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50,000 bulbs to sparkle Rockefeller Christmas tree

NEW YORK (AP): The Rockefeller Center Christmas tree arrived in New York City on Saturday, signalling the start of the holiday season in the Big Apple. The 74-foot Norway spruce was driven into Manhattan's Center Plaza, where it was hoisted in...




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‘One-burner’ life - Vybz Kartel credits fiancée for new chapter

Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'...




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ENTERTAINMENT DIARY

TODAY KINGSTON...




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Near-death experience inspires Benzly Hype’s album

An out-of-body experience is the inspiration behind Benzly Hype's latest album Star Its The 7th Year. Released on November 7, the entertainer said the project was done to bring back joy in music and will leave its listeners in an upbeat mood....




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Genetic diseases of the Kennedy pathways for membrane synthesis [Molecular Bases of Disease]

The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease.




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A mom’s worst nightmare - East Kingston mother mourns teen son after deadly clash with cops

Kadian Morgan was overwhelmed with grief as she leaned against a wall outside her gate on Jackson Lane, East Kingston, yesterday, tears streaming down her face. Her 19-year-old son, Kayshan 'Bem Bem' Smith, was lying in the morgue after being...




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Childhood rape survivor earns university degree

Earlier this month when Alicea Samaru-Brown walked across the stage at The University of the West Indies (UWI) graduation, she beamed with pride. Her husband, Dennis Brown, and her son, Orlando Brown, cheered the loudest from the audience and this...




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Fisherman shot and killed in Old Harbour Bay

The St Catherine South police are probing the fatal shooting of a fisherman in Old Harbour Bay in the parish on Sunday.




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Police make arrest relating to bags of cash that allegedly fell from Beryllium vehicle

The police have arrested an individual in the probe surrounding two bags of cash that allegedly fell from a Beryllium security vehicle en route to the Norman Manley International Airport in Kingston last week. 




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Bridge over troubled water - Bushy Park residents construct new walkway after floodwaters sweep away old one

After parking his taxi cab along the sidewalk, Leon Thompson exited his vehicle and held on tightly to the tiny hands of his four small passengers. They all walked towards a makeshift bridge, and Thompson lifted each child, making four trips,...




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Manchester man charged with smoking ganja in public

Twenty-eight-year-old labourer Michael Ennis, of Manning's Hill district in Manchester, has been charged with smoking ganja in a public place following an incident in May Pen, Clarendon on Monday.




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Landscaper charged for allegedly stealing oranges

The Clarendon police have arrested and charged 25-year-old landscaper Anthony Marshall, of Lamparth district, Trout Hall in the parish for allegedly stealing oranges from a property in his community on Sunday.




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SAS Notes for SAS®9 - 66562: Negative values appear for distinct counts in SAS Visual Analytics reports

When using the distinct count function in SAS Visual Analytics reports, you might find that a negative value is displayed instead of the actual distinct count: imgalt="distinct_count" src="{fusion_66562_1_disti




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Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery [Enzymology]

Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection.




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Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice [Developmental Biology]

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.




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ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit [Developmental Biology]

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.




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Peptidoglycan analysis reveals that synergistic deacetylase activity in vegetative Clostridium difficile impacts the host response [Glycobiology and Extracellular Matrices]

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.




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Fluctuation in O-GlcNAcylation inactivates STIM1 to reduce store-operated calcium ion entry via down-regulation of Ser621 phosphorylation [Molecular Bases of Disease]

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.




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N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation [Molecular Bases of Disease]

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.




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Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure [Molecular Bases of Disease]

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.




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Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding [Glycobiology and Extracellular Matrices]

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.




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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]

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.




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Structural and biochemical characteristics of two Staphylococcus epidermidis RNase J paralogs RNase J1 and RNase J2 [Protein Structure and Folding]

RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity.




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The cation diffusion facilitator protein MamM's cytoplasmic domain exhibits metal-type dependent binding modes and discriminates against Mn2+ [Molecular Biophysics]

Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.




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Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging [Protein Structure and Folding]

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.




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Representative cancer-associated U2AF2 mutations alter RNA interactions and splicing [Molecular Bases of Disease]

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.




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Characterizing human {alpha}-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases [Protein Structure and Folding]

Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins. Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8). The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality. Elevated core fucosylation has also been identified in several human cancers. However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity. The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite. Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity. The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis. These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.




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The heptameric structure of the flagellar regulatory protein FlrC is indispensable for ATPase activity and disassembled by cyclic-di-GMP [Protein Structure and Folding]

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.




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Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus [Protein Structure and Folding]

Aspergillus terreus is an allergenic fungus, in addition to causing infections in both humans and plants. However, the allergens in this fungus are still unknown, limiting the development of diagnostic and therapeutic strategies. We used a proteomic approach to search for allergens, identifying 16 allergens based on two-dimensional immunoblotting with A. terreus susceptible patient sera. We further characterized triose-phosphate isomerase (Asp t 36), one of the dominant IgE (IgE)-reactive proteins. The gene was cloned and expressed in Escherichia coli. Phylogenetic analysis showed Asp t 36 to be highly conserved with close similarity to the triose-phosphate isomerase protein sequence from Dermatophagoides farinae, an allergenic dust mite. We identified four immunodominant epitopes using synthetic peptides, and mapped them on a homology-based model of the tertiary structure of Asp t 36. Among these, two were found to create a continuous surface patch on the 3D structure, rendering it an IgE-binding hotspot. Biophysical analysis indicated that Asp t 36 shows similar secondary structure content and temperature sensitivity with other reported triose-phosphate isomerase allergens. In vivo studies using a murine model displayed that the recombinant Asp t 36 was able to stimulate airway inflammation, as demonstrated by an influx of eosinophils, goblet cell hyperplasia, elevated serum Igs, and induction of Th2 cytokines. Collectively, our results reveal the immunogenic property of Asp t 36, a major allergen from A. terreus, and define a new fungal allergen more broadly. This allergen could serve as a potent candidate for investigating component resolved diagnosis and immunotherapy.




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The C-terminal region of the plasmid partitioning protein TubY is a tetramer that can bind membranes and DNA [Protein Structure and Folding]

Bacterial low-copy-number plasmids require partition (par) systems to ensure their stable inheritance by daughter cells. In general, these systems consist of three components: a centromeric DNA sequence, a centromere-binding protein and a nucleotide hydrolase that polymerizes and functions as a motor. Type III systems, however, segregate plasmids using three proteins: the FtsZ/tubulin-like GTPase TubZ, the centromere-binding protein TubR and the MerR-like transcriptional regulator TubY. Although the TubZ filament is sufficient to transport the TubR-centromere complex in vitro, TubY is still necessary for the stable maintenance of the plasmid. TubY contains an N-terminal DNA-binding helix-turn-helix motif and a C-terminal coiled-coil followed by a cluster of lysine residues. This study determined the crystal structure of the C-terminal domain of TubY from the Bacillus cereus pXO1-like plasmid and showed that it forms a tetrameric parallel four-helix bundle that differs from the typical MerR family proteins with a dimeric anti-parallel coiled-coil. Biochemical analyses revealed that the C-terminal tail with the conserved lysine cluster helps TubY to stably associate with the TubR-centromere complex as well as to nonspecifically bind DNA. Furthermore, this C-terminal tail forms an amphipathic helix in the presence of lipids but must oligomerize to localize the protein to the membrane in vivo. Taken together, these data suggest that TubY is a component of the nucleoprotein complex within the partitioning machinery, and that lipid membranes act as mediators of type III systems.




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Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins [Molecular Biophysics]

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.




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Bacterial iron detoxification at the molecular level [Protein Structure and Folding]

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.




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Unique active-site and subsite features in the arabinogalactan-degrading GH43 exo-{beta}-1,3-galactanase from Phanerochaete chrysosporium [Enzymology]

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.




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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]

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.




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Determinants of replication protein A subunit interactions revealed using a phosphomimetic peptide [Molecular Biophysics]

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.




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A highly potent CD73 biparatopic antibody blocks organization of the enzyme active site through dual mechanisms [Methods and Resources]

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.




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Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation [Molecular Biophysics]

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.




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Molecular characterization of the RNA-protein complex directing -2/-1 programmed ribosomal frameshifting during arterivirus replicase expression [Protein Structure and Folding]

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.




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Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood [Microbiology]

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.




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Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes [Molecular Bases of Disease]

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.




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Europe’s Clean Energy Future: Shared Challenges for Norway and the UK

3 July 2020

Antony Froggatt

Senior Research Fellow and Deputy Director, Energy, Environment and Resources Programme

Professor Paul Stevens

Distinguished Fellow, Energy, Environment and Resources Programme

Siân Bradley

Senior Research Fellow, Energy, Environment and Resources Programme
European oil and gas producers, such as Norway and the UK, face serious challenges in terms of the direction their energy sectors should take. There is an opportunity for both countries to place an accelerated energy transition at the heart of their post-pandemic economic recovery.

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Students gather to protest inaction on climate change in front of the parliament building in Oslo, Norway on 22 March 2019. Photo: Getty Images.

Even before the COVID-19 pandemic, it was clear that the world is undergoing a transition away from fossil fuels and carbon-intensive sectors, towards renewable energy and clean growth. The collapse of oil demand and prices have simply compounded the challenges that oil and gas producers already faced.

What happens next will have significant implications for Norway, as one of the world’s largest exporters of both energy and capital, and for the UK, as it plans its recovery and looks ahead to its hosting of the next major climate change summit in 2021 - COP26.

While the speed and scale of the transition has always been uncertain and contested, an accelerated transition with deep implications for future oil and gas demand looks plausible.

There has long been a debate over when global demand will peak, but what happens after demand has peaked is perhaps the more critical question. Now there is the additional uncertainty of how this post-peak demand might be affected by an oncoming global recession and potentially by the greening of recovery measures implemented in response to it. Will there be an extended plateau, a gentle decline or a sudden collapse?

The post-peak trend will impact oil producers and exporters to varying degrees, in terms of their vulnerability to reduced volumes and lower prices, and their ability to compete in a shrinking market. There is also growing scepticism over whether natural gas can act as a bridge between coal-fired power and renewables, as increasingly, renewables directly replace coal.  There is also significant uncertainty over extent to which hydrogen, either produced from fossil fuels or renewable energy, will play a significant role in a decarbonizing energy sector.

Even before the pandemic, there was growing public and political pressure in most EU member states for more ambitious action on climate change. More challenging climate targets now look certain as a growing number of governments and companies commit to becoming carbon-neutral by ever-earlier dates.

While market developments, such as the rate of change and the costs of technologies such as renewable energy and electric vehicles will heavily influence their deployment rates, policy interventions and large-scale investment in core infrastructure are still crucial to their scaling up. We are now seeing the EU refocus its Green Deal in support of post-COVID recovery, and scale its support for transition in coal-dependent and carbon-intensive regions with its €100bn Just Transition Mechanism.  

These developments have significant implications for fossil fuel producers and energy consumers both inside and outside the EU. It will particularly affect Norway, not only as a significant supplier of energy to the EU, but as a member of the European Economic Area, with likely pressure to adopt similarly binding domestic carbon reduction legislation. Similarly, as the UK forges new post-Brexit trading and regulatory relationships, it will need to align with European policies for efficiency.

As the host of the critical COP26 UN Climate Change Summit in Glasgow next year, the UK will also need to at least match the EU in terms of its ambition on national emissions reductions, and in placing decarbonization and sustainability at the heart of COVID-19 recovery measures. However, unfortunately, the early indications are that 'Project Speed' will focus on traditional infrastructure projects are less than promising.    

The UK and Norway face similar challenges, as oil and gas producers that recognize the importance of climate change, and will rightly face scrutiny where they reinvest in their oil and gas sectors. They are both outside, yet highly dependent on developments within the EU. However, they are also both, somewhat surprisingly, world leaders in different aspects of decarbonization, such as off-shore wind or electric vehicle deployment, in part due their offshore capabilities and advanced manufacturing capabilities. This presents an opportunity for both countries and their industries to place an accelerated energy transition at the heart of their economic recovery and their relationship with the EU.

There will of course be different opinions on how to do this. A new Chatham House paper – Expert Perspectives on Norway’s Energy Future – explores these issues in the Norwegian context, and draws upon the views of 15 international experts on energy transition and climate change, each interviewed in depth. While unsurprisingly there is little consensus, these views provide valuable background from which to consider the future of future of energy for Norway, and for its partners including the UK and the EU.




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Clearer Role for Business Regulators Needed in Monitoring Trade Agreements

6 July 2020

Dr Jennifer Ann Zerk

Associate Fellow, International Law Programme
As the economic recovery from coronavirus is worked through, careful steps are needed to ensure actions to enforce human rights commitments in trade agreements do not worsen human rights impacts.

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Garment workers hold stickers bearing US$177 during a demonstration to demand an increase of their minimum salary in Phnom Penh, Cambodia. Photo by Omar Havana/Getty Images.

Trade policy is a blunt instrument for realizing human rights. Although many trade agreements now include commitments on human rights-related issues - particularly labour rights - not everyone agrees that linking trade to compliance with human rights norms is appropriate, let alone effective.

Sceptics point out that such provisions may become an excuse for interference or ‘disguised protectionism’ and admittedly anyone would be hard-pressed to identify many concrete improvements which can be directly attributed to social and human rights clauses in trade agreements.

This lack of discernible impact has a lot to do with weak monitoring and enforcement. A more fundamental problem is the tendency of trading partners to gloss over – both in the way that commitments are framed and in subsequent monitoring efforts – significant implementation gaps between the standards states sign up to, and the reality.

Working from ‘baseline’ international standards and treating each state’s human rights treaty ratification record as an indicator of compliance does offer objective verifiability. But it also means underlying economic, structural, cultural, social, and other problems, often go unidentified and unaddressed in the trading relationship.

Regulatory failings of trading partners

Those with sufficient leverage can use dispute resolution or enforcement proceedings to signal displeasure at the regulatory failings of their trading partners, as recently shown by the European Commission (EC) in relation to labour violations by trading partners – against South Korea under the 2011 EU-South Korea Free Trade Agreement (FTA) and Cambodia under the EU’s Generalised Scheme of Preferences (GSP) scheme.

These actions do show a more proactive and rigorous EU approach to monitoring and enforcement and have been largely welcomed – especially by trade unions – as a necessary political response to persistent failings by the states to address violations of fundamental labour rights. However, claiming any major victories on behalf of the workers who produce the goods being traded seems premature.

The ‘implementation gaps’ - between human rights commitments made in a state-to-state context and the reality of the human rights situation on the ground - mean there may be cases where enforcement action under a trading arrangement, such as the removal of trade preferences, may actually make things worse. Some local unions have expressed concern that the EU action against Cambodia may be detrimental to vulnerable migrant women factory workers, especially in the context of a worsening economic situation due to the pandemic.

Making stakeholder voices heard

There are routes through which people with first-hand knowledge of human rights-related problems arising from trading relationships – such as labour rights abuses in global supply chains – can make their voices heard. Unions have used consultative bodies set up under trade agreements to highlight labour abuses in trading partner countries - this helped to shift the Commission’s strategy towards South Korea.

But the rather vague and open-ended mandates of these consultative bodies, and their reliance on cash-strapped civil society organisations to do much of the heavy lifting, means they are not a solid basis for systematic follow-up of human rights problems.

And yet, every country is likely to have a number of agencies with interests and expertise in these issues. Beyond labour inspectorates, this could include environmental regulators, licensing bodies, ombudsmen, national healthcare bodies, special-purpose commissions, ‘responsible business’ oversight and certification bodies, local government authorities and national human rights institutions.

At present these groups are barely mentioned in trade agreements with monitoring frameworks for human rights. And if they do feature, there tends to be little in the agreement terms to guarantee their participation.

To seriously address implementation gaps, there needs to be much greater and more systematic use of these domestic regulatory bodies in human rights monitoring and enforcement activities. These bodies are potentially vital sources of information and analysis about the many different social, economic, environmental and human rights consequences of trade, and can also contribute to designing and delivering ‘flanking measures’ needed to assist with the mitigation of human rights-related risks or adverse impacts which have been detected.

Looking further ahead, monitoring practitioners may find - as those involved in the EU GSP+ scheme have already noticed - that close and visible engagement with domestic regulatory bodies helps strengthen a regulator in getting clearer political support and better resources. It can also help with greater ‘buy-in’ to human rights reform agendas, creating conditions for a positive legacy in the form of more confident, committed, and capable domestic regulatory bodies.

Paying more attention to synergies that exist between the work of domestic regulatory bodies and the principles and objectives which cause states to seek human rights commitments from their trading partners is a vital contribution to the concept of ‘building back better’ from the present crisis.

The goal should be to move from the present system – which veers between largely ineffective consultative arrangements and adversarial, often high stakes, dispute resolution – to more cooperative and collaborative systems which draw more proactively from the knowledge and expertise of domestic regulatory bodies, not only in the identification and monitoring of risks, but also in the delivery of jointly agreed strategies to address them.

This article is part of the Chatham House Global Trade Policy Forum, promoting research and policy recommendations on the future of global trade.




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Tackling Malnutrition: Harnessing the Power of Business

8 July 2020

Simon Pringle

Associate Fellow, Energy, Environment and Resources Programme
Malnutrition negatively impacts individuals, families, societies and economies around the world. Now is the time to align corporate, government and third sector efforts to relegate it to the past.

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A view of a market area in Goma, Democratic Republic of Congo on 10 October 2019. Congo is among the countries with the highest number of acutely malnourished people on a global level. Photo by JC Wenga/Anadolu Agency via Getty Images.

Many people are aware that the scourge of malnutrition affects a vast number of individuals and communities around the world. However, most tend to view it as a problem to be addressed by governments, charities or donors, rather than the corporate sector.

Certainly, when considered at a societal scale, malnutrition makes the complexities of delivering inclusive growth all the harder. It ratchets up the public health burden while restricting the potential for at-risk populations to take part in productive employment.  Economies are hindered, lives are blighted and the potential for people to reach their full potential can be severely limited.

A number of upcoming summits represent a window of opportunity to address nutrition in the context of resilience, particularly in the wake of COVID-19 and the much-referenced ambition for governments to ‘build back better’. The opportunity is there to foster a true partnership between governments, third sector organizations and businesses of all sizes, sectors and geographies to work for the betterment of society and deliver benefits to all participants in such a partnership. 

So what is the role of business in relation to nutrition - where does it sit on their list of priorities and why should it matter to them? A new Chatham House report represents an important contribution to the discussion about the role of business in addressing malnutrition. Through thorough research and direct engagement with businesses, it seeks to find out if malnutrition is on the corporate radar and the extent to which it is considered a material issue.

Surprisingly, whilst many large corporates recognize malnutrition as a matter for concern, this is typically defined only in the context of CSR programmes or related ambitions. These types of commitments have their limitations though; most notably the fact that the communities more severely affected by malnutrition typically sit outside of the sphere of influence of the multi-national companies with the greatest ability to mobilize resources and make an impact. Where populations are marginalized, operating within the informal economy and living in settings that are too fragile for large-scale business investment, corporate CSR programmes are unlikely to have a meaningful impact.

Report Launch: The Business Case for Investment in Nutrition

As COVID-19 pushes UN targets to end global hunger and malnutrition even further off-course, now is the time for businesses to step up and improve nutrition in their workforce and beyond.

The report also asked businesses whether they considered malnutrition to have a material impact on their ability to create value, protect value and manage risk. In the majority of instances the answer was no. This may be surprising, particularly given the evidence provided by new modelling – done for this report using a purpose-built model by Vivid Economics – that illustrates the costs posed to business by malnutrition within a population. On an immediate and direct level, the impacts can be considerable due to lost or reduced productivity from the employee base. However, if even that immediate impact is addressed, the externalities associated with malnutrition can come back and have a negative effect on businesses and investors alike.

When reflecting on externalities and the landscape of risk within which business operates, it is worth considering climate change by way of comparison. Climate change is well embedded in the risk profiling of most progressive and well-managed corporates – although in some instances meaningful action may be well overdue. That said, it is recognized that the direct and indirect impacts have the potential to conspire and permanently reduce shareholder, stakeholder and societal value. 

Similarly, if left unchecked, the externalities associated with malnutrition will undoubtedly contribute to an increased level of risk in terms of both operating and investment environments. This is both an issue of social equity and enlightened self-interest given that good nutrition is key to the success of many of the Sustainable Development Goals (SDGs), and is essential to driving sustainable economic growth. One of the lessons of the COVID-19 pandemic is the manner in which widespread malnutrition can significantly reduce the resilience of populations to external risks, including the outbreaks of infectious disease. We need only to look at the impact of climate stress and related events to understand how closely linked malnutrition is – or may become – to the incidence of social unrest and armed conflict in low-income countries.

Progressive companies and investors have already identified the ability to drive inclusive and sustainable growth as a compelling imperative for investment. In this context, the potential for improved nutrition – both in the workforce and amongst the communities upon which the firms depend – should be a true priority. As fund managers seek increasingly meaningful insight into the way that companies within their portfolio(s) create value, protect value and manage risk, the scope of environmental and social governance is expanding. Many recognize the link between delivering on the SDG agenda and protecting or enhancing shareholder value into the longer term. This is a powerful lever for change, particularly when considering that good nutrition is integral to the success of the ambitions laid out by the various SDGs. Successfully delivering against nutrition-focused targets could unlock growth in developing markets and create an enabling environment for achieving the broader SDG agenda. This may in turn help companies to deliver enduring shareholder value in a way that does not undermine their corporate sustainability commitments.

So, given the insights provided by this report, what can businesses do that have the potential to make a practical and effective impact? There are three main action points around which the private sector can galvanize its efforts and work in partnership to deliver a meaningful impact. 

The first action point is a basic requirement to be proactive and make supportive interventions with existing and future workforces, ensuring that staff are well fed and have appropriate facilities for breastfeeding and childcare. Beyond that foundational commitment, the second action point is to work to build impactful and well-governed partnerships to work within local communities and deliver outcomes at an appropriate scale. The third and final action point sets out the importance of reporting. Businesses should thoroughly assess the impacts of their operations, investments and influence. They should be transparent about those impacts and report both on the current situation and the commitments made to deliver on measurable targets.

Malnutrition is a scourge; it negatively impacts individuals, families, societies and economies. Now is the time to align corporate, government and third sector efforts to consign it to the past. We just need leaders to be bold enough to seize the opportunity.




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Flaring in MENA: The Multibillion Dollar Decarbonization Lever

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.

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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.




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New Fighting Brings Three-year Armenian-Azerbaijani Truce to an End

16 July 2020

Laurence Broers

Associate Fellow, Russia and Eurasia Programme
Deadly clashes at the border between Armenia and Azerbaijan have followed renewed disappointment in the peace process, and cast a new shadow over its future.

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A man shows a piece of shrapnel after attacks carried out by the Armenian army at Dondar Kuscu village near Tovuz, Azerbaijan. Photo by Aziz Karimov/Getty Images.

Although the Armenian-Azerbaijani conflict is focused on the Line of Contact around Nagorny Karabakh, a new - and significant - outbreak of violence has happened some 300 kilometres away on high ground along the de jure Armenia-Azerbaijan border.

Although not a first, violence in this area has generally been contained by the proximity of major transport and infrastructure arteries, and of civilian populations on both sides of the border. Plus, unlike in Nagorny Karabakh, the extended deterrents conferred by Armenia’s membership of the Collective Security Treaty Organization (CSTO) and bilateral agreements with Russia are also – theoretically at least – in force.

Despite this, battlespaces opened rapidly, with bombardment of civilian homes, drone strikes and cyberattacks on government and other sites being widely reported by both sides. At the time of writing, combined reported casualties were already at least 16, the highest for a single incident since April 2016’s ‘four-day war’.

Most are known to be Azerbaijani combatants, including the highest-ranking Azerbaijani serviceman to be killed in action since the 1990s – the respected Major General Polad Hashimov. And, although rumoured to be removed soon anyway following a campaign of negative briefing, Azerbaijani foreign minister Elmar Mammadyarov was publicly blamed in the immediate aftermath for ‘meaningless’ diplomacy and dismissed. He was replaced by education minister Jeyhun Bayramov.

Origins of the clashes

How the fighting began remains unclear. The escalation did not appear to result from a coordinated offensive operation of the kind that led to the four-day war, nor are there obvious strategic goals for either side in terms of the international border. There does appear to have been an element of surprise as an Azerbaijani vehicle unexpectedly encountered a new Armenian post, triggering deadly artillery exchanges.

Unclear boundaries in highland terrain may have played a role. Although referred to as the international border, the de jure boundary between Armenia and Azerbaijan - previously an inconsequential internal administrative boundary in the Soviet Union - is not clearly demarcated in many areas and does not coincide with lines of actual control.

Here, as in Nakhichevan - Azerbaijan’s exclave bordering Armenia and Iran - Armenian and Azerbaijani forces have been engaged in long-term, incremental competition for tactical advantage by claiming higher ground in ‘no man’s lands’. But in remote and cartographically ambiguous areas, the precise location of borders - and even place-names - are unclear, and rival forces can unexpectedly meet their adversaries.

Although clear strategic objectives appear absent, what might then have been a lesser incident escalated purposefully into a crisis – suggesting a political rationale.

A missed opportunity for a negotiations reset

Both Armenia and Azerbaijan began 2020 with unfinished consolidations of domestic power - whether bottom-up in the case of Armenia’s ‘Velvet Revolution’, or top-down in the case of Azerbaijan elite renewal. COVID-19 then added further challenges, with the government of Armenia facing significant domestic criticism for its handling of the pandemic, while numerous opposition activists in Azerbaijan were arrested, and the country’s economic vulnerability to external shocks was highlighted.

But throughout this, the frontlines did remain calm - as they generally have since the three-year period from 2014-2017 which witnessed regular skirmishes, use of heavy weaponry and four days of intensive combat in April 2016. In January 2019, the OSCE Minsk Group made the often-cited announcement that the foreign ministers of Armenia and Azerbaijan had agreed on the necessity of ‘preparing their populations for peace’.

Although the quietest year on the frontline since the 1990s then followed, neither side invested seriously in a peace strategy. After a reasonable start and moves towards humanitarian cooperation, relations between President Ilham Aliyev and Prime Minister Nikol Pashinyan eventually visibly soured.

Several moves, such as the go-ahead for new infrastructure in the occupied territories and Pashinyan’s attendance at de facto leader Arayik Harutyunyan’s inauguration in Nagorny Karabakh, were received in Azerbaijan as evidence of Armenian insincerity towards the peace process.

More inflammatory rhetoric then resumed, leading the OSCE Minsk Group to call for calm at the end of June. As recently as July 7, President Aliyev expressed public criticism of the peace process and emphasised the validity of Azerbaijan’s right to use force.

Each new round of Armenian-Azerbaijani fighting serves as an audit of the various restraining factors preventing a larger war. A Russian-Euro-Atlantic-Iranian consensus on proactively containing any new Armenian-Azerbaijani war appears to still hold, although senior-level attention from US secretary of state Mike Pompeo trailed that of his counterparts.

Russia acted quickly to offer mediation, reflecting the reality that any large-scale Armenia-Azerbaijan war would test Russia’s extended deterrence guarantees to Armenia. As in April 2016, Turkey has been vigorous in its support of Azerbaijan, raising concerns in Armenia and drawing oblique warnings from Russia. On the other hand, the CSTO - much to Armenian chagrin - dithered, initially calling then postponing a meeting citing the need for more time to study the situation.

Unprecedented spontaneous demonstrations in Baku called for war with Armenia, broke into the Azerbaijani parliament and, in some cases, articulated anti-government slogans. In the absence of reliable polling, such protests cannot be taken as evidence of a popular consensus in favour of war.

But they do underline the importance of the conflict as the one issue in Azerbaijan where open protest is accepted as legitimate and cannot easily be dispersed. As losses over the past week are counted, the dismissal of the foreign minister may not be sufficient to quell public anger.

Prospects are now real of a return to the dynamics in 2014-15: recursive low-level violence aimed at influencing the diplomatic calendar and public opinion while remaining below the deterrence threshold for triggering active external involvement.




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Elections in Côte d’Ivoire: President Ouattara’s Dilemma

28 July 2020

Paul Melly

Consulting Fellow, Africa Programme
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.

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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 dilemma

Gon 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 challenges

In 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.




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COVID-19 Teaches Resilience and the ‘Vulnerability Paradox’

7 August 2020

Dr Gareth Price

Senior Research Fellow, Asia-Pacific Programme

Christopher Vandome

Research Fellow, Africa Programme
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.

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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.




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Why the Corrupt President of Belarus Deserves Sanctions

10 August 2020

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
Sanctions would be a wake-up call for those who oversaw this brutal and dirty election campaign.

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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.




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Choosing Kamala Harris Puts Identity at the Heart of Presidential Race

12 August 2020

Dr Leslie Vinjamuri

Director, US and the Americas Programme; Dean, Queen Elizabeth II Academy for Leadership in International Affairs
Joe Biden’s choice of Kamala Harris as his running mate will have a lasting impact on how Americans think about the presidential ticket, and confirms the violent killing of George Floyd unleashed a demand for racial equality that continues to have dramatic impact.

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Senator Kamala Harris speaks during a Senate Homeland Security and Governmental Affairs hearing. Photo by ALEXANDER DRAGO/POOL/AFP via Getty Images.

Despite being such a historic selection, in certain aspects, Kamala Harris does not actually signal change. She is a moderate in the Democratic Party, an insider more than an outsider, and a highly experienced leader with national, state level and city level credentials. She worked as a district attorney in San Francisco for several years before being elected attorney general for the state of California, and then to the US Senate in 2016. Harris also stood as a candidate against Biden in the contest to become the Democratic Party's presidential candidate.

Like Joe Biden, she is a highly experienced leader with strong credentials. But California is solidly blue, so she cannot deliver a new state for him. In many ways she is a safe choice and — at a time when Biden is far ahead of Donald Trump in the polls and America faces a lot of uncertainty — many leading political analysts say safe is exactly what the Democratic candidate needs.

The 2020 US Presidential Elections and the State of the Nation

Amy Walter and Adam Boulton discuss the current state of the nation and what this means for the US presidential election.

But certainly as a signal to the American people, and the rest of the world, of what America is and what it stands for, the choice of Kamala Harris is truly historic. The senator from California is the first African-American woman, and the first Asian-American woman, on the presidential ticket. If Biden wins in November, Harris becomes the first female vice-president.

The historic aspects do not end there. Harris also represents a rapidly growing segment of the US population, but one that gets far less mention — multi-racial Americans. The exact size of America’s multi-racial population has been notoriously hard to measure, especially as it has only been 15 years since the US Census Bureau allowed Americans to choose more than one race when completing their census form. But America has long seen itself as a melting pot, so Harris’s place on the ballot underscores a national narrative with a deep resonance across the country, not least among America’s schoolchildren.

In recent weeks, it came to feel inevitable Biden would choose an African-American running mate. His selection comes at a time when more Americans than ever before have taken to the streets to protest the brutal killing of George Floyd and racial injustice. And the demand for racial equality has been accelerated by the COVID-19 pandemic which has disproportionately affected African-Americans who are dying from the virus at around double the rate of their white American counterparts, while twice the number of black businesses are closing relative to their white counterparts.

The choice of Harris also speaks to another fundamental aspect of the ‘American dream’. She is the daughter of two immigrant parents, her father being from Jamaica and her mother from India. Immigration has become one of the toughest issues in US politics, and immigrants have suffered repeated rhetorical attacks from Trump. One of Harris’s first stands in the US Senate was against President Trump’s entry ban to the US on several countries with majority Muslim populations.

When it comes to questions of identity, the choices that the US electorate now face in November could not be more stark. President Trump used the opportunity of the July 4 weekend to deliver a speech at Mount Rushmore which appeared to actively seek division and to ignite America’s cultural wars.

By choosing Kamala Harris, Biden also continues to signal that he will lead from the moderate wing of the Democratic Party.

Harris may be left of Biden, but she is far to the right of other well-known progressive candidates, especially Elizabeth Warren. She has not, for example, supported more far-reaching measures to redistribute wealth, especially the proposal for a wealth tax. And she has a track record of being tough on crime during her years as a prosecutor. Although she played an active role in recent protests and signalled her commitment to police reform and anti-lynching laws, not all young or progressive protesters will be easily persuaded by her credentials.

However, for voters who hoped for a more progressive candidate, two factors play to the advantage of the Biden-Harris ticket. This election still looks set to be a referendum on President Trump and — especially now — his ability to manage the public health and economic crises at home. And Biden has continued to include the progressive side of the Democratic Party in his plans, giving Bernie Sanders and Alexandria Ocasio-Cortez key roles in developing climate proposals, and establishing a series of Unity task forces to bring the party together.

There are also other more conventional factors at play. Biden has relied on the support of African-American and also female voters. While Harris may not broaden this support, it should help ensure these voters turn out — if primarily via their postal box — to vote for Biden. His choice of Kamala Harris answers the one big outstanding question facing his candidacy and signals the true beginning of the race to the White House.




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Belarus Policy: Time to Play Hardball

12 August 2020

James Nixey

Director, Russia-Eurasia and Europe Programmes
Predictably, Aliaksandr Lukashenka’s regime has betrayed its people and the West’s trust yet again. A new, tougher approach is now the only option, and sanctions are only one of several actions that should be taken.

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Women take part in an event in support of detained and injured participants in mass protests against the results of the 2020 Belarusian presidential election. Photo by Natalia FedosenkoTASS via Getty Images.

Aliaksandr Lukashenka’s 26-year rule — one of the world’s longest — is itself testament to his regime’s unwillingness to change. Most of Belarus’s immediate neighbours — particularly Lithuania, Latvia, and Poland — are far more prosperous. Now, with the farce of last week’s vote and the subsequent renewed violence that Minsk is willing to use on its citizens, Belarus finds itself at the very bottom of the post-Soviet legitimacy league table. But others share a portion of blame for this saga. The West — and the EU in particular — have failed the people of Belarus.

Russia — as ever in its relationships with the Soviet Union’s other successor states — has much to answer for. Like a drug pusher, it made a loss-leading investment in getting Belarus hooked on subsidised energy with meaningless security guarantees thrown in. Lukashenka may not have been the most compliant of post-Soviet leaders — especially recently — but he is still preferred by the Kremlin over any other potential contender, especially the reforming ones currently at the fore. ‘A son-of-a-bitch, but our son-of-a-bitch’ is Russia’s take.

But if Russia is the pusher, Western countries have been the enablers. Lukashenka has played them — and played them off against Russia — by frequently rejecting the offers of one and getting closer to the other, then switching and doing the same. The inability or unwillingness to recognize — and act on — evidence of the regime’s insincerity and its propensity to inflict harm on its own citizens has encouraged Minsk’s worst excesses. At the time of writing, more than 3,000 are reported to have been arrested and many tortured.

The EU bears special responsibility for this enabling. Ever since Belarus’s independence almost 30 years ago, it has offered plenty of carrots but few meaningful sticks. President of the European Commission Ursula von der Leyen said that ‘harassment & violent repression of peaceful protesters has no place in Europe’, but statements alone are inadequate. The Belarusian people are risking their freedoms and their lives on the streets of Minsk while the EU simply ‘calls on’ the Belarusian authorities to respect the democratic process.

Never too late

There is plenty that can be done. Sanctions are a much-touted first step and they have been proven to change the calculus, if not the character, of a regime. The EU, the UK and the US should act decisively and in unison to impose them immediately. Included in this would be the immediate halting of direct EU support to state entities.

But — as with Russia — it is lazy to limit responses to sanctions alone. Expulsion from international groups and values-based organizations should also be expedited. The EU’s Eastern Partnership (EaP) project with Belarus and five other countries is a prime example of supposedly conditional offers of financial assistance having been accepted, claimed and then defaulted on, time and again. It is time to make an example of Belarus and expel it from the EaP since it is abundantly clear it has no intention of adopting the values demanded of it.

The OSCE (Organization for Security and Co-operation in Europe) was invited by the Belarusian authorities too late to observe last Sunday’s vote-rigging, so why, in the face of such obvious obstruction, is Belarus even a member? The OSCE often claims its strength is its inclusivity, but this has rarely stood up to scrutiny. Inclusivity may have advantages, but one should also acknowledge its propensity to dilute effectiveness. Belarus should be expelled from here too.

The same goes for the IMF, the World Bank group, and its WTO observer status. It is time to make an example of this regime.

There should be less diplomatic nicety. It is natural that foreign service officials are hard-wired to want to make things better through their undoubted skills of sensitivity and tact, and sometimes this is the right answer. But not always. It would be better in some instances, such as this one, to give a tougher message — making it clear this regime is no longer seen as legitimate and that, where possible, western countries will seek relationships with more representative figures. This is neither easy nor especially pleasant, but it is not the same as breaking off diplomatic relations entirely, which is not wise as sometimes the organs of power must be dealt with.

And in terms of immediate practical help, the EU has an obligation to open its borders to Belarusian refugees who will surely come its way as conditions deteriorate. Lithuania is already showing the way in this regard.

Belarus is not one of the more difficult countries. It has no influence, no natural resources and therefore no leverage. It could resort to even more brutal repression of its citizens, but it should be made clear that such a desperate move by the authorities would entail even greater sanction. A common argument against a tougher approach is that it will drive Belarus into the arms of Russia. But this is to fall into the same trap — blackmail in reality — that we have seen for 20 years. In fact, it would be a good litmus test for a similar policy towards other ‘abuser countries’, such as Hungary.

Russia is certainly watching closely right now, and the last thing it wants is another colour revolution. The probability is that it will get this wish for now, as the demonstrations will surely cool off and key opposition figures not already in jail have been forced to flee. But western quiescence, as it always does, encourages Russia to act with further impunity. No invasion needed this time though if it already has most of what it wants — Union State notwithstanding — and the West stands aside.

A Chinese proverb maintains that ‘the best time to plant a tree was 20 years ago. The second-best time is now’. This holds true for dealing with Belarus. It is not too late to act decisively and play hardball. In doing so, the EU would help repair its reputation for hand-wringing and the people of Belarus might look at the EU with a respect they have lost.