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Lysine Acetylation Is a Highly Abundant and Evolutionarily Conserved Modification in Escherichia Coli

Junmei Zhang
Feb 1, 2009; 8:215-225
Research




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Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues

Roland Bruderer
May 1, 2015; 14:1400-1410
Research




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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.




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In Next Round of EU Negotiations, Britain Faces Familiar Pitfalls

31 January 2020

Thomas Raines

Director, Europe Programme

Professor Richard G Whitman

Associate Fellow, Europe Programme
Despite being free of the constraints and the theatre of a hung parliament, there is a risk that over the coming year the British government repeats too many of the mistakes of the withdrawal negotiations.

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The Elizabeth Tower remains under renovation on 31 January 2020. Photo: Getty Images.

Whether feared or longed for, Brexit day has arrived. It is positive for all sides that the process is thus far managed and ordered, with debts paid, rights guaranteed and borders still invisible on the island of Ireland. But in a difficult new phase of negotiations, as the UK and EU try to hammer out the terms of their relationship after 2020, Britain is at risk of repeating many of its mistakes from the withdrawal talks.

First, the government, through the negotiation timeline, has reduced its own room for manoeuvre. The failure of the initial withdrawal agreement and subsequent turbulent politics have reduced a planned 21-month transition to an 11-month one. Even though half the original negotiation time has been lost, 31 December 2020 remains in place and indeed has been written into UK law as the date the transition arrangement ends. Boris Johnson has followed Theresa May in investing symbolism and significance in an arbitrary date.

By promising not to extend negotiations, the UK is boxing itself in, creating domestic political barriers where it may well need flexibility. The familiar face of Michel Barnier, who proved adept in leading the withdrawal negotiations for the EU side, will be back in phase two to tell Britain the clock is ticking. This new timeline is intended to focus minds but more likely it will limit ambitions. 

Second, this government has continued the pattern of its predecessor in making no effort to manage public expectations about the consequences of Brexit. It is naïve to have followed the last years of British politics and expect an outbreak of sobriety and levelheadedness. The entrenched positions of each side have offered little political space or electoral incentive for realism.

During the 2020 transition period, the UK will lose the political rights of EU membership but it will retain the benefits and obligations. Most citizens and business will not be able to tell the difference. But a reckoning is inevitable. There will come a moment when the effects of this slow-motion political revolution – particularly in the hard form envisioned by Boris Johnson – become real, when the trade-offs and compromises, especially for business and the economy, will bite. The public deserve some realism about the price of sovereignty.

Third, there is a risk that government remains underprepared. While its headline goals are clear – at least in terms of what it does not want – the UK government will need thorough, realistic and coherent proposals on what it wants in every area of negotiations, and crucially develop a process by which to make political trade-offs between the demands of different sectors and issues. The government must also then prepare for their implementation in every area. This would be a huge challenge even if the final destination was already known, which it is not. 

Fourth, the continued uncertainty in the process means businesses and civil servants will again be left with little time to adapt to what will face them in January 2021 and must prepare for multiple outcomes.

‘Transition’ has always been a misleading term, since it implies clarity about the destination to which the UK–EU relationship will be transitioning. The government’s red lines for that future relationship provide a sketch: outside of the single market and the jurisdiction of the European Court of Justice, with an independent trade policy and free movement ended.

But businesses and civil servants are not likely to know until very late in the process if the basis for future trade with the EU will be in the form of a free trade agreement, to be negotiated and implemented by the end of the year, or no trade deal at all. This last outcome is a realistic prospect.

Michel Barnier speaks in the European Parliament on 29 January. Photo: Getty Images.

During withdrawal negotiations, the extensions were both unlimited in number and required decisions only at the last moment. In this phase, the talks may only be extended once, and that decision must be taken six months from the final deadline. It is difficult to see circumstances in which Boris Johnson agrees to break a political promise and manifesto pledge when he still has six more months to achieve his desired outcome.

The UK, it is often noted, is already fully compliant with EU law and this shared starting point is often cited as a reason this negotiation will be simple, since the parties begin in alignment. But this novel negotiation will create new trade barriers in goods and services rather than remove them. Trade deals are often politically difficult since they create winners and losers. The Brexit negotiations, in terms of UK–EU trade at least, will generally create only different levels of losers, on both sides of the Channel.

That means difficult politics, challenging negotiations and hard compromises, another reason to expect some ugly politics along the way and accept that failure is a plausible outcome.

We do not yet know how Brexit will change Britain in the long term, whether a settled majority will ever come to view it as political folly or liberation, choice or inevitability. If its politically fragile union can withstand the pressures of the next few years, the UK may yet find a new stable position on the EU’s periphery and, after a period of economic adjustment, begin to address the many pressing domestic challenges which have suffered from neglect amid the all-consuming Brexit saga.

But whatever happens in this next chapter, the EU can no longer be an excuse for national problems. As the UK takes back control it also returns accountability. In the future, there will be no one else to credit or to blame.




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Another CDU Leadership Race Begins in Merkel’s Shadow

28 February 2020

Quentin Peel

Associate Fellow, Europe Programme
The election of a new leader of the chancellor’s party will be another contest over her legacy.

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German Chancellor Angela Merkel is depicted on a float in the Rosenmontag parade in Mainz on 24 February. Photo: Getty Images.

Perhaps it will be second time lucky. At the end of April, Germany’s Christian Democratic Union (CDU) will elect a new party leader to follow in the footsteps of Angela Merkel. An emergency party congress has been summoned to do that after the surprise resignation of Annegret Kramp-Karrenbauer, Merkel’s chosen successor.

The plan is to leave the decision on who will be the CDU candidate for chancellor at the next election until after Germany’s EU presidency concludes in December. So Merkel will keep her job until 2021, and the new leader will have to learn to live with her.

The three leading candidates are Armin Laschet, Friedrich Merz and Norbert Röttgen, all from the state of North Rhine-Westphalia. Two of the three – Merz and Röttgen – were sacked by Merkel from their former jobs. They have not forgotten. Only Armin Laschet, currently CDU leader in North Rhine-Westphalia and state premier, can be described as a Merkel loyalist, true to her centrist mantra.

He is the man to beat, having teamed up with Jens Spahn, the 39-year-old health minister, who is popular with party conservatives. Spahn will run as his deputy, so the team straddles the left-right divide in the party. But the contest still seems set to be a bitter battle between pro- and anti-Merkel factions that could leave the party badly split.

After nearly 15 years as chancellor, and 18 years as CDU leader, Merkel remains the most popular politician in Germany. In spite of criticism that she lacks vision, her caution and predictability appear to be just what most German voters like.

But her term in office has also seen the steady shrinking of the centre ground in German politics, with the rise of the environmentalist Green party and the far-right Alternative for Germany (AfD) at the expense of the centre-right CDU and the centre-left Social Democratic Party (SPD).

The battle for the soul of the CDU is between those who think Merkel has been too left-wing, and want a more conservative leader to win back AfD voters, and those who believe that the CDU must stay in the centre, and prepare for a future coalition with the Greens. Merz is seen as the former, Laschet and Röttgen the latter.

Unless Laschet emerges as the clear winner in April, the leadership contest is likely to leave Germany sorely distracted by domestic politics just as it takes over the EU presidency in the second half of the year. Instead of Merkel having a triumphant international swansong on the EU stage, she could be battling to protect her inheritance at home.

The one area on which all three leadership candidates seem to agree is foreign policy: they all want Germany to take more leadership and responsibility, and for the European Union to play a bigger role in security, defence and international affairs. They are all Atlanticists, but critical of Donald Trump’s ‘America First’ stance. All are on the record criticizing the chancellor – at least tacitly – for not having a more vigorous foreign policy.

There the similarity ends.

On the right, the 64-year-old Merz is both the most conservative and the most popular with the party grassroots. He fell out with the chancellor when she took over his job as CDU leader in parliament in 2002. He quit politics to become a corporate lawyer (and a millionaire), but never lost his political ambition. He is an economic liberal but socially conservative, a strong critic of Merkel’s migration policy and her lack of clear leadership. Critics say he is a man of the past, and not a team player.

On the EU, he believes Germany is ‘leaving too much to the French’. If France and Germany cannot agree on financial matters, he said at the London School of Economics in February, they should instead forge a stronger EU industrial policy focused on creating more ‘European champions’.

Laschet, the Merkel loyalist, is four years younger, and from the left of the party. Like Merz, he is a former member of the European parliament. In 2015, he defended Merkel’s open border policy to accept refugees stranded in the Balkans. On Russia, however, he is more critical, calling for a new effort to re-engage with Vladimir Putin. Most recently, at the Munich Security Conference, he called for stronger Franco-German relations, and more support for the eurozone reforms proposed by Emmanuel Macron.

As CDU leader in North Rhine-Westphalia, Laschet has the strongest power base. He earned his political spurs there by winning the last state election in 2017, in contrast to Röttgen, who lost to the SPD and Greens five years earlier.

Röttgen, chairman of the Bundestag foreign affairs committee, is the surprise candidate. Once a Merkel favourite, they fell out when she sacked him as environment minister after he lost the North Rhine-Westphalia election. By throwing his hat in the ring, he has forced it to become an open contest. He is independent-minded and outspoken, but not as bitterly hostile to the chancellor as Merz, so he could be a compromise candidate.

Laschet is clearly the man Merkel would find it easiest to live with. The decision will be taken by a party congress, not a grassroots ballot, which gives him a better chance. But Merz is the most eloquent orator and seen as the best campaigner. The challenge for party members is whether they believe it is better to swing right and squeeze the AfD, or stick to the centre to hold onto voters tempted by the Greens, who have replaced the SPD as the second-most popular party in Germany.

The race is wide open. So is the future of the CDU. The only prediction one can make with much certainty is that as long as Merkel remains chancellor, any successor will struggle to get out of her shadow.




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Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices]

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.




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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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Developmental peace in east Asia and its implications for the Indo-Pacific

8 January 2020 , Volume 96, Number 1

Ling Wei

This article adopts a constructive approach to examining the problem of the Indo-Pacific construct. Through reflection on the east Asian experience, it proposes an analytical framework of developmental peace as a constellation of international practices, which means that the more economic development is prioritized by states in regional processes, the more likely it is that a sustainable peace will be achieved. States participating in regional integration comprise a community of practice. On the basis of a shared understanding that development is of overriding importance and underpins security and state legitimacy, the community takes economic development as the anchoring practice; this practice embodies and enacts constitutive rules and fundamental norms for a broader set of practices in regional processes, such as peaceful coexistence and non-interference. The more economic development is prioritized on domestic and regional agendas, the more likely it is that conflicts in the security realm will be relaxed or even resolved to protect security interests. The author draws some useful implications from the developmental peace in east Asia for the Indo-Pacific construct, among which the most important include building shared understandings on the prioritization of economic development, taking advantage of the Regional Comprehensive Economic Partnership (RCEP), Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) and the Asian Infrastructure Investment Bank, and using the code of conduct process as a vehicle and best practice to facilitate rule-making for the maritime order. Finally, the author briefly discusses the contributions of the study and limitations of the model.




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The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace

Invitation Only Research Event

12 May 2020 - 10:00am to 11:30am
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Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria.
 
This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication.
 
Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation.

Nilza Amaral

Project Manager, International Security Programme




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Inclusive Peacebuilding

Members Event

9 March 2020 - 6:00pm to 7:00pm

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

Event participants

Dr Awino Okech, Chair, Centre for Gender Studies, SOAS
Wajd Saleh Barahim, Post-war Recovery Specialist, Peace Track Initiative

Chair: Dr Patricia Lewis, Research Director, Conflict, Science & Transformation; Director, International Security Programme, Chatham House

In October 2000, the United Nations Security Council unanimously adopted Resolution 1325 which recognizes women’s rights in the context of international peace and security.

It stresses the importance of women’s meaningful participation in post-conflict peacebuilding and calls on member states to incorporate a gender perspective in peacekeeping and peacebuilding operations.

The 1325 framework has paved the way for the development of numerous institutions, initiatives and resolutions. Despite these developments – and considering the disproportionate impact of conflict on women – women remain underrepresented in peace processes.

This panel brings together women peacebuilders from around the world to share their experiences of being involved in peace processes and to discuss the critical importance of women’s involvement in achieving lasting stability.

What roles do women currently play in peacebuilding processes and how can we maximize cross-learning from their experiences? Why have multilateral and international commitments failed to normalize women’s participation in peace processes?

And how do we deconstruct narratives that might suggest women’s participation in peace processes is more legitimate if it is institutional?

Members Events Team




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The Security Council's peacekeeping trilemma

4 March 2020 , Volume 96, Number 2

Paul D. Williams

The United Nations (UN) Security Council is stuck in a peacekeeping trilemma. This is a situation where the Council's three strategic goals for peacekeeping operations—implementing broad mandates, minimizing peacekeeper casualties and maximizing cost-effectiveness—cannot be achieved simultaneously. This trilemma stems from longstanding competing pressures on how the Council designs UN peacekeeping operations as well as political divisions between peacekeeping's three key groups of stakeholders: the states that authorize peacekeeping mandates, those that provide most of the personnel and field capabilities, and those that pay the majority of the bill. Fortunately, the most negative consequences of the trilemma can be mitigated and perhaps even transcended altogether. Mitigation would require the Council to champion and implement four main reforms: improving peacekeeper performance, holding peacekeepers accountable for misdeeds, adopting prioritized and sequenced mandates, and strengthening the financial basis for UN peacekeeping. Transcending the trilemma would require a more fundamental reconfiguration of the key stakeholder groups in order to create much greater unity of effort behind a re-envisaged peacekeeping enterprise. This is highly unlikely in the current international political context.




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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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Webinar: Can Responsible Behaviour in Cyberspace Be Achieved?

Members Event Webinar

26 May 2020 - 5:00pm to 6:00pm
Add to Calendar

Online

Carmen Gonsalves, Head, International Cyber Policy, Ministry of Foreign Affairs, Netherlands
Suzanne Spaulding, Senior Adviser for Homeland Security, Center for Strategic and International Studies
Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme and Co-Editor, Journal of Cyber Policy, Chatham House

Over the past couple of decades, cyberspace has evolved to become a truly global digital communication space. Managed by a multitude of state and non-state actors, it has enabled a huge range of positive innovations and developments. However, it has also become an arena of intense international competition and rivalry – a reflection of its increasing economic and political importance and broader geopolitical tensions. Despite a number of efforts and some progress in the United Nations and other forums, there are still disagreements on key issues between major powers on how to achieve responsible behaviour in cyberspace.

In light of this, the panel will explore how state and non-state actors can work together to encourage responsible behaviour in cyberspace. What challenges do various actors face in implementing agreed upon norms and principles? Is the existing global model for reaching an agreement a non-starter? What are the remaining challenges around attribution, accountability and enforcement? And what is the role for civil society, the private sector and NGOs in this debate?

This event is for Chatham House members only. Not a member? Find out more.




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Power and diplomacy in the post-liberal cyberspace

7 May 2020 , Volume 96, Number 3

André Barrinha and Thomas Renard

It is becoming widely accepted that we have transitioned, or are now transitioning, from an international liberal order to a different reality. Whether that reality is different solely in terms of power dynamics, or also in terms of values and institutions, is up for discussion. The growing body of literature on ‘post-liberalism’ is used as an entry-point for this article, which aims to explore how the post-liberal transition applies to cyberspace. We explore how power dynamics are evolving in cyberspace, as well as how established norms, values and institutions are contested. The article then looks at the emergence of cyber diplomacy as a consequence and response to the post-liberal transition. As it will be argued, if cyberspace was a creation of the liberal order, cyber-diplomacy is a post-liberal world practice. What role it plays in shaping a new order or building bridges between different political visions, and what it means for the future of cyberspace, will constitute key points of discussion.




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Webinar: Can Responsible Behaviour in Cyberspace Be Achieved?

Members Event Webinar

26 May 2020 - 5:00pm to 6:00pm
Add to Calendar

Online

Carmen Gonsalves, Head, International Cyber Policy, Ministry of Foreign Affairs, Netherlands
Suzanne Spaulding, Senior Adviser for Homeland Security, Center for Strategic and International Studies
Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme and Co-Editor, Journal of Cyber Policy, Chatham House

Over the past couple of decades, cyberspace has evolved to become a truly global digital communication space. Managed by a multitude of state and non-state actors, it has enabled a huge range of positive innovations and developments. However, it has also become an arena of intense international competition and rivalry – a reflection of its increasing economic and political importance and broader geopolitical tensions. Despite a number of efforts and some progress in the United Nations and other forums, there are still disagreements on key issues between major powers on how to achieve responsible behaviour in cyberspace.

In light of this, the panel will explore how state and non-state actors can work together to encourage responsible behaviour in cyberspace. What challenges do various actors face in implementing agreed upon norms and principles? Is the existing global model for reaching an agreement a non-starter? What are the remaining challenges around attribution, accountability and enforcement? And what is the role for civil society, the private sector and NGOs in this debate?

This event is for Chatham House members only. Not a member? Find out more.




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Scotland's Place in the World

Members Event

2 September 2014 - 6:00pm to 7:00pm

Chatham House, London

Event participants

Rt Hon Danny Alexander MP, Chief Secretary to the Treasury, UK
Chair: Faisal Islam, Political Editor, Sky News 

Ahead of the referendum on Scottish independence, the speaker will set out his vision for Scotland to remain as an integral and full member of the United Kingdom. He will explain that Scotland’s global influence and international reach – in terms of diplomacy, peacekeeping and aid relief – is significantly enhanced by being part of a bigger, stronger and more powerful state such as the UK.

LIVE STREAM: This event will be live streamed. The live stream will be made available here at 18:00 BST on Tuesday 02 September.

ASK A QUESTION: Send questions for the speaker by email to questions@chathamhouse.org or using #askCH on Twitter. A selection will be put to him during the event.

Event attributes

Livestream

Members Events Team




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Labour Cannot Be Complacent About UKIP’s Advance

2 September 2014

Professor Matthew Goodwin

Visiting Senior Fellow, Europe Programme
Support for UKIP is growing among the groups in which Labour is struggling.

20140902Farage.jpg

Nigel Farage speaks to voters in Clacton-on-Sea the day after Douglas Carswell MP announced he is switching allegiance from the Conservative party to UKIP. Photo by Oli Scarff/Getty Images.

The UK Independence Party (UKIP) turns 21 years old this month and has cause to celebrate. The insurgent party won a national election in May and last week enjoyed the most significant coup in its history when Conservative MP Douglas Carswell defected to UKIP and announced a forthcoming by-election. Given that his coastal seat of Clacton is UKIP’s most demographically favourable seat in the country, Carswell has almost certainly handed the party its first elected member of parliament.

The events in Clacton will be seen by many as validating one of the oldest myths about UKIP; that it is nothing more than a second home for disgruntled Conservatives. Carswell’s defection will be especially welcomed on the left, where many argue UKIP is dividing the right and clearing the path for Labour’s return to power in 2015. This is dangerously misguided.

To understand why, we can start with Clacton. The seat has the largest concentration of the 'left behind' demographic; older, white, blue-collar voters who lack qualifications, felt excluded from Britain’s economic transformation long before the crisis, are cut adrift from politics, and are intensely anxious over the cultural as well as economic effects of migration.

But as a Conservative-held seat, Clacton is also an outlier. For our book, Revolt on the Right, Robert Ford and I ranked all seats according to their demographic receptiveness to UKIP. Contrary to the prevailing wisdom, most are in Labour territory where MPs are battling with the same cocktail as Carswell: economic stagnation, unease over migration, an entrenched anti-politics consensus and anxieties over rapid social change. Of the 20 seats most demographically receptive to UKIP, 18 have Labour incumbents. Of the top 50, Labour holds 42. Of course, demography alone is not necessarily destiny. Aside from a receptive local population, UKIP also needs a favourable political context. Unlike Conservative-held seats that are at genuine risk from UKIP, Labour’s heartland seats are currently protected by large majorities.

But a cursory glance at the recent European parliament results reveals the direction of travel. UKIP comfortably won the popular vote in a swath of Labour territory, and talks ambitiously of becoming the main rival to Labour in northern England. It appears to be succeeding. Across 39 local authorities in the northwest, UKIP won more votes than Labour in 13 and finished as its main rival in 23. It is similarly bleak in the northeast; across 12 authorities UKIP won the popular vote in five and finished second to Labour in seven.

Since 2010, UKIP has grown fastest among the groups in which Labour is struggling most: the over-65s, the working-class and those who left education early. UKIP is tearing off this section of the electorate, creating a fundamental divide in British politics between those with the skills, education and resources to adapt, and those who have little and feel intensely angry. This is why some Ukippers talk of a '2020 strategy' and plot further advances under an Ed Miliband-led post-2015 government.

Those who compare the party to earlier attempts to redraw the political map, such as the Social Democratic Party in the 1980s, or populist crusaders like the French Poujadists in the 1950s, miss a crucial point. UKIP is anchored in modern Britain’s most socially distinctive support base; it is the most working-class movement since Michael Foot’s Labour Party. Labelling UKIP as 'populist' implies that it appeals across society. It does not. Its strength is concentrated in the 'left behind', who cluster in specific geographical areas. Crucially, this is essential for success under first-past-the-post.

Labour should be under no illusion. UKIP is attracting the Carswells of this world but it is also emerging as the main opposition in many northern heartlands, where it benefits from the toxicity of the Tories, moribund Labour machines that have not had to compete for decades, and the short-sightedness of some close to Ed Miliband who think only of the impact UKIP might have in 2015, and not beyond. Should UKIP’s insurgency continue, not only will it cause a rupture on the centre right, but also bring back into play Labour constituencies that have not been competitive for generations.

This article was originally published in the Financial Times

To comment on this article, please contact Chatham House Feedback




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Syria: Destruction of Civil Society Means Dictatorship, Extremism and Displacement

7 October 2016

Rana Marcel Khalaf

Former Academy Associate
The void in governance in Syria caused by the conflict has enabled a previously oppressed civil society to rise. Now this new society is under threat. Sustained commitment from the international community is required.

2016-10-07-white-helmets-syria2.jpg

Syrian civil defence volunteers, known as the White Helmets, search amid the rubble of destroyed buildings following an air strike on the rebel-held neighbourhood of Aleppo, on October 4, 2016. Photo: Getty Images.

The void in governance created by the ongoing Syrian conflict has been capitalized upon by warlords, militias and extremist groups to expand and consolidate their power – but has also helped to generate activism, with new leaders born as a reaction to authoritarian governance and conflict limitations.

As public social services have been taken over as war tools, local coordination committees, local councils, humanitarian support groups, citizen journalist networks, women’s groups, and more, have mushroomed across all of Syria. But this new civil society continues to be threatened by many challenges.

It remains hindered by structural weakness and limited capacity - largely as a result of the legacy of Ba’athist policies, which did not allow civil society to exist in the so-called Damascus Spring, but only under the umbrella of the Government, First Lady Asma al-Assad and business NGOs (GoNGOs, FLNGOs and BoNGOs). Beyond this, civil society was limited to purely charitable and religious causes, known as “moujtamaa ahli”.

In addition, Syrian civil society is often a victim of counter-terrorism legislation, with laws and regulations across many countries and institutions prohibiting Syrians from registering an organization and opening bank accounts.  This makes it difficult to secure financial support in an environment where funding has already been dwindling due to a “Syria fatigue” among potential donors, and where any money available is mainly directed at large, often international, NGOs.

Trust, hope and legitimacy

To reach funds, many organizations have to submit to this “NGOization” process. But even this rarely allows for civil society to foster its own interests through core funding. Civil society in Syria is treated more as a “project” with strict indicators, deals and deadlines, when working under conflict necessitates building relationships of trust with a community over time and often has to cover the direct needs on the ground to gain local legitimacy and increase effectiveness. Trust, hope and legitimacy are not aspects you can report against or cover in a sophisticated proposal.

But despite such obstacles, activists and civil society groups continue to volunteer for various causes, ensuring many have not had to seek refuge elsewhere. And their work has included challenging authoritarian and extremist governance.

In Aleppo in 2014, it was civil society with the support of a military faction of Jaish Al Mujahideen that helped expel ISIS. Local councils have since been providing services ranging from humanitarian aid and garbage collection to re-establishing order and resolving local conflicts, thus challenging the legitimacy of jihadist institutions.

NGOs such as the Civil Defense Forces (known as the White Helmets) continually risk their lives to save others by rescuing people from bombed out buildings. On September 19, when a UN sanctioned aid convoy was attacked in Aleppo – reportedly by Russian aircraft – it was the White Helmets that responded, before then coming under attack themselves.

Human rights activists, meanwhile, persist in documenting human rights abuses in the hope that the perpetrators will eventually be held accountable.

However, a Syrian civil society tragedy is unfolding as their work is struggling to survive. To give but one example, Kesh Malek, one of the biggest groups running home-based schooling for children in Aleppo, has already had to close some of its schools.

Lacking international protection, the fate of these children in relation to arms and radicalization is all the more alarming.  Several local councils have also been much weakened, especially vis-à-vis warlords, authoritarian and/or extremists actors.

At its best, the current bombing campaign serves to kill any potential alternatives to an authoritarian regime, and only boosts human suffering, radicalization and displacement.

If this situation is to be reversed, international actors need to ensure security at the local Syrian level, showing that Syrian security is as important as that of Europe.

This means financial security through a deeper and more sustainable capacity building and funding to civil society, and it means protecting civilians and civil society groups though the creation of a safe haven.

To comment on this article, please contact Chatham House Feedback




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Pace Your Prose — Three Thoughts on Timing

Have you ever come across a section of a book where it felt like everything happened at breakneck speed, and you could only just barely read fast enough to keep up? Or have you seen the opposite, where it’s all nice and slow and mellow, and where you’re able to really take your time and enjoy the beauty of the words?

That’s the kind of thing I’ll be musing on today. Prose and pacing. Time and reading.

Do note, this is not about how to pace your story, that’s an entirely different topic.

The Basics

Most writers will at one point or another have heard that a full stop is a signal for the reader to breathe. The shorter the sentences are, the quicker the breathing becomes, like when you’re excited. With longer sentences, the breaths grow longer, and deeper, and you calm down.

And when you write really long sentences and don’t include any commas or other forms of punctuation your reader might just run out of breath and begin to feel a little panicked.

There’s no ideal sentence length to strive for – rather the opposite.

Continue reading Pace Your Prose — Three Thoughts on Timing at Mythic Scribes.



  • Writing Craft & Technique

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Intracellular cholesterol transport

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews




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Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles




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Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews




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Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol

William R. Morrison
Oct 1, 1964; 5:600-608
Articles




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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




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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




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Webinar: Can Responsible Behaviour in Cyberspace Be Achieved?

Members Event Webinar

26 May 2020 - 5:00pm to 6:00pm
Add to Calendar

Online

Carmen Gonsalves, Head, International Cyber Policy, Ministry of Foreign Affairs, Netherlands
Suzanne Spaulding, Senior Adviser for Homeland Security, Center for Strategic and International Studies
Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme and Co-Editor, Journal of Cyber Policy, Chatham House

Over the past couple of decades, cyberspace has evolved to become a truly global digital communication space. Managed by a multitude of state and non-state actors, it has enabled a huge range of positive innovations and developments. However, it has also become an arena of intense international competition and rivalry – a reflection of its increasing economic and political importance and broader geopolitical tensions. Despite a number of efforts and some progress in the United Nations and other forums, there are still disagreements on key issues between major powers on how to achieve responsible behaviour in cyberspace.

In light of this, the panel will explore how state and non-state actors can work together to encourage responsible behaviour in cyberspace. What challenges do various actors face in implementing agreed upon norms and principles? Is the existing global model for reaching an agreement a non-starter? What are the remaining challenges around attribution, accountability and enforcement? And what is the role for civil society, the private sector and NGOs in this debate?

This event is for Chatham House members only. Not a member? Find out more.




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Power and diplomacy in the post-liberal cyberspace

7 May 2020 , Volume 96, Number 3

André Barrinha and Thomas Renard

It is becoming widely accepted that we have transitioned, or are now transitioning, from an international liberal order to a different reality. Whether that reality is different solely in terms of power dynamics, or also in terms of values and institutions, is up for discussion. The growing body of literature on ‘post-liberalism’ is used as an entry-point for this article, which aims to explore how the post-liberal transition applies to cyberspace. We explore how power dynamics are evolving in cyberspace, as well as how established norms, values and institutions are contested. The article then looks at the emergence of cyber diplomacy as a consequence and response to the post-liberal transition. As it will be argued, if cyberspace was a creation of the liberal order, cyber-diplomacy is a post-liberal world practice. What role it plays in shaping a new order or building bridges between different political visions, and what it means for the future of cyberspace, will constitute key points of discussion.




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Keeping the Peace: The New Landscape for European Security and Defence




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Undercurrents: Episode 9 - Digital Subversion in Cyberspace, and Oleg Sentsov's Hunger Strike




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




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Securing Peace in the 21st Century: The Roles of Diplomacy and Statesmanship




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Is Responsible State Behaviour in Cyberspace Achievable?




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Undercurrents: Episode 25 - The End of Liberal Foreign Policy, and the Legacy of the Paris Peace Conference




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China and the Future of the International Order – Peace and Security




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Stacey Abrams: Democracy and the Politics of Identity




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Sustainable Solutions to Challenges Faced by Displaced People and Refugees




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Serbia-Kosovo Dialogue: The Future of Peace and Security in the Western Balkans




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Screening Room: Displaced




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Peacemaking in an Era of Global Extremism




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Rethinking 'The Economic Consequences of the Peace'




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Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics]

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.




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Structural basis of cell-surface signaling by a conserved sigma regulator in Gram-negative bacteria [Molecular Biophysics]

Cell-surface signaling (CSS) in Gram-negative bacteria involves highly conserved regulatory pathways that optimize gene expression by transducing extracellular environmental signals to the cytoplasm via inner-membrane sigma regulators. The molecular details of ferric siderophore-mediated activation of the iron import machinery through a sigma regulator are unclear. Here, we present the 1.56 Å resolution structure of the periplasmic complex of the C-terminal CSS domain (CCSSD) of PupR, the sigma regulator in the Pseudomonas capeferrum pseudobactin BN7/8 transport system, and the N-terminal signaling domain (NTSD) of PupB, an outer-membrane TonB-dependent transducer. The structure revealed that the CCSSD consists of two subdomains: a juxta-membrane subdomain, which has a novel all-β-fold, followed by a secretin/TonB, short N-terminal subdomain at the C terminus of the CCSSD, a previously unobserved topological arrangement of this domain. Using affinity pulldown assays, isothermal titration calorimetry, and thermal denaturation CD spectroscopy, we show that both subdomains are required for binding the NTSD with micromolar affinity and that NTSD binding improves CCSSD stability. Our findings prompt us to present a revised model of CSS wherein the CCSSD:NTSD complex forms prior to ferric-siderophore binding. Upon siderophore binding, conformational changes in the CCSSD enable regulated intramembrane proteolysis of the sigma regulator, ultimately resulting in transcriptional regulation.




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Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology]

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.




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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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Episode 28: The Place Beyond the Pines/From Up On Poppy Hill

  • The Place Beyond the Pines Review
  • From Up On Poppy Hill Review
  • Movie Homework: Beasts of the Southern Wild/Shame
  • What We Watched: Evil Dead, Game of Thrones, The Staircase & A Dangerous Method

Next Episode: Oblivion/Trance 




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Episode 39: American Hustle/The Hobbit 2/Anchorman 2/Out of the Furnace

  • American Hustle
  • The Hobbit: The Desolation of Smaug
  • Anchorman 2: The Legend Continues
  • Out of the Furnace
  • 2014 Bucket List Films
  • What We Watched: Bully, Prisoners, Powwow Highway, Miss Representation, The Spectacular Now, Knuckle, Shut Up And Play The Hits, Mike Birbiglia: My Girlfriend's Boyfriend and The Act of Killing. 


Next Episode: Martin Scorcese's The Wolf of Wall Street and Spike Jonze's Her. 




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SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles]

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.




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The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews]

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.




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Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries]