2

The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology]

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.




2

SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation]

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.




2

12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction]

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.




2

Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology]

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.




2

Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology]

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.




2

Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction]

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.




2

The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining {alpha}-tubulin acetylation [Signal Transduction]

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.




2

Polarization of protease-activated receptor 2 (PAR-2) signaling is altered during airway epithelial remodeling and deciliation [Immunology]

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.




2

Phosphoproteomic characterization of the signaling network resulting from activation of the chemokine receptor CCR2 [Genomics and Proteomics]

Leukocyte recruitment is a universal feature of tissue inflammation and regulated by the interactions of chemokines with their G protein–coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CC chemokine ligand 2 (CCL2), plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to conduct an unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition MS analysis, we quantified both the proteome and phosphoproteome in FlpIn-HEK293T cells stably expressing CCR2 at six time points after activation with CCL2. Differential expression analysis identified 699 significantly regulated phosphorylation sites on 441 proteins. As expected, many of these proteins are known to participate in canonical signal transduction pathways and in the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors and GTPase-activating proteins. Moreover, we identified regulated phosphorylation sites in numerous proteins that function in the nucleus, including several constituents of the nuclear pore complex. The results of this study provide an unprecedented level of detail of CCR2 signaling and identify potential targets for regulation of CCR2 function.




2

Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.




2

Turkey in 2020 and Beyond: What Lies Ahead for Turkish Politics?

Invitation Only Research Event

25 November 2019 - 12:30pm to 1:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Fadi Hakura, Manager, Turkey Project, Europe Programme, Chatham House

Turkey witnessed some major developments over the last year. In August 2018, the dramatic Lira devaluation caused the Turkish economy to go into recession. In the 2019 local elections, which took place during the economic downturn, the Republican Peoples’ Party (CHP) mayoral candidates took control of Ankara and Istanbul after 25 years of dominance by the ruling Justice and Development Party (AKP).

The election results might lead to a rethink of the AKP leadership and consequences on Turkish politics will depend on Erdoğan’s interpretation of this reversal of his political fortune.

Will this affect the long-standing alliance between AKP and MHP that has characterised Turkish foreign policy for the past few years? What impact will this have on both the domestic and international level? Finally, will Turkey’s recent incursion into Syria have lasting effect on the country’s alliances with other powers and its standing?

In this context, the speaker will analyse the significance of these changes and the future trajectory of Turkish politics, economics and foreign policy.

Event attributes

Chatham House Rule

Department/project

Alina Lyadova

Europe Programme Coordinator




2

Why Britain’s 2019 Election Is Its Most Unpredictable in Recent History

7 November 2019

Professor Matthew Goodwin

Visiting Senior Fellow, Europe Programme
Leadership concerns and a collapse of traditional party loyalties make the December vote uncommonly volatile.

On 12 December, Britain will hold the most consequential election in its postwar history. The outcome of the election will influence not only the fate of Brexit but also the likelihood of a second referendum on EU membership, a second independence referendum in Scotland, the most economically radical Labour Party for a generation, Britain’s foreign and security policy and, ultimately, its position in the wider international order.

If you look only at the latest polls, then the outcome looks fairly certain. Ever since a majority of MPs voted to hold the election, the incumbent Conservative Party has averaged 38%, the opposition Labour Party 27%, the Liberal Democrats 16%, Brexit Party 10%, Greens 4% and Scottish National Party 3%. Prime Minister Boris Johnson and his party continue to average an 11-point lead which, if this holds until the election, would likely deliver a comfortable majority.

Johnson can also point to other favourable metrics. When voters are asked who would make the ‘best prime minister’, a clear plurality (43%) say Johnson while only a small minority (20%) choose the Labour Party leader, Jeremy Corbyn. Polls also suggest that, on the whole, Johnson is more trusted by voters than Corbyn to deal with Brexit, the economy and crime, while Jeremy Corbyn only tends to enjoy leads on health. All of this lends credence to the claim that Britain could be set for a Conservative majority and, in turn, the passing of a withdrawal agreement bill in early 2020.

But these polls also hide a lot of other shifts that are taking place and which, combined, make the 2019 general election unpredictable. One concerns leadership. While Boris Johnson enjoys stronger leadership ratings than Jeremy Corbyn, it should be remembered that what unites Britain’s current generation of party leaders is that they are all unpopular. Data compiled by Ipsos-MORI reveals that while Johnson has the lowest ratings of any new prime minister, Labour’s Jeremy Corbyn has the lowest ratings of any opposition leader since records began.

Another deeper shift is fragmentation. One irony of Britain’s Brexit moment is that ever since the country voted to leave the European Union its politics have looked more ‘European’. Over the past year, one of the world’s most stable two-party systems has imploded into a four-party race, with the anti-Brexit Liberal Democrats and Nigel Farage’s strongly Eurosceptic Brexit Party both presenting a serious challenge to the two mainstream parties.

In the latest polls, for example, Labour and the Conservatives are attracting only 61 per cent of the overall vote, well down on the 80 per cent they polled in 2017. Labour is weakened by the fact that it is only currently attracting 53 per cent of people who voted Labour at the last election, in 2017. A large number of these 2017 Labour voters, nearly one in four, have left for the Liberal Democrats, who are promising to revoke Article 50 and ‘cancel Brexit’. This divide in the Remain vote will produce unpredictable outcomes at the constituency level.

At the other end of the spectrum, the Conservatives are grappling with a similar but less severe threat. Nigel Farage and the Brexit Party are attracting around one in ten people who voted Conservative in 2017, which will make Boris Johnson’s task of capturing the crucial ‘Labour Leave’ seats harder. There is clear evidence that Johnson has been curbing Farage’s appeal, but it remains unclear how this rivalry on the right will play out from one seat to the next.

One clue as to what happens next can be found in those leadership ratings. While 80 per cent of Brexit Party voters back Johnson over Corbyn, only 25 per cent of Liberal Democrat voters back Corbyn over Johnson. Johnson may find it easier to consolidate the Leave vote than Corbyn will find the task of consolidating the Remain vote.

All of this reflects another reason why the election is unpredictable: volatility. This election is already Britain’s fifth nationwide election in only four years. After the 2015 general election, 2016 EU referendum, 2017 general election and 2019 European parliament elections, Britain’s political system and electorate have been in a state of almost continual flux. Along the way, a large number of voters have reassessed their loyalties.

As the British Election Study makes clear, the current rate of ‘vote-switching’ in British politics, where people switch their vote from one election to the next, is largely unprecedented in the post-war era. Across the three elections held in 2010, 2015 and 2017, a striking 49 per cent of people switched their vote.

This is not all about Brexit. Attachment to the main parties has been weakening since the 1960s. But Brexit is now accelerating this process as tribal identities as ‘Remainers’ or ‘Leavers’ cut across traditional party loyalties. All this volatility not only gives good reason to expect further shifts in support during the campaign but to also meet any confident predictions about the election result with a healthy dose of scepticism.




2

UK General Election 2019: Britain's New Foreign Policy Divide

9 December 2019

Thomas Raines

Director, Europe Programme
A breakdown of foreign policy consensus means voters have a meaningful choice between two different visions of Britain’s place in the world.

2019-12-09-JohnsonCorbyn.jpg

Boris Johnson and Jeremy Corbyn at the state opening of Parliament in October. Photo: Getty Images.

Genuine ideological differences have returned to British politics. That is as true in foreign policy as in questions of domestic politics. The post-Cold War foreign policy consensus in UK politics around liberal multilateralism is fraying.

This tradition had some key characteristics. It saw Britain as one of the cornerstones of an international order built on a liberal (or neo-liberal if you prefer) approach to economic globalization. EU membership was considered central to Britain’s influence and prosperity (even if further political integration never had deep support). Security policy was grounded in a stable package of NATO membership, close ties to the US, nuclear deterrence and a willingness to conduct military intervention.

Both main parties accepted that foreign policy had a commercial dimension. Both were willing to sell arms abroad to regimes with dubious domestic records.

Despite differences of emphasis, and some moments of genuine disagreement, foreign policy did not undergo big shifts as different parties traded periods in office. That may be set to change. 

Party divides

On the one hand, Labour wants to reset and re-orientate Britain’s international role based on human rights and international law. It promises a new internationalism and to end what it glibly calls the ‘bomb first, talk later’ approach, alongside a human rights-driven trade policy. More concretely, it promises to legislate to ensure Parliament takes decisions on military action, boost resources for the underfunded Foreign Office and suspend arms sales to Saudi Arabia for use in Yemen.  

In Jeremy Corbyn, they have a leader with roots in a distinct left-wing ideological tradition of internationalism that blends a commitment to international solidarity alongside anti-imperial and anti-war sentiment. He has spent his career as a sharp critic of Israeli and US policy, while championing various international political causes, some more radical or fringe than others. His historic positions on issues like NATO and nuclear deterrence, while not represented in the party manifesto, demonstrate a personal radicalism that no recent Labour PM has embodied.

His willingness to challenge the failures of the hitherto centre ground of foreign policy – particularly on military interventions from Iraq to Libya – is an under-appreciated aspect of his appeal among many supporters, even while it is one of the sharpest lines of attack from his critics. Boris Johnson’s chauvinistic rhetoric could not stand in sharper contrast to Labour’s commitment to conduct an audit of the effect of Britain’s colonial legacy on violence and insecurity.  

The Conservative manifesto asserts their pride in Britain’s historical role in the world, followed by a broad set of largely rhetorical commitments to bolster alliances and expand influence. An ambitious free trade agenda points to a more economic and commercially driven foreign policy, the inevitable trade-offs and constraints of which are only beginning to be addressed and debated.

There is an underlying sense that Britain will be liberated from the constraints of EU membership, although beyond trade there is little that would not have been possible, or in most cases easier, from within the EU. As my colleague Richard Whitman has observed, the empty bromide ‘Global Britain’ has been dropped altogether, though beyond the idea of a new UK space command and a stronger sanctions regime, there is little that is new or specific.  

Not all the consensus centre-ground position has been abandoned. Both major parties remain committed to spending 2 per cent of GDP on defence and 0.7 per cent of gross national income on development in their 2019 manifestos.

But beyond their manifesto commitments, prime ministers can exercise extensive powers in foreign affairs through the royal prerogative. Their government can choose to recognize other states, as Labour intends to do with Palestine. They can sign international treaties. And at present, in the absence of the sort of war powers act proposed by Labour, they can conduct military action without recourse to Parliament, which has no legally established role in this area.

Even a weak minority government would have considerable scope to transform the tone of Britain’s diplomacy.

Foreign policy as a partisan political issue

If UK foreign policy becomes more partisan, this will have longer term implications. Voters will theoretically have greater scope to shape and influence foreign policy more directly. Foreign policy may become divisive if it becomes more partisan. It may also become less consistent, which will affect the capacity of the UK to show leadership over the longer term on issues on which there is no domestic consensus. Britain’s allies may need to manage a less reliable partner. The diplomatic and security apparatus of Whitehall will need to be more adaptable.  

British elections generally don’t turn on foreign policy questions; 2019 will not buck that trend. At the same time, this election will be very influential in shaping Britain’s position on the world stage and its approach to international issues. Boris Johnson and Jeremy Corbyn represent very different ideas about Britain’s role: its foreign policy, its alliances, and indeed its idea of itself. The Brexit context makes these political undercurrents on foreign policy matter all the more.

Foreign policy may not matter that much to most voters, but these elections matter for foreign policy. 




2

Germany in 2020: European and Global Priorities

Invitation Only Research Event

28 February 2020 - 8:30am to 11:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

This roundtable brings together German experts to discuss the country’s role in Europe and the world. Over the course of two sessions, Germany’s EU and wider foreign policy will be examined, with speakers sharing their views on where the country finds itself at the beginning of 2020 and what drives its current priorities across a number of areas. Participants will also compare perspectives on what a post-Merkel Germany might look like, now that the future leadership of CDU, Germany’s largest political party, is under question.

The event will comprise two separate sessions. Participants are welcome to attend either one or both.

08.30 – 09.30
Germany in the EU and the Eurozone

Speaker: Mark Schieritz, Economics Correspondent, Die Zeit
Chair: Quentin Peel, Associate Fellow, Europe Programme, Chatham House

Germany’s voice remains possibly the most important in any debate within the EU, including in those around the future of the Eurozone. The country has long been seen as the stalwart of the European economy and its government has always played a key role in driving Eurozone policy. However, most recent EU-wide attempts at reform have fallen short of what many claim needs to be done to complete the monetary union. The recently announced Eurozone budgetary instrument, for instance, remains very small and only focused on investment instead of stabilisation. The German government has been reluctant to go along with French President Emmanuel Macron and his structural reform proposals, though some other member states remain sceptical of his ideas for further integration too.

How can German attitudes towards the future of the Eurozone be explained? Is the government’s resistance to ambitious EU-wide economic reforms shared across the political spectrum in Germany? What stands in the way of further Eurozone reform when it comes to other EU member states? And will Germany’s reluctance to engage with reforms in this area, make it more difficult for the country to build coalitions when it comes to other EU policy areas?

09.45 – 11.00
German Foreign Policy in Perspective

Speakers: Joshua Webb, Programme Manager, Berlin Foreign Policy Forum and the Berlin Pulse, Koerber Stiftung
Dr Nicolai von Ondarza, Deputy Head, EU/Europe Research Division, German Institute for International and Security Affairs (SWP)
Chair: Dr Uta Staiger, Executive Director, UCL European Institute

Historically, Germany has been reluctant to play too active a role on the global stage, relying on its place at the heart of Europe and the transatlantic alliance. However, the current uncertain global context appears to have led to some rethinking on how the country can ensure its voice is being heard internationally, especially where its values are being challenged and its interests are at stake.

What drives German foreign policy in 2020? What are domestic priorities when it comes to trade, security and Germany’s place in the world? What shifts in public opinion may have been engendered by Brexit and Donald Trump’s presidency? What does the rise of China – and China’s growing interest in Europe – mean for Germany’s wider Asia policy?  Finally, what role will Germany play in a post-Brexit Europe? And what are the country’s priorities in its future relationship with the UK?

The speakers will discuss these and other questions, sharing the findings of a recent German public opinion survey and compare these with international expert perspectives. 

Event attributes

Chatham House Rule

Alina Lyadova

Europe Programme Coordinator




2

Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2 [Enzymology]

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.




2

The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding]

Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis.




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Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology]

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.




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The Escherichia coli cellulose synthase subunit G (BcsG) is a Zn2+-dependent phosphoethanolamine transferase [Glycobiology and Extracellular Matrices]

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.




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Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics]

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.




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Ten Conflicts to Watch in 2020

Members Event

12 February 2020 - 1:00pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Robert Malley, President & CEO, International Crisis Group

Chair: Dr Leslie Vinjamuri, Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme

Following a year of protests, extreme politics and the emergence of new and sophisticated security challenges, Robert Malley and Leslie Vinjamuri examine the International Crisis Group’s Ten Conflicts to Watch in 2020.

They identify key challenges for international relations, discuss the potential for national and regional political instability and consider how these issues may impact foreign policy, international security and democratic governance.

Members Events Team




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Building LGBTIQ+ Inclusivity in the Armed Forces, 20 Years After the Ban Was Lifted

16 January 2020

Will Davies

Army Chief of General Staff Research Fellow, International Security Programme
Change was slow to come but progress has since been swift. Not only can a continuing focus on inclusivity benefit service people and the organization, it is also an essential element of a values-based foreign policy.

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Crew members from HMS Westminster march through Admiralty Arch as they exercise their freedom of the city in August 2019 in London. Photo: Getty Images.

The new UK government will conduct a review of foreign, security and defence policy in 2020. If the UK decides to use values as a framework for foreign policy this needs to be reflected in its armed forces. One area where this is essential is continuing to deepen inclusivity for LGBTIQ+ personnel, building on the progress made since the ban on their service was lifted in 2000.

I witnessed the ban first-hand as a young officer in the British Army in 1998. As the duty officer I visited soldiers being held in the regimental detention cells to check all was well. One day a corporal, who I knew, was there awaiting discharge from the army having been convicted of being gay. On the one hand, here was service law in action, which was officially protecting the army’s operational effectiveness and an authority not to be questioned at my level. On the other, here was an excellent soldier in a state of turmoil and public humiliation. How extreme this seems now.

On 12 January 2000 Tony Blair’s Labour government announced an immediate lifting of the ban for lesbian, gay and bisexual personnel (LGB) and introduced a new code of conduct for personal relationships. (LGB is the term used by the armed forces to describe those personnel who had been banned prior to 2000.) This followed a landmark ruling in a case taken to the European Court of Human Rights in 1999 by four LGB ex-service personnel – supported by Stonewall – who had been dismissed from service for their sexuality.

Up to that point the Ministry of Defence's long-held position had been that LGB personnel had a negative impact on the morale and cohesion of a unit and damaged operational effectiveness. Service personnel were automatically dismissed if it was discovered they were LGB, even though homosexuality had been decriminalized in the UK by 1967.

Proof that the armed forces had been lagging behind the rest of society was confirmed by the positive response to the change among service personnel, despite a handful of vocal political and military leaders who foresaw negative impacts. The noteworthy service of LGBTIQ+ people in Iraq and Afghanistan only served to debunk any residual myths.

Twenty years on, considerable progress has been made and my memories from 1998 now seem alien. This is a story to celebrate – however in the quest for greater inclusivity there is always room for improvement.

Defence Minister Johnny Mercer last week apologized following recent calls from campaign group Liberty for a fuller apology. In December 2019, the Ministry of Defence announced it was putting in place a scheme to return medals stripped from veterans upon their discharge.

The armed forces today have a range of inclusivity measures to improve workplace culture including assessments of workplace climate and diversity networks supported by champions drawn from senior leadership.

But assessing the actual lived experience for LGBTIQ+ people is challenging due to its subjectivity. This has not been helped by low participation in the 2015 initiative to encourage people to declare confidentially their sexual orientation, designed to facilitate more focused and relevant policies. As of 1 October 2019, only 20.3 per cent of regular service people had declared a sexual orientation.

A measure of positive progress is the annual Stonewall Workplace Equality Index, the definitive benchmarking tool for employers to measure their progress on LGBTIQ+ inclusion in the workplace; 2015 marked the first year in which all three services were placed in the top 100 employers in the UK and in 2019 the Royal Navy, British Army and Royal Air Force were placed 15th=, 51st= and 68th respectively.

Nevertheless, LGBTIQ+ service people and those in other protected groups still face challenges. The 2019 Ministry of Defence review of inappropriate behaviour in the armed forces, the Wigston Report, concluded there is an unacceptable level of sexual harassment, bullying and discrimination. It found that 26-36% of LGBTIQ+ service people have experienced negative comments or conduct at work because of their sexual orientation.

The Secretary of State for Defence accepted the report’s 36 recommendations on culture, incident reporting, training and a more effective complaints system. Pivotal to successful implementation will be a coherent strategy driven by fully engaged leaders.

Society is also expecting ever higher standards, particularly in public bodies. The armed forces emphasise their values and standards, including ‘respect for others’, as defining organisational characteristics; individuals are expected to live by them. Only in a genuinely inclusive environment can an individual thrive and operate confidently within a team.

The armed forces also recognize as a priority the need to connect to and reflect society more closely in order to attract and retain talent from across all of society. The armed forces’ active participation in UK Pride is helping to break down barriers in this area.

In a post-Brexit world, the UK’s values, support for human rights and reputation for fairness are distinctive strengths that can have an impact on the world stage and offer a framework for future policy. The armed forces must continue to push and promote greater inclusivity in support. When operating overseas with less liberal regimes, this will be sensitive and require careful handling; however it will be an overt manifestation of a broader policy and a way to communicate strong and consistent values over time.

The armed forces were damagingly behind the times 20 years ago. But good progress has been made since. Inclusion initiatives must continue to be pushed to bring benefits to the individual and the organization as well as demonstrate a values-based foreign policy.




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Unpacking the role of religion in political transnationalism: the case of the Shi'a Iraqi diaspora since 2003

4 March 2020 , Volume 96, Number 2

Oula Kadhum

This article explores the role of religion in political transnationalism using the case of the Shi'a Iraqi diaspora since 2003. The article focuses on three areas that capture important trends in Shi'a transnationalism and their implications for transnational Shi'a identity politics. These include Shi'a diasporic politics, transnational Shi'a civic activism, and the cultural production of Iraqi Shi'a identity through pilgrimages, rituals and new practices. It is argued that understanding Shi'a Islam and identity formation requires adopting a transnational lens. The evolution of Shi'a Islam is not only a result of the dictates of the Shi'a clerical centres, and how they influence Shi'a populations abroad, but also the transnational interrelationships and links to holy shrine cities, Shi'i national and international politics, humanitarianism and commemorations and rituals. The article demonstrates that Shi'a political transnationalism is unexceptional in that it echoes much of the literature on diasporic politics and development where diaspora involve themselves from afar in the politics and societies of their countries of origin. At the same time, it shows the exceptionalism of Shi'a diasporic movements, in that their motivations and mobilizations are contributing to the reification of sectarian geographical and social borders, creating a transnationalism that is defined by largely Shi'a networks, spaces, actors and causes. The case of Shi'a political transnationalism towards Iraq shows that this is increasing the distance between Shi'is and Iraq's other communities, simultaneously fragmenting Iraq's national unity while deepening Shi'a identity and politics both nationally and supra-nationally.




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20 Years Promoting Women in Peace and Security

6 March 2020

Gitika Bhardwaj

Editor, Communications & Publishing, Chatham House

Dr Joan Johnson-Freese

Professor and Charles F. Bolden Jr. Chair in Science, Space & Technology, US Naval War College
In a series exploring women in international affairs, Dr Joan Johnson-Freese speaks to Gitika Bhardwaj about the women in peace and security agenda, 20 years since its adoption, and how far women’s inclusion in space security is being considered, 50 years since women helped men take their first steps on the moon.

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The UN's first all-female peacekeeping force of more than 100 Indian women stand in Monrovia, Liberia. Photo: Getty Images.

This year marks the 20th anniversary of the adoption of UN Security Council Resolution 1325 on women, peace and security – the first to recognize the important role of women in peacebuilding. How did the resolution come into being and how significant was its adoption in 2000?  

Well it has quite an amazing history that goes back to other UN resolutions, such as the International Covenant on Civil and Political Rights and the International Covenant on Economic and Social Rights, which were passed in the 1960s and came into force in the 1970s. These were some of the biggest covenants on human and civil rights at the time but it was only later that people realised, that those who passed them, did not assume that they applied to women.

There was an attempt, subsequently, to pass the UN Convention on the Elimination of All Forms of Discrimination Against Women – commonly called the CEDAW Convention – which was widely adopted in 1979, when 187 out of 194 UN members signed, although the United States was not one of them, and in fact, the US has still not ratified the treaty. But the understanding that women’s rights were not necessarily assumed in human and civil rights action was beginning to gain recognition.

Then, in 1995, Hillary Clinton spoke in Beijing and really put it forward that women’s rights were human rights and also civil rights and we all have to address them as such. So, ‘95 really brought together all the different social groups – women’s groups, human’s rights groups, civil rights groups, and more, who pushed for the women, peace and security agenda to be passed in 2000 at the United Nations. 

The resolution on women, peace and security was a significant moment because it recognized gender equality issues were national security issues – not just social justice issues – and was soon followed by a number of other resolutions which make up the women, peace and security agenda today. 

Conflict has a disproportionate effect on women and girls, with global security threats, such as climate change,  reported to impact women more than men. In light of this, growing numbers of women are now serving on the frontlines of conflicts, in comparison to 1957-1989, when  only 20 women served as UN peacekeepers. In your view, what have been the successes of the women, peace and security agenda so far?

I think some of the successes specific to peacekeeping have been, as you mentioned, that women are increasingly part of peacekeeping forces being deployed to conflict and post-conflict situations.

Importantly, the nature of war is changing – we are no longer primarily engaged in interstate work in some places – it’s mostly intrastate work where there are often ethnic or religious overtones.

In this landscape, women are often caught up in the battle lines. They often become the heads of their households when the men are gone or injured or killed. There have also been instances of rape being used as a weapon of war and other forms of sexual violence being committed in conflict and post-conflict situations even by peacekeepers.

So, having more women as peacekeepers is important because, number one, when women see women peacekeepers, they are much less likely to fear them, and therefore, feel less threatened speaking to them. Number two, women are a less threatening presence so civil society begins to build again. Number three, women peacekeepers give women in the local area a role model of strength showing them that they can play an active role in their own security. Finally, I would say that women peacekeepers are all impressively trained to guard those under their protection.

What other successes have there been more broadly outside of peacekeeping? Well, I think one that is often cited is that there’s a 20 per cent increase in the probability of a peace agreement lasting at least two years and a 35 per cent increase in the probability of that peace agreement lasting 15 years if women are at the negotiating table. The reason being that women bring things to the table – for example focussing on the root causes of conflict – that men neglect either because they’re not aware of them or it’s not considered an issue of importance to them. 

We have a pretty abysmal history of peace agreements holding so including more women in peace negotiations, given these increases in the probability of agreements holding, seems to me the only logical thing to do.

You mentioned the inclusion of women in peace processes increases the likelihood of agreements succeeding, however, women continue to be underrepresented, comprising under 10 per cent of peace negotiators and under 4 per cent of signatories to peace agreements. Do you think there are any shortcomings with focusing on increasing the presence of women over the positions they hold and how their positions are used to further gender equality?  

I think there are a couple of aspects to this. Importantly, women have been extremely effective in leadership positions, for example, in Liberia. But it is true having women at the table does not necessarily further gender equality in the long-term and I think this was the case in Northern Ireland where the women who were at the table did not include provisions for women. But, I think, we’ve learned since then.

The most important case to cite right now, in my view, is that of women in Afghanistan. They came out of their homes, they went to school, they identified themselves as proponents of gender equality, yet now, with the US-Taliban deal, there were almost no women at the table and not a single provision in the peace agreement that deals with women. So what’s going to happen to all of these women?

Since 2000, the number of agreements referring to women has grown to 28 per cent – more than double the number between 1990-2000. However, some critics have pointed to the gap between theory and practice since many peace agreements still omit a gender perspective on peacekeeping operations. What, in your opinion, have been the failings of realising the women, peace and security agenda so far?

You know, it’s not just critics who point this out, it’s advocates as well, that there is a big gap between rhetoric and implementation. I think the reason for this, in most cases, is political will. It’s the idea that gender equality is an optional luxury – we’ll get to it when we can – and that we have more important issues to work out. Well the agency of 50 per cent of the population should not be seen as an optional luxury.

In all cases, however, it’s a question of power. There are only so many seats at the table where power is doled out and nobody wants to give up theirs to let somebody else sit down. So, I think, there is active resistance to implementing gender equality in the peace and security arena because it would mean sharing power. 

There are also some other reasons. The first is something we call the ‘blind fish’ – people who are simply unaware of gender equality issues – the second, which is interestingly by adamant supporters of the women in peace and security agenda, and that’s they are not given the budget and the authority to carry out the agenda as it should be.

A female Italian soldier from the United Nations Interim Force in Lebanon (UNIFIL) talks with a Lebanese woman in Tibnine, south Lebanon. Photo: Getty Images.

The concept of a feminist foreign policy, which places gender equality and women’s rights at the centre of its foreign policy goals, has been gaining momentum globally. Sweden became the first country in the world to adopt a feminist foreign policy in 2015, and since then, 82 countries have adopted national action plans to raise the role of women in peace processes. How effective have these measures been to furthering women in peace and security? 

That, I think, is one of the issues that women in peace and security advocates, such as myself, are currently looking at because the word ‘feminist’, for better or for worse, is a trigger in many countries.

In many countries, it’s a negative trigger, which is kind of ironic because, if you ask people, ‘Do you believe in gender equality?’, a lot of people will say, ‘Yes absolutely.’  But if you ask people, ‘Are you a feminist?’, a lot of people will say, ‘No not me.’ 

So, the question is, do we aim for a broad goal like a feminist foreign policy which would look at defining peace as, not just the absence of war, but a lot more then than that, such as creating the conditions needed for gender equality and aiming for peace and stability among other broader goals.

Or do we aim to work on a more incremental basis by trying to get more women into peacekeeping, trying to get more women into leadership positions, trying to move gender equality up the agenda as the more effective path forward?

I think the answer to the question is that it depends. If you’re Sweden, Canada or Mexico, a feminist foreign policy might be acceptable. But, if you’re the United States, it’s nowhere near acceptable. Even getting the US Defence Department to take the incremental steps of the women, peace and security agenda has been challenging.

Why do you think that is the case in the United States?

I think a lot of it has to do with power as I mentioned earlier. It has to do with an assumption that women aren’t assertive and don’t see security under the same lens as men, which is true, but which is why they are needed in this space.

I think it also, again, goes back to the point that some see it as an optional luxury rather than an absolute necessity and everybody is too busy – or simply unwilling – to change the status quo.

You mentioned the cases of Liberia and Northern Ireland, but another example that struck me was Rwanda, where women make up 62 per cent of the national legislature, far more proportionally than any other country, following provisions included in its constitution in the aftermath of the genocide of 1994.

Though equal representation between men and women is still far off for most of the world, what does the case of Rwanda and other post-conflict countries demonstrate about how to go about including more women in peacebuilding?

Well, I think the number one way to get more women into political leadership roles, where the women, peace and security agenda could then be implemented, is quotas. 

Many countries use quotas to increase more women in political participation, which Rwanda certainly does, although there are different types. There are quotas that say each political party must have X number of women as candidates and then there are quotas that say the overall number of women in the parliament must reach a certain level. 

So there are different varieties of quotas but they are all used as, kind of, affirmative action methods to at least temporarily bring the numbers up to where women’s voices are inclusive not token. 

Research has shown that until you have at least 33 per cent of a minority in an overall group – so if it’s all men then 33 per cent of this group as women – then you won’t see any change because having one or two will likely be drowned out. But, at about 33 per cent, they’re able to have political power which then means their views and their agendas are seriously considered. So, in Rwanda, that has certainly been the case and that’s been one of the big lessons learned. 

As I mentioned earlier, in Northern Ireland, the lesson learned was that it’s not enough to just have women in on peace agreements. There need to be implementation assurances written into the peace agreement that says it must be taken forward. So, in this vein, women have been learning over the years how to make a difference in male-dominated spaces. 

50 years ago, humans landed on the moon, becoming one of the most significant moments in human history. The stories of women, from Margaret Hamilton, to Katherine Johnson, to JoAnn Morgan, who all helped men take their first steps on the moon at the height of the space race, have since come into the spotlight. How will the inclusion of women need to be considered more in space security as it becomes increasingly important in international relations?

Right now, space security is at a very critical point. We have moved from a situation where there was both co-operation and competition during the space race to a situation of great power competition in space where the United States, China and Russia are, for the first time, overtly weaponizing space. When I say overtly, much of space technology is dual-use, meaning it could be used as a weapon or it could be used as something for non-military purposes.

In the past, the United States and other countries have been very careful, kind of, not to cross the Rubicon into the overt weaponization of space but that’s now ending which I think puts us in a very precarious situation. 

What seems to be missing from considerations of space security at the moment is the most threatening issue – space debris – which can only be dealt with on a multinational basis meaning it inherently requires co-operation. 

So, what I think more women in space security positions would bring, would be that inclusion and the insistence on inclusion as a pillar of space diplomacy.

If there was just a fraction of the money, and manpower, spent on space diplomacy as there is on planning for space warfare, I think we’d all be a lot better off.

NASA engineer, JoAnn Morgan, watches the blast off of Apollo 11 at the Kennedy Space Center on 16 July 1969. She was at the time NASA's only female engineer. Photo: NASA via Getty Images.

How far do current discussions about women in peace and security factor in space security?

Not at all.

Do you see the role of women in space security progressing in the future in spite of this and also despite what some have described as a broader backlash against women around the world whether in the political or in the security space?

I think there have been events over the past five or so years that have made women around the world, if anything, more acutely insistent on their participation than ever before.

We saw the marches in 2017, in the United States and worldwide, in response to what women felt was a rise in authoritarian and misogynistic governments and we have seen the rollbacks in gender equality rights in areas like reproduction too but I don’t think they’re going to take it lying down. The backlash, if anything, is going to spur women to be more, not less, active in all spaces. 

Some have argued for the need of a men, peace and security agenda, to compliment the work on women, with proponents arguing that men are needed to realise gender equality worldwide. How far are men needed as allies to realise the women, peace and security agenda? 

Well, I think, though the women, peace and security agenda has women in the title, it argues for gendered perspectives, that policies affect men and women differently. So, I think it is very important that it not be seen as dealing only with women’s issues – it deals with gendered perspectives. 

In that regard, it is very much needed to have a broadening of all of those involved. I mentioned earlier it was all women’s groups that got the women, peace and security agenda passed and now we need to include men. In fact, I would point out, NATO is a great example of an organization that has recognized the importance of looking at how policies affect men and women, girls and boys. 

So bringing more men in to support gendered perspectives is absolutely essential and looking at gendered perspectives in things like leadership roles is critical as well as gendered perspectives in everything from space policy to nuclear policy to human security issues too.

In your view, what are the greatest challenges to the uptake of gendered perspectives across the board and what, if anything, needs to change in order to realise the goals set out by the UNSC 20 years ago?

On a macro level, we need accountability. We have lots of policies, laws, national action plans and strategies of all kinds but we need accountability.

In the United States, in particular, I very much hope that accountability comes from Congress. In 2017, Congress passed the Women, Peace and Security Act on a bipartisan basis but I think it’s now up to Congress to hold organizations responsible for its implementation. 

On an organizational level, we need to get, as you said, more men involved. But, interestingly, not all women agree, so we need to have more talks among women too, be they liberal, conservative, working, non-working, mothers, not mothers etc. We may have different views but where we’re trying to go is the same and we need to work together better. 

I think among the advocates of women, peace and security, there are still issues that are up for debate like do we go for big feminist foreign policies or do we go for incremental change? In addition, are there lynchpin issues such as reproductive rights, women’s healthcare, gender equality or budget? 

You know, in the United States, I wrote in an article that although the US Defence Department gave $4 million for women, peace and security in 2018, which they were patting themselves on the back for, the Military Times pointed out that they are spending $84 million a year on Viagra.

But this is not just in the United States. 140 countries stood up at the UN to advocate for women, peace and security in 2000 but only 25 per cent of those have national action plans and any budget connected to those plans. Everyone everywhere needs to put their money where their mouths are if we are to realise the goals set out by the UNSC 20 years ago.




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Perspectives on Nuclear Deterrence in the 21st Century

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

Dr Beyza Unal

Senior Research Fellow, International Security Programme

Yasmin Afina

Research Assistant, International Security Programme

Dr Patricia Lewis

Research Director, Conflict, Science & Transformation; Director, International Security Programme

Dr John Borrie

Associate Fellow, International Security Programme

Dr Jamie Shea

Associate Fellow, International Security Programme

Peter Watkins

Associate Fellow, International Security Programme

Dr Maria Rost Rublee

Associate Professor of International Relations, Monash University

Cristina Varriale

Research Fellow in Proliferation and Nuclear Policy, RUSI

Dr Tanya Ogilvie-White

Adjunct Senior Fellow, Griffith Asia Institute, Griffith University

Dr Andrew Futter

Associate Professor of International Politics, University of Leicester

Christine Parthemore

Chief Executive Officer, Council on Strategic Risks (CSR)

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Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence.

Summary

  • This collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.
  • Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.
  • Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.
  • Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.
  • Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. 
  • While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice.




2

China and Russia in R2P debates at the UN Security Council

7 May 2020 , Volume 96, Number 3

Zheng Chen and Hang Yin

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.




2

Webinar: Director's Briefing – US Elections: The Road to November 2020

Corporate Members Event Webinar Partners and Major Corporates

16 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Edward Luce, US National Editor and Columnist, Financial Times
Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As the coronavirus crisis deepens globally, the effects have reverberated through the American economy, and in only a few short weeks, the US presidential election race has changed beyond recognition. Unemployment claims have hit unprecedented levels and look set to continue to rise with stark warnings that the worst is still to come. Polling, however, has suggested that over half the country approves of the way President Trump is handling the crisis. No issue is likely to be more important to voters come November than the recovery and rebuilding of America once the pandemic subsides.
 
In this discussion, Ed Luce and Dr Lindsay Newman will examine the new uncertain outlook for the November 2020 election and discuss how it might play out in these challenging circumstances. Where are we versus where we thought we would be at this point in the election cycle? What should we be watching for in the coming months as the US looks to hold elections in these uncharted waters? Will the elections effectively become a referendum on Trump’s handling of the coronavirus pandemic? And what will this mean for potential policy priorities of the president?

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to rsvp@chathamhouse.org.




2

COP26 Diplomatic Briefing Series: Money Matters: Climate Finance and the COP

Research Event

20 April 2020 - 9:00am to 10:30am

Event participants

Tenzin Wangmo, Lead Negotiator of the Least Developed Countries (LDC) Group 
Mattias Frumerie, Director at the Swedish Ministry for Foreign Affairs
Rachel Ward, Programme Director and Head of Policy at the Institutional Investors Group on Climate Change
Iseoluwa Akintunde, Mo Ibrahim Academy Fellow at Chatham House
Chair: Kirsty Hamilton, Associate Fellow, Chatham House

Finance plays a key role in enabling climate change mitigation and adaptation. It is also a contested issue in the UN climate negotiations. The fourth event in the Chatham House COP26 Diplomatic Briefing Series will explore the politics of climate finance in the context of the COP, and provide a comprehensive update of the main climate finance-related negotiation items and processes. The topic is particularly timely given that the UK Government has made climate finance one of its top thematic priorities for COP26 and that 2020 constitutes the deadline for developed countries to mobilise USD 100 billion per year to support climate action in developing countries.

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




2

COP26 Diplomatic Briefing Series: Climate Change and National Security

Research Event

25 March 2020 - 9:00am to 10:30am

Event participants

Lieutenant General Richard Nugee, Departmental Lead for Climate Change and Sustainability in the UK Ministry of Defence
Rear Admiral Neil Morisetti, Vice Dean (Public Policy) Engineering Sciences at the University College London and Associate Fellow at Chatham House
Dr. Patricia Lewis, Research Director for Conflict, Science and Technology, and Director of the International Security Programme at Chatham House
Professor Yacob Mulugetta, Professor of Energy and Development Policy at the University College London
Chair: Glada Lahn, Senior Research Fellow, Chatham House
Extreme weather, rising sea levels and a melting Arctic - the effects of climate change are posing an increasingly large threat to national security worldwide. Although the issue has gained traction within the international community in recent years, including within the UN Security Council, it is urgent that governments act more decisively to mitigate and respond to the threat, not least given that climate change is happening faster and in a more powerful way than originally anticipated.
 
The third event in the Chatham House COP26 Diplomatic Briefing Series – 'Climate Change and National Security' - will analyze how climate change acts as a threat multiplier, fuelling instability and endangering economic, social and political systems across the globe. The briefing will also provide recommendations of what governments and other stakeholders should do to develop effective responses.
 

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




2

Victory and Memory: WW2 Narratives in Modern Day Russia and Ukraine

Invitation Only Research Event

11 May 2020 - 4:00pm to 5:30pm
Add to Calendar
Nina Tumarkin, Kathryn Wasserman Davis Professor of Slavic Studies; Professor of History; Director, Russian Area Studies Program, Wellesley College
Georgiy Kasianov, Head, Department of Contemporary History and Politics, Institute of History of Ukraine, National Academy of Sciences of Ukraine
Chair: Robert Brinkley, Chairman, Steering Committee, Ukraine Forum, Chatham House
In 2020 the world commemorates the 75th anniversary of the end of World War II. The Russian government has organized a wide range of activities to mark the USSR’s victory, aiming to raise the already prominent role of the USSR to a new level. Moscow also uses its narrative about the war as a propaganda tool. Ukraine, which suffered disproportionally huge human losses and material destruction during WWII, is departing from its Soviet legacy by focusing commemorative efforts on honouring the victims of WWII rather than on glorifying victory. 
 
This event will analyze the evolution of the WWII narratives in Russia and Ukraine in recent years. The panellists will discuss the role of those narratives in shaping national discourses and their implications for the countries' respective futures.
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274

Department/project




2

Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya

Research Event

12 May 2020 - 1:00pm to 2:00pm
Add to Calendar
Natasha Kimani, Academy Associate, Chatham House; Head of Partnerships and Programmes, Shujaaz Inc.
Chair: Tighisti Amare, Assistant Director, Africa Programme, Chatham House
While gender equality was enshrined in Kenyan law under the 2010 constitution, gender-based marginalization remains a significant issue across all levels of society. The advent of devolution in 2013 raised hopes of enhanced gender awareness in policymaking and budgeting, with the 47 newly instituted county governments expected to tackle the dynamics of inequality close to home, but implementation has so far failed to match this initial promise. As Kenya approaches the tenth anniversary of the constitution, and with the COVID-19 pandemic throwing the challenges of gender inequality into sharper relief, it is critical to ensure that constitutional pathways are followed with the requisite level of urgency, commitment and investment to address entrenched gender issues.
 
This event, which will launch the report, Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya, will assess the current status of efforts to devolve and adopt gender-responsive budgeting and decision-making in Kenya, and the priorities and potential future avenues to tackle the implementation gap.
 
This event will be held on the record.

To express your interest in attending, please follow this link. You will receive a Zoom confirmation email should your registration be successful.

Hanna Desta

Programme Assistant, Africa Programme




2

India in Transition: The 2014 Election in Perspective

Research Event

16 October 2013 - 12:00pm to 1:00pm

Chatham House, London

Event participants

Sumantra Bose, Professor of International and Comparative Politics, LSE; Author, Transforming India: Challenges to the World's Largest Democracy

India's 16th general election in 2014 is shaping up to be a critical juncture in the evolution of the nation's politics. The speaker will discuss its significance, focusing particularly on the decisive emergence of regional leaders and parties as the dominant actors of India's democracy.

Department/project




2

Turkey-Armenia Relations in 2015: Thaw or Freeze?

Invitation Only Research Event

26 June 2014 - 4:00pm to 5:30pm

Chatham House, London

Event participants

Tunç Aybak, Programme Leader, International Politics and Law, Middlesex University
Thomas de Waal, Senior Associate, Russia and Eurasia Program, Carnegie Endowment for International Peace
Hratch Tchilingirian, Associate Faculty Member, Faculty of Oriental Studies, University of Oxford

The mass killings of Armenians in the Ottoman Empire during the First World War continue to be a divisive and highly politicized issue. The mixed reactions to Prime Minister Recep Tayyip Erdoğan's message of condolence on 23 April highlighted the obstacles standing in the way of normalization of relations between Turkey and Armenia. This event will explore whether the upcoming centenary of the genocide represents an opportunity for improvement. The speakers will offer initial remarks for approximately 10 minutes each, followed by an hour for questions and discussion.

Attendance at this event is by invitation only.

Lubica Pollakova

+44 (0)20 7314 2775




2

Writing Groups Part 2

In my previous article on writing groups (which you can read here),  I talked about some popular ways writers connect. From online forums like the Mythic Scribes writing forums to community workshops, there’s no shortage of ways writers find each other, and just as many reasons they’re out there searching in the first place. In this follow-up article I’d like to explore some ways to start a writing group, and to keep a good group running by avoiding common pitfalls that lead to trouble.

What’s the Point?

Whether you’ve been searching for an established group and have had zero luck finding the right one, or you’re trying to start a specific group to fill a niche, the first thing to consider when starting a group is the scope—what you’re hoping to get from it. Writing solo can work for years, until one day…it just doesn’t, and it helps to know what you’re looking for in a writers’ group. Motivation, accountability, advice, feedback, critique, support—you name it, there’s a group for it, or at least other folks looking for the same thing.

Are you searching for a relaxed place for people to share their journey as writers?

Continue reading Writing Groups Part 2 at Mythic Scribes.




2

Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles




2

US 2020: America’s National Security Strategy and Middle East Policy

Invitation Only Research Event

10 February 2020 - 10:30am to 11:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Kori Schake, Resident Scholar and Director of Foreign and Defense Policy Studies, American Enterprise Institute 
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

In the run-up to the 2016 US presidential election, then-candidate Donald Trump made a series of campaign promises concerning US foreign policy towards the Middle East. Since assuming office, President Trump has withdrawn the US from the Joint Comprehensive Plan of Action, withdrawn troops from Syria, relocated the US embassy in Israel to Jerusalem and orchestrated the strike against ISIS leader Abu Bakr al-Baghdadi.

Against a backdrop of Trump's inclination towards withdrawing from the region, countries across the Middle East are being rocked by protests, Turkey’s purchase of Russia’s S-400 missile has threatened to undermine cohesion within NATO and the much hoped for ceasefire in Libya between UN-backed government leader, Fayez al-Sarraj, and opposition leader, Khalifa Haftar, failed to materialize.

In light of the upcoming US elections in November 2020, the future of US national security policy promises to be a prominent issue for the next administration. In this vein, the US and Americas Programme at Chatham House plans a yearlong focus on the pivotal US 2020 elections.

At this event, Dr Kori Schake, director of foreign and defense policy studies at the American Enterprise Institute will discuss the future of US foreign policy towards the Middle East. How have domestic and party politics in the US – and the unfolding presidential campaign – shaped recent policy decisions by the Trump administration? Should we expect policy objectives in the Middle East to remain consistent or shift under a second Trump term? And what direction could US foreign policy towards the region take under a Democratic administration?

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




2

US 2020: Super Tuesday and Implications for the General Election

Invitation Only Research Event

5 March 2020 - 12:00pm to 1:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Professor Peter Trubowitz, Professor of International Relations, London School of Economics and Political Science; Associate Fellow, US and the Americas Programme, Chatham House
Amy Pope, Associate Fellow, US and the Americas Programme, Chatham House; Deputy Homeland Security Advisor, US National Security Council, 2015-17
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

The US 2020 election season enters a potentially decisive next phase with the Super Tuesday primaries on 3 March. With these fifteen, simultaneously-held state elections, the Democrats hope to have greater clarity about their party’s likely nominee for the general race against President Donald Trump in November. Concerns around intraparty divisions in the Democratic party between progressives (represented by Senators Elizabeth Warren and Bernie Sanders) and moderates (represented by former Vice President Joe Biden and former mayor Pete Buttigieg) have surrounded the primary races so far, and are unlikely to dissipate even if one candidate emerges from the field on 3 March.

Against this backdrop, Chatham House brings together a panel of experts to discuss the state of the Democratic primary race, implications for the general election, and the Trump campaign’s priorities ahead of its re-election bid. Will the Democratic party resolve its divisions and unite behind a progressive or moderate in light of the Super Tuesday election results? How is Trump positioned to fair against the Democratic candidates left in the race? Did Former Mayor of New York Michael Bloomberg’s primary gamble to focus on Super Tuesday pay off? And what policy priorities are likely to be pursued under either a Trump 2.0 or a Democratic administration?

Event attributes

Chatham House Rule

US and Americas Programme




2

US 2020: State of the Union and State of the Race

Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates

11 March 2020 - 8:00am to 9:15am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Leslie Vinjamuri, Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme, Chatham House

The US is eight months out from consequential presidential and congressional elections. Since his election in 2016, US President Donald Trump has presided over economic expansion and record unemployment rates following a 2017 tax overhaul and deregulation policies. Trump’s approval rating is at the highest level of his presidency, while on the Democratic side, the once-wide field is in a process of narrowing as intra-party ideological differences persist.
 
As we look ahead to the presidential elections in November 2020, Dr Lindsay Newman will reflect on Donald Trump’s presidency, the state of the 2020 election and preview the potential directions of travel ahead under a Trump 2.0 or a Democratic administration. How can we understand the health of Trump’s presidency post-impeachment and post-State of the Union address? What will Trump’s likely foreign policy priorities be ahead of his re-election bid including prospects for a US-UK or a US-Europe trade deal? And, across the aisle, how can we understand the Democratic primary so far and how are the Democrats positioned going into the general election? 
 

This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you would like to register your interest, please RSVP to Linda Bedford. We will contact you to confirm your attendance.

To enable as open a debate as possible, this event will be held under the Chatham House Rule.


COVID-19
This event is proceeding as scheduled, as are other Chatham House events, in accordance with the advice from the UK Government, Foreign and Commonwealth Office and Public Health England. However, we are closely monitoring the spread of COVID-19 and will send updates to attendees as the situation warrants. 
In the meantime, in line with the official advice for returning travellers or visitors to the UK from specified countries and areas (see guidance here), we ask that:

  • If you have travelled from Category 1 countries/areas, you refrain from attending the event even if asymptomatic (i.e. even if you are showing no symptoms);
  • If you have travelled from Category 2 countries/areas, you refrain from attending the event should you develop symptoms.

If you fall under one of these affected categories and have any questions, please call +44 (0)207 314 3638 or email lbedford@chathamhouse.org

 

Event attributes

Chatham House Rule

Members Events Team




2

Virtual Roundtable: Tectonic Plates of 2020 – Developments in the US Presidential Race

Invitation Only Research Event

18 March 2020 - 1:00pm to 1:45pm

Event participants

John Zogby, Founder and Senior Partner, John Zogby Strategies
Chair: Dr Lindsay Newman, Senior Research Fellow, US and Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only. Participants should not come to Chatham House for these events.

US and Americas Programme




2

Webinar: Director's Briefing – US Elections: The Road to November 2020

Corporate Members Event Webinar Partners and Major Corporates

16 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Edward Luce, US National Editor and Columnist, Financial Times
Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As the coronavirus crisis deepens globally, the effects have reverberated through the American economy, and in only a few short weeks, the US presidential election race has changed beyond recognition. Unemployment claims have hit unprecedented levels and look set to continue to rise with stark warnings that the worst is still to come. Polling, however, has suggested that over half the country approves of the way President Trump is handling the crisis. No issue is likely to be more important to voters come November than the recovery and rebuilding of America once the pandemic subsides.
 
In this discussion, Ed Luce and Dr Lindsay Newman will examine the new uncertain outlook for the November 2020 election and discuss how it might play out in these challenging circumstances. Where are we versus where we thought we would be at this point in the election cycle? What should we be watching for in the coming months as the US looks to hold elections in these uncharted waters? Will the elections effectively become a referendum on Trump’s handling of the coronavirus pandemic? And what will this mean for potential policy priorities of the president?

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to rsvp@chathamhouse.org.




2

Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology]

Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals.




2

{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




2

Victory and Memory: WW2 Narratives in Modern Day Russia and Ukraine

Invitation Only Research Event

11 May 2020 - 4:00pm to 5:30pm
Add to Calendar
Nina Tumarkin, Kathryn Wasserman Davis Professor of Slavic Studies; Professor of History; Director, Russian Area Studies Program, Wellesley College
Georgiy Kasianov, Head, Department of Contemporary History and Politics, Institute of History of Ukraine, National Academy of Sciences of Ukraine
Chair: Robert Brinkley, Chairman, Steering Committee, Ukraine Forum, Chatham House
In 2020 the world commemorates the 75th anniversary of the end of World War II. The Russian government has organized a wide range of activities to mark the USSR’s victory, aiming to raise the already prominent role of the USSR to a new level. Moscow also uses its narrative about the war as a propaganda tool. Ukraine, which suffered disproportionally huge human losses and material destruction during WWII, is departing from its Soviet legacy by focusing commemorative efforts on honouring the victims of WWII rather than on glorifying victory. 
 
This event will analyze the evolution of the WWII narratives in Russia and Ukraine in recent years. The panellists will discuss the role of those narratives in shaping national discourses and their implications for the countries' respective futures.
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274

Department/project




2

Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya

Research Event

12 May 2020 - 1:00pm to 2:00pm
Add to Calendar
Natasha Kimani, Academy Associate, Chatham House; Head of Partnerships and Programmes, Shujaaz Inc.
Chair: Tighisti Amare, Assistant Director, Africa Programme, Chatham House
While gender equality was enshrined in Kenyan law under the 2010 constitution, gender-based marginalization remains a significant issue across all levels of society. The advent of devolution in 2013 raised hopes of enhanced gender awareness in policymaking and budgeting, with the 47 newly instituted county governments expected to tackle the dynamics of inequality close to home, but implementation has so far failed to match this initial promise. As Kenya approaches the tenth anniversary of the constitution, and with the COVID-19 pandemic throwing the challenges of gender inequality into sharper relief, it is critical to ensure that constitutional pathways are followed with the requisite level of urgency, commitment and investment to address entrenched gender issues.
 
This event, which will launch the report, Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya, will assess the current status of efforts to devolve and adopt gender-responsive budgeting and decision-making in Kenya, and the priorities and potential future avenues to tackle the implementation gap.
 
This event will be held on the record.

To express your interest in attending, please follow this link. You will receive a Zoom confirmation email should your registration be successful.

Hanna Desta

Programme Assistant, Africa Programme




2

The multilevel identity politics of the 2019 Eurovision Song Contest

7 May 2020 , Volume 96, Number 3

Galia Press-Barnathan and Naama Lutz

This article uses the 2019 Eurovision Song Contest (ESC) that took place in Tel Aviv to explore how cultural mega-events serve both as political arenas and as tools for identity construction, negotiation and contestation. These processes of identity politics are all conducted across national–subnational–international–transnational levels. The hosting of mega-events fleshes out these multiple processes in a very strong manner. We first discuss the politics of hosting mega-events in general. We then examine the identity politics associated more specifically with the Eurovision Song Contest, before examining in depth the complex forms of identity politics emerging around the competition following the 2018 Israeli victory. We suggest that it is important to study together the multiple processes—domestic, international and transnational—of identity politics that take place around the competition, as they interact with each other. Consequently, we follow the various stakeholders involved at these different levels and their interactions. We examine the internal identity negotiation process in Israel surrounding the event, the critical actors debating how to use the stage to challenge the liberal, western, ‘normal’ identity Israel hoped to project in the contest and how other stakeholders (participating states, national broadcasting agencies, participating artists) reacted to them, and finally we examine the behaviour of the institution in charge, the European Broadcasting Union, and national governments. We contribute to the study of mega-events as fields of contestation, to the understanding of the complex, multilevel nature of national identity construction, negotiation and contestation in the current era, and more broadly to the role that popular culture plays in this context.




2

China and Russia in R2P debates at the UN Security Council

7 May 2020 , Volume 96, Number 3

Zheng Chen and Hang Yin

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.




2

Undercurrents: Episode 2 – The Calabrian Mafia and Transatlantic Relations




2

Egypt in 2018: Elections, Divisions and Suppression




2

Equality by 2030: The Press for Progress




2

Argentina: Political Change and the G20 Presidency




2

Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20