of total probabilities. Atomic force microscopy imaging of ringlike structures of Cx26/Cx30-HA hemichannels confirmed these findings and also detected a polydisperse distribution of stoichiometries. Our results indicate a dominant subunit stoichiometry of 3Cx26:3Cx30 with the most abundant subunit arrangement of Cx26-Cx26-Cx30-Cx26-Cx30-Cx30. To our knowledge, this is the first time that the molecular architecture of heteromeric Cx channels has been revealed, thus providing the basis to explore the functional effect of these channels in biology. Full Article
v Representative cancer-associated U2AF2 mutations alter RNA interactions and splicing [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 High-throughput sequencing of hematologic malignancies and other cancers has revealed recurrent mis-sense mutations of genes encoding pre-mRNA splicing factors. The essential splicing factor U2AF2 recognizes a polypyrimidine-tract splice-site signal and initiates spliceosome assembly. Here, we investigate representative, acquired U2AF2 mutations, namely N196K or G301D amino acid substitutions associated with leukemia or solid tumors, respectively. We determined crystal structures of the wild-type (WT) compared with N196K- or G301D-substituted U2AF2 proteins, each bound to a prototypical AdML polypyrimidine tract, at 1.5, 1.4, or 1.7 Å resolutions. The N196K residue appears to stabilize the open conformation of U2AF2 with an inter-RNA recognition motif hydrogen bond, in agreement with an increased apparent RNA-binding affinity of the N196K-substituted protein. The G301D residue remains in a similar position as the WT residue, where unfavorable proximity to the RNA phosphodiester could explain the decreased RNA-binding affinity of the G301D-substituted protein. We found that expression of the G301D-substituted U2AF2 protein reduces splicing of a minigene transcript carrying prototypical splice sites. We further show that expression of either N196K- or G301D-substituted U2AF2 can subtly alter splicing of representative endogenous transcripts, despite the presence of endogenous, WT U2AF2 such as would be present in cancer cells. Altogether, our results demonstrate that acquired U2AF2 mutations such as N196K and G301D are capable of dysregulating gene expression for neoplastic transformation. Full Article
v The heptameric structure of the flagellar regulatory protein FlrC is indispensable for ATPase activity and disassembled by cyclic-di-GMP [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 The bacterial enhancer-binding protein (bEBP) FlrC, controls motility and colonization of Vibrio cholerae by regulating the transcription of class-III flagellar genes in σ54-dependent manner. However, the mechanism by which FlrC regulates transcription is not fully elucidated. Although, most bEBPs require nucleotides to stimulate the oligomerization necessary for function, our previous study showed that the central domain of FlrC (FlrCC) forms heptamer in a nucleotide-independent manner. Furthermore, heptameric FlrCC binds ATP in “cis-mediated” style without any contribution from sensor I motif 285REDXXYR291 of the trans protomer. This atypical ATP binding raises the question of whether heptamerization of FlrC is solely required for transcription regulation, or if it is also critical for ATPase activity. ATPase assays and size exclusion chromatography of the trans-variants FlrCC-Y290A and FlrCC-R291A showed destabilization of heptameric assembly with concomitant abrogation of ATPase activity. Crystal structures showed that in the cis-variant FlrCC-R349A drastic shift of Walker A encroached ATP-binding site, whereas the site remained occupied by ADP in FlrCC-Y290A. We postulated that FlrCC heptamerizes through concentration-dependent cooperativity for maximal ATPase activity and upon heptamerization, packing of trans-acting Tyr290 against cis-acting Arg349 compels Arg349 to maintain proper conformation of Walker A. Finally, a Trp quenching study revealed binding of cyclic-di-GMP with FlrCC. Excess cyclic-di-GMP repressed ATPase activity of FlrCC through destabilization of heptameric assembly, especially at low concentration of protein. Systematic phylogenetic analysis allowed us to propose similar regulatory mechanisms for FlrCs of several Vibrio species and a set of monotrichous Gram-negative bacteria. Full Article
v Cholesterol sensing by CD81 is important for hepatitis C virus entry [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in both health and disease. Full Article
v A structural and kinetic survey of GH5_4 endoglucanases reveals determinants of broad substrate specificity and opportunities for biomass hydrolysis [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset. Full Article
v Snapshots during the catalytic cycle of a histidine acid phytase reveal an induced-fit structural mechanism [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes. Full Article
v Bacterial iron detoxification at the molecular level [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron. Full Article
v Evolving the naturally compromised chorismate mutase from Mycobacterium tuberculosis to top performance [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity. Full Article
v Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics. Full Article
v Unique active-site and subsite features in the arabinogalactan-degrading GH43 exo-{beta}-1,3-galactanase from Phanerochaete chrysosporium [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Arabinogalactan proteins (AGPs) are plant proteoglycans with functions in growth and development. However, these functions are largely unexplored, mainly because of the complexity of the sugar moieties. These carbohydrate sequences are generally analyzed with the aid of glycoside hydrolases. The exo-β-1,3-galactanase is a glycoside hydrolase from the basidiomycete Phanerochaete chrysosporium (Pc1,3Gal43A), which specifically cleaves AGPs. However, its structure is not known in relation to its mechanism bypassing side chains. In this study, we solved the apo and liganded structures of Pc1,3Gal43A, which reveal a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family 35 (CBM35) binding domain. GH43_sub24 is known to lack the catalytic base Asp conserved among other GH43 subfamilies. Our structure in combination with kinetic analyses reveals that the tautomerized imidic acid group of Gln263 serves as the catalytic base residue instead. Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite −1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the β-1,6–linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s, including those that bind galactomannan. Specifically, we noted a Gly → Trp substitution, which affects pyranose stacking, and an Asp → Asn substitution in the binding pocket, which recognizes β-linked rather than α-linked Gal residues. These findings should facilitate further structural analysis of AGPs and may also be helpful in engineering designer enzymes for efficient biomass utilization. Full Article
v Seeded fibrils of the germline variant of human {lambda}-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure. Full Article
v Determinants of replication protein A subunit interactions revealed using a phosphomimetic peptide [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection. Full Article
v A highly potent CD73 biparatopic antibody blocks organization of the enzyme active site through dual mechanisms [Methods and Resources] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity. Full Article
v Nitro-fatty acids as activators of hSIRT6 deacetylase activity [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Sirtuin 6, SIRT6, is critical for both glucose and lipid homeostasis and is involved in maintaining genomic stability under conditions of oxidative DNA damage such as those observed in age-related diseases. There is an intense search for modulators of SIRT6 activity, however, not many specific activators have been reported. Long acyl-chain fatty acids have been shown to increase the weak in vitro deacetylase activity of SIRT6 but this effect is modest at best. Herein we report that electrophilic nitro-fatty acids (nitro-oleic acid and nitro-conjugated linoleic acid) potently activate SIRT6. Binding of the nitro-fatty acid to the hydrophobic crevice of the SIRT6 active site exerted a moderate activation (2-fold at 20 μm), similar to that previously reported for non-nitrated fatty acids. However, covalent Michael adduct formation with Cys-18, a residue present at the N terminus of SIRT6 but absent from other isoforms, induced a conformational change that resulted in a much stronger activation (40-fold at 20 μm). Molecular modeling of the resulting Michael adduct suggested stabilization of the co-substrate and acyl-binding loops as a possible additional mechanism of SIRT6 activation by the nitro-fatty acid. Importantly, treatment of cells with nitro-oleic acid promoted H3K9 deacetylation, whereas oleic acid had no effect. Altogether, our results show that nitrated fatty acids can be considered a valuable tool for specific SIRT6 activation, and that SIRT6 should be considered as a molecular target for in vivo actions of these anti-inflammatory nitro-lipids. Full Article
v MMP activation-associated aminopeptidase N reveals a bivalent 14-3-3 binding motif [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Aminopeptidase N (APN, CD13) is a transmembrane ectopeptidase involved in many crucial cellular functions. Besides its role as a peptidase, APN also mediates signal transduction and is involved in the activation of matrix metalloproteinases (MMPs). MMPs function in tissue remodeling within the extracellular space and are therefore involved in many human diseases, such as fibrosis, rheumatoid arthritis, tumor angiogenesis, and metastasis, as well as viral infections. However, the exact mechanism that leads to APN-driven MMP activation is unclear. It was previously shown that extracellular 14-3-3 adapter proteins bind to APN and thereby induce the transcription of MMPs. As a first step, we sought to identify potential 14-3-3–binding sites in the APN sequence. We constructed a set of phosphorylated peptides derived from APN to probe for interactions. We identified and characterized a canonical 14-3-3–binding site (site 1) within the flexible, structurally unresolved N-terminal APN region using direct binding fluorescence polarization assays and thermodynamic analysis. In addition, we identified a secondary, noncanonical binding site (site 2), which enhances the binding affinity in combination with site 1 by many orders of magnitude. Finally, we solved crystal structures of 14-3-3σ bound to mono- and bis-phosphorylated APN-derived peptides, which revealed atomic details of the binding mode of mono- and bivalent 14-3-3 interactions. Therefore, our findings shed some light on the first steps of APN-mediated MMP activation and open the field for further investigation of this important signaling pathway. Full Article
v Humanin selectively prevents the activation of pro-apoptotic protein BID by sequestering it into fibers [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP. Full Article
v A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications [Neurobiology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Abnormal changes of neuronal Tau protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer's disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remain ill-defined. Tau contains ∼85 potential phosphorylation sites, which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, methodological limitations (e.g. in MS of phosphopeptides, or antibodies against phosphoepitopes) led to conflicting results regarding the extent of Tau phosphorylation in cells. Here we present results from a new approach based on native MS of intact Tau expressed in eukaryotic cells (Sf9). The extent of phosphorylation is heterogeneous, up to ∼20 phosphates per molecule distributed over 51 sites. The medium phosphorylated fraction Pm showed overall occupancies of ∼8 Pi (± 5) with a bell-shaped distribution; the highly phosphorylated fraction Ph had 14 Pi (± 6). The distribution of sites was highly asymmetric (with 71% of all P-sites in the C-terminal half of Tau). All sites were on Ser or Thr residues, but none were on Tyr. Other known posttranslational modifications were near or below our detection limit (e.g. acetylation, ubiquitination). These findings suggest that normal cellular Tau shows a remarkably high extent of phosphorylation, whereas other modifications are nearly absent. This implies that abnormal phosphorylations at certain sites may not affect the extent of phosphorylation significantly and do not represent hyperphosphorylation. By implication, the pathological aggregation of Tau is not likely a consequence of high phosphorylation. Full Article
v Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Cα, 13Cβ, 1Hα, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca2+, but do bind Zn2+, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested. Full Article
v Molecular characterization of the RNA-protein complex directing -2/-1 programmed ribosomal frameshifting during arterivirus replicase expression [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism. Full Article
v Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood [Microbiology] By www.jbc.org Published On :: 2018-11-09T03:40:54-08:00 The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets. Full Article
v Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes [Molecular Bases of Disease] By www.jbc.org Published On :: 2016-12-30T00:06:37-08:00 Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations. Full Article
v Economy Must Not Get Stuck Between Lockdown and Recovery By www.chathamhouse.org Published On :: Thu, 02 Jul 2020 17:29:32 +0000 2 July 2020 Creon Butler Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme LinkedIn Despite recent outbreaks in several countries which had appeared to be close to excluding the virus, focusing on suppression and elimination is the best economic as well as health strategy. 2020-07-02-Plane-Virus-Business An almost empty British Airways passenger plane flies from Milan to London. Photo by Laurel Chor/Getty Images. Lockdowns are being eased in many countries, but from different starting points in terms of prevalence of the virus, and with different near-term trade-offs between protecting life and easing constraints on economic activity.The pressure to ease is understandable. The IMF estimates $10tn has been spent so far on official support measures worldwide, and forecasts global GDP will contract by an unprecedented 4.9% in 2020.However, the WHO director general, Dr Tedros Adhanom Ghebreyesus, recently insisted that there is an ‘urgent responsibility to do everything we can with the tools we have now to suppress transmission and save lives’, even as research into vaccines and therapeutics continues.Focusing on suppressing and eliminating the virus as quickly as possible is not just the best strategy for saving life, it also makes most sense in terms of minimising the long-term economic damage from the pandemic.The alternatives remain uncertainNeither a vaccine nor improved treatment are currently sufficiently certain to be the focal point for an economic recovery strategy. Despite optimism about vaccine development, there is no certainty of a decisive outcome by a given date. And, even if a vaccine proved effective, manufacturing and distributing it to 8bn people will present an unprecedented set of logistical and economic challenges and take many months, if not years.In the meantime, although substantial progress has been made in reducing loss of life among those made seriously ill by the virus - and who have access to advanced medical facilities - it remains highly dangerous for a significant proportion of the population - around 20% in advanced economies.An alternative containment strategy based on gradually reducing the prevalence of the virus in the population by maintaining an “R” number (replication coefficient) just below one will be both economically costly and highly risky when compared with a decisive push to eliminate the virus quickly.With an R number just below one it is true the virus may eventually disappear, but only over a lengthy period, during which economically damaging social distancing measures will have to stay in place, dragging out the impact on both demand and supply.Wage support measures to limit ‘economic scarring’ will have to be maintained, and kickstarting the economy with a conventional fiscal stimulus will be difficult, if not impossible, especially when the ability - or willingness - of consumers to spend is still heavily constrained either by social distancing measures or a lack of confidence.There is also a major risk when the R number is close to one that the virus could suddenly take off again, leading to a complete failure of the strategy.Benefits of suppress and eliminateA successful policy focused on suppressing and eliminating the virus offers much better prospects. First, the government can then protect the vast bulk of the economy within its territory, even if it means continuing travel restrictions for some time vis-a-vis countries that are less committed to or less successful in eliminating the virus.Some sectors - particularly long-haul air transport - will be hard hit, but other critical high value or employment intensive sectors - such as domestic hospitality, leisure and the arts - will be able to make a substantial recovery. To put it bluntly, the authorities may have to hold back some sectors to save others. Such a strategy would also ensure an economy can participate sustainably in free travel zones with other countries.Second, a drive to suppress and eliminate the virus in the shortest possible timeframe, and then maintain that status, will help authorities communicate clearly to the public the overarching framework guiding the application of social distancing measures, and the nature of the ‘new normal’ economy that can be expected to emerge over the medium to long-term.Achieving such clarity will enhance the public’s trust in the government’s strategy and hence responsiveness to government instructions. It will also minimise unnecessary and costly adaptations by business and increase its ability to target new opportunities arising from the genuine long-term changes brought about by the crisis.In addition, a suppress and eliminate strategy is the only sure way to address the disproportionate impact of the virus on ethnic minorities and the poor, and to put an end to the isolation of the millions who currently have to shield themselves.We know that suppressing the virus almost completely within a given territory is possible because some countries have already done it - notably New Zealand, South Korea, and Taiwan. Some which started with a serious epidemic, such as China, Spain and Italy, have also managed to reach a point where almost complete elimination within their territory can be envisaged.Renewed outbreaks are likely to happen, particularly while the virus remains in active circulation globally. But this does not invalidate the underlying suppress and eliminate strategy.Key policies to suppress and eliminate the virus include: a rapid and decisive national lockdown to reduce the disease to levels low enough for test, trace and quarantine systems to identify and suppress local outbreaks; social distancing measures for a limited period or in a specific locality to limit spread while, as far as possible, minimising economic impact; and effective quarantine and track systems applied at borders to prevent the disease from being re-introduced by non-essential travellers and returning nationals.The precise form of these policies is evolving rapidly as we learn more about the virus. For example, if there is a need today to stop a rapidly escalating epidemic in a given territory, it won’t necessarily mean adopting exactly the same package of lock down measures across the board as were applied three months ago. Several activities had to cease then simply because the virus was spreading so fast there was no time to put in place effective mitigation measures. This does not have to be repeated.In addition, the benefits of the widespread use of face masks are now much better understood. As is the value of deploying a battery of measures, each one only partially effective on its own but, in combination, with a decisive impact. Financial support measures may need to be adjusted or extended to underpin local lockdowns and, at any given point, the authorities will need to work within an overall budget for relaxation measures and prioritise - getting pupils back in school may mean holding back easing of restrictions elsewhere.Choosing an effective strategy inevitably means making tough choices. Delaying short-term recovery measures, even by a matter of weeks in whole economies or specific localities, can make a decisive difference to delivering a long-term sustainable economic outcome. The authorities may also be forced to hold back some economic sectors, possibly even leading to permanent damage, as the price of a general recovery. But if we are not ready to make these choices, the economy may become permanently stuck in a halfway house between lockdown and recovery. Full Article
v Chatham House History: Five Key Moments on Africa By www.chathamhouse.org Published On :: Thu, 09 Jul 2020 15:47:08 +0000 9 July 2020 Christopher Vandome Research Fellow, Africa Programme LinkedIn To mark the centenary of Chatham House, the Africa programme curated an exhibition of archive material which charts how the institute has been both a major forum for discussion on Africa, and an important platform for African leaders to engage in international affairs. Mandela1a.jpg President Nelson Mandela of South Africa addresses an audience at an event co-hosted by Chatham House, the CBI and COSAT on July 10, 1996. As with any history, Chatham House has a long and complex one. Progress has come in fits and starts, sometimes driven by wider social change, but often led by individuals within the institute. When examining the institute's work on Africa, five seminal moments from the history really stood out.The FoundersLionel Curtis is credited as the founder of the institute, having proposed the idea at a meeting at the Hotel Majestic while attending the Treaty of Versailles talks.Curtis served in South Africa during the Second Boer war and subsequent period of unification. He was one of the cohort of officials that served under Lord Milner, later dubbed ‘Milner’s Kindergarten’. Several of this group were involved in the foundation of the institute. A Century of Supporting African Engagement in International Affairs A short presentation highlighting how Chatham House has been both a major forum for discussion on Africa, and an important platform for African leaders. His experiences in South Africa undoubtedly informed his political philosophy - a strong belief in liberal imperialism. This is captured in the emblems of empire inlaid into the roundtable which is still in the Chatham House library, given to Curtis as a wedding gift.But more importantly than his political philosophy, Curtis was an astute social networker and fundraiser who unlocked the finance required to establish the institute. Curtis’s papers in the Chatham House archives depict his almost obsessive following of the career of the South African diamond tycoon Sir Abe Bailey that eventually led to the first significant endowment to the institute - after the building. South African Prime Minister Jan Smuts, a friend of Curtis and early champion of the institute, spoke at a dinner in honour of Bailey’s contribution.Curtis’s connections meant much of the early finance came from South Africa, including from Otto Beit and Percy Molteno, who was also an early financer of the African National Congress (ANC).Hailey’s Africa SurveyIn 1938, Chatham House published Lord Hailey’s monumental Africa Survey. Its detailed 1,837 pages of study came to represent a seismic shift in attitudes towards the continent. Lord Lothian’s foreword emphasises that it grew from an idea of Smuts from 1929, although these origins remain disputed.What is known is that Oxford University had submitted a proposal for a study of the continent to an American foundation which rejected it on the grounds that they didn’t want American money to be used to expand Smut’s doctrine of dominion. The group then merged their own plan into an emerging study by progressive missionary Joseph Oldham.Curtis brought in his friend Lord Hailey to lead the initiative. Hailey was a distinguished civil servant who served in India but never in Africa. The project moved to Chatham House and received a substantial grant from the Carnegie Foundation. Having been originally conceived as a study to reinforce segregationist ideas, the final survey was groundbreaking. Its underlying assumption of basic racial equality debunked the premises of segregation and re-set British attitudes towards Africa.This shift in mindset was hugely significant at the time, but the work would later be criticized for not including any African voices. And, despite carrying his name, Lord Lothian wrote very little of the text. He fell ill, in part due to the pressure of the four-year project, and the work was largely written by notable Africanists Lucy Mair, Charlotte Leubuscher, and Margery Perham. The Africa Survey was updated and reprinted in 1956, including a pull-out map depicting newly-independent Sudan. A sign of real change.Independence and National LiberationThe 1960s was a decade of transformation both on the continent and at Chatham House. The institute became an important conduit for newly-independent African states to engage in international affairs, hosting several independence presidents, including Prime Minister Modibo Keita of Mali, President Léopold Senghor of Senegal, and President Julius Nyerere of Tanzania. Many of these speeches were republished in the Institute’s journal, International Affairs.In January 1962, the Nigerian government invited Chatham House to host a conference in Lagos on the external international relations of the newly-independent African states. But it wasn’t just presidents that were offered a platform. Liberation leaders were also invited to speak as well as conduct research. African Liberation – The Historical and Contemporary Significance of Re-discovered Nationalist Speeches at Chatham House of Dr Eduardo Mondlane and Oliver Tambo Two speeches at Chatham House in 1968 and 1985 by African nationalist leaders Dr Eduardo Mondlane and Oliver Tambo at key moments of their liberation struggle for majority rule are re-examined for their significance. Dr Bernard Chidzero, a later finance minister in independent Zimbabwe, wrote on African nationalism in International Affairs in 1960, and conducted a multi-year study at the institute resulting in the publication of a book. In 1968, Eduardo Mondlane, founding president of FRELIMO, made an important speech on the nationalist fight for independence in Mozambique.In 1961, Kenneth Younger, a new director of the institute, increased its research capacity on Africa through significant new hires. Catherine Hoskyns’s 1965 book on the Congo crisis became the seminal study on the topic. Dennis Austin, who had experience in West Africa, wrote the definitive work on Ghana’s transition to independence in 1964.African InstitutesChatham House has also been involved in the establishment of think-tanks across the world, including three in Africa.The South African Institute of International Affairs (SAIIA) was founded in 1934, in response to proposals made by Chatham House the previous year at the inaugural British Commonwealth Relations Conference. An East African Institute of International Affairs was also established in Nairobi but did not survive. The Nigerian Institute of International Affairs (NIIA) was formed in 1961 in Lagos. Its founding director general Dr L A Fabunmi, said ‘the main task of the Nigerian Institute of International Affairs will be to create, develop, and sustain an African perspective in world affairs’.Chatham House has maintained a good working relationship with its sister institutes. In 2005 a special edition of International Affairs was launched at NIIA, the first time in the journal’s history it was launched outside the UK. And SAIIA staff and leaders are regular contributors to Chatham House events and research, including a partnership on the study of Central and Eastern European relations with Africa.The Africa ProgrammeCreated in 2002. this was the first time Chatham House had a dedicated research team working on Africa, producing a sustained and balanced assessment of events on the continent. Throughout the 1980s and 1990s, work on Africa had been conducted by regionally-focused study groups, and the personal interests of the director for studies, Dr Jack Spence – a leading authority on South African foreign policy. An earlier attempt to create a more formal programme in the late 1990s fell victim to staff turnover.In 1998, the British Angola Forum (BAF) was formed and found a home at Chatham House. It marked a departure from the institute’s focus on post-colonial 'Anglophone Africa'. At the end of Angola's civil war in 2002, under the leadership of Dr Alex Vines, the BAF morphed into a continent-wide programme.Since then, the Africa Programme has produced more than 160 original research publications, and organizes between 120-140 events on Africa every year. The Africa Programme is marking the centenary of the institute with a major research theme on Foreign Relations and African Agency in International Relations.Chatham House’s work on Africa has its roots in the liberal imperialism of the post war leaders. But throughout the last 100 years, it has been a platform for progress, playing a vital role in informing policymakers and facilitating debate on African affairs, as well as highlighting African perspectives on global issues.The exhibition on the History of Africa at Chatham House was first displayed at the world-renowned fine art auctioneers and valuers Bonham’s in London for a reception in February 2020 marking the centenary of the Institute. It was curated by Christopher Vandome with the assistance of the Chatham House Library, and digitized with the help of the Institute’s communications department. Please contact the Library team for further information regarding the archive.Chatham House Centenary:Throughout our centenary year in 2020, Chatham House marks a century of influence, independent analysis and trusted dialogue with a number of exciting initiatives. Throughout the year, we explore key political moments from the institute's history and reflect on how Chatham House and other think-tanks should approach the future. Full Article
v Is Evaluating COVID-19 About the WHO or Country Responses? By www.chathamhouse.org Published On :: Sat, 11 Jul 2020 13:23:41 +0000 11 July 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks Striking the right balance in membership and terms of reference is challenging for the evaluation panel set up to examine the coordinated international health response to coronavirus. 2020-07-11-WHO-Data-Coronavirus-Tedros Examining the global response of indivudual countries and the World Health Organization (WHO) to coronavirus. Photo Illustration by Rafael Henrique/SOPA Images/LightRocket via Getty Images. When the resolution was passed by World Health Organization (WHO) member states at the World Health Assembly (WHA) in May requesting an evaluation ‘at the earliest appropriate moment’ of lessons learned from the WHO-coordinated international health response to COVID-19, it was generally thought the appropriate moment would be when the pandemic was on the wane.Yet the Independent Panel for Pandemic Preparedness and Response has actually been established at a time when - as noted by WHO director-general Dr Tedros Adhanom Ghebreyesus in his announcement of the panel - the pandemic is still accelerating.In most of the world the virus is not under control, and cases have actually doubled in the last six weeks. So why now?Emphasis on global solidarityThroughout the pandemic so far, Dr Tedros has emphasised two main points – the need for urgent action by countries, and the imperative need for global solidarity. In announcing the panel, he said this is the ‘defining crisis of our age’ and that ‘we cannot defeat this pandemic as a divided world … the COVID-19 pandemic is a test of global solidarity and global leadership’.He may well see establishing the panel now - when the pandemic still has a long way to run - as an opportunity to reinforce messages which have hitherto seemed to fall on deaf ears, notably saying ‘we are in the midst of the battle of our lives, and we have to do better’. And he has also said that we should learn lessons now that will be useful in the continuing fight against the pandemic.Establishing both the membership of the panel and its terms of reference has been left largely in the hands of the co-chairs – distinguished ex-politicians Helen Clark of New Zealand and Ellen Johnson Sirleaf of Liberia. But they will have to construct the panel in close consultation with member states on the basis of their proposals for membership – a process that will likely be fraught by the divisive politics which have already so upset Dr Tedros.In addition, embedded in the mandate from the WHA resolution is the phrase ‘WHO-coordinated international health response’ – negotiated language which is intentionally ambiguous and reveals an unresolved tension.Does it mean the panel should principally focus on WHO’s performance, which is what several countries – including the US – want to see? Or should it give at least equal weight to the way countries have responded individually and collectively, as Dr Tedros and the WHO may want to see?These different interpretations mean both the construction of the panel and its terms of reference could be highly contentious. Most countries, including China and the US but also others, will not want their responses to be subjected to independent investigation. Nor will they want to include panel members likely to be critical of their responses. This suggests the possibility that there will be political pressure to focus the enquiry principally on the performance of WHO rather than that of countries – an outcome Dr Tedros would not welcome.It remains to be seen how the co-chairs will manage these highly political issues, and avoid the panel becoming an extension of ‘pandemic politics’ by other means. Can it come to definitive conclusions in the midst of a pandemic and, if so, how likely are they to be heeded?It is also highly likely that several other reviews will be launched, wholly independently of oversight by WHO and its member states, as happened following the 2014 Ebola outbreak. This provides opportunities for a variety of perspectives on both the performance of WHO, and of individual countries.Already, The Lancet has announced its own Commission on COVID-19 with a broad mandate covering both the health and economic responses to the pandemic. Both this and the Independent Panel for Pandemic Preparedness and Response are likely to be only the first of many COVID-19 reviews. Full Article
v COVID-19: The Hidden Majority in India's Migration Crisis By www.chathamhouse.org Published On :: Mon, 13 Jul 2020 12:58:13 +0000 13 July 2020 Dr Champa Patel Director, Asia-Pacific Programme @patel_champa While the social and economic costs of coronavirus lockdowns, travel bans and social distancing initially focused on international migrants, there has been increasing attention paid to the plight of internal migrants. 2020-07-13-India-Farming-Migration Migrant workers plant paddy in a field at Jhandi village in Patiala, India. Photo by Bharat Bhushan/Hindustan Times via Getty Images. The World Bank estimates that the magnitude of internal migration is about two‐and‐a‐half times that of international migration. Within India, an estimated 40 million internal migrant workers, largely in the informal economy, were severely impacted by the government’s COVID-19 lockdown.With transportation systems initially shut down, many had no recourse to travel options back to homes and villages, resulting in harrowing journeys home. Those who were able to make it home found, in some instances, villages refusing entry because of fears of transmission.The shocking images of migrants forced to walk in desperation showed the enormity of the crisis as well as some of the challenges posed by an extended lockdown in India where so many people live hand to mouth and cannot afford not to work.Migrant workers and the informal economyThe complete failure of the government to anticipate the needs of this group, and the subsequent distress caused, has made visible a large workforce who experience precarity of work and often live hand to mouth.One key challenge is the lack of robust data on the scale of internal migration. While estimates abound, there is no proper data collection system in place to accurately record temporary, seasonal and circular migration patterns. However, it is estimated that more than 90% of working people in India are engaged in the informal economy, with states such as Uttar Pradesh and Bihar accounting for more than 80% of workers in this sector.A recent government labour force survey estimated that more than 71% of people with a regular salary working in non-agricultural industries had no written job contract. Nearly half of workers are not eligible for social security benefits.Daily-wage workers are particularly vulnerable, with limited or no access to social security and most living in poverty. Living hand to mouth, their loss of livelihoods has led to a lack of money to pay rents or pay for food. Women are impacted whether because of their gender, responsibilities as caregivers, or as members of disadvantaged castes and communities.COVID-19 has massively impacted this group of workers. Stranded Workers Action Network found that 50% of workers had rations left for less than one day; 74% had less than half their daily wages remaining to survive for the rest of the lockdown period; and 89% had not been paid by their employers at all during the lockdown.According to Supreme Court proceedings, relief camps are housing some 660,000 workers; some 2.2 million people also rely on emergency food supplies. Job losses, and home and food insecurity have left this group highly vulnerable.In March 2020, in response to COVID-19, the Indian government instituted the Pradhan Mantri Garib Kalyan Package (PMGKB), a $22.6 billion relief package. The World Bank announced $1 billion funding to accelerate social protection support, in part through the PMGKB.This support would work alongside pre-existing initiatives such as the Public Distribution System (PDS), which covers 800 million people, and Direct Benefit Transfers (DBT). This cash injection could help address one of the key challenges facing India’s piecemeal and uneven social protection programmes – inadequate funding. India’s spending on public social protection excluding health is just 1.3% of the GDP.However, there are still other challenges to overcome. One is how to ensure coordination and coverage within, and across, differing states. The second is how to transition multiple schemes into one integrated system that can be accessed anywhere within the country, particularly important when many workers are on the move. There is an urgent need for a comprehensive system, which is adaptive and flexible to needs and provides adequate social and income support.Another coverage issue relates to the use of direct cash transfers (DCTs) to support people impacted by the loss of livelihoods, where funds are deposited within bank accounts. Such measures fail to consider the significant numbers of people who do not have access to banks and will not be able to access this support.Wider impact on livelihoods and remittancesThere is a risk, with extended lockdown and risks of further waves of infection, that labour shortages could negatively impact the economy. There is a wider need to support re-entry back into the workforce and support livelihoods. National Survey Sample data shows that between 2007 and 2008, internal remittances amounted to US$10 billion. These domestic transfers financed over 30% of all household consumption in remittance-receiving households.But future migration for work is likely to be severely impacted. As restrictions begin to ease, employers and businesses cannot necessarily rely on cheap available labour. Having faced destitution and hardship, many may wish to stay closer to families and local support networks.As Irudaya Rajan notes in The New Humanitarian, it is likely ‘there will be a reduction in long-distance migration in India after this’, as many migrants will be wary of being stranded again. This would be hugely detrimental to stimulating the economy as reverse migration could push down wages and subsequently demand.Another issue may be returning migrant workers, who have been working overseas, over half of whom work in the Gulf. It is unclear if, or when, migrants will be able to return to work, with the World Bank estimating that remittances from this group could fall by about 23%.However, what is striking has been India’s support for this group - the Vande Bharat Mission has deployed flights and naval ships to help return migrant workers, especially vulnerable groups - in marked contrast to the lack of preparation and care for internal migrants.One factor for this may be the volume of remittances these migrant workers bring to the Indian economy, but it overlooks the contribution of internal remittances, on which there is far less robust data.But the current challenges can also be an opportunity. The scale of the migrant crisis has made visible an often-overlooked population of workers. With political will, and investment at federal and state levels, this could be an opportunity to transform livelihoods.As thoughts will turn to how to stimulate economies and get people back to work, it is imperative that those in authority turn their minds to how to create a more just society, that invests in healthcare, and has a social protection system that supports the most vulnerable in society.Migrants are not just objects of charity that need support. Internal migrants are key income generators that play a vital role in Indian society and should never be overlooked again.This article was originally published in Routed Magazine. Full Article
v West Bank Annexation: International Rhetoric vs. Action By www.chathamhouse.org Published On :: Mon, 13 Jul 2020 16:30:48 +0000 14 July 2020 Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme @renizhelyazkova Professor Yossi Mekelberg Senior Consulting Research Fellow, Middle East and North Africa Programme @YMekelberg Israel may have delayed announcing its plans to annex West Bank lands but the international community now needs to transform its rhetoric into action if there is to be a lasting solution to the Israel-Palestine conflict, argue Reni Zhelyazkova and Yossi Mekelberg. GettyImages-1223719050.jpg Houses are pictured in the Maale Adumim settlement in the West Bank east of Jerusalem. The Israeli government has delayed plans to annex Jewish settlements in the West Bank and in the Jordan Valley. Photo: Getty Images Observers of the Israel-Palestine conflict have been anticipating Israeli Prime Minister, Benjamin Netanyahu’s, announcement to annex parts of the West Bank. It has been a tumultuous year for Israeli politics which has seen three inconclusive elections and resulted in a sharing of power between Netanyahu and Benny Gantz of the Blue and White party. However, since the coalition government was sworn in, Netanyahu has appeared to not lose any time in moving forward with his plans.Annexation has long been Netanyahu’s political aspiration and was part of his recent re-election platform but the anticipated announcement from the Israeli government didn’t come straight away. The determining factor in the delay was the inability to reach an agreement with Washington about the scope of the annexation while divisions within the Israeli government itself, in addition to international condemnation from the region and beyond, has also played a part.Discussions around annexation have so far yielded one major outcome: it has introduced a different rhetoric by the Trump-Netanyahu axis even though things on the ground don’t necessarily follow. Ever since President Donald Trump took office in 2016, there has been a marked change in Washington’s language around the Israel-Palestine conflict. It has shifted towards legitimizing Israel’s expansionist ambitions in the West Bank while marginalizing, and considerably weakening, the Palestinian Authority (PA) through a series of punitive measures.This has further damaged relations between Israel and Palestine and has resulted in a fundamental change in the public discourse around the conflict, from emphasizing a just solution based on self-determination for both sides, to focusing on a de-facto one-state solution.But how has the discourse shifted so dramatically in less than four years? First came the announcement of the US embassy move to Jerusalem, and with it, recognition of the city as Israel’s capital. In his statement, President Trump avoided recognizing Palestinian claims over Jerusalem and did not acknowledge their historical connection with the city. When the PA rejected the move, the US administration then retaliated by cutting aid and development funding and closing the PLO mission in Washington stating: ‘We have permitted the PLO office to conduct operations that support the objective of achieving a lasting...peace between Israelis and the Palestinians … However, the PLO has not taken steps to advance the start of...meaningful negotiations with Israel.’ On the question of Israel’s settlements in the West Bank, the current US administration has shied away from calling them ‘illegal’ despite being deemed illegitimate under international law and condemned on numerous occasions by the UN Security Council, the UN General Assembly, the EU, the Arab League and the Palestinians themselves. US Secretary of State, Mike Pompeo, has even gone as far as saying that the establishment of Israeli settlements in the West Bank is not inconsistent with international law.The culmination of US discourse in recent months has been the unveiling of the ‘Peace to Prosperity’ plan. The language of the proposal, once again, has shown partiality towards Israel by not mentioning the illegality of Israel’s occupation of the West Bank, or that of settlements, and entirely ignoring previous Palestinian positions or acknowledging their sensitivities. There is little doubt that the current US administration understands the power of rhetoric and has been using it to change the trajectory of discussions away from a two-state solution towards an outcome that would only serve Israeli interests.Indeed, US rhetoric has empowered Netanyahu immensely too, ushering in a new reality that has rendered a Palestinian state nothing more than a hypothetical option. The language, combined with a multitude of unilateral actions, is helping to dismantle any efforts towards a two-state solution and the upholding of previous international agreements.Many European and regional governments have condemned any move towards annexation. Indeed, 1,000 European parliamentarians from across political lines have urged Israel to abandon its plans. This has notably included, German Foreign Minister, Heiko Mass, whose first overseas visit during the coronavirus crisis was to Israel to reinforce Germany’s position against unilateral action.But actions speak louder than words, and in the case of the US, its rhetoric has been matched by action unlike its EU counterparts whose statements of condemnation have rarely been followed by concrete action. For instance, the EU ratified a landmark aviation agreement with Israel just days before 1 July and economic, technological and scientific cooperation between Israel and Europe has never been stronger casting doubt on the strength of political will among EU countries to take action against Israel.In the Middle East, the United Arab Emirates has been the most vociferous in disapproving Israel’s annexation plans. However, again, it is important to look beyond the rhetoric. Cooperation between the UAE and Israel has in fact increased in recent years mainly due to common opposition to Iran’s regional influence but also due to shared interests. In May, for instance, the first publicly acknowledged commercial flight between the UAE and Israel landed at Ben Gurion airport carrying aid aimed at mitigating the effects of COVID-19 in the Palestinian territories. But, to many, it looked like a stepping-stone towards a normalization of relations between Abu Dhabi and Jerusalem.Similarly, Jordan and Egypt have also expressed their concern but it is difficult to imagine a scenario where either country would go as far as abrogating peace agreements that they currently have in place with Israel.In spite of this, the global response has overwhelmingly been critical of Israel’s plans to annex parts of the West Bank. This has demonstrated some level of unity among world leaders which has not been seen for some time and may have played a significant role in delaying the Israeli government’s plans. In parallel, united international condemnation has also prevented the US from dominating the Israeli-Palestinian conflict entirely.While the US approach has played a key role in the Israel-Palestine conflict so far, it remains to be seen how the international community will translate its voice into action to prevent the annexation of occupied Palestinian land. Full Article
v Flaring in MENA: The Multibillion Dollar Decarbonization Lever By www.chathamhouse.org Published On :: Wed, 15 Jul 2020 12:05:58 +0000 15 July 2020 Adel Hamaizia Associate Fellow, Middle East and North Africa Programme Dr Mark Davis CEO, Capterio The climate crisis and ‘energy transition’ is driving a response from the oil and gas industry to decarbonize, with flaring – the deliberate combustion of gas associated with oil production – as a critical lever, especially in the Middle East and North Africa, write Adel Hamaizia and Mark Davis. 2020-07-15-Flare-Oil-Iraq Iraqi Southern Oil Company engineers look towards the flares in the Zubair oil field in southern Iraq. Photo by ESSAM -AL-SUDANI/AFP via Getty Images. Flaring is a significant source of economic and environmental waste. Except when safety-related, flared gas can often be captured and monetised using low-cost proven solutions.In doing so, governments can improve health and safety, reduce emissions (of carbon dioxide, methane, and particulates) and add value by driving up revenue, increasing reserves and production, creating jobs and improving the industry’s ‘social license to operate’.Flare capture also helps countries to deliver on the Paris Agreement and the UN’s Sustainable Development Goal #13 while, for example, providing affordable alternatives for heating and cooking.The Middle East and North Africa (MENA) region accounts for 40% of the world’s flaring. In the region, flaring has increased year-on-year - apart from 2018 - to almost six billion cubic feet of gas per day, generating up to 300-500 million tonnes of CO2-equivalent emissions per year.These emissions result not only from the combustion of gas, but also from the venting, from inefficient flares, of un-combusted methane, a more potent greenhouse gas. Yet much of this is avoidable.There are many commercially attractive options to reduce flaring in MENA. The key is to use the right proven technology and to be agile in commercial structuring. And the prize could be a boost to MENA’s annual revenues by up to $200 per second (up to $6.4 billion per year) by delivering wasted gas to market by pipeline, as power or in liquid form.The chart highlights the abundance of flaring across the MENA region, and in many cases, their proximity to population centres. While Iran, Iraq, and Algeria generate 75% of MENA’s flaring, Saudi Arabia, Kuwait, UAE and Qatar are notable for their relatively low ‘flaring intensity’ i.e. flaring normalized to oil production.In today’s world of lower energy prices, it makes sense to monetise every molecule. Even more so for national oil companies, which are responsible for most of the flaring, since they are not only the custodians of their countries’ natural resources, but they also generate a dominant source of government revenue.Most oil producers in MENA have already made commitments to the World Bank’s flaring-reduction initiatives (e.g. ‘Zero Routine Flaring by 2030’), but to date, delivery is mostly lacking. Three main issues have hindered progress.Firstly, operators, regulators, and governments highlight that flaring is often not ‘sufficiently on the radar’. Flaring is often underreported if not ignored or denied - although satellite detection gives unavoidable transparency. In MENA alone, more than 1,700 flare clusters are visible every day from space.Secondly, flare capture is sometimes not perceived to be economically viable due to costs, taxes, or inappropriate technology. Thirdly, there are often issues around resources, especially concerning management bandwidth, delivery capabilities or financing.Yet these issues can be solved if the right proven technologies are combined with the right commercial structures. To accelerate flare capture projects, stakeholders in the MENA hydrocarbons sector must consider several complementary, action-oriented initiatives.In particular, they should:Promote transparency and disclosure to drive greater awareness of flaring. Governments, regulators and operators must understand the real scale of their gas flaring opportunity and be capable of acting, as a recent report for the EBRD on Egypt highlighted. Compliance with clear standards for measuring, monitoring and verification is critical.Advance policies and incentives which encourage action. Better commercial terms will incentivise and accelerate flare investments. Stronger penalties will help, but independent and capable regulators must actually enforce these penalties. Through the use of such clear anti-flaring policies, Norway’s flaring intensity is almost 20 times lower than the MENA region.Improve the investment climate, beyond economics and open access to a broader range of players. Local market failures can be avoided by reducing the complexity and cost of in-country operations and by removing excessive, rigid, or redundant regulations. By enabling greater ‘third-party’ access to gas and power projects and infrastructure, new players can accelerate change by deploying new technologies and new operating models. Better third-party access will also unlock ideas, capital, skills and project-specific financing options. Algeria is making steps towards such liberalisation through its new 2019 Hydrocarbon Law.Reduce subsidies and improve energy efficiency and reduce demand, increase gas exports and boost national revenues. Countries with large subsidies on transport fuels and power, such as Algeria and Iraq, stand to gain the most.Encourage collaboration between stakeholders in industry and government by creating working groups to radiate best practices, build capacity, deploy technology and local content, such as the flare minimization programme in Saudi Arabia or Iraq’s major flare-to-power project operated by the Basrah Gas Company.The industry needs to prepare for a greener world after COVID-19 and investors and consumers are demanding cleaner fuels. Since gas is widely viewed as a transition fuel, MENA governments and stakeholders must work to eliminate its wastage and seize the revenue, production and environmental opportunities that flare capture projects offer.There is much new leadership in the region in government and critical institutions with new mandates for change. The time to act is now. Full Article
v Domestic Violence in Russia: The Impact of the COVID-19 Pandemic By www.chathamhouse.org Published On :: Fri, 17 Jul 2020 12:00:04 +0000 20 July 2020 Ekaterina Aleynikova Research Assistant, Russia and Eurasia Programme @AleynikovaKatya LinkedIn The COVID-19 pandemic has made Russia’s domestic violence problem more visible, with shifting public opinion potentially incentivizing the government to change its approach, argues Ekaterina Aleynikova. GettyImages-1159506648 (1).jpg Campaigners during a rally held in 2019 in support of a Russian law on domestic violence. Photo: Getty Images Russia is one of the few countries in the region to have no legal definition of domestic violence and, as a result, there are no protective measures specific to domestic violence such as restraining orders or compulsory anger management training for abusers. In fact, the government has taken steps in recent years to remove any legal distinction between assault happening in one’s home, and elsewhere, with battery among family or household members for first-time offences decriminalized in 2017.The Russian Ministry of Justice explicitly defended this position in its response to an enquiry into Russian domestic violence cases by the European Court of Human Rights (ECtHR) in November 2019. The ministry claimed existing legislation adequately protects citizens from domestic violence, ‘even though it has never been considered a separate offence’, reiterating that there is ‘no need’ for adopting specific legislation.However, the four cases that led to the ECtHR’s enquiry demonstrate that current legislation is not sufficient. The most prominent case is that of Margarita Gracheva whose ex-husband severed her hands in 2017 despite her having made multiple complaints to the police ahead of the act being committed. If Russian legislation had mechanisms in place to isolate victims from their abusers, then Gracheva could have been protected by the law.Instead, systemic impunity for abusers is supported by statements from people in power excusing domestic violence. The most recent of such statements came from the head of the Chechen Republic, Ramzan Kadyrov, in June 2020. When meeting with the family of a young woman allegedly murdered by her husband, Chechnya’s leader said, husbands beating their wives ‘happens’ and that the young woman should have tried harder to hold on to her marriage. These statements send clear signals to abusers that their actions are justified, and to the victims, that they won’t be protected if they were to come forward.Similarly, to other parts of the world, civil society organizations in Russia have reported an increase in the number of cases of domestic violence during the COVID-19 pandemic. On a personal level, the pandemic has often exacerbated many of the factors that can lead to domestic violence such as stress, economic anxiety or social isolation.On a systemic level, many of the provisions intended to protect victims of violence, which were already ineffective in Russia, have been worsened during the lockdown. Where police may not have rapidly responded to reports of domestic violence previously, under lockdown, they have become focused on other priorities and, where shelters and support networks for the victims may have been scarce in the past, they have been further constrained.Unsurprisingly, the strategy of the Russian state so far has been to deny that there is a problem of domestic violence, with the Ministry of Interior reporting that, according to their statistics, the number of domestic violence cases have gone down during the lockdown. Indeed, Chairwoman of the Federation Council, Valentina Matvienko, has said she does not believe lockdown has increased domestic violence because, on the contrary, families have been ‘brought together’, reflecting wishful thinking at best and negligence at worst.The pandemic has also been used as an excuse to postpone discussion of a federal law on domestic violence, drafted by civil society, that was submitted for review by the Duma last year. This bill would have introduced different types of domestic violence such as psychological and economic violence and transferred domestic violence offences from private to public prosecutions to make it easier for victims to seek justice.The government’s disregard for domestic violence reflects, in part, the patriarchal mindsets of those in power but perhaps, more significantly, the Kremlin’s belief that conservative social groups constitute its main support base. This has been made evident by the politicization of Russia’s ‘traditional’ values in recent years which was vigorously deployed throughout the constitutional amendments campaign. While it is clear that the true purpose of amending the constitution has always been to allow Vladimir Putin to stay in power beyond 2024, amendments relating to this were absent from the government’s campaign. Instead, Russians were encouraged to vote by populist socially-conservative messages, hence why respect for traditional values has been added to the constitution.Despite this, attitudes in Russian society are changing. A February 2020 survey by the Levada Centre showed that 61 per cent of Russians – and 74 per cent of Russian women – think domestic violence is a serious problem.Moreover, the survey shows that women are much more aware of domestic violence than men – with every third woman in Russia admits being aware of domestic violence in their social circles while only every fifth man admits the same. This could be a sign that Russian men and women, on average, have a different understanding of what constitutes domestic violence. If so, adopting a law that defines domestic violence and holding a public awareness campaign is of paramount importance to eliminate any misunderstanding.The difference could also be a sign that victims of domestic violence are more likely to confide in women hence making domestic violence less visible to men. This awareness gap perhaps explains the difference between men’s and women’s assessments of how serious the issue in Russia is.The pandemic has provoked a new wave of discussions of domestic violence among Russia’s population with stories and statistics widely shared in the media and on the internet. As domestic violence becomes more visible, public perceptions are likely to shift further towards recognizing, and hopefully condemning, it. But, while legislation is crucial, the experience of other countries in the region, such as Armenia or Kazakhstan, shows that adopting laws on domestic violence is not enough. Measures are needed to ensure implementation of the law including training police officers and state officials and instituting disciplinary action for negligence of victims’ complaints.Nevertheless, admitting there is a problem with domestic violence in Russia, and introducing laws, are an essential first step. The Russian government seems to have placed its bet on the support of conservative social groups but changing public opinion may prove this strategy unsustainable. Full Article
v Domestic Violence in Ukraine: Lessons from COVID-19 By www.chathamhouse.org Published On :: Thu, 23 Jul 2020 13:45:42 +0000 23 July 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn The pandemic has shed light on domestic violence in Ukraine, mobilizing civil society to demand more nuanced policy on the issue. 2020-07-23-UkraineIWD.jpg A protester chants slogans on a megaphone during an International Women's Day protest on 8 March 2019 in Kyiv, Ukraine. Photo: Getty Images. The virus of violenceDuring quarantine, the greater economic vulnerability of Ukrainian women has locked many of them with abusive partners. The uncertainty of personal finances, health and security in confinement has exacerbated domestic violence against women, in certain cases aggravated by the perpetrator’s war-related post-traumatic stress disorder (PTSD).In pre- pandemic times, only one third of domestic violence victims, 78% of whom are women, reported the abuse. During the pandemic, the calls to domestic violence helplines increased by 50% in the Donbas war zone and by 35% in other regions of Ukraine.However, more precise estimates are hard to make. This is largely because some fractions of Ukrainian society still see domestic violence as a private family matter, which will get little assistance from the police. Also, reporting from a small confinement place permanently shared with a perpetrator during the lockdown can trigger more abuse.The COVID-19-tested legal frameworkThe spike in domestic violence during lockdown has intensified the debate about the inadequacy of Ukraine’s approach.Ukraine adopted the law on domestic violence in 2017 and made such behaviour punishable under administrative and criminal law. Importantly, the law does not limit domestic violence to physical abuse, but recognizes its sexual, psychological and economic variations. Domestic violence is further not limited to a married couple or close family members, but can be perpetrated against a distant relative or a cohabiting partner.The extended definition of rape now includes rape of a spouse or a family member as an aggravating circumstance. A special police unit has been designated to deal with domestic abuse cases. Police can now issue protection orders in prompt reaction to an offence and immediately distance a perpetrator from a victim.The victim can also spend time in a shelter - a system which the Ukrainian government has promised to create. A special registry of domestic violence cases has been set up for the exclusive use by the designated law enforcement and social security authorities to help them be more holistically informed in building a response.However important, the introduced legal and institutional infrastructure was slow in proving its efficiency pre-COVID-19. It is struggling even more to stand the test of the coronavirus.Changing the established mindset takes time. 38% of Ukraine’s judges and 39% of prosecutors still struggle to see domestic violence not as a household issue. Even though the police are becoming more reactive to home abuse complaints, getting emergency protection orders is still difficult. The court restraining orders are more effective, however they require the unnecessarily protracted and humiliating procedures of proving one’s own victimhood to different state authorities.In response to the challenges of coronavirus for women, the police spread information posters and created a special chat-bot about the available help. However, while the domestic violence helplines of La Strada and other human rights NGOs are busier than ever, the police statistics suggest that the lockdown has not catalyzed home abuse.This could indicate a higher trust to non-state institutions and the inability of a considerable group of women to use more sophisticated communication means such as chat-bots when they cannot call the police in the presence of an abuser. This problem is exacerbated by a current lack of shelters in rural areas, as most are located in urban settings. Overcrowded in ordinary times, the shelters’ capacity to accept survivors during the lockdown is further limited by the social distancing rules.Istanbul Convention – The bigger pictureUkraine failed to ratify the Council of Europe Convention on preventing and combating violence against women, better known as the Istanbul Convention, largely due to the opposition of religious organizations. Concerned that the treaty’s terms ‘gender’ and ‘sexual orientation’ would contribute to the promotion of same-sex relationships in Ukraine, they argued that Ukraine’s current legislation provides adequate protection against domestic violence. However, this is not the case.The Istanbul Convention does not ‘promote’ same-sex relationships, it only mentions sexual orientation among the non-exhaustive list of prohibited discrimination grounds. Remarkably, Ukraine’s domestic violence law itself is against such discrimination.The Convention defines ‘gender’ as the socially constructed roles a society attributes to women and men. Ukraine’s overcautiousness about the term is ironic at least in two dimensions.First, the 2017 domestic violence law restates its aim to eliminate discriminating beliefs about the social roles of each ‘sex’. In doing so, the law supports the rationale of what the Istanbul Convention denotes as ‘gender’ without using the term itself.Second, it is exactly the constraints of the rigidly defined niches for both sexes in Ukraine that have substantially contributed to the intensified domestic violence, whether it be war or coronavirus-related. The lack of sustainable psychological support for traumatized veterans and the stigma of mental health struggles, especially among men, mars their reintegration to peaceful life. This often results in alcohol abuse or even suicide.As the economic uncertainty of the war and the virus prevents some men from fully living up to their traditional socially - and self-imposed - breadwinner role, this increases the risk of problematic behaviour and domestic violence.By diverting the focus of the debate to the term ‘gender’ used in the Istanbul Convention, conservative groups have ignored the fact that it describes the priority already enshrined in Ukraine’s 2017 law - to eliminate discriminatory beliefs about the socially constructed roles of men and women. This has drawn away time and resources needed to protect those vulnerable to domestic abuse.Ukraine has not addressed the pigeonholing of women and men into gendered stereotypes. This has harmed men while further victimizing women and children, especially during the lockdown. Ironically, this is leading to the undermining of the very traditional family values certain opponents of the Istanbul Convention appealed to.Fortunately, Ukraine’s ever-vigilant civil society, dismayed at the wave of the lockdown domestic violence, petitioned President Zelenskyy to ratify the Convention. With a new draft law on ratification, the ball is now in the parliament’s court. It remains to be seen whether Ukraine’s policymakers will be up to the task. Full Article
v UK Should Focus on Better Defining Objectives in the Sahel By www.chathamhouse.org Published On :: Fri, 24 Jul 2020 11:19:46 +0000 22 July 2020 Dr Alex Vines OBE Managing Director, Ethics, Risk & Resilience; Director, Africa Programme The Sahel is one of Africa’s poorest and most fragile regions witnessing an escalation in jihadist activity and illegal migration, writes Alex Vines. GettyImages-1204470166.jpg Pictured is a Nigerian refugee living in the Awaradi settlement that houses some 9,000 displaced people fleeing violence from Boko Haram. Image: Getty Images. The UK has been redeploying diplomatic, defence and development capabilities towards the Sahel since 2018 – a strategic pivot intended to deliver development impact, address long term security threats to UK interests and support alliances with international partners.The Sahel is one of Africa’s poorest and most fragile regions and has witnessed an escalation in jihadist activity, illegal migration and trafficking since a security crisis erupted in Mali in 2012.The crisis spread to Niger and Burkina Faso and may now spill over into Côte d’Ivoire, Ghana and Senegal. With Nigeria also facing insurgency in the Lake Chad basin, all major regional security and economic anchors in the region are under threat including key UK partners. Reviewing the Sahel pivotThis pivot has already resulted in the expanding of UK embassies in Senegal, Mauritania and Mali and public commitments to opening new ones in Chad and Niger.Back in London, there has also been a large uplift of staff including the setting up of a cross-Whitehall Joint Sahel Department in late 2018 and plans for more UK civil servants to have placements with the French government on the Sahel.Yet in light of looming economic shocks from Brexit and Covid-19, there has been a lively debate in Whitehall on whether this is stretching UK resources too thin in an area of Africa that does not have close ties with the UK.UK ministers are this week reviewing the Sahel pivot and will decide if it continues or grinds to a standstill including whether full embassies are opened in Niger and Chad.This debate is not new. The UK has opened and closed its diplomatic missions in the Sahel in fits and starts since the early 1960s. More recently, MI6 pushed the re-opening of the embassy in Bamako in 2010 foreseeing Mali’s fragility before the current crisis started.Partnering with the FrenchBut though the Sahel is likely to dominate the Africa peace and security agenda for decades to come, the UK’s serious engagement in the region is not just about strategic foresight.It also fulfils two other objectives: of partnership with two key bilateral allies, particularly France, and authority and leverage in multilateral fora such as the United Nations, African Union and the EU.Partnering with the French in the Sahel has become even more important due to Brexit and the need to reinforce relationships with key European partners.In 2012, David Cameron concluded that the rapid French response to stop a jihadist advance on the Malian capital Bamako was 'in our interests' and authorized the deployment of 330 UK military personnel, two cargo aircraft and a surveillance plane.In July 2018, the UK announced further support to French led Opération Barkhane sending three Royal Air Force Chinook helicopters – supported by almost 100 personnel – which remain in theatre to this day.UN commitmentDemonstrating the UK’s commitment to UN peacekeeping has also resulted in the deployment of 250 troops to join a UN peacekeeping mission to Mali later this year.Based in Gao, these troops will form a long-range reconnaissance capability providing threat awareness, contributing to the protection of civilians and helping to prevent conflict from spilling over to neighbouring states.This represents one of the biggest British peacekeeping deployments since Bosnia and it will be the most dangerous mission for British forces since Afghanistan.The UK is also one of the largest humanitarian donors to the region and has contributed over £500 million in bilateral development and humanitarian assistance since 2015.With COVID-19 now an additional challenge in the Sahel, a significant part of the UK’s £764 million contribution to the global COVID-19 effort will be channelled to the region.New embassies are 'global Britain' strategy pillarsKeeping an eye on the impact of these initiatives requires a meaningful UK diplomatic network on the ground.New embassies in the Sahel cost a fraction of maintaining three Chinook helicopters in the region providing the government real time insight in the post-Brexit absence of a regular supply of country analysis from the European External Action Service and support for the UK’s international relationships.It also underlines the UK’s commitment to UN peacekeeping and standing as a permanent member of the UN Security Council in light of regular discussions of the Sahel.The tripartite ministerial review of the Sahel pivot by the secretaries of state for foreign affairs, international development and defence that is underway should not penny pinch by reversing the opening of small embassies in Niger and Chad nor threaten the overall strategic focus on the Sahel – most recently welcomed by the House of Lord’s Select Committee on International Relations and Defence in its July report on UK Africa policy.Instead, UK ministers should focus on better defining what the UK’s specific objectives are in the Sahel and particularly what the UK plans to do about Burkina Faso whose rapidly deteriorating security threatens to over-spill into key UK partner Ghana.This article was first published in the Daily Telegraph. Full Article
v Russia’s Behaviour Risks Weaponizing Outer Space By www.chathamhouse.org Published On :: Mon, 27 Jul 2020 14:19:39 +0000 27 July 2020 Dr Beyza Unal Deputy Director, International Security Programme @beyzaunal Google Scholar Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar With negotiations in Vienna between the US and Russia hoping to prevent the weaponization of space, how much do Russia’s satellites pose a threat to the peaceful use of outer space, ask Beyza Unal and Mathieu Boulègue? GettyImages-1209576417.jpg Russia's President, Vladimir Putin, during a video link with cosmonauts on the International Space Station (ISS). Photo: Getty Images. Days before the publication of last week’s report into Russian activity in the UK, and the subsequent call from several UK parliamentarians for a swift response to the ‘Russian threat’, Russia tested a new anti-satellite weapon capability releasing a small projectile from its Kosmos-2543 sub-satellite.Kosmos-2543, a small satellite contained inside a larger satellite, Kosmos-2542, and 'birthed’ into orbit in late 2019, recently came under scrutiny in January 2020 when it was reportedly caught ‘buzzing’ US spy satellites in Low Earth Orbit.By releasing a small projectile from the Kosmos-2543 sub-satellite, the US claims that Russia has launched a new projectile into orbit with relatively high speed – estimated at around 500 km per hour – leading to concerns about the potential of Russia to develop this technology as a weapon to target foreign satellites.It is not the first time Moscow has relied on a Russian doll – or matryoshka – approach to launching satellites into outer space. In October 2017, a sub-satellite, Kosmos-2521, was ejected from its main satellite, Kosmos-2519, into a high-speed object in low orbit.The Russian Ministry of Defence has declared that its latest activity is just for ‘routine’ inspections and surveillance of Russia’s other space assets, with the government’s official statement avoiding recognizing the existence of the new object while, at the same time, Kremlin spokesperson, Dmitry Peskov, recalling Russia’s commitment for the ‘complete demilitarization’ of space.While it is possible that Russia’s matryoshka satellites have indeed been developed to carry out routine repairs of Russia’s space fleet, they also have the potential to interfere with, and destroy, other satellites with such action needing to be considered a threat until Russia demonstrates otherwise.Russia’s use of outer spaceRussia is not the only state investigating anti-satellite weaponry capabilities. There is a wider trend (e.g. China, India, US) to demonstrate advanced space capabilities with nefarious, if not directly offensive, intent. But, for the past few years, Russia in particular, has been provocative in testing its space weapon capabilities. For example, in April 2020, Russia launched and tested into low orbit the PL-19 Nudol direct-ascent anti-satellite (DA-ASAT) interceptor missile system from the Plesetsk Cosmodrome demonstrating its space assets with potential offensive capabilities, in particular, Russia’s capacity to destroy satellites in Low Earth Orbit.In addition, the satellites, Kosmos-2535 and Kosmos-2536, launched in July 2019, are also suspected to be operating beyond their official mission of studying Russian orbital assets. It is reported that these satellites conducted a close proximity activity, coming within one kilometre from each other, which led to the creation of orbital debris.Russia’s space strategyBy exploiting asymmetric advantages in space, Russia seeks to leverage its capabilities against competitors in space and in other domains, falling in line with its wider military strategy as well as its current Federal Space Programme for 2016 to 2025.Russian space activities also have a cyber and electronic warfare angle. With the help of remote-sensing capabilities, Russian spy satellites potentially seek to disrupt military and civilian satellite communications and navigation systems. Indeed, in 2018, French authorities publicly accused Russia of seeking to intercept communication satellites for French and Italian armed forces putting data transmission through Western civilian and military satellites at risk of interception.Furthermore, earlier this year, both Kosmos-2542 and 2543 came within 160 kilometres of a US spy satellite, US KH-11, similarly to Russia ‘buzzing’ around the British Isles or submarine surveillance that Norway and Sweden have been subjected to recently.Shadowing and tailing in space is regarded as spying and this recent anti-satellite weapon test is part of a trend which demonstrates Russia’s persistent space strategy for close-proximity operations with foreign countries.Orbital hypocrisyDespite Russia’s calls for a treaty to prevent the placement of weapons in outer space, there remains little international trust in Russia’s behaviour in space so far with a US-Russia Space Security Exchange meeting scheduled to take place in Vienna on 27 July to discuss outer space stability and security.This is amid a backdrop of bilateral nuclear arms control talks on the extension of the extant nuclear weapons reduction treaty, New START, which is scheduled to expire in February 2021. There is no guarantee, however, that the talks will achieve anything especially since the future of outer space requires a wider multilateral dialogue with all parties involved – including China.Anti-satellite tests (ASATs) are a particularly dangerous form of weapon. Not only do they create major vulnerabilities in a domain where so much of humanity depends on for navigation, communications and environmental monitoring, they are also primarily a target for destabilization and undermining global positioning information in times of crisis.And, perhaps most significantly, they possess the highly destructive potential to create even more space debris in Earth’s orbits that endanger the peaceful use of satellites and could do serious damage to large parts of the economies of developed and developing countries.Avoiding space warfareSpace is for all but there is a risk that it is being hijacked by a few. It is time to re-assert and reinforce the rules, principles and norms of responsible state behaviour in outer space enshrined in the 1967 Outer Space Treaty and its associated international agreements.And, because the treaty specifically prohibits stationing nuclear weapons and other weapons of mass destruction in orbit or on celestial bodies, it is necessary to build on it to ban other types of weapons in space.Space has been militarized since 1957 with the launch of Soviet satellite Sputnik. But the increasing weaponization of space adds more uncertainty, and unveils more vulnerabilities, that states need to address before space warfare becomes a reality. Full Article
v Elections in Côte d’Ivoire: President Ouattara’s Dilemma By www.chathamhouse.org Published On :: Mon, 27 Jul 2020 19:08:37 +0000 28 July 2020 Paul Melly Consulting Fellow, Africa Programme @paulmelly2 After the sudden death of Côte d’Ivoire’s Prime Minister Amadou Gon Coulibaly, President Ouattara is now deciding whether to stand for a third term. However, such a move would face challenges internationally, and particularly in West Africa. GettyImages-1227751629.jpg President of Ivory Coast Alassane Ouattara arrives in Bamako on 23 July 2020, where West African leaders gathered in a push to end an escalating political crisis in Mali. Photo: Getty Images. Gon Coulibaly, an economic technocrat and Ouattara loyalist since the 1990s, was earmarked in March as the candidate for the ruling Rassemblement des Houphouëtistes pour la Démocratie et la Paix (RHDP) party in the elections due in October, and represented a handpicked heir, trusted to sustain the strategy established during Ouattara’s nine years in power.Many RDHP parliamentarians and local mayors are now pressing the 78-year-old Ouattara to run again. This was not what he had planned. He hoped to go out on a high – ‘par la grande porte’ – and set a statesmanlike example of retirement by choice, making way for the next generation. His leadership of reform of the regional currency that will see the end of the West African CFA franc would have been the crowning achievement of a presidency that had taken his country from post-war stagnation to sustained growth GDP growth rates around seven per cent before COVID-19 forced a slowdown, as it has worldwide.A profound strategic dilemmaGon Coulibaly had undergone a heart transplant in 2012, and when he hurried to Paris in early May and was fitted with a stent, some wondered whether he would have the energy required for an election campaign. Yet he returned home on 2 July, with his formal nomination by the RHDP pencilled in for early the next month. His sudden death on 8 July, at the age of just 61, was a terrible personal blow for Ouattara, who had regarded him almost as a son, and much more than a purely political protégé. But it also left the president facing a profound strategic dilemma.Names of alternative potential RHDP candidates have been floated – notably the defence minister, and now interim premier, Hamed Bakayoko and the secretary general of the presidency Patrick Achi. Both have solid electoral track records and ample experience of government. But over recent days the impression has grown that they do not command the ultimate confidence of Alassane Ouattara to take on the leadership of the nation.Speculation has grown that the president will conclude that he has no choice but to go back on his promise to retire and stand for yet another term. Although some respected legal experts disagree, he has always made a point of insisting that the constitutional reform of 2016 allows him to run again. And many influential voices within the RHDP are now pressing him to do so.This is not ‘rentacrowd’ fawning. Many members of the governing party have always felt that Ouattara offers the strongest blend of political appeal, governing capability and international profile required to lead a country that likes to see itself as West Africa’s ‘elephant’.A weak opposition, but third term challengesIn electoral terms, Ouattara’s greatest campaign asset might be the unconvincing state of the opposition figures who are actually free to stand, after the Ivorian authorities’ strong-armed the judicial system into blocking the hopes of the of the smooth-talking former parliamentary speaker Guillame Soro, who had great appeal for Cote D’Ivoire’s growing young population. Soro is now exiled in France after conviction in absentia for corruption. Ex-president Laurent Gbagbo remains in Brussels, while the International Criminal Court considers the prosecution appeal against his acquittal on charges of human rights crimes. He is now allowed to travel and has applied for a passport to come home, but it is unclear if this will be granted. That leaves another former head of state, the 86-year old Henri Konan Bédié, as the main opposition challenger.However, even if the RHDP party machine delivers victory for Ouattara, a third term risks hard questions from those who dispute its legitimacy and it may generate other significant political challenges too. Some 60 per cent of Ivorians are under the age of 25, and many young people are impatient for leaders more in tune with their concerns and outlook. Some 51 per cent now live in towns and cities.The sprawling Abidjan conurbation, in particular, weighs heavily in the political culture and national mood. Street protest and urban frustrations are a real factor, and something that fuels vocal grassroots support for both the Soro and Gbagbo camps.Moreover, despite the government’s capable management, the COVID-19 crisis has struck a severe economic and social blow that is sure to impose painful legacy pressures. Even when real GDP was rising by seven per cent per annum, increasingly evident inequality was brewing popular resentment. Corruption appeared to be on the rise, and the obvious prosperity, construction and consumption in parts of Abidjan were not reflected nationwide nor in all sections of society.In the latter years of his second term, Ouattara recognized this and launched an ambitious programme to broaden the reach of development and nudge growth towards a more ‘inclusive’ model. But selling this as the core of an election agenda would be harder for a political veteran who has been in power since 2011 and who now went back on his rhetoric about making way for a younger generation.A third term Ouattara would also face challenges internationally, and particularly in West Africa. He has always presented himself as a statesmanlike figure with restraint and respect for institutional values, setting a tone that has helped in the management of numerous regional crises – exemplified by his participation in a five-president mission to Bamako last week, an effort to broker a solution to Mali’s political and protest deadlock. If a third term run sparks mass domestic protest or accusations of constitutional manipulation, the diplomatic standing and influence so associated with Ouattara will be jeopardized.So Côte d’Ivoire’s president faces profoundly awkward questions as he ponders the third term bid that he had forsworn less than five months ago. And yet he may well conclude that, from his political perspective, there is no viable alternative. Full Article
v COVID-19 Teaches Resilience and the ‘Vulnerability Paradox’ By www.chathamhouse.org Published On :: Fri, 07 Aug 2020 17:37:37 +0000 7 August 2020 Dr Gareth Price Senior Research Fellow, Asia-Pacific Programme @DrGarethPrice Google Scholar Christopher Vandome Research Fellow, Africa Programme LinkedIn Humility from decision-makers, building trust in leaders and institutions, and learning from international experience are critical if countries are to better prepare for the next global crisis. 2020-08-07-Vietnam-Health-Virus-Art An information poster on preventing the spread of COVID-19 in Hanoi, Vietnam. Photo by MANAN VATSYAYANA/AFP via Getty Images. While we must wait for the final reckoning of most successful national coronavirus responses, it does still appear those countries with memories of MERS and SARS - such as Singapore, Taiwan, Hong-Kong, and South Korea – led the way in being best prepared for COVID-19, with strong contract tracing and isolation measures.Experience of previous outbreaks informed the containment strategies adopted by countries in East Asia in response to COVID-19. Vietnam reported its first case of COVID-19 in January but, over the following four months with rapid targeted testing, contact tracing and successful containment, only around 300 additional cases with no deaths were confirmed.These countries learned to be flexible fast when new transmissions occurred, establishing quick lockdown measures targeted at key groups such as Singapore’s schools or South Korea’s night clubs and religious centres. In stark contrast, most European countries were overwhelmed by the pandemic despite enjoying world-class health systems, predictive models, scientific expertise, wealth, and resources.Asia may have suffered first from coronavirus, but there is no ‘first mover advantage’ in dealing with a pandemic. The more resilient a society, the better placed it is to cope with a variety of risks and challenges. But to become resilient, a society needs to have faced setbacks and learned from them. And to remain resilient, it needs to stay aware of its own vulnerabilities and avoid complacency.Prior experience of crises and disturbances, coupled with a ‘trial and error’ process of learning to deal with them, makes a society more resilient, whereas high levels of economic welfare and relative lack of recent crises leave some societies less prepared to face shocks. This is known as the ‘vulnerability paradox’.Within Europe, it has actually been the Greek handling of COVID-19 that so far appears more successful than others. Greece is a country which has suffered a decade of austerity leading to a weakened healthcare system. And with one of Europe’s oldest populations, the Greek government was keenly aware of its own vulnerabilities. This prompted an early lockdown and a rapid increase in intensive care beds.Although better state capacity and health system capability are clearly positives for mitigating disasters, citizens do tend to be less familiar with risk preparedness. This lack of experience can then breed complacency which threatens societies where risks are often complex, numerous, transboundary and inter-related.Conversely, the absence of systemic resilience at a national level often puts the onus on family units or local communities – creating resilience as a necessary response to weak government capacity. There is little choice but to learn to look after yourself and your community.However, although the vulnerability paradox helps explain why prior experience makes a system more resilient, societies need to stay aware of their own vulnerabilities and avoid complacency if they are to continually remain resilient.Complacency coupled with a belief in the virtues of the free market has left some countries hit harder than others by the pandemic. In normal times, ‘just in time’ business models can be highly efficient compared to holding vast stocks. But it does not require hindsight to know that a global health crisis will see demand for protective equipment soar and these business models severely challenged.Several societies have also witnessed a decline in trust towards institutions, especially politicians or the media. The deployment of science as justification for political decisions around coronavirus was presumably intended to help garner trust in those decisions. But when the science itself is inexact because of inadequate or emerging knowledge, this strategy is hardly fail-safe.COVID-19 does provide an opportunity to rebuild trust by rethinking the relationship between the state and its citizens, to engage people more directly in a discussion about societal resilience with empowered citizens, and to rebuild a social contract between state and society in the context of recent significant changes and further potential threats.It should also provide a salutary wake-up call to a range of ‘strongmen’ leaders prone to portraying issues rather simplistically. Although COVID-19 may be one of the few complex problems to which simplistic measures do apply - such as wearing a mask and using social distancing – these do not provide the whole solution.Generally, declining trust in politicians reflects the ongoing inability of current politics to deal with a range of societal challenges. COVID-19 is certainly the most sudden and presents the biggest immediate economic shock of recent times, but it is just the latest in a long line of examples of political failure, such as conflict in the Middle East, climate change, terrorism, and cyber-attacks.Along with the growth of automation and digitization which provide opportunities at the macro-level but threats at a more micro-level, what most of these issues have in common is that national responses are likely to fail. Restoring trust requires re-energized global governance, and this means compromise and humility – qualities which appear in short supply to many current politicians.But, regardless of political will, building resilience to tackle ongoing or rapidly forthcoming challenges also rubs up against free market beliefs, because building resilience is a long-term investment and comes at a price. But by acknowledging vulnerabilities, avoiding complacency, implementing lessons from past experiences, and learning from others, policymakers will be better prepared for the next crisis.Reconstructing societies through the prism of resilience creates fundamentally different outcomes to global challenges, and can build trust between elected representatives and the wider population. Accepting the vulnerability paradox and acknowledging that those generally less prone to disasters are actually less able to cope when change happens creates a powerful argument for this new approach. Full Article
v Why the Corrupt President of Belarus Deserves Sanctions By www.chathamhouse.org Published On :: Mon, 10 Aug 2020 19:31:05 +0000 10 August 2020 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn Sanctions would be a wake-up call for those who oversaw this brutal and dirty election campaign. 2020-08-10-Belarus-Protest-Election People protest at a rally of solidarity with political prisoners in Belarus. Photo by Beata Zawrzel/NurPhoto via Getty Images. Belarusian president Aliaksandr Lukashenka deserves sanctions. This election campaign in Belarus, which culminated in a vote on Sunday is the most brutal and dirty in its history. But, so far, the EU, the UK and the US have only issued familiar-sounding and futile appeals to the Belarusian authorities condemning their actions. Not imposing sanctions is a de facto licence to continue with repression.Despite all this, the West is unlikely to impose significant sanctions afterwards. There are several questionable reasons for this. First, Western policymakers fear sanctions against Lukashenko will make him more likely to genuflect to Russia. However, relations with Russia have already deteriorated as Belarus accuses Russia of trying to interfere with its domestic affairs.Sanctions serve as a wake-up call. The Belarusian authorities then might seek - once again - to repair relations with the West and reduce repression for greater assistance in any direct confrontation with Russia.Second, the West is reluctant to implement sanctions because it has already invested somewhat in warming relations with Belarusian authorities. Punishing Lukashenko could mean burying the - admittedly modest - achievements of a Belarus-West dialogue that started in 2014 after the conflict in Ukraine began.Even US secretary of state Mike Pompeo met with Lukashenko in Minsk this year, after which Belarus replaced a small but symbolic amount of Russian oil for American. All the same, the West has its conscience to answer to if dialogue is won but repressions continue.The third reason why the West may not resort to targeted economic sanctions and visa restrictions is a latent concern whether such measures have any effect on democratization processes at all. They may be appropriate punishment, but there is little evidence they ever change the nature of a regime.According to this logic, if the West imposes sanctions, the Belarusian authorities will continue to crack down with repression because they will have nothing to lose. That said, in previous years, the Belarusian authorities have released political prisoners in response to sticks and carrots brandished by the West. If Belarusian political prisoners did not have a price tag, the authorities would most likely keep everyone in jail.To be fair, there are reasonable arguments in favour of and against sanctions. But if the West fails to impose them - be it through lack of political will or out of genuine concern about their effectiveness - at least it should focus on helping ordinary Belarusians withstand Lukashenko’s repressions. After the vote, arrested and jailed Belarusian citizens might lack money for lawyers and arbitrarily imposed fines.If repression spreads further, independent media and human rights organizations will need funds to keep their structures running in the heat of the crackdown. Many entrepreneurs might lose their companies for openly supporting free elections. Thus, if the West will not sanction Lukashenko, it should at least show solidarity with these Belarusians in peril.This article was originally published in The Telegraph. Full Article
v Nigeria’s Recovery Means Rethinking Economic Diversification By www.chathamhouse.org Published On :: Fri, 14 Aug 2020 15:17:01 +0000 14 August 2020 Iseoluwa Akintunde Mo Ibrahim Foundation Academy Fellow, Energy, Environment and Resources Programme @Ise0luwa LinkedIn With more than half its revenue derived from oil exports, Nigeria’s economic fortunes are tied to the boom and bust cycles of the oil market. Those fortunes have waned way below expectations this year and, with more than one-quarter of its labour force jobless, it is time to question the country’s economic pathway. 2020-08-14-Nigeria-Bottles-Building Yahaya Musa, 19-year old local mason, inspects a wall of a 'plastic bottle house' in Sabongarin Yelwa village, near Kaduna, Nigeria. Photo by AMINU ABUBAKAR/AFP via Getty Images. For decades, the mantra of ‘economic diversification’ characterized attempts to reverse Nigeria’s dependence on oil with little real progress. Despite numerous reforms, international loans and restructuring programmes, 85 million Nigerians live in deteriorating conditions of poverty. The current coronavirus pandemic combined with mounting debt obligations and declining GDP gives new urgency to this issue.The fall in international oil prices, which led government to slash its oil benchmark price from $57 to $30 a barrel and cut 20% of the capital budget, worsens these problems, but it is far from the only factor. Biomass, which drives household pollution and contributed to the death of 114,000 people in Nigeria in 2017, is the most dominant source of energy in Nigeria, amounting to more than 80% of the total energy mix, followed by fossil fuels (18%), and a negligible amount of renewable energy.Although a diversified energy sector with a strong emphasis on renewables is known to reduce health and economic risks of combustion, there has been little emphasis on the role a diversified energy mix could play in ensuring sustainable development – even though the estimated potential of 427,000MW of solar power and photovoltaic generation means Nigeria has enormous renewable energy opportunities.The global economy is also undergoing tectonic structural changes that will affect demand for Nigeria’s oil, leaving a fossil fuel-dependent economy more vulnerable. Improvements in global fuel efficiency, the ascent of electricity as a substitute for oil in the transport sector, and the falling prices of renewables and storage technologies all lead to a reduction in demand for fossil fuel products.Creating structures for transitionThis is not a ‘get out of oil’ prescription, and energy transition is complex. But it is inevitable. There are no universal strategies applicable to all countries; local contexts and political realities inform what is possible. Nigeria can take advantage of its abundant natural gas deposit as a ‘transition fuel’ to buy it time for putting the appropriate transition structures in place. The country has made progress in reducing the amount of gas flared, but much remains to be done for Nigeria to meet the 2030 global deadline to end flaring, after failing to meet its 2020 national target.The first step to proper transition is to align Nigeria’s international obligations with its domestic policies and legislations - the distance between words and action must be bridged and the institutional capacity to implement raised. And, while they contain symbolic green gestures, the economic recovery and growth plan developed in response to the 2016 recession, and the post-COVID-19 economic sustainability plan, do not espouse green growth as a fundamental objective.Nigeria must start looking inwards, investing its resources in designing and funding a green transition strategy. Its leadership role in floating Africa’s first Sovereign Green Bonds should be followed with non-debt funding options. Faced with a pandemic that has shattered the boundaries of what is politically possible, the Buhari government has overcome initial inertia to announce a halt in oil subsidy payments, although whether it will see through that policy is yet to be seen.If it does, how it uses the savings will be significant. The money could provide support for Nigeria’s renewable sector to counteract the price disparity with fossil fuels and encourage rapid research and development. The Nigerian Ecological Fund — which is 3% of the Federation Account — should be reformed and expanded beyond its current scope of addressing ‘serious ecological problems’ to cover climate change with a strong emphasis on mitigation and resilience. That would increase Nigeria’s climate finance and minimize reliance on multilateral climate funds.Beyond public investments in green infrastructure, the government can also incentivize the private sector to drive a green economy. As the largest purchaser of goods and services in the country, it can leverage purchasing power to green the procurement process. With the release of about $421 million to the Ministry of Works, the 2020 budgetary allocation for road projects has been fully disbursed to the Ministry, making procurement in the construction sector ripe for green reforms. The application of sustainable building techniques and materials could reduce Nigeria’s 17 million housing deficit and create more jobs.But the task of greening the Nigerian economy is too important to be left to the federal government alone. It also requires mainstreaming climate change and sustainable development into the operations, governance, and budgets of government ministries, departments, and private entities at the sub-national and national levels.There has been much focus on reviving agriculture, which is laudable, but agrarian practices have radically changed from the 1970s when the sector accounted for 57% of Nigeria’s GDP and generated 64.5% of export earnings. Beset by a loss of biodiversity, drought, and desertification, extreme weather events, rise in sea levels and variable rainfall, it is no longer smart for Nigeria to invest in this area without due regard for the significant climate risks. Any effort to revive agriculture and its export potential must be green-centred and integrate regenerative and climate-smart practices.The right policy mix combined with aggressive funding can position the country as a renewable energy leader, both on the African continent and globally. And it will reap the benefits in technology development, foreign investment, decreased emissions, poverty reduction, and energy for the 80 million people currently without access to the national grid – all of which could ripple into millions of clean energy jobs in manufacturing and installation across the country.The road to a green future must be paved with deliberate and consistent policies. Reforms hatched because oil prices have plunged should not be ditched when there is a boom. On the brink of a second recession in four years, Nigeria has learnt that the economic turmoil caused by COVID-19 is only the latest warning that pinning economic growth on a boom-bust market and the generosity of foreign donors and creditors is a failing strategy. There is another way and there is an opportunity for Nigeria to lead. Full Article
v Conflict-Related Sexual Violence in Ukraine: An Opportunity for Gender-Sensitive Policymaking? By www.chathamhouse.org Published On :: Mon, 17 Aug 2020 23:55:05 +0000 18 August 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Meaningful change is needed in Ukraine’s response to the conflict-related sexual violence, which affects both women and men. 2020-08-18-Ukraine-Intl-Womens-Day.jpg Ukrainian feminists and human rights activists carry posters at an International Women's Day protest in Kyiv, Ukraine on 8 March 2019. Photo: Getty Images. The virus of violenceAccording to the UN (para. 7) and the International Criminal Court (ICC, para. 279), conflict-related sexual violence (CRSV) is quite prevalent in hostilities-affected eastern Ukraine. Both sexes are subjected to sexualized torture, rape, forced nudity, prolonged detention in unsanitary conditions with members of the other sex and threats of sexual violence towards detainees or their relatives to force confessions. Men are castrated. Women additionally suffer from sexual slavery, enforced and survival prostitution, and other forms of sexual abuse. Women are more exposed to CRSV: in the hostilities-affected area, every third woman has experienced or witnessed CRSV as opposed to every fourth man.COVID-19 has redirected funding priorities, affecting the availability of medical and psychological help for CRSV survivors worldwide. In Ukraine, the very reporting of such violence, stigmatized even before the pandemic, has been further undermined by the country-wide quarantine-induced restrictions on movement and the closure of checkpoints between the government-controlled and temporarily uncontrolled areas.Addressing CRSV in UkraineThe stigma of CRSV, the patchy domestic legislation, and the unpreparedness of the criminal justice system to deal with such cases prevent the authorities from properly helping those harmed in the ongoing Russia-Ukraine armed conflict.CRSV is equally traumatizing yet different in nuance for men and women. Female victims often choose not to report the violence. Women avoid protracted proceedings likely to cause re-traumatization and the disclosure of their experience, which could be particularly excruciating in small communities where everybody knows everyone.Men also struggle to provide their accounts of CRSV. Their suppressed pain and shame of genital mutilation and other CRSV result in sexual and other health disfunctions. Combined with the post-conflict mental health struggles, this has been shown to lead to increased domestic violence and even suicide.The very investigation of CRSV in Ukraine is challenging. Certain tests and examinations need to be done straight after an assault, which in the context of detention and grey zones of hostilities is often impossible. Specialized medical and psychological support is lacking. Investigators and prosecutors are hardly trained to deal with CRSV to the point that they do not ask questions about it during the interviews. Burdened by trauma and stigma, survivors are inclined to report torture or inhuman treatment, but not the sexualized aspects thereof.Seven years into the conflict, the state still has not criminalized the full spectrum of CRSV in its domestic law. Ukraine’s Criminal Code contains a brief list of the violations of the rules and customs of warfare in article 438. It prohibits the inhuman treatment of civilians and POWs but does not list any types of CRSV.The article has an open-ended reference to Ukraine’s ratified international treaties, from which the responsibility for other armed conflict violations may be derived. For the more detailed norms on CRSV, Ukraine should refer at least to Geneva Convention IV protecting civilians and two additional protocols to the Geneva Conventions, to which it is a party.However, the novelty of the war context for Ukrainian investigators, prosecutors and judges and their overcautiousness about the direct application of international conventions mean that in practice, observing the treaty or jurisprudential instruction on CRSV has been slow.Use of the Criminal Code’s articles on sexual violence not related to an armed conflict is not viable. Such provisions fail to reflect the horrible variety and complexity of CRSV committed in hostilities. They also envisage lesser punishment than a war crime of sexual violence would entail. Cumulatively, this fails to account for the intention of a perpetrator, the gravity of the crime and the trauma of its victims.The lack of public debate and state action on CRSV understates its magnitude. Ukraine should break its silence about CRSV in Donbas and make addressing this violence part of its actionable agenda - in law and in implementation.Ukraine should incorporate all war crimes and crimes against humanity of CRSV in its domestic legislation; ensure a more gendered psychological and medical support for both sexes; establish rehabilitation and compensation programmes for CRSV survivors; create special victims and witness protection schemes; consider the different stigmatizing effects of CRSV on men and women in criminal proceedings and engage the professionals of the same sex as the victim; map CRSV in the bigger picture of other crimes in Donbas to better understand the motives of the perpetrators; submit more information about CRSV to the ICC and educate the public to destigmatize the CRSV survivors.The drafters of Ukraine’s transitional justice roadmap should ensure that it highlights CRSV, adopts a gendered approach to it and endorses female participation as a crucial component of reconciliation and broader policymaking.Embracive policymakingAlthough ‘the discriminatory line almost inevitably hurts women,’ 'every gender discrimination is a two-edged sword’, Ruth Bader Ginsburg famously argued before the US Supreme Court. This could not be more relevant for Ukraine. The conflict - and lockdown-related violence has reverberated deeper within Ukrainian society, raising fundamental questions about the roles of both sexes and gender equality.The failure to address CRSV and its different stigmas for both sexes mirrors the general lack of sustainable gender lenses in Ukraine's policymaking. It is no coincidence that a June 2020 proposal for gender parity in political parties coincided with another spike of sexist remarks by top officials. While women get access to more positions in the army, sexual harassment in the military is investigated slowly. Despite all the impressive female professionals, no woman made it to the first four-member consultative civic group in the Minsk process. Such lack of diversity sends an unfortunate message that women are not important for Ukraine’s peace process.Ginsburg said, ‘women belong in all places where decisions are being made.’ CRSV against either sex won’t be addressed properly until both sexes contribute with their talents and their grievances to all pillars of Ukraine’s state governance and strategy. Ukraine should look to engage professional women - and there are plenty - to join its public service not just in numbers, but as the indispensable equal voices of a powerful choir. Full Article
v By Inventing Military Threats, Lukashenka Is Playing with Fire By www.chathamhouse.org Published On :: Thu, 20 Aug 2020 11:42:32 +0000 20 August 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar In a bid to reassert control in Belarus, Aliaksandr Lukashenka is trying to stir the worst fears of his supporters by playing the war card. But overplaying his hand could prove disastrous if it leads to confrontation with either Russia or NATO. 2020-08-20-Belarus-Protest-Election A mass rally in Grodno, Belarus where factory workers went on strike in protest against the election results and actions of law enforcement officers. Photo by Viktor DrachevTASS via Getty Images. Having failed to swiftly translate popular support into tangible political achievements, there are signs the protests against the fraudulent presidential election in Belarus may be losing momentum in the face of the state’s resilience and still-confident security and enforcement apparatus.Attempts to blame the unrest on the West have focused on groups Lukashenka and Russia can both call enemies. And now Aliaksandr Lukashenka is not only inventing anti-Russian policies supposedly held by the opposition, such as suppressing the Russian language and closing the border with Russia, but also a supposed military threat from NATO.Border movementsIncreased military activity inside Belarus does give Lukashenka a wider range of options. Unscheduled activation of military units includes airspace defence practice with missiles and aircraft, electronic warfare (EW) units put on round-the-clock alert, and a number of infantry brigades preparing for live firing exercises.Lukashenka is drawing attention to the north-west corner of Belarus, singling out the city of Grodno near the border with Poland and Lithuania as a supposed target for Western efforts at destabilization. Grodno is also the destination for an airborne brigade moving from the east to the west of the country and the focus of military exercises under way on the country’s western borders.All this feeds Lukashenka’s narrative that Belarus is in danger from NATO and the West who are supposedly both stirring up the protests and seeking to exploit disorder - and that this danger extends to possible military clashes.The Belarusian exercises are over the border from where NATO troops - including elements of the Light Dragoons, a British reconnaissance unit - have been in place in Poland as part of NATO's enhanced forward presence (eFP) since 2017. Pointing to NATO activity in Poland and Lithuania, Lukashenka said on Wednesday ‘we have to follow their movements and plans’ and that ‘they will answer for it if something happens’.The danger is that having invented a tense situation in Grodno, Lukashenka may now need to be proved right. There may be staged incidents or ‘provocations’ against Belarus military forces, either supposedly instigated by protesters or even by NATO forces on the border - all aimed at bolstering the narrative that NATO, the EU, and the West in general are hostile to Belarus and that more drastic measures are necessary for protection.Russia’s options still openAlthough initial fears of a Russian move into Belarus have receded, Lukashenka’s complaints about NATO also bolster the case for Moscow to intervene. The military exercises fit the narrative that Belarus is under threat from the West - which is exactly the pretext Russia would need.If this is believed in Moscow, where foreign minister Sergey Lavrov has already described events in Belarus as part of a ‘struggle for the post-Soviet space’, this makes a Russian intervention more likely. Moving forces away from their base near the border with Russia to the other end of the country near Poland and Lithuania also means any Russian entry into Belarus could go more smoothly, with fewer wild cards of possible Belarusian opposition to consider.There are plenty of sensible, rational, logical reasons why a Russian military intervention in Belarus would be disastrous and counter-productive. But what seems sensible and rational in Europe and North America does not always carry weight in Moscow, which may see the situation completely differently and measure options by completely different standards.One key area of doubt is the sympathies of the Belarus armed forces. Although some elements of the Belarusian army - particularly airborne and special forces - work closely with their Russian counterparts, more general suggestions that the Belarusian military is merely an extension of Russia’s and is not capable of taking decisions for itself are an over-simplification.The Belarus armed forces do know that hosting Russian ground troops, airbases or air defence systems would fatally undermine the country’s hopes of avoiding being caught up in any confrontation between Russia and NATO.And although the great majority of Belarusian officers are Russian-speaking and many have been trained and educated in Russia, there may be sufficient pride in national identity and resentment at heavy-handed treatment by Russia to lead to substantial obstruction of Russian initiatives.The Belarus General Staff has already refused permission for a Russian aircraft carrying 155 personnel from the Rosgvardiya militarized security force and three tonnes of cargo ‘for the Belarusian interior ministry’ to land in Belarus. This could indicate not only tension between Russia and Belarus, but even between ministries within Belarus itself.Like Russia, Lukashenka has plenty of options in reserve if his situation deteriorates further. Announcing a state of emergency would allow the Belarusian army to support the security forces in dealing with protests. If the army is on the move with their equipment they are better prepared to be brought into action if needed, but testing the loyalty of the armed forces could prove dangerous if the sympathies of army units turn out to lie more with civilians than with their oppressors from the interior ministry.The military preparations against fictitious threats and a patiently-waiting Russia is a toxic mix and Belarus’s friends abroad must tread carefully. A key task for the European Union (EU) is to help the Belarusian people without providing a pretext for further violence and Russian intervention.The right level of engagement needs to be carefully calibrated, avoiding disasters of strategic communication such as European Commissioner Thierry Breton being translated into English as saying Belarus is not part of Europe – with the lack of EU interest that that implies. Although the EU statement promising sanctions and offering funds received a mixed reception, at least it cannot be used by Lukashenka and Vladimir Putin as evidence that their warnings of a Western military threat are genuine. Full Article