ac Bacterial iron detoxification at the molecular level [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron. Full Article
ac Evolving the naturally compromised chorismate mutase from Mycobacterium tuberculosis to top performance [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity. Full Article
ac Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics. Full Article
ac Unique active-site and subsite features in the arabinogalactan-degrading GH43 exo-{beta}-1,3-galactanase from Phanerochaete chrysosporium [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Arabinogalactan proteins (AGPs) are plant proteoglycans with functions in growth and development. However, these functions are largely unexplored, mainly because of the complexity of the sugar moieties. These carbohydrate sequences are generally analyzed with the aid of glycoside hydrolases. The exo-β-1,3-galactanase is a glycoside hydrolase from the basidiomycete Phanerochaete chrysosporium (Pc1,3Gal43A), which specifically cleaves AGPs. However, its structure is not known in relation to its mechanism bypassing side chains. In this study, we solved the apo and liganded structures of Pc1,3Gal43A, which reveal a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family 35 (CBM35) binding domain. GH43_sub24 is known to lack the catalytic base Asp conserved among other GH43 subfamilies. Our structure in combination with kinetic analyses reveals that the tautomerized imidic acid group of Gln263 serves as the catalytic base residue instead. Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite −1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the β-1,6–linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s, including those that bind galactomannan. Specifically, we noted a Gly → Trp substitution, which affects pyranose stacking, and an Asp → Asn substitution in the binding pocket, which recognizes β-linked rather than α-linked Gal residues. These findings should facilitate further structural analysis of AGPs and may also be helpful in engineering designer enzymes for efficient biomass utilization. Full Article
ac Determinants of replication protein A subunit interactions revealed using a phosphomimetic peptide [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection. Full Article
ac A highly potent CD73 biparatopic antibody blocks organization of the enzyme active site through dual mechanisms [Methods and Resources] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity. Full Article
ac Nitro-fatty acids as activators of hSIRT6 deacetylase activity [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Sirtuin 6, SIRT6, is critical for both glucose and lipid homeostasis and is involved in maintaining genomic stability under conditions of oxidative DNA damage such as those observed in age-related diseases. There is an intense search for modulators of SIRT6 activity, however, not many specific activators have been reported. Long acyl-chain fatty acids have been shown to increase the weak in vitro deacetylase activity of SIRT6 but this effect is modest at best. Herein we report that electrophilic nitro-fatty acids (nitro-oleic acid and nitro-conjugated linoleic acid) potently activate SIRT6. Binding of the nitro-fatty acid to the hydrophobic crevice of the SIRT6 active site exerted a moderate activation (2-fold at 20 μm), similar to that previously reported for non-nitrated fatty acids. However, covalent Michael adduct formation with Cys-18, a residue present at the N terminus of SIRT6 but absent from other isoforms, induced a conformational change that resulted in a much stronger activation (40-fold at 20 μm). Molecular modeling of the resulting Michael adduct suggested stabilization of the co-substrate and acyl-binding loops as a possible additional mechanism of SIRT6 activation by the nitro-fatty acid. Importantly, treatment of cells with nitro-oleic acid promoted H3K9 deacetylation, whereas oleic acid had no effect. Altogether, our results show that nitrated fatty acids can be considered a valuable tool for specific SIRT6 activation, and that SIRT6 should be considered as a molecular target for in vivo actions of these anti-inflammatory nitro-lipids. Full Article
ac MMP activation-associated aminopeptidase N reveals a bivalent 14-3-3 binding motif [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Aminopeptidase N (APN, CD13) is a transmembrane ectopeptidase involved in many crucial cellular functions. Besides its role as a peptidase, APN also mediates signal transduction and is involved in the activation of matrix metalloproteinases (MMPs). MMPs function in tissue remodeling within the extracellular space and are therefore involved in many human diseases, such as fibrosis, rheumatoid arthritis, tumor angiogenesis, and metastasis, as well as viral infections. However, the exact mechanism that leads to APN-driven MMP activation is unclear. It was previously shown that extracellular 14-3-3 adapter proteins bind to APN and thereby induce the transcription of MMPs. As a first step, we sought to identify potential 14-3-3–binding sites in the APN sequence. We constructed a set of phosphorylated peptides derived from APN to probe for interactions. We identified and characterized a canonical 14-3-3–binding site (site 1) within the flexible, structurally unresolved N-terminal APN region using direct binding fluorescence polarization assays and thermodynamic analysis. In addition, we identified a secondary, noncanonical binding site (site 2), which enhances the binding affinity in combination with site 1 by many orders of magnitude. Finally, we solved crystal structures of 14-3-3σ bound to mono- and bis-phosphorylated APN-derived peptides, which revealed atomic details of the binding mode of mono- and bivalent 14-3-3 interactions. Therefore, our findings shed some light on the first steps of APN-mediated MMP activation and open the field for further investigation of this important signaling pathway. Full Article
ac Humanin selectively prevents the activation of pro-apoptotic protein BID by sequestering it into fibers [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP. Full Article
ac A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications [Neurobiology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Abnormal changes of neuronal Tau protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer's disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remain ill-defined. Tau contains ∼85 potential phosphorylation sites, which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, methodological limitations (e.g. in MS of phosphopeptides, or antibodies against phosphoepitopes) led to conflicting results regarding the extent of Tau phosphorylation in cells. Here we present results from a new approach based on native MS of intact Tau expressed in eukaryotic cells (Sf9). The extent of phosphorylation is heterogeneous, up to ∼20 phosphates per molecule distributed over 51 sites. The medium phosphorylated fraction Pm showed overall occupancies of ∼8 Pi (± 5) with a bell-shaped distribution; the highly phosphorylated fraction Ph had 14 Pi (± 6). The distribution of sites was highly asymmetric (with 71% of all P-sites in the C-terminal half of Tau). All sites were on Ser or Thr residues, but none were on Tyr. Other known posttranslational modifications were near or below our detection limit (e.g. acetylation, ubiquitination). These findings suggest that normal cellular Tau shows a remarkably high extent of phosphorylation, whereas other modifications are nearly absent. This implies that abnormal phosphorylations at certain sites may not affect the extent of phosphorylation significantly and do not represent hyperphosphorylation. By implication, the pathological aggregation of Tau is not likely a consequence of high phosphorylation. Full Article
ac Molecular characterization of the RNA-protein complex directing -2/-1 programmed ribosomal frameshifting during arterivirus replicase expression [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism. Full Article
ac Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes [Molecular Bases of Disease] By www.jbc.org Published On :: 2016-12-30T00:06:37-08:00 Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations. Full Article
ac Tackling Malnutrition: Harnessing the Power of Business By www.chathamhouse.org Published On :: Tue, 07 Jul 2020 08:56:38 +0000 8 July 2020 Simon Pringle Associate Fellow, Energy, Environment and Resources Programme @simonpringle LinkedIn 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. GettyImages-1175994321.jpg 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. Full Article
ac West Bank Annexation: International Rhetoric vs. Action By www.chathamhouse.org Published On :: Mon, 13 Jul 2020 16:30:48 +0000 14 July 2020 Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme @renizhelyazkova Professor Yossi Mekelberg Senior Consulting Research Fellow, Middle East and North Africa Programme @YMekelberg Israel may have delayed announcing its plans to annex West Bank lands but the international community now needs to transform its rhetoric into action if there is to be a lasting solution to the Israel-Palestine conflict, argue Reni Zhelyazkova and Yossi Mekelberg. GettyImages-1223719050.jpg Houses are pictured in the Maale Adumim settlement in the West Bank east of Jerusalem. The Israeli government has delayed plans to annex Jewish settlements in the West Bank and in the Jordan Valley. Photo: Getty Images Observers of the Israel-Palestine conflict have been anticipating Israeli Prime Minister, Benjamin Netanyahu’s, announcement to annex parts of the West Bank. It has been a tumultuous year for Israeli politics which has seen three inconclusive elections and resulted in a sharing of power between Netanyahu and Benny Gantz of the Blue and White party. However, since the coalition government was sworn in, Netanyahu has appeared to not lose any time in moving forward with his plans.Annexation has long been Netanyahu’s political aspiration and was part of his recent re-election platform but the anticipated announcement from the Israeli government didn’t come straight away. The determining factor in the delay was the inability to reach an agreement with Washington about the scope of the annexation while divisions within the Israeli government itself, in addition to international condemnation from the region and beyond, has also played a part.Discussions around annexation have so far yielded one major outcome: it has introduced a different rhetoric by the Trump-Netanyahu axis even though things on the ground don’t necessarily follow. Ever since President Donald Trump took office in 2016, there has been a marked change in Washington’s language around the Israel-Palestine conflict. It has shifted towards legitimizing Israel’s expansionist ambitions in the West Bank while marginalizing, and considerably weakening, the Palestinian Authority (PA) through a series of punitive measures.This has further damaged relations between Israel and Palestine and has resulted in a fundamental change in the public discourse around the conflict, from emphasizing a just solution based on self-determination for both sides, to focusing on a de-facto one-state solution.But how has the discourse shifted so dramatically in less than four years? First came the announcement of the US embassy move to Jerusalem, and with it, recognition of the city as Israel’s capital. In his statement, President Trump avoided recognizing Palestinian claims over Jerusalem and did not acknowledge their historical connection with the city. When the PA rejected the move, the US administration then retaliated by cutting aid and development funding and closing the PLO mission in Washington stating: ‘We have permitted the PLO office to conduct operations that support the objective of achieving a lasting...peace between Israelis and the Palestinians … However, the PLO has not taken steps to advance the start of...meaningful negotiations with Israel.’ On the question of Israel’s settlements in the West Bank, the current US administration has shied away from calling them ‘illegal’ despite being deemed illegitimate under international law and condemned on numerous occasions by the UN Security Council, the UN General Assembly, the EU, the Arab League and the Palestinians themselves. US Secretary of State, Mike Pompeo, has even gone as far as saying that the establishment of Israeli settlements in the West Bank is not inconsistent with international law.The culmination of US discourse in recent months has been the unveiling of the ‘Peace to Prosperity’ plan. The language of the proposal, once again, has shown partiality towards Israel by not mentioning the illegality of Israel’s occupation of the West Bank, or that of settlements, and entirely ignoring previous Palestinian positions or acknowledging their sensitivities. There is little doubt that the current US administration understands the power of rhetoric and has been using it to change the trajectory of discussions away from a two-state solution towards an outcome that would only serve Israeli interests.Indeed, US rhetoric has empowered Netanyahu immensely too, ushering in a new reality that has rendered a Palestinian state nothing more than a hypothetical option. The language, combined with a multitude of unilateral actions, is helping to dismantle any efforts towards a two-state solution and the upholding of previous international agreements.Many European and regional governments have condemned any move towards annexation. Indeed, 1,000 European parliamentarians from across political lines have urged Israel to abandon its plans. This has notably included, German Foreign Minister, Heiko Mass, whose first overseas visit during the coronavirus crisis was to Israel to reinforce Germany’s position against unilateral action.But actions speak louder than words, and in the case of the US, its rhetoric has been matched by action unlike its EU counterparts whose statements of condemnation have rarely been followed by concrete action. For instance, the EU ratified a landmark aviation agreement with Israel just days before 1 July and economic, technological and scientific cooperation between Israel and Europe has never been stronger casting doubt on the strength of political will among EU countries to take action against Israel.In the Middle East, the United Arab Emirates has been the most vociferous in disapproving Israel’s annexation plans. However, again, it is important to look beyond the rhetoric. Cooperation between the UAE and Israel has in fact increased in recent years mainly due to common opposition to Iran’s regional influence but also due to shared interests. In May, for instance, the first publicly acknowledged commercial flight between the UAE and Israel landed at Ben Gurion airport carrying aid aimed at mitigating the effects of COVID-19 in the Palestinian territories. But, to many, it looked like a stepping-stone towards a normalization of relations between Abu Dhabi and Jerusalem.Similarly, Jordan and Egypt have also expressed their concern but it is difficult to imagine a scenario where either country would go as far as abrogating peace agreements that they currently have in place with Israel.In spite of this, the global response has overwhelmingly been critical of Israel’s plans to annex parts of the West Bank. This has demonstrated some level of unity among world leaders which has not been seen for some time and may have played a significant role in delaying the Israeli government’s plans. In parallel, united international condemnation has also prevented the US from dominating the Israeli-Palestinian conflict entirely.While the US approach has played a key role in the Israel-Palestine conflict so far, it remains to be seen how the international community will translate its voice into action to prevent the annexation of occupied Palestinian land. Full Article
ac Domestic Violence in Russia: The Impact of the COVID-19 Pandemic By www.chathamhouse.org Published On :: Fri, 17 Jul 2020 12:00:04 +0000 20 July 2020 Ekaterina Aleynikova Research Assistant, Russia and Eurasia Programme @AleynikovaKatya LinkedIn The COVID-19 pandemic has made Russia’s domestic violence problem more visible, with shifting public opinion potentially incentivizing the government to change its approach, argues Ekaterina Aleynikova. GettyImages-1159506648 (1).jpg Campaigners during a rally held in 2019 in support of a Russian law on domestic violence. Photo: Getty Images Russia is one of the few countries in the region to have no legal definition of domestic violence and, as a result, there are no protective measures specific to domestic violence such as restraining orders or compulsory anger management training for abusers. In fact, the government has taken steps in recent years to remove any legal distinction between assault happening in one’s home, and elsewhere, with battery among family or household members for first-time offences decriminalized in 2017.The Russian Ministry of Justice explicitly defended this position in its response to an enquiry into Russian domestic violence cases by the European Court of Human Rights (ECtHR) in November 2019. The ministry claimed existing legislation adequately protects citizens from domestic violence, ‘even though it has never been considered a separate offence’, reiterating that there is ‘no need’ for adopting specific legislation.However, the four cases that led to the ECtHR’s enquiry demonstrate that current legislation is not sufficient. The most prominent case is that of Margarita Gracheva whose ex-husband severed her hands in 2017 despite her having made multiple complaints to the police ahead of the act being committed. If Russian legislation had mechanisms in place to isolate victims from their abusers, then Gracheva could have been protected by the law.Instead, systemic impunity for abusers is supported by statements from people in power excusing domestic violence. The most recent of such statements came from the head of the Chechen Republic, Ramzan Kadyrov, in June 2020. When meeting with the family of a young woman allegedly murdered by her husband, Chechnya’s leader said, husbands beating their wives ‘happens’ and that the young woman should have tried harder to hold on to her marriage. These statements send clear signals to abusers that their actions are justified, and to the victims, that they won’t be protected if they were to come forward.Similarly, to other parts of the world, civil society organizations in Russia have reported an increase in the number of cases of domestic violence during the COVID-19 pandemic. On a personal level, the pandemic has often exacerbated many of the factors that can lead to domestic violence such as stress, economic anxiety or social isolation.On a systemic level, many of the provisions intended to protect victims of violence, which were already ineffective in Russia, have been worsened during the lockdown. Where police may not have rapidly responded to reports of domestic violence previously, under lockdown, they have become focused on other priorities and, where shelters and support networks for the victims may have been scarce in the past, they have been further constrained.Unsurprisingly, the strategy of the Russian state so far has been to deny that there is a problem of domestic violence, with the Ministry of Interior reporting that, according to their statistics, the number of domestic violence cases have gone down during the lockdown. Indeed, Chairwoman of the Federation Council, Valentina Matvienko, has said she does not believe lockdown has increased domestic violence because, on the contrary, families have been ‘brought together’, reflecting wishful thinking at best and negligence at worst.The pandemic has also been used as an excuse to postpone discussion of a federal law on domestic violence, drafted by civil society, that was submitted for review by the Duma last year. This bill would have introduced different types of domestic violence such as psychological and economic violence and transferred domestic violence offences from private to public prosecutions to make it easier for victims to seek justice.The government’s disregard for domestic violence reflects, in part, the patriarchal mindsets of those in power but perhaps, more significantly, the Kremlin’s belief that conservative social groups constitute its main support base. This has been made evident by the politicization of Russia’s ‘traditional’ values in recent years which was vigorously deployed throughout the constitutional amendments campaign. While it is clear that the true purpose of amending the constitution has always been to allow Vladimir Putin to stay in power beyond 2024, amendments relating to this were absent from the government’s campaign. Instead, Russians were encouraged to vote by populist socially-conservative messages, hence why respect for traditional values has been added to the constitution.Despite this, attitudes in Russian society are changing. A February 2020 survey by the Levada Centre showed that 61 per cent of Russians – and 74 per cent of Russian women – think domestic violence is a serious problem.Moreover, the survey shows that women are much more aware of domestic violence than men – with every third woman in Russia admits being aware of domestic violence in their social circles while only every fifth man admits the same. This could be a sign that Russian men and women, on average, have a different understanding of what constitutes domestic violence. If so, adopting a law that defines domestic violence and holding a public awareness campaign is of paramount importance to eliminate any misunderstanding.The difference could also be a sign that victims of domestic violence are more likely to confide in women hence making domestic violence less visible to men. This awareness gap perhaps explains the difference between men’s and women’s assessments of how serious the issue in Russia is.The pandemic has provoked a new wave of discussions of domestic violence among Russia’s population with stories and statistics widely shared in the media and on the internet. As domestic violence becomes more visible, public perceptions are likely to shift further towards recognizing, and hopefully condemning, it. But, while legislation is crucial, the experience of other countries in the region, such as Armenia or Kazakhstan, shows that adopting laws on domestic violence is not enough. Measures are needed to ensure implementation of the law including training police officers and state officials and instituting disciplinary action for negligence of victims’ complaints.Nevertheless, admitting there is a problem with domestic violence in Russia, and introducing laws, are an essential first step. The Russian government seems to have placed its bet on the support of conservative social groups but changing public opinion may prove this strategy unsustainable. Full Article
ac The UK’s Huawei Decision: Why the West is Losing the Tech Race By www.chathamhouse.org Published On :: Fri, 17 Jul 2020 16:36:31 +0000 17 July 2020 Dr Yu Jie Senior Research Fellow on China, Asia-Pacific Programme @yu_jiec LinkedIn Joyce Hakmeh Senior Research Fellow, International Security Programme; Co-Editor, Journal of Cyber Policy @joycehakmeh LinkedIn On 5G and the technological race, the answer is a visionary rather than a reactive approach and, so far, the West has opted for the latter. GettyImages-1140107267.jpg A pedestrian walks past a Huawei product stand at a telecommunications shop in central London on 29 April 2019. Photo: Getty Images. The UK’s decision to ban its mobile providers from buying new Huawei 5G equipment after December 2020 and removing all the company’s 5G kit from their networks by 2027 is a blow to Huawei and China, but it is one battle in a long war that the West is currently losing.5G’s significance for the next generation of technology is indisputable and so is its critical role in helping countries achieve digital transformation and economic success. Not only does it offer faster and better connection speeds and greater capacity, it also transforms the way people interact with online services. And it will allow industry to automate and optimize processes that are not possible today.Due to its transformative importance, what is in essence a technological issue has turned into a contest over global technological leadership that extends beyond the US-China rivalry and has created tensions between the US and its long-time allies. Yet 5G is just one key technology in a more expansive landscape that will underpin the future of the world’s critical infrastructure, including in areas such as quantum computing, biotechnology, artificial intelligence, the internet of things and big data.To achieve technological leadership in these domains requires governments to invest in a long-term, strategic and agile vision that is able to encompass the interdependencies between these areas and then leverage the resulting technological advances for economic progress. It also requires governments working with each other and with the private sector to support research and development and to create companies with leading-edge technologies that can compete globally.China understands this and has a national and international vision to establish itself as a technological superpower. Re-balancing from a hub of labour-intensive manufacturing to a global innovation powerhouse is the absolute priority of the ruling Chinese Communist Party.China’s state-led approachIn the earlier part of this journey, commercial espionage and IP theft of western R&D were at the heart of the Chinese way of competing. Now, Beijing is cultivating national champions that can drive China’s technological innovation, with the goal of using domestic suppliers to reduce reliance on foreign technology at home as well as extending its international outreach. In the 5G area, Beijing has introduced domestically the so-called ‘New Infrastructure Investments Fund’, which earmarks special loans to boost 5G technology applications in medical devices, electric vehicles and communication platforms. This Fund constitutes a major part of the stimulus package for China’s post-COVID economic recovery.Apart from 5G, China's recent launch of a second state-funded semiconductor development fund valued at $29 billion, following an earlier $20 billion fund for the same purpose, shows the extent to which state financial resources are being utilized in China’s quest to become technologically self-sufficient.It is too early to know if the Chinese government’s industrial policies will eventually achieve the technological self-sufficiency Beijing has long desired. But its growing national capabilities have stoked serious concerns across the West and led to the current US administration’s determined effort to dismantle Chinese high-tech companies.China’s approach to macroeconomic management diverges significantly from that of the US and other market economies, particularly in its policy towards driving innovation. Due to the legacy of a state-planned economy, China is certain that simply relying on market forces is insufficient.While Beijing financially supports government-controlled technological enterprises, Washington takes a laissez-faire, light-touch approach by the state to the business sector. The US believes that a politicized process of distributing public money is inherently susceptible to rent-seeking and corruption, and gets in the way of competitive innovation. In line with most liberal economists, many Western governments believe the government should refrain from market intervention. For its part, Beijing stresses a state-dominated economy as a necessary precondition both to the future growth of the Chinese economy and to the legitimization of one-party rule. If the pro-market economists’ view is correct, the US should have little to fear from Chinese industrial innovation policy in the long-term. Let Beijing waste money and distort resource allocation, while Washington follows its private sector-led principles, confident that this approach will produce a more competitive economy in the long run.Using the leverage of technical standardsBut one area that should concern the US and that illustrates the Chinese vision for global technological dominance is technical standard setting. Technical standards determine how technologies work with each other, enabling their interoperability around the world, meaning they can function irrespective of where they are being used.The Chinese leadership has long understood the relationship between technical standards and economic power. Standards help to monetize technological innovation and research and can help shape new technologies. China has therefore been playing an increasingly active role in international standards organizations to legitimize Chinese technologies, whereas the US, which historically has been highly influential in this area, has not been participating as much or as effectively.China has also been using its Belt and Road Initiative (BRI) as an opportunity to internationalize the distribution of its standards to countries signed up to the BRI. The so-called Digital Silk Road, which has been described as China’s most important global governance initiative, acts as a route to accelerate this process. Later this year, China is expected to launch its new ‘China Standards 2035’ plan, which aims to shape how the next generation of technologies will work together.China’s preferred model and its recent actions have given Western leaders much to worry about. But standing up to China’s growing global influence in high technology and re-establishing the West’s desired technological edge will take much more than achieving a common front on excluding China from their 5G networks. It requires a long-term vision built on the power of competitive markets, backed by solid investment in the next generation of technology. This will require, in turn, much greater cooperation between Western governments and between them and their private sectors.And, whilst recent protective steps taken in Washington and other Western capitals may slow down China’s trailblazing in the technology sphere, it will only hasten China's determination to become tech self-sufficient in the long term. This will increase the probability of a splintered internet, which will have negative repercussions for all. Full Article
ac Russia’s Behaviour Risks Weaponizing Outer Space By www.chathamhouse.org Published On :: Mon, 27 Jul 2020 14:19:39 +0000 27 July 2020 Dr Beyza Unal Deputy Director, International Security Programme @beyzaunal Google Scholar Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar With negotiations in Vienna between the US and Russia hoping to prevent the weaponization of space, how much do Russia’s satellites pose a threat to the peaceful use of outer space, ask Beyza Unal and Mathieu Boulègue? GettyImages-1209576417.jpg Russia's President, Vladimir Putin, during a video link with cosmonauts on the International Space Station (ISS). Photo: Getty Images. Days before the publication of last week’s report into Russian activity in the UK, and the subsequent call from several UK parliamentarians for a swift response to the ‘Russian threat’, Russia tested a new anti-satellite weapon capability releasing a small projectile from its Kosmos-2543 sub-satellite.Kosmos-2543, a small satellite contained inside a larger satellite, Kosmos-2542, and 'birthed’ into orbit in late 2019, recently came under scrutiny in January 2020 when it was reportedly caught ‘buzzing’ US spy satellites in Low Earth Orbit.By releasing a small projectile from the Kosmos-2543 sub-satellite, the US claims that Russia has launched a new projectile into orbit with relatively high speed – estimated at around 500 km per hour – leading to concerns about the potential of Russia to develop this technology as a weapon to target foreign satellites.It is not the first time Moscow has relied on a Russian doll – or matryoshka – approach to launching satellites into outer space. In October 2017, a sub-satellite, Kosmos-2521, was ejected from its main satellite, Kosmos-2519, into a high-speed object in low orbit.The Russian Ministry of Defence has declared that its latest activity is just for ‘routine’ inspections and surveillance of Russia’s other space assets, with the government’s official statement avoiding recognizing the existence of the new object while, at the same time, Kremlin spokesperson, Dmitry Peskov, recalling Russia’s commitment for the ‘complete demilitarization’ of space.While it is possible that Russia’s matryoshka satellites have indeed been developed to carry out routine repairs of Russia’s space fleet, they also have the potential to interfere with, and destroy, other satellites with such action needing to be considered a threat until Russia demonstrates otherwise.Russia’s use of outer spaceRussia is not the only state investigating anti-satellite weaponry capabilities. There is a wider trend (e.g. China, India, US) to demonstrate advanced space capabilities with nefarious, if not directly offensive, intent. But, for the past few years, Russia in particular, has been provocative in testing its space weapon capabilities. For example, in April 2020, Russia launched and tested into low orbit the PL-19 Nudol direct-ascent anti-satellite (DA-ASAT) interceptor missile system from the Plesetsk Cosmodrome demonstrating its space assets with potential offensive capabilities, in particular, Russia’s capacity to destroy satellites in Low Earth Orbit.In addition, the satellites, Kosmos-2535 and Kosmos-2536, launched in July 2019, are also suspected to be operating beyond their official mission of studying Russian orbital assets. It is reported that these satellites conducted a close proximity activity, coming within one kilometre from each other, which led to the creation of orbital debris.Russia’s space strategyBy exploiting asymmetric advantages in space, Russia seeks to leverage its capabilities against competitors in space and in other domains, falling in line with its wider military strategy as well as its current Federal Space Programme for 2016 to 2025.Russian space activities also have a cyber and electronic warfare angle. With the help of remote-sensing capabilities, Russian spy satellites potentially seek to disrupt military and civilian satellite communications and navigation systems. Indeed, in 2018, French authorities publicly accused Russia of seeking to intercept communication satellites for French and Italian armed forces putting data transmission through Western civilian and military satellites at risk of interception.Furthermore, earlier this year, both Kosmos-2542 and 2543 came within 160 kilometres of a US spy satellite, US KH-11, similarly to Russia ‘buzzing’ around the British Isles or submarine surveillance that Norway and Sweden have been subjected to recently.Shadowing and tailing in space is regarded as spying and this recent anti-satellite weapon test is part of a trend which demonstrates Russia’s persistent space strategy for close-proximity operations with foreign countries.Orbital hypocrisyDespite Russia’s calls for a treaty to prevent the placement of weapons in outer space, there remains little international trust in Russia’s behaviour in space so far with a US-Russia Space Security Exchange meeting scheduled to take place in Vienna on 27 July to discuss outer space stability and security.This is amid a backdrop of bilateral nuclear arms control talks on the extension of the extant nuclear weapons reduction treaty, New START, which is scheduled to expire in February 2021. There is no guarantee, however, that the talks will achieve anything especially since the future of outer space requires a wider multilateral dialogue with all parties involved – including China.Anti-satellite tests (ASATs) are a particularly dangerous form of weapon. Not only do they create major vulnerabilities in a domain where so much of humanity depends on for navigation, communications and environmental monitoring, they are also primarily a target for destabilization and undermining global positioning information in times of crisis.And, perhaps most significantly, they possess the highly destructive potential to create even more space debris in Earth’s orbits that endanger the peaceful use of satellites and could do serious damage to large parts of the economies of developed and developing countries.Avoiding space warfareSpace is for all but there is a risk that it is being hijacked by a few. It is time to re-assert and reinforce the rules, principles and norms of responsible state behaviour in outer space enshrined in the 1967 Outer Space Treaty and its associated international agreements.And, because the treaty specifically prohibits stationing nuclear weapons and other weapons of mass destruction in orbit or on celestial bodies, it is necessary to build on it to ban other types of weapons in space.Space has been militarized since 1957 with the launch of Soviet satellite Sputnik. But the increasing weaponization of space adds more uncertainty, and unveils more vulnerabilities, that states need to address before space warfare becomes a reality. Full Article
ac COVID-19 Teaches Resilience and the ‘Vulnerability Paradox’ By www.chathamhouse.org Published On :: Fri, 07 Aug 2020 17:37:37 +0000 7 August 2020 Dr Gareth Price Senior Research Fellow, Asia-Pacific Programme @DrGarethPrice Google Scholar Christopher Vandome Research Fellow, Africa Programme LinkedIn Humility from decision-makers, building trust in leaders and institutions, and learning from international experience are critical if countries are to better prepare for the next global crisis. 2020-08-07-Vietnam-Health-Virus-Art An information poster on preventing the spread of COVID-19 in Hanoi, Vietnam. Photo by MANAN VATSYAYANA/AFP via Getty Images. While we must wait for the final reckoning of most successful national coronavirus responses, it does still appear those countries with memories of MERS and SARS - such as Singapore, Taiwan, Hong-Kong, and South Korea – led the way in being best prepared for COVID-19, with strong contract tracing and isolation measures.Experience of previous outbreaks informed the containment strategies adopted by countries in East Asia in response to COVID-19. Vietnam reported its first case of COVID-19 in January but, over the following four months with rapid targeted testing, contact tracing and successful containment, only around 300 additional cases with no deaths were confirmed.These countries learned to be flexible fast when new transmissions occurred, establishing quick lockdown measures targeted at key groups such as Singapore’s schools or South Korea’s night clubs and religious centres. In stark contrast, most European countries were overwhelmed by the pandemic despite enjoying world-class health systems, predictive models, scientific expertise, wealth, and resources.Asia may have suffered first from coronavirus, but there is no ‘first mover advantage’ in dealing with a pandemic. The more resilient a society, the better placed it is to cope with a variety of risks and challenges. But to become resilient, a society needs to have faced setbacks and learned from them. And to remain resilient, it needs to stay aware of its own vulnerabilities and avoid complacency.Prior experience of crises and disturbances, coupled with a ‘trial and error’ process of learning to deal with them, makes a society more resilient, whereas high levels of economic welfare and relative lack of recent crises leave some societies less prepared to face shocks. This is known as the ‘vulnerability paradox’.Within Europe, it has actually been the Greek handling of COVID-19 that so far appears more successful than others. Greece is a country which has suffered a decade of austerity leading to a weakened healthcare system. And with one of Europe’s oldest populations, the Greek government was keenly aware of its own vulnerabilities. This prompted an early lockdown and a rapid increase in intensive care beds.Although better state capacity and health system capability are clearly positives for mitigating disasters, citizens do tend to be less familiar with risk preparedness. This lack of experience can then breed complacency which threatens societies where risks are often complex, numerous, transboundary and inter-related.Conversely, the absence of systemic resilience at a national level often puts the onus on family units or local communities – creating resilience as a necessary response to weak government capacity. There is little choice but to learn to look after yourself and your community.However, although the vulnerability paradox helps explain why prior experience makes a system more resilient, societies need to stay aware of their own vulnerabilities and avoid complacency if they are to continually remain resilient.Complacency coupled with a belief in the virtues of the free market has left some countries hit harder than others by the pandemic. In normal times, ‘just in time’ business models can be highly efficient compared to holding vast stocks. But it does not require hindsight to know that a global health crisis will see demand for protective equipment soar and these business models severely challenged.Several societies have also witnessed a decline in trust towards institutions, especially politicians or the media. The deployment of science as justification for political decisions around coronavirus was presumably intended to help garner trust in those decisions. But when the science itself is inexact because of inadequate or emerging knowledge, this strategy is hardly fail-safe.COVID-19 does provide an opportunity to rebuild trust by rethinking the relationship between the state and its citizens, to engage people more directly in a discussion about societal resilience with empowered citizens, and to rebuild a social contract between state and society in the context of recent significant changes and further potential threats.It should also provide a salutary wake-up call to a range of ‘strongmen’ leaders prone to portraying issues rather simplistically. Although COVID-19 may be one of the few complex problems to which simplistic measures do apply - such as wearing a mask and using social distancing – these do not provide the whole solution.Generally, declining trust in politicians reflects the ongoing inability of current politics to deal with a range of societal challenges. COVID-19 is certainly the most sudden and presents the biggest immediate economic shock of recent times, but it is just the latest in a long line of examples of political failure, such as conflict in the Middle East, climate change, terrorism, and cyber-attacks.Along with the growth of automation and digitization which provide opportunities at the macro-level but threats at a more micro-level, what most of these issues have in common is that national responses are likely to fail. Restoring trust requires re-energized global governance, and this means compromise and humility – qualities which appear in short supply to many current politicians.But, regardless of political will, building resilience to tackle ongoing or rapidly forthcoming challenges also rubs up against free market beliefs, because building resilience is a long-term investment and comes at a price. But by acknowledging vulnerabilities, avoiding complacency, implementing lessons from past experiences, and learning from others, policymakers will be better prepared for the next crisis.Reconstructing societies through the prism of resilience creates fundamentally different outcomes to global challenges, and can build trust between elected representatives and the wider population. Accepting the vulnerability paradox and acknowledging that those generally less prone to disasters are actually less able to cope when change happens creates a powerful argument for this new approach. Full Article
ac Nile Basin States Must Persist with Water Diplomacy By www.chathamhouse.org Published On :: Tue, 11 Aug 2020 14:03:31 +0000 11 August 2020 Owen Grafham Assistant Director, Energy, Environment and Resources Programme LinkedIn Google Scholar Ahmed Soliman Research Fellow, Horn of Africa, Africa Programme @AhmedSolHoA Dr Nouar Shamout Water Resources and Sustainability (Independent Researcher) After multiple failed negotiations, any serious breakdown in current talks mediated by the African Union would be dangerous for regional stability. The international community must ramp up its support for this crucial diplomacy to ensure that an agreement is reached. 2020-08-12-Dam-Nile-Ethiopia The Blue Nile river passes through the Grand Ethiopian Renaissance Dam (GERD) near Guba in Ethiopia. Photo by EDUARDO SOTERAS/AFP via Getty Images. Ongoing talks between Egypt, Ethiopia and Sudan attempting to find a diplomatic and peaceful solution to the dispute over the Blue Nile Basin offer a unique opportunity for trans-boundary cooperation and have huge significance for a region dealing with multiple complex issues.With trust clearly at a premium, the continuation of talks demonstrates good faith, but there is an urgent need to strengthen negotiations through all available diplomatic channels. The African Union (AU) is well-placed to continue mediating, but sustained high-level engagement is also needed from regional and international partners such as the EU and US, as well as multilateral support in terms of both financial and technical resources.A tense history to overcomeAt the heart of this dispute is the new Grand Ethiopian Renaissance Dam (GERD) – set to become Africa's biggest hydroelectric dam when complete. Egypt and Sudan, who lie downstream, fear that Ethiopia, as the dam builders, will effectively gain control of the flow of the Nile, a turn of events that radically changes the way that water resources have been shared in the region.Egypt - widely described as a ‘gift of the Nile’ - is almost entirely dependent on the Nile to meet its various water needs, and is the major beneficiary of the 1929 and 1959 agreements on using the shared river’s water. The 1959 agreement gives Egypt a share of 55.5 billion cubic meters (BCM) annually out of 74 billion available, and a veto right over projects being developed upstream, while Sudan is allocated 18.5 BCM.Crucially neither of these old agreements recognises the interests of other upstream countries on the Nile, some of which have asserted their own development ambitions on the river over the last two decades and pushed for a new agreement to enshrine equitable rights and harmonious use of the water.One such country is Ethiopia where the Blue Nile River originates. The GERD is a central part of Ethiopia’s ambitions for economic prosperity. The dam, which is largely self-financed, will have a capacity of 74 BCM when completed, enough to provide abundant cheap energy to power both national and regional developments. Currently, more than half Ethiopia’s 110 million people do not have access to electricity, but demand is increasing by 30 per cent annually.Unclear impactsThe unclear impact of the GERD – and lower volumes of water – on food security and agriculture complicate the negotiations. Egypt, Ethiopia and Sudan’s populations are set to increase significantly in the coming decades and each are already dealing with significant challenges around food insecurity and nutrition, which in Egypt and Sudan, are partly exacerbated by the colonial-era agricultural structures set up to exploit cash crops.Any change in water quality would have a huge impact on the 67% of Egyptian farm holdings considered as ‘small’ – the majority of which are on the banks of the Nile. And changes in water volumes might increase desertification and loss of livelihoods, potentially causing civil unrest if not addressed properly.The environmental impact of the GERD on the complex Nile River system also raises concerns about the river’s ecosystem, the surrounding environment, and the river’s downstream course. Despite talks in 2015 leading to an agreement on declaration of principles, thorough technical studies have not been implemented.Although there is little evidence that overall water levels in the Nile Basin have reduced in recent years, climate change is causing more variation in the Nile’s flow which increases the risk of flooding and extended droughts. Downstream states are also concerned about impacts from any breaches, damage or failure of the dam, including possible seismic activity.Of course, the GERD also offers some added value to the downstream states. The dam can help manage floods in Sudan, reduce the significant water loss to evaporation - as in the case of Lake Nasser - and lessen the effect of sediment on downstream dams. In Sudan, where less than one-quarter of the estimated 70 million hectares of arable land is currently cultivated, any reduction in seasonal flooding would boost agricultural output and aid economic recovery. The dam will offer Ethiopia significant opportunities for the trade of cheap renewable energy to Sudan and neighbouring states earning it a possible $1bn a year in revenues. And adopting a more ‘basin-integrated’ management approach can be a springboard for enhanced regional cooperation between the three states.But geopolitical tensions between the three have escalated since satellite imagery revealed apparent significant filling of the dam prior to reaching any agreement. Ethiopia has long said it would begin filling the dam during its rainy season, but insists the filling occurred naturally through June-July from rainfall and runoff and its first-year target of 4.9 BCM was reached without needing to close the dam gates. Egypt and Sudan have restated their calls for a binding legal agreement on the rules for filling and management of disputes.Security response not the answerInternal pressures are particularly acute, with all three countries experiencing public uprisings and regime change in the last decade, and current leaders are under pressure not to appear weak from influential sections of society pushing a hard nationalist line.Hawkish elements in Egypt have long supported a more securitized response to any potential threats from the GERD, and the recent request from President Sisi that Egyptian air forces be ready to handle targets inside and outside of the country was interpreted as a threat to Turkey in Libya, and Ethiopia.Egypt has also asked for the GERD to be discussed at the UN Security Council but Ethiopia’s Nobel peace prize-winning prime minister Abiy Ahmed, facing significant internal unrest himself, has made it clear that a costly confrontation is not in anyone’s interests. Meanwhile, Sudan’s transitional government - being jointly run by civilians and the military - is keen to assert its own interests on the Nile but has also played a conciliatory role with its neighbours. Increased engagement of Gulf states in the Horn of Africa and the impacts of conflicts in Libya, Yemen and Syria add more complexity to the overall regional picture.Certainly none of the major parties sharing the river would benefit from a hard security response to the dam. For Egypt, such a move would torpedo its re-engagement in Sub-Saharan Africa under President Sisi and likely lead to its expulsion from the AU. For Ethiopia, overt conflict would be a huge setback for its development and regional integration ambitions. And Sudan’s nascent transition can ill-afford to be part of another regional conflict.Thankfully, such an outcome is both highly unlikely and historically rare, and behind the scenes there has been significant progress. Some reports suggest a provisional agreement has been reached on the volume of filling required and the timeframe for the filling to happen. If so, most dispute now revolves around what to do in the event of a drought, provisions for information exchange, and how to translate all this into a binding agreement.A two-phase approach, consisting of a short-term deal on filling and operating the GERD followed by discussions on future developments and allocation, could be the best way to reach a lasting settlement and replace the extremely outdated existing water-sharing agreements.Reaching a successful deal between the three countries is not easy as it requires brave leadership and political goodwill, a de-escalation of long-standing rhetoric and brinkmanship, and a willingness to compromise on all sides to ensure the gaps between the countries' positions are significantly narrowed.What is required is a determined effort to keep the countries talking and provide the solutions which can bridge the parties’ differences, build confidence, and secure the vital diplomatic success so badly needed for wider stability and progress in the region. Full Article
ac Choosing Kamala Harris Puts Identity at the Heart of Presidential Race By www.chathamhouse.org Published On :: Wed, 12 Aug 2020 10:06:36 +0000 12 August 2020 Dr Leslie Vinjamuri Director, US and the Americas Programme; Dean, Queen Elizabeth II Academy for Leadership in International Affairs @londonvinjamuri Google Scholar 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. 2020-08-12-Kamala-Harris 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. Full Article
ac Is the Juba Peace Agreement a Turning Point for Sudan? By www.chathamhouse.org Published On :: Mon, 14 Sep 2020 13:34:19 +0000 14 September 2020 Dame Rosalind Marsden Associate Fellow, Africa Programme @MarsdenRosalind Sudan is looking towards a brighter future after the initialling of the Juba peace agreement on August 31, an important first step towards bringing peace to the conflict zones and laying the foundation for democratic transition and economic reform throughout the country. 2020-09-14-Sudan-Peace-Deal-Juba Chairman of Sudan’s Sovereign Council, Lt General Abdel Fattah al Burhan (left), South Sudan President Salva Kiir (centre) and the Sudanese Prime Minister Dr Abdalla Hamdok (right) greet people gathering during the initialling of the Sudan peace deal with the rebel groups in Juba, South Sudan. Photo by AKUOT CHOL/AFP via Getty Images. Although there is a long road ahead to achieve sustainable peace and formidable challenges remain, the hope is Sudan can turn the page on decades of war that has left hundreds of thousands dead and millions displaced, particularly in Darfur and the Two Areas (South Kordofan and Blue Nile).The peace agreement, between Sudan’s transitional government and the Sudan Revolutionary Front (SRF), a broad alliance of armed and other movements, and Minni Minawi’s Sudan Liberation Movement, is not yet comprehensive as it did not include two other important armed movements.Expected to be formally signed in early October, the deal has been hailed as a ’historic achievement’ by the UN secretary-general, and the international community also commended the government of South Sudan for its positive role as mediator and urged hold-out groups to join the peace process. Much does depend on delivering on the agreement, and the experience of implementing past peace accords in Sudan has been dismal, particularly when it comes to bringing tangible benefits to people on the ground.What potentially makes the Juba agreement different is that Sudan’s civilian-led transitional government aspires to deliver peace, justice and democracy in line with the goals of the revolution; that the agreement was negotiated between the Sudanese themselves, with a light touch from the South Sudanese mediation and low-key logistical and technical support from the international community; and that much of the negotiations were conducted between former comrades, in marked contrast to the confrontational atmosphere that prevailed during the Bashir era.As Prime Minister Abdalla Hamdok put it: ’This is a Sudanese peace, made with our own hands and by our own efforts’ and: ’This is not a paper agreement, but is a living organism that needs care, attention and political will from all of us’.Achievements of the agreementThe result of almost one year’s hard work in Juba, the agreement is comprehensive in scope and addresses the fundamental issues of Sudan’s crises in Darfur, the Two Areas and other marginalized regions, albeit in a mixture of regional and national protocols. It goes a long way to realizing the vision of a democratic ‘New Sudan’ based on respect for the diversity of the Sudanese people and equal citizenship without religious, ethnic, cultural or gender discrimination.There is a focus on the concerns of historically marginalized populations in Sudan’s conflict zones and disadvantaged areas, and it addresses root causes of conflict, such as issues of identity, marginalization, the relationship between religion and state, governance, resource-sharing, land issues, social justice, and equality at the national level.The deal also looks to resolve the consequences of conflict, such as humanitarian relief, the safe and voluntary return of IDPs and refugees to their original lands and compensation, eviction of illegal settlers and the development and reconstruction of the conflict-affected areas. It provides for significant devolution of power and resources to the regions, including autonomy for the Two Areas and restoration of a single Darfur region. On transitional justice, the government has committed to cooperate fully with the International Criminal Court (ICC) and ensure Bashir and others subject to arrest warrants will ‘appear before’ the ICC.This deal will change the face of the transitional government by bringing marginalized forces to the centre of the political process. The transitional period will extend to 2023, with the armed movements having three seats in the (currently 11-member) Sovereign Council and 25% of seats in the Cabinet and soon-to-be-formed Legislative Assembly.The power-sharing provisions have been criticized as disproportionate to the size of the movements’ political constituencies and military presence inside Sudan. But the movements argue significant representation in the government is necessary to support implementation and that their arrival in Khartoum will help to strengthen the transition to democracy.Establishing a single, national professional army, reflective of the diversity of Sudan and with a new military doctrine opens the way for much-needed comprehensive security sector reform. During the transition, this will include the creation of a 12,000 strong joint force between government security forces and the armed movements to help protect civilians in Darfur. Importantly, mechanisms allowing for civilian input on security reforms are also established.The deal also guarantees religious freedom and the separation of religion from politics. This ensures religion will not be exploited by state institutions as it was during the Bashir-era, provides for the constitution to be based on equal citizenship, and for the establishment of a National Commission for Religious Freedom to protect the rights of Christians and other minorities. In the Two Areas, the autonomous government will have special legislative powers to pass laws based on the secular 1973 Constitution.Increasing inclusivityKey to achieving inclusive and sustainable peace is ensuring popular ownership and finding ways to engage civil society stakeholders and marginalized communities such as nomads in dialogue, reconciliation and social peace initiatives. The negotiations were mainly a top-down elitist process. Although the UN brought IDPs, tribal leaders and women’s groups to Juba for short periods, there was limited participation by civil society. However, the agreement provides for a wider range of stakeholders to feed into a comprehensive peace through reconciliation and transitional justice mechanisms, follow-on conferences and an inclusive National Constitutional Conference.Achieving a comprehensive peace will also mean bringing other armed movements on board, particularly those led by Abdel Aziz Al Hilu and Abdel Wahid Al Nur, both of whom hold significant territory, forces and support (in the Two Areas and Darfur respectively). Negotiations in Juba with Abdel Aziz had stalled over his demands for a secular state or, failing that, the right to self-determination, but he has now reached a preliminary agreement with Prime Minister Hamdok on a way forward.Other challenges of implementing peaceTurning the peace agreement into reality on the ground will face many other challenges given the fragility of a civilian-military transitional government, distrust, and competition between the signatory movements and some political parties, as well as increasing insecurity in many parts of the country caused by armed militias, inter-tribal violence, the proliferation of weapons, and sabotage by elements of the former regime. There is also likely to be resistance from groups such as illegal settlers who see their interests being threatened.With its economy in meltdown because of economic mismanagement by the Bashir regime, COVID-19, and unprecedented floods, finding resources to implement the peace deal is far beyond the means of Sudan’s cash-strapped government. Implementation therefore requires sustained and generous support from its regional and international partners, including the country’s urgent removal from the US State Sponsors of Terrorism list, which is preventing debt relief, access to concessionary loans and large-scale foreign investment. With donor budgets under heavy pressure, raising money will be hard, but by continuing to support a nascent democracy in a strategically important but unstable region, Sudan’s allies will be safeguarding their long-term interests.If properly implemented, the Juba peace agreement is a major first step towards creating a ‘New Sudan’ based on peace, equal citizenship and social justice. Key tests of whether Sudan can finally turn the page are whether the signatory movements and other revolutionary forces can unite to deliver the dividends of peace for the victims of Sudan’s conflicts, and embrace inclusion rather than tribalism and narrow political affiliation; whether the remaining armed movements are ready to start serious negotiations for a comprehensive peace; and whether Sudan now receives the support and attention it deserves from the international community. Surely Sudan has already come too far for this historic opportunity to be lost. Full Article
ac Economic Diplomacy in the Era of Great Powers By www.chathamhouse.org Published On :: Thu, 17 Sep 2020 10:04:54 +0000 17 September 2020 Dr Linda Yueh Associate Fellow, Global Economy and Finance Programme and US and the Americas Programme @lindayueh The 21st-century global economy has different drivers from those in the previous century. Amid ever more politicized trade relations, economic diplomacy needs a more transparent framework. 2020-09-17-Trump-Economy-WEF-World-Economic-Forum-Davos US president Donald Trump at the World Economic Forum in Davos, Switzerland, on January 22, 2020. Photo by JIM WATSON/AFP via Getty Images. The emergence of a multipolar global economy in which the US is no longer the main engine of growth has boosted the role of economic diplomacy, the setting of foreign economic policy. While the EU remains the world’s biggest economic bloc and the US is still an economic powerhouse, it is Asia – China in particular – which has created hundreds of millions of new middle-class consumers, helping to drive global economic growth.This shift has ignited an era of competition between the US and China and, by implication, a debate about the merits of different political and legal systems. The difficulty for the rest of the world is how best to navigate this highly polarized climate – in recent history, only the Cold War comes close to having matched the adversarial dynamics of such a divided international community.In conducting economic diplomacy, governments should consider their economic strengths, the importance of transparency, and how best to operate in a fragmented international system.First, the setting of trade and investment policy should take into account developments in the global economy. One trend worth noting is the rising importance of services – in particular digital services – in international trade. The expanding cross-border trade in intangibles such as business services and data means the negotiation, definition and enforcement of standards to regulate these are of growing importance for the global economy, and for policymakers in many countries.In contrast, negotiations around merchandise trade are likely to take a somewhat lower profile. Under the World Trade Organization (WTO), tariffs on manufactured goods have dropped significantly in any case – though there is still scope to lower them. Contemporary diplomacy, as well as disputes, around the lowering or raising of barriers to international trade will increasingly concern non-tariff measures applicable to services rather than those, such as tariffs, that traditionally apply to goods.For service-based economies, it is vital free-trade agreements (FTAs) encompass regulations and standards for intangibles. But this is difficult in a multipolar global economy where the US, China and the EU all have different legal and regulatory systems, and raises the prospect of a fragmented global trading system divided into blocs of countries adhering to different standards.A pluralistic or mini-multilateral approach to trade such as the stalled Trade in Services Agreement (TiSA) could help resolve elements of this division. TiSA was launched in 2013 by a group of advanced economies, not the entirety of the WTO, to further opening up global services trade. However, talks have been on hold since 2016 and, in the current climate, it is near impossible to conclude negotiations when the major economies do not come to the table and instead promote their own standards with their closest trading partners.Second, policymakers should consider that, in an era of heightened trade tensions, any framework for economic diplomacy needs to be transparent if it is to be trusted and credible. Such a framework could centre on commercial openness and consistency with a country’s foreign and intelligence policy aims. For example, clearly spelling out how a country reviews prospective foreign investment and applying this consistently would demonstrate that all projects are treated equally without singling out any individual country. This would be an improvement over an ad hoc and less transparent approach .A major challenge in creating a ‘principle-based’ economic diplomacy framework of this kind is reconciling competing policy aims. To this end, several key questions need answering. Should trade agreements encompass non-economic elements, such as foreign policy aims? Do concerns over national security mean that trade and investment agreements should favour allies? Could such a framework assess a trading or investment partner in terms of national security as well as potential economic benefit?A country should also re-think how to undertake a wider international role when embarking on economic diplomacy. The inability of the major powers to set new global rules has had a detrimental impact on an international system under significant strain. The stalling of multilateral trade talks and urgency of international coordinated action on global public goods, such as health and the environment, shows there is a pressing need for a new approach to international relations.Economic diplomacy could, and should, bolster the rules-based multilateral system. The challenge is engaging the major powers without whom widespread adoption of global policies and standards is less likely. Yet the chances of wider adoption might actually be better if a proposal does not come from either the US or China. This opens up the opportunity for other countries to be ‘honest brokers’ and potentially improve their own international standing.In an era of increasing tension between great powers, economic diplomacy requires re-tooling. It should consider not just economic considerations, but also broader foreign policy aims, greater transparency, and a pluralistic approach to global rules to strengthen the multilateral system. Full Article
ac CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPK{alpha}2-SIRT1-PPAR{alpha} signaling pathway [Metabolism] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of in vivo and in vitro approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, p16 overexpression was associated with triglyceride accumulation and increased lipid droplet numbers in vitro, and decreased ketogenesis and hepatic mitochondrial activity in vivo. Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between CDKN2A expression and PPARA and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility. Full Article
ac The glucose-sensing transcription factor ChREBP is targeted by proline hydroxylation [Metabolism] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Cellular energy demands are met by uptake and metabolism of nutrients like glucose. The principal transcriptional regulator for adapting glycolytic flux and downstream pathways like de novo lipogenesis to glucose availability in many cell types is carbohydrate response element–binding protein (ChREBP). ChREBP is activated by glucose metabolites and post-translational modifications, inducing nuclear accumulation and regulation of target genes. Here we report that ChREBP is modified by proline hydroxylation at several residues. Proline hydroxylation targets both ectopically expressed ChREBP in cells and endogenous ChREBP in mouse liver. Functionally, we found that specific hydroxylated prolines were dispensable for protein stability but required for the adequate activation of ChREBP upon exposure to high glucose. Accordingly, ChREBP target gene expression was rescued by re-expressing WT but not ChREBP that lacks hydroxylated prolines in ChREBP-deleted hepatocytes. Thus, proline hydroxylation of ChREBP is a novel post-translational modification that may allow for therapeutic interference in metabolic diseases. Full Article
ac The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance [Immunology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance. Full Article
ac Ascertaining the biochemical function of an essential pectin methylesterase in the gut microbe Bacteroides thetaiotaomicron [Metabolism] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Pectins are a major dietary nutrient source for the human gut microbiota. The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II–derived oligosaccharide ΔBT1017oligoB generated by a BT1017 deletion mutant (ΔBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of ΔBT1017oligoB using a combination of enzymatic, mass spectrometric, and NMR approaches revealed that it is a bimethylated nonaoligosaccharide (GlcA-β1,4-(2-O-Me-Xyl-α1,3)-Fuc-α1,4-(GalA-β1,3)-Rha-α1,3-Api-β1,2-(Araf-α1,3)-(GalA-α1,4)-GalA) containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an α/β-hydrolase fold, consisting of a central twisted 10-stranded β-sheet sandwiched by several α-helices. This constitutes a new fold for pectin methylesterases, which are predominantly right-handed β-helical proteins. Bioinformatic analyses revealed that the family is dominated by sequences from prominent genera of the human gut microbiota, including Bacteroides and Prevotella. Our re-sults not only highlight the critical role played by this family of enzymes in pectin metabolism but also provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut. Full Article
ac Serum lipoprotein-derived fatty acids regulate hypoxia-inducible factor [Metabolism] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Oxygen regulates hypoxia-inducible factor (HIF) transcription factors to control cell metabolism, erythrogenesis, and angiogenesis. Whereas much has been elucidated about how oxygen regulates HIF, whether lipids affect HIF activity is un-known. Here, using cultured cells and two animal models, we demonstrate that lipoprotein-derived fatty acids are an independent regulator of HIF. Decreasing extracellular lipid supply inhibited HIF prolyl hydroxylation, leading to accumulation of the HIFα subunit of these heterodimeric transcription factors comparable with hypoxia with activation of downstream target genes. The addition of fatty acids to culture medium suppressed this signal, which required an intact mitochondrial respiratory chain. Mechanistically, fatty acids and oxygen are distinct signals integrated to control HIF activity. Finally, we observed lipid signaling to HIF and changes in target gene expression in developing zebrafish and adult mice, and this pathway operates in cancer cells from a range of tissues. This study identifies fatty acids as a physiological modulator of HIF, defining a mechanism for lipoprotein regulation that functions in parallel to oxygen. Full Article
ac The bacterial cell division protein fragment EFtsN binds to and activates the major peptidoglycan synthase PBP1b [Metabolism] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Peptidoglycan (PG) is an essential constituent of the bacterial cell wall. During cell division, the machinery responsible for PG synthesis localizes mid-cell, at the septum, under the control of a multiprotein complex called the divisome. In Escherichia coli, septal PG synthesis and cell constriction rely on the accumulation of FtsN at the division site. Interestingly, a short sequence of FtsN (Leu75–Gln93, known as EFtsN) was shown to be essential and sufficient for its functioning in vivo, but what exactly this sequence is doing remained unknown. Here, we show that EFtsN binds specifically to the major PG synthase PBP1b and is sufficient to stimulate its biosynthetic glycosyltransferase (GTase) activity. We also report the crystal structure of PBP1b in complex with EFtsN, which demonstrates that EFtsN binds at the junction between the GTase and UB2H domains of PBP1b. Interestingly, mutations to two residues (R141A/R397A) within the EFtsN-binding pocket reduced the activation of PBP1b by FtsN but not by the lipoprotein LpoB. This mutant was unable to rescue the ΔponB-ponAts strain, which lacks PBP1b and has a thermosensitive PBP1a, at nonpermissive temperature and induced a mild cell-chaining phenotype and cell lysis. Altogether, the results show that EFtsN interacts with PBP1b and that this interaction plays a role in the activation of its GTase activity by FtsN, which may contribute to the overall septal PG synthesis and regulation during cell division. Full Article
ac Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses. Full Article
ac War in Ukraine: The world reaction - Brazil and Africa By www.chathamhouse.org Published On :: Thu, 09 Jun 2022 11:22:19 +0000 War in Ukraine: The world reaction - Brazil and Africa Audio NCapeling 9 June 2022 The ninth episode of our podcast mini-series examines perspectives from Brazil and the Africa region and the impact on their relations with Russia. How have Brazil and Africa reacted to the war in Ukraine? With impending elections in Brazil, how is President Bolsonaro’s relationship with Putin received by the public? How will food insecurity affect African nations’ response to the war? This episode was produced by David Dargahi and Anouk Millet of Earshot Strategies on behalf of Chatham House. Full Article
ac Enhancing the role of women in peacebuilding and politics in Ethiopia By www.chathamhouse.org Published On :: Thu, 16 Jun 2022 16:47:14 +0000 Enhancing the role of women in peacebuilding and politics in Ethiopia 29 June 2022 — 1:00PM TO 2:30PM Anonymous (not verified) 16 June 2022 Online Panellists discuss the priorities for promoting the agency of women in politics and peacebuilding in Ethiopia and approaches for combatting gender-based discrimination and violence. The war in northern Ethiopia and conflicts elsewhere have disproportionately affected women and girls – including through the infliction of physical and sexual violence, the heightened impacts of displacement and disruptions to education, and the co-option of women’s experiences in narratives by aggressors of conflict. Hard-won political gains in women’s rights have been undermined and deep-rooted gender inequalities exacerbated. Despite this, women remain central actors in politics, as well as in conflict resolution and mediation efforts. However, more needs to be done to promote the security and inclusion of women in finding sustainable solutions for Ethiopia’s long-term recovery and to institutionalize reforms for gender equity and development. At this public event, panellists will discuss the priorities for improving women’s participation and equality in public decision-making in Ethiopia and how to strengthen the implementation of legislation on women’s rights. They will also discuss what societal shifts and approaches are needed to combat gender-based discrimination and violence and to promote the agency of women in peacebuilding. This webinar is part of a series of events and outputs on Ethiopia’s political transition. This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page. Full Article
ac What challenges does the new president of Somalia face? By www.chathamhouse.org Published On :: Tue, 28 Jun 2022 12:56:43 +0000 What challenges does the new president of Somalia face? Explainer Video aboudiaf.drupal 28 June 2022 Ahmed Soliman examines the challenges the new president Hassan Sheikh Mohamud faces in his first 100 days as president. Key issues for the new administration are a deteriorating situation with regards to drought as close to half the population are facing food insecurity due to a fourth failed rainy season. Combined with an inflation rate above ten per cent, many Somalis are at risk of famine and starvation. Many areas of the country are affected from the pastoralist regions to those which house IDP camps around the capital city and other towns, all being exacerbated by the war in Ukraine as Somalia was importing much of its wheat imports from Ukraine and Russia. Full Article
ac Will Africans’ calls for better democracy be met? By www.chathamhouse.org Published On :: Fri, 29 Jul 2022 18:50:23 +0000 Will Africans’ calls for better democracy be met? The World Today mhiggins.drupal 29 July 2022 Voters want the continent’s ageing leaders to step aside to usher in a new age of political engagement and robust democracy, say the experts of Afrobarometer. Across Africa, recent years have been marked by both encouraging democratic highs and troubling anti-democratic lows. Notable advances from last year include the Gambia’s successful presidential election, a ruling-party transition in Zambia and the first democratic transfer of power in Niger. In the lead up to this, add Malawi’s retake of its flawed presidential election in 2020 and an earlier succession of oustings of long-serving autocrats in Sudan, Zimbabwe and the Gambia. Contrast these gains, though, with setbacks elsewhere, including increasing restrictions on opposition parties in Benin, Senegal and Tanzania; the use of violence and intimidation during elections in Côte d’Ivoire and Uganda; and military coups, with the latest in Burkina Faso this year and last year in Chad, Mali, Sudan and Guinea. These contradictory developments join dire warnings from experts that democracy is losing ground on the continent. But what can we learn about the state of democracy on the continent from Africans themselves? Afrobarometer, a pan-African, non-partisan research network, has been surveying people about their views on democracy, governance and quality of life for more than 20 years. After interviewing nearly 50,000 citizens across 34 countries during Afrobarometer Round 8, which spans 2019-2021, we find that despite the efforts of some leaders to undermine democratic norms, Africans remain committed to democracy and democratic institutions. They believe that the military should stay out of politics, that political parties should freely compete for power, that elections are an imperfect but essential tool for choosing their leaders, and that it is time for the old men who cling to power to step aside. But their political reality falls short of these expectations. The perception of widespread and worsening corruption is particularly corrosive, leaving people increasingly dissatisfied with political systems that are yet to deliver on their aspirations to live in societies that are democratically and accountably governed. And although citizens find myriad ways to voice their concerns, they feel that their governments are not listening. Simply put, Africans want more democratic and accountable governance than they think they are getting. Africans’ democratic aspirations Over the past decade, democracy watchers have been alarmed by declining trends in Africa. Concerns have been exacerbated in the past two years as some governments have taken advantage of the Covid pandemic to limit freedoms, restrict fair campaigning or postpone elections. Activists fear that supposedly temporary rollbacks in hard-won governance reforms could become permanent. But for the most part, African citizens remain committed to democracy and democratic institutions. Across 30 countries that Afrobarometer has surveyed consistently since Round 5 (2011–2013), most indicators are strong and quite steady. For example, seven in 10 Africans say that ‘democracy is preferable to any other kind of government’. While this is down modestly from 73 per cent a decade ago, more specific indicators seem to affirm popular commitment to democracy. Large and steady majorities consistently reject authoritarian alternatives, including one-person or ‘strongman’ rule (82 per cent), one-party rule (77 per cent) and military rule (75 per cent), which is clearly rejected even in many of the countries rocked by recent military coups. Africans also express strong support for a limit to presidential terms, a feature of democratic governance that researchers and activists argue nurtures political participation, demonstrates that change via the ballot box is possible, and reduces the risk of personality cults, authoritarianism, corruption and coups. Across 34 countries, an average of 76 per cent favour limiting their presidents to two terms, including a majority (54 per cent) who ‘strongly’ support this rule. Term limits enjoy majority support in every surveyed country. The public’s democratic commitment is undergirded by strong and in some cases growing support for core democratic institutions. Support for multiparty competition and parliamentary oversight of leaders remains steady, while expectations that governments should be accountable to the courts have increased significantly over the past decade. In addition, growing numbers of people say it is more important to have a government that is accountable to the people rather than one that just ‘gets things done’, an especially strong indicator of deepening commitment to democratic norms among citizens. Trouble at the polling booth Elections remain a central, though controversial, institution of democracy for Africans. They have served as the foundation for real change, as in Zambia last year. But in other cases, such as Uganda’s January 2021 poll, they have been marred by violence and human rights abuses, as well as the weaponization of Covid to justify restrictions on campaigning. The public is also sceptical about the capacity of elections to bring about real change: fully 50 per cent say they do not think elections are effective in enabling voters ‘to remove from office leaders who do not do what the people want’. At the same time, large majorities report positively on their country’s election environment. Asked about their most recent election, at least eight in 10 say they did not observe intimidation (87 per cent) or interference (81 per cent) by security forces and did not fear violence (80 per cent). We must keep in mind that these encouraging averages can obscure deep problems in some countries. For example, while only 3 per cent of Namibians say votes are ‘often’ not counted fairly, between a quarter and one-third cite inaccurate counts as a frequent problem in Zimbabwe, Sudan and Gabon. In addition, confidence in the fairness of the media environment is drastically lower, on average just 36 per cent. But perhaps most importantly, almost nine in 10 Africans (87 per cent) say they are free to vote as they choose, including sizeable majorities in every surveyed country. And a solid majority of 63 per cent rate their most recent election as completely or mostly free and fair. All of this may help to explain still-strong support for competitive elections as the best system for selecting leaders. A robust three-quarters confirm their commitment to elections, though this has fallen slightly over the past decade, probably reflecting disillusionment with electoral processes that are too often torn by violence and produce contested results. A growing number of people may also be recognizing that elections, especially poor-quality ones, are not enough to guarantee democracy and better governance, and that a healthy democracy must include such other features as government accountability, respect for the rule of law, responsiveness and citizen participation. The ‘democratic disappointment’ gap To what extent does political reality align with Africans’ democratic aspirations? Our findings suggest that it is falling well short of expectations. While a slim majority has steadily reported that their country is a ‘full democracy’ or one ‘with minor problems’ over the past decade, satisfaction, however, has dropped to 43 per cent in that time. What explains this growing dissatisfaction? Other indicators of democratic supply offer some clues. While ratings of election quality have held steady, favourable public assessments of presidential accountability to parliament and to the courts have both declined. The rising scourge of corruption But one of the most significant driving factors may be burgeoning corruption, a trend that appears to parallel declining democratic satisfaction. On average across 34 countries, around six in 10 say both that corruption in their country increased over the past year, and that their government is doing a poor job of controlling it. These perceptions matter. Over time, when perceptions of corruption rise or fall, levels of dissatisfaction with democracy tend to follow suit. In South Africa, dissatisfaction with democracy grew steadily alongside scandals involving President Jacob Zuma, and has continued to rise under his successor, Cyril Ramaphosa, whose office has been tainted by ‘Farmgate’ and a major Covid-relief scandal. The ‘Fishrot’ scandal in Namibia has had similar consequences. Are governments listening? African citizens are raising their voices, calling on their governments to fulfil their democratic aspirations. Since April 2017, the Carnegie Endowment for International Peace has recorded more than 70 episodes in 35 African countries of protests focused on issues ranging from demands for democracy in eSwatini to resisting police brutality, presidential third-term attempts and Covid restrictions. Citizen participation and government responsiveness are cornerstones of democracy. But are governments listening? Voting is the most obvious and popular way for citizens to express themselves, and Africans take advantage of this opportunity. Two-thirds said they voted in their most recent national election. But elections occur only occasionally, and they force individuals to compress a wide array of views into very few choices. How do Africans find their voice during the long intervals between elections? Many invest in personal efforts to act as agents of change. In fact, nearly half say they joined with others to raise an issue at least once in the past year, and a third contacted a political leader. A quarter report they acted with others to request government action. Less common but still important modes of engagement include asking for help from or lodging a complaint with government, contacting the media, and joining a demonstration. These robust levels of citizen engagement suggest that people feel they can make a difference. Unfortunately, decision-makers aren’t always receptive or responsive to citizen voices. Less than a quarter of people think local government officials listen to them – and even fewer think their members of parliament do. What is more troubling is that fully two-thirds say they are at risk of retaliation or some form of negative consequences if they take action by reporting incidents of corruption. Lack of government responsiveness and respect for popular voices may have direct implications for both citizen engagement and citizen satisfaction. For example, we find that people are more likely to contact leaders or take other actions to solve problems if they believe that government officials respect and listen to them; that they will get a response if they raise an issue; and if they do not need to fear retaliation. Similarly, when we compare country averages for government responsiveness to the percentage of citizens who are satisfied with democracy, we again find positive associations. When governments are responsive, citizens are more likely to engage in addressing community needs and to be satisfied with their political system and optimistic about the future. Respectful and responsive governance has the potential to spur citizen action to solve critical development challenges – and may be the cure for what ails democracy. Full Article
ac Now is the moment to launch an African vaccine industry By www.chathamhouse.org Published On :: Sun, 31 Jul 2022 17:05:22 +0000 Now is the moment to launch an African vaccine industry The World Today mhiggins.drupal 31 July 2022 The continent plans to make 60 per cent of its vaccines by 2040. After the failure of the world to help in the pandemic, it’s high time, says Ngozi Erondu. The lack of an African vaccine industry has been a glaring concern for decades. Before the pandemic, 99 per cent of Africa’s vaccines were manufactured outside the continent. As well as endangering the lives of millions, this situation has inhibited social and economic progress on the continent. In response, the Africa Centres for Disease Control and Prevention (Africa CDC) has undertaken an ambitious plan, outlined in the Partnerships for African Vaccine Manufacturing (PAVM) Framework for Action, to develop the nascent African vaccine manufacturing sector into an end-to-end industry by 2040. The framework aims to raise the share of African-manufactured vaccines used across the continent to 60 per cent by 2040, or the equivalent to up to 1.7 billion doses annually. Seven of every 10 vaccines used in Africa are currently donated through Gavi, the Vaccine Alliance. Most are administered within childhood immunization programmes and are largely manufactured either in India, or by multinational vaccine manufacturers in North America or Japan. Vaccine donations have inhibited the development in Africa of vaccines and other countermeasures against diseases. Though the Ebola virus was discovered in Central Africa in 1976, vaccine development was not adequately funded until it emerged in Europe in 2014. Human monkeypox resurfaced in Nigeria in 2017, yet the global Coalition for Epidemic Preparedness Innovations only targeted it for vaccine development in July this year. The pandemic highlighted Africa’s fatal dependency on imported vaccines. Only 20 per cent of Africans are fully vaccinated against Covid-19, due to the failure of countries in the Global North to ensure the equitable distribution of vaccines via the COVAX facility to 40 per cent of the world’s most vulnerable people. The pandemic also confirmed that Africa could not rely on fellow states of the Global South. At the height of the Delta variant outbreak in early 2021, India halted vaccine exports to Africa, where only 1.5 per cent of the population had at that time received any vaccine doses. After decades of discussions, there are signs that Africa could soon succeed in creating its own vaccine industry. First, the 55-member African Union is in the process of establishing the African Medicines Agency, a regional regulatory body. ‘The new public health order’ Additionally, the African Export-Import Bank and African Development Bank (AfDB) have established a foundation to provide financial and strategic support for the development of the pharmaceutical industry and the consolidation of regional vaccination programmes in Africa (the foundation would potentially negotiate intellectual property rights and licensing issues but that remains to be seen). Second, studies show there is an emerging middle class in Africa. In a 2011 report by the AfDB, this was estimated at some 56 million households. Potentially, this means many people will be able to buy vaccines and medicines made in Africa. About a third of African countries currently pay for their vaccine needs. According to PAVM forecasts, the value of the total African market could reach between $3 billion and $17 billion by 2040. The recent entry into effect of the African Continental Free Trade Area should also prove conducive to African vaccine development. Through economic integration, free movement and harmonized regional standards, countries that invest in their biopharmaceutical and medical technology sectors may attract employees, regional and international businesses, and investment. Further, the pandemic has encouraged people to relocate to countries with, or planning for, universal healthcare. Building an African pharmaceutical industry from the ground up could take much longer than two decades and cost tens of billions of dollars. Nevertheless, the moment seems ripe, and timely support has been forthcoming from influential regional actors, including Rwandan President Paul Kagame, South Africa’s Cyril Ramaphosa, and private sector business executives, including the Zimbabwean-born billionaire Strive Masiyiwa. With a pandemic treaty embedding equity in prevention, preparedness and response some way off, and given the limitations surrounding the recent World Trade Organization compromise on the TRIPS waiver – which temporarily waives Covid-19 vaccine patent protections for poorer countries – it is doubly important for Africa to build up its own pharmaceutical industry and emergency systems. With a pandemic treaty some way off, it is important for Africa to build up its own pharmaceutical industry In 2021, John Nkengasong, then director of Africa CDC, wrote of the necessity of a post-pandemic ‘new public health order’ for Africa. Such a change may threaten the global health organizations, industries and institutes who derive payment from ‘saving Africa’ during emergencies. Additionally, through strengthening Africa CDC, other actors such as the World Health Organization may find that they have a diminished strategic role on the continent. While Africa should not dismiss these valuable and long-standing partnerships, it must take the opportunity to advance its interests and to assume leadership in this important area. Full Article
ac Why Africa needs to be in space By www.chathamhouse.org Published On :: Mon, 01 Aug 2022 07:40:43 +0000 Why Africa needs to be in space The World Today mhiggins.drupal 1 August 2022 From agriculture and navigation to banking and tele-education, satellite technology can have a huge impact on rapidly developing societies, says Val Munsami. Africa’s socio-economic and environmental development is widely acknowledged as being crucial to its growth and long-term sustainability – and the prosperity of its more than one billion residents. Increasingly, though, attention is also turning to the contribution that the space industry can make to progress on the continent. Space-based products and services have a critical role to play in meeting national and continental priorities, as underpinned by the UN’s Sustainable Development Goals and the African Union’s Agenda 2063 – the bloc’s strategic framework for development, democracy and peace. With this in the mind of policymakers, the African Union’s space policy and strategy is embedded in Agenda 2063 as one of its 15 key programmes. It guides the sector’s development and the nascent African Space Agency, to become operational later this year from its headquarters in Egypt. The continental agency is expected to leverage the benefits of space science and technology for socio-economic and environmental development. It will lead on bridging the space divide, especially for those countries that do not have a focus on, or activities in, space science and technology – and simultaneously inject some momentum into improving capabilities of existing national space programmes. The African Union’s commitment to space has accelerated the growth of the African space industry. More than 20 national space agencies or space-related institutions have been established on the continent over the past five or so years. Our modern lifestyles are intimately dependent on space products and services. Meteorological and communication satellites are placed in geostationary orbits at an altitude of 36,000km above the equator. At this point above the Earth, they complete one orbit every 24 hours in the direction of the planet’s rotation, appearing, essentially, motionless – and providing a constant gaze on the same geographic location. They provide a wealth of information that fuels the everyday services we take for granted, but that are essential for our everyday lives, from health to education to the economy. From their vantage point, geostationary orbit satellites provide our daily weather reports, monitor climate-related cycles and offer a platform for near-instantaneous communications across the globe to relay multimedia, live sporting events and up-to-the-minute global news. This lightning-fast communication is also indispensable for tele-education and tele-medicine, by which professionals in urban areas can deliver educational content and health services to rural schools and clinics, respectively. Banking transactions also rely on telecommunication satellites to communicate between an automated teller machine and the data servers located at the bank. How satellites can detect disease Other satellites are placed in low Earth orbits. These complete on average one polar orbit around the Earth every 100 minutes. Because the planet rotates across the plane of the orbit, such a satellite eventually covers the whole Earth, which is immensely useful for remote sensing and navigation and positioning applications. Remote sensing applications provide a myriad of products and services, including monitoring the state of our natural resources, observing ship traffic in our coastal economic zones and providing information for precision farming that can help a farmer decide, for example, when to irrigate and how much fertilizer to use. They can also detect changes that might indicate encroaching water-borne diseases, aid peacekeeping missions and help ensure public safety and security. Navigation applications are vital for aviation and marine navigation, whereas positioning applications are important for safety-of-life services. The rich source of information derived from satellites is vital for evidence-based decision and policymaking Another way that positioning applications in developing countries are put to good use is the assignment of geolocation addresses to dwellings in informal settlements where postbox addresses do not exist. This then allows the overlaying of key vector data about populations on to geophysical base maps. This type of data is vital for town planning in terms of how many schools and clinics are needed to serve the population, and the extent of the road, water, sanitation and electrical infrastructure needed. The rich source of information derived from satellites, overlaid with in-situ data, is vital for evidence-based decision and policymaking. Datasets accessed from historical archives can be used to observe the time evolution of environmental and statistical data. When policy decisions are taken, we can utilize the same satellite and in-situ platforms to monitor progress after their implementation. The utility of data to inform decision-making is being enhanced through the adoption of AI and big-data analytics, which is placing key information at our disposal in near real time. It is therefore not surprising to notice the increasing focus on space science and technology activities on the continent. However, to ensure the effective uptake and utilization of space products and services, certain building blocks are needed to establish robust national and regional space ecosystems. Africa’s route into space These ecosystems must include four primary elements to function: the human capital required to establish and operate the space initiatives; a significant industry base to capitalize on the commercial aspects of the space sector; the requisite infrastructure needed to support the space value chain; and international cooperation to ensure knowledge transfer and diffusion – so that we don’t have to reinvent the wheel. To take advantage of the space ecosystem, Africa needs strong governance and institutional architectures The applications and problem-solving innovations provided by space products and services are endless. To take advantage of this, Africa needs strong governance and institutional architectures. The evolution of the space ecosystem on the continent must be premised on key instruments such as a space policy – which areas to focus on and why – and a space strategy that outlines which programmes and performance indicators to pursue. The conceptualization of a space ecosystem is by no means a simple endeavour and there is certainly a dearth of skills and experience on the African continent to establish effective and relevant space ecosystems. There are many institutions leading efforts to build space capacity and skills on the continent, such as the International Space University in France, which offers programmes that provide a holistic overview of the complex global space sector, and the African Space Leadership Institute, which has been recently created to develop capacity in space policy, law and strategy. With the right approach, commitment and investment, Africa can rapidly change the fate of its citizens by effectively using space science and technology to support and drive its developmental agenda. Full Article
ac Towards democracy in Sudan: Reflections on the transitional period By www.chathamhouse.org Published On :: Wed, 31 Aug 2022 09:27:13 +0000 Towards democracy in Sudan: Reflections on the transitional period 20 September 2022 — 2:00PM TO 4:00PM Anonymous (not verified) 31 August 2022 Online In this webinar, panellists discuss the key outcomes of the evaluation workshop and reflect on how the experience of the transition to date should inform the realization of Sudan’s democratic aspirations going forward. The military coup on 25 October 2021 halted Sudan’s transition to democracy and prospects for sustainable peace. Since then, members of the former regime have regained political influence, with many reinstated to senior positions. The coup has provoked a strong reaction from the country’s pro-democracy movement and youth-led resistance committees who have led continuous peaceful protests demanding civilian democratic transition, despite a brutal crackdown by state security forces. Those supportive of the coup have blamed the Forces of Freedom and Change (FFC), a wide coalition of pro-democracy political and civilian groups, for the mistakes of the transitional government. However, the country’s political, security and economic situation has sharply deteriorated since the military’s action, and the progress achieved by the transitional government has been reversed, leading to an accelerating economic crisis, increased food insecurity and political instability. The FFC, which played a key role in appointing the transitional government, has acknowledged its errors. In July 2022, it held a workshop in Khartoum, which was broadcast on social media, to evaluate its performance and identify lessons learned, in discussion with civil society actors and activists. In this webinar, leading pro-democracy movement figures and independent experts discuss the key outcomes of the evaluation workshop and reflect on how the experience of the transition to date should inform the realization of Sudan’s democratic aspirations going forward. This event is part of a Chatham House Africa programme project on supporting Sudan’s civilian-led democratic transition. Full Article
ac Sudan’s gold boom: Connections to conflict and transnational impacts By www.chathamhouse.org Published On :: Thu, 24 Nov 2022 11:27:14 +0000 Sudan’s gold boom: Connections to conflict and transnational impacts 7 December 2022 — 2:00PM TO 3:30PM Anonymous (not verified) 24 November 2022 Online At this event, experts will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts. At this webinar panellists will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts. Sudan is one of the largest gold producers on the continent, with the industry constituting Sudan’s foremost source of hard currency since the secession of South Sudan in 2011 and resulting loss of oilfields. The gold rush that has ensued has had important implications for domestic and transnational conflict dynamics. Military actors and armed groups have sought control of gold-producing areas in the peripheries and to capitalize on the flow of labour migrants, against a wider backdrop of conflict partly stemming from contestation for control between central and local actors. International interests are prominent, including increased Russian involvement in the sector, while gold smuggling has also interlaced with mercenary activity in neighbouring CAR, Chad and Libya. At this event, panellists will discuss Sudan’s gold trade, its connections to conflict, and transnational impacts, including the international politics of Sudan’s gold extraction and role of armed groups. It will also explore the environmental and socio-economic dimensions of gold in Sudan’s border areas. This roundtable is an output of the Cross-Border Conflict: Evidence, Policy and Trends (XCEPT) research programme, funded by UK Aid from the UK government. Full Article
ac Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI By jnm.snmjournals.org Published On :: 2020-05-15T05:25:22-07:00 Full Article
ac Impact of the ISCHEMIA Trial on Stress Nuclear Myocardial Perfusion Imaging By jnm.snmjournals.org Published On :: 2020-06-08T14:17:36-07:00 Full Article
ac The Annual Journal Impact Factor Saga By jnm.snmjournals.org Published On :: 2021-07-08T14:20:31-07:00 Full Article
ac The Translation of Dosimetry into Clinical Practice: What It Takes to Make Dosimetry a Mandatory Part of Clinical Practice By jnm.snmjournals.org Published On :: 2024-09-05T07:37:49-07:00 Full Article
ac Challenges with 177Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice By jnm.snmjournals.org Published On :: 2024-09-19T06:38:07-07:00 Full Article
ac Impact of 18F-FDG PET/MRI on Therapeutic Management of Women with Newly Diagnosed Breast Cancer: Results from a Prospective Double-Center Trial By jnm.snmjournals.org Published On :: 2024-10-10T08:33:38-07:00 Visual Abstract Full Article
ac Diagnostic Radiopharmaceuticals: A Sustainable Path to the Improvement of Patient Care By jnm.snmjournals.org Published On :: 2024-10-10T08:33:38-07:00 Full Article
ac SNMMI Procedure Standard/EANM Practice Guideline for Brain [18F]FDG PET Imaging, Version 2.0 By jnm.snmjournals.org Published On :: 2024-10-17T09:03:09-07:00 PREAMBLEThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective. Full Article
ac MIRD Pamphlet No. 31: MIRDcell V4--Artificial Intelligence Tools to Formulate Optimized Radiopharmaceutical Cocktails for Therapy By jnm.snmjournals.org Published On :: 2024-10-24T11:58:49-07:00 Visual Abstract Full Article
ac Modeling PET Data Acquired During Nonsteady Conditions: What If Brain Conditions Change During the Scan? By jnm.snmjournals.org Published On :: 2024-10-24T11:58:49-07:00 Researchers use dynamic PET imaging with target-selective tracer molecules to probe molecular processes. Kinetic models have been developed to describe these processes. The models are typically fitted to the measured PET data with the assumption that the brain is in a steady-state condition for the duration of the scan. The end results are quantitative parameters that characterize the molecular processes. The most common kinetic modeling endpoints are estimates of volume of distribution or the binding potential of a tracer. If the steady state is violated during the scanning period, the standard kinetic models may not apply. To address this issue, time-variant kinetic models have been developed for the characterization of dynamic PET data acquired while significant changes (e.g., short-lived neurotransmitter changes) are occurring in brain processes. These models are intended to extract a transient signal from data. This work in the PET field dates back at least to the 1990s. As interest has grown in imaging nonsteady events, development and refinement of time-variant models has accelerated. These new models, which we classify as belonging to the first, second, or third generation according to their innovation, have used the latest progress in mathematics, image processing, artificial intelligence, and statistics to improve the sensitivity and performance of the earliest practical time-variant models to detect and describe nonsteady phenomena. This review provides a detailed overview of the history of time-variant models in PET. It puts key advancements in the field into historical and scientific context. The sum total of the methods is an ongoing attempt to better understand the nature and implications of neurotransmitter fluctuations and other brief neurochemical phenomena. Full Article
ac Intraarterial Administration of Peptide Receptor Radionuclide Therapy in Patients with Advanced Meningioma: Initial Safety and Efficacy By jnm.snmjournals.org Published On :: 2024-10-24T11:58:49-07:00 Visual Abstract Full Article
ac Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Visual Abstract Full Article
ac Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with 213Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Visual Abstract Full Article