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{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.




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Five Lessons From the New Arab Uprisings

12 November 2019

Dr Georges Fahmi

Associate Fellow, Middle East and North Africa Programme
Georges Fahmi examines how protesters across the region have adapted their tactics after the experiences of the Arab Spring.

The second wave of Arab uprisings that started in Sudan in December last year and extended to Algeria, Lebanon and Iraq this year have built on past experiences of political transitions during the Arab Spring, both its mistakes and achievements. Protesters from this new wave have already learned five lessons from previous transitions.

The first lesson is that toppling the head of a regime does not mean that the political regime has fallen.  In Tahrir Square on 11 February 2011, Egyptian protesters celebrated the decision of Hosni Mubarak to step down and left the square, thinking his resignation was enough to allow a democratic transition to take place. In contrast, in Sudan and Algeria, protesters continued to demonstrate after the resignation of Abdelaziz Bouteflika and the military-led ousting of Omar al-Bashir.

Protesters understood the lesson that the regime is found not only in the head of the state, but rather in the rules that govern the political sphere. By extension, political change requires changing the rules, not just the names of those in charge of implementing them.

The second lesson is that resorting to violence is the fastest way to end any hope for democratic change. Protesters who decided to take up arms offered their regimes the chance to reframe the political uprisings as civil war, as was the case in Syria. Even when armed groups manage to bring down the regime, their presence endangers the transitional phase afterwards, as is the case in Libya.

Although protesters in Sudan and Iraq have been faced with government violence and repression, they have insisted on their non-violent approach. In Sudan, the protesters responded to the massacre outside of the General Command of the Armed Forces on 3 June by organizing a mass demonstration on 30 June, which put pressure on the military to resume talks with the revolutionary forces.

The third lesson is that once the old regime has fallen, the transition period must be a collective decision-making process in which the opposition has, at least, veto power. The example of Tunisia after 2011 is a case in point. The Higher Authority for Realization of the Goals of the Revolution, Political Reform and Democratic Transition, which formulated the planned course of the transition, included representatives from across the political spectrum and civil society.

Although the military forces in Algeria and Sudan will not cease to play a political role any time soon, this does not have to mean exerting complete control over the transitional period. Sudan could offer a positive example in this regard, if it succeeds in implementing a power-sharing deal according to which a joint civilian-military sovereign council will govern Sudan during the transitional period.

The fourth lesson is that political transitions should achieve agreement on the rules of the game before proceeding to elections. In Egypt after 2011, rushed elections served to divide the political opposition and dramatically increase polarization in society. In this second wave, protesters have perceived elections as a trap which enable old regimes to reproduce themselves with new names.

In both Algeria and Sudan, protesters have resisted attempts by the military to hold elections as soon as possible. In Sudan, the agreement between the revolutionary forces and the military council postponed the elections until after the end of a three-year transitional period of technocratic rule. In Algeria, protesters are taking to the streets every Friday to demonstrate against the authorities’ decision to hold presidential elections in December.

The fifth and final lesson is that the call for change in the region goes beyond electoral democracy and extends to deep socioeconomic reforms. Iraq and Lebanon show this clearly: relatively free and fair elections have already been held but have served only to reinforce corrupt sectarian regimes.

According to the fifth wave of the Arab Barometer, the economic situation and corruption are perceived as the main challenge for Algerians (62.2%), Sudanese (67.8%), Lebanese (57.9%), and Iraqis (50.2%), while democracy is perceived as the main challenge for only 2.3%, 3.9%, 5% and 1.4% respectively.  The experience of the Arab Spring has shown people that democratic measures are only a means to an end.

Unlike in 2011, when the Arab Spring revolts enjoyed broad international support, this second wave is taking place in a hostile environment, with stronger Russian and Iranian presences in the region and an indifferent international climate. But where protesters have the advantage is in experience, and across the region they are clearly adapting their tactics to lessons learned from the early part of the decade.




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Libya Needs an Economic Commission to Exit From Violence

20 November 2019

Tim Eaton

Senior Research Fellow, Middle East and North Africa Programme
A new effort to manage the economy, one that brings together both sides of the war with international partners, is an essential step forward.

2019-11-20-LD.jpg

Angela Merkel greets Fayez al-Serraj, prime minister of the Government of National Accord of Libya, in May. Photo: Getty Images.

There has been a stark contrast between messaging coming from the international community and trends on the ground as Libya’s latest bout of civil war enters its eighth month.

Led by Germany, some states have been trying to build consensus for a ceasefire ahead of a summit that is expected to be held in Berlin in the next few months. Today marks the date of one of the final planning meetings for the summit.

The increasing use of drone technology, airstrikes and further influxes of fighters trend points in the opposite direction. Warring groups in Libya continue to receive support from external states, undermining international efforts to de-escalate the conflict. A UN arms embargo goes largely unenforced. As the Berlin process unfolds, there is little evidence to suggest that these external states will shift their positions.

The launch of Field Marshal Khalifa Haftar’s Libyan Arab Armed Forces (LAAF) offensive on Tripoli in April sunk a UN-planned ‘national conference’, intended to be held less than two weeks later, to negotiate a framework for transition out of Libya’s governance crisis. Yet, Haftar has so far failed in his objective of capturing Tripoli. While his offensive continues, had he the capacity to capture the city, he would have done so already.

This has created a conundrum for peace talks: there appears to be little chance of negotiating a deal with Haftar, while it is also hard to see how a deal could be reached without him.

The field marshal has little interest in accepting a withdrawal, even a partial one, of his forces. His opponents – who have found unity in their shared efforts to defeat Haftar’s forces – will not accept a ceasefire that leaves the LAAF on the hinterlands of the capital. Similarly, a deal apparently agreed in Abu Dhabi between Haftar and Prime Minister Fayez al-Serraj in February is also dead in the water.

Amid this logjam, there has been an increasing interest in the economic content of the Berlin summit. Countries supportive of Haftar argue that his alliance has legitimate concerns over the management of Libya’s economy and, particularly, the dominant role of the Tripoli-based central bank and its governor in supporting armed groups.

For some within these countries, changing the leadership of the central bank and a finding means of limiting the dominance of the UN-backed Government of National Accord (GNA) over the state’s resources – thus reducing flows of funding to armed groups fighting Haftar – could present a point of agreement in Berlin.

But their focus on financial management in Tripoli is not mirrored by interest in holding the rival central bank in the eastern city of Bayda – an institution unrecognized by the international community – to account for its pursuit of its own monetary policy. This is built on approximately $23 billion of unsecured debt from commercial banks and $11 billion of currency supplied by Russia.

Indeed, very few of the conversations surrounding parameters for Berlin contain details of what would be asked of eastern-based actors beyond pursuit of an audit of the Tripoli and Bayda central banks (only the Tripoli bank is recognized by the international community).

Clearly, the GNA and its allies would have no incentive to accept provisions that limit their means to mobilize resources for the war while its opponents do not receive the same scrutiny. 

However, it is possible to capitalize on the broad interest in economic content to reach some points of agreement over the management of the economy and state institutions. Rather than seeking to replace individuals aligned with one faction for those aligned with another, or expecting asymmetrical concessions from the GNA and its allies, this effort must instead focus on structures and processes that exacerbate the conflict and represent major grievances for the warring parties.

Importantly, this would include the establishment of a system of transparency and accountability for the management of Libya’s finances.  The opacity of current processes enables the support of patronage-based networks with no effective oversight.

Linked to this, the development of effective processes for budgeting and allocating funds could help to reduce graft.

And, finally, rationalizing the role of state institutions to agree their roles and responsibilities, creating the room for reforms to Libya’s system of state employment and subsidies through provision of direct payments to Libyan citizens, is essential.  

An economic commission that comprises members from across political and institutional divides – receiving political support from international powers and technical support from international financial institutions – could be an effective approach. Such a commission could match an inclusive, Libyan-led process with international support to progressively harmonize economic and financial policy between rival authorities and develop consensus for a process of institutional reunification in Libya.

This would constitute a major element of an eventual political settlement and reduce the risk of a limited set of actors capturing the system at the expense of the others – an outcome which would likely result in future bouts of violence.

Such a commission would offer a means of addressing a key driver of the conflict by decentralizing aspects of Libya’s governance, moving away from the dominance of Tripoli and the current winner-take-all system. 

These issues cannot be put to one side, to follow progress on the security front. The remarkable resilience that Libya’s economy has shown over the last seven months should not be taken for granted. It has become increasingly difficult for Libya’s institutions to insulate themselves from the conflict as both sides seek to mobilize resources to sustain their war effort.

The LAAF is increasingly looking to sideline civilian authorities in eastern Libya. On the other side, the GNA has found means of routing funds to armed groups fighting Haftar.

In September, a dispute over the supply of jet fuel between the LAAF and the National Oil Corporation resulted in the establishment of a parallel Brega Petroleum Marketing Company, the state-owned company that possesses a monopoly over fuel distribution.

Meanwhile, other major problems lurk under the surface.  The banking sector is in an increasingly perilous state and debts continue to mount all around, with those in the east not accounted for by Tripoli’s official authorities.  

Through the establishment of an economic commission, the Berlin process provides an opportunity and – most importantly – a mechanism to address these problems while also helping to maintain the basic functionality of the state.  Even if a ceasefire deal does not materialize, initiating negotiations about the future shape of the state and its economy would be a significant step forward.




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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system [Molecular Bases of Disease]

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.




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Implementing the NATO Wales Summit: From Strategy to Action

Invitation Only Research Event

26 February 2015 - 1:00pm to 27 February 2015 - 5:00pm

German Institute for International and Security Affairs, Berlin, Germany

Event participants

Xenia Wickett, Project Director, US; Dean, The Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House
Dr Christian Moelling, International Security Division Associate, SWP-Berlin

The NATO Summit, held in September 2014 in Newport, Wales, was a waypoint in the larger strategic vision for NATO over the coming decade. As the alliance continues to confront challenges on its eastern and southern frontiers, it must find ways to adapt its strategy for more effective responses, while also staying ahead of emerging threats and risks. 

The event will bring together senior representatives from a number of the NATO member states, NATO partners and external experts from industry, the media and the think-tank and academic communities, to examine what NATO member states have done thus far to move the deliverables forward, and how to most effectively work together in continuing to do so. 

Attendance at this event is by invitation only.

This is the second of two workshops held in collaboration with SWP-Berlin; the first took place at Chatham House in October 2014.

Event attributes

External event




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How to Fight the Economic Fallout From the Coronavirus

4 March 2020

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
Finance ministries and central banks have a critical role to play to mitigate the threat Covid-19 poses to the global economy.

2020-03-03-TokyoCV.jpg

A pedestrian wearing a face mask walks past stock prices in Tokyo on 25 February. Photo: Getty Images.

Epidemics, of the size of Covid-19, have huge economic impacts – not just from the costs of managing the health of people, but stopping them, and keeping the economy working. The 10% fall in global stock markets since it became clear that Covid-19 would not be limited to China has boldly highlighted this.

Suppressing the epidemic, but allowing the economy to still function, requires key decisions, in which central banks and finance ministries play a part.

The role of fiscal and monetary authorities in managing an epidemic economy

The scope to use monetary policy to manage the economic impact of Covid-19 is limited. The fact that the underlying cause of the shock is an infectious disease outbreak (rather than a banking crisis, as in 2008-09) and nominal interest rates are currently close to zero in most major advanced economies reduces the effectiveness of monetary policy.

Since 2010, reductions in fiscal deficits mean there is more scope for supportive fiscal action. But even here, high public debt levels and the desire not to underwrite ‘zombie’ companies that may have been sustained by a decade of ultra-low interest rates remain constraints. 

However, outside broad based fiscal and monetary policies there are six ways in which finance ministries and central banks will play a critical role in responding to the crisis.

first crucial role for finance ministries and central banks is in helping provide the best possible economic evaluation of strict containment measures (trying to isolate each potential case) versus managing the epidemic (delaying the spread of the virus, protecting the most vulnerable and treating the sick, while enabling the majority of people to get on with daily life). Given the economic consequences, they must play a full part, alongside health experts, in advising political leaders on this key decision.

Second, if large numbers of staff are required to work from home to manage the epidemic, they have the lead role in doing whatever is necessary to ensure that financial markets – and thus the wider economy – will continue to function smoothly.

Third, they need to ensure adequate funding for the public health response. Steps that can make an enormous difference to the success of containment strategies, such as strengthening surveillance, and guaranteeing the availability of testing kits and protective equipment for front line health workers, must not fail because of a lack of funding. 

Fourth, they have a lead role in designing targeted economic interventions for the wider economy. Some of these are needed immediately to re-enforce and incentivize strict containment strategies, such as ensuring that employees without full or adequate sick leave cover have the financial support to enable them to report and self-isolate when they get sick. 

Other interventions may help improve the resilience of the economy in accommodating moderate ‘social distancing’ measures; for example, by providing assistance to small firms to help them gear up for home working.

Yet others are needed, as a contingency, to safeguard the most vulnerable sectors (such as tourism, retail and transport) in circumstances where there is a prolonged downturn. The latter may include schemes to allow deferral of tax payments by SMEs, or steps to encourage loan extensions and other forms of liquidity support from the banking system, or by moves to underwrite continued provision of business insurance.

Fifth, national economic authorities will need to play their part in combatting ‘fake news’ through providing transparent and high-quality analysis. This includes providing forecasts on the likely economic impact of the virus under different scenarios, but also detailed information on the support and contingency measures they are considering, so they can be improved and refined through feedback. 

Sixth, they will need to ensure that there is generous international support for poor countries, by ensuring the available multilateral support facilities from the international financial institutions and multilateral development banks are adequately funded and fit for purpose. The World Bank has already announced an initial $12 billion financing package, but much more is likely to be needed.

They also need to support coordinated bilateral aid where this is more effective, as well as special measures to support particularly vulnerable groups, for example, in refugee camps and prisons. Given the importance of distributing sophisticated medical equipment and expertise quickly, it is also important that every effort is made to avoid delays due to customs and migration checks.

Managing the future

The response to the immediate crisis will rightly take priority now, but economic authorities must also play their part in ensuring the world finally takes decisive steps to prevent a repeat of Covid-19 in future.

The experience with SARS, H1N1 and Ebola shows that, while some progress is made after each outbreak, this is often not sustained. This epidemic shows that managing diseases is absolutely critical to the long-term health of global economy, and doubly so in circumstances where traditional central bank and finance ministry tools for dealing with major global economic shocks are limited.

Finance ministries and central banks therefore need to push hard within government to ensure sustained long-term funding of research on prevention and strengthening of public health systems. They also need to ensure that the right lessons are drawn by the private sector on making international supply chains more robust.

Critical to the overall success of the economic effort will be effective international coordination. The G20 was established as the premier economic forum for international economic cooperation in 2010, and global health issues have been a substantive part of the G20 agenda since the 2017 Hamburg Summit. At the same time, G7 finance ministers and deputies remain one of the most effective bodies for managing economic crises on a day-to-day basis and should continue this within the framework provided by the G20.

However, to be effective, the US, as current president of the G7, will need to put aside its reservations on multilateral economic cooperation and working with China to provide strong leadership.




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Let's Emerge From COVID-19 with Stronger Health Systems

26 March 2020

Robert Yates

Director, Global Health Programme; Executive Director, Centre for Universal Health
Heads of state should grasp the opportunity to become universal health heroes to strengthen global health security

2020-03-26-Health-Protest

A "Big Insurance: Sick of It" rally in New York City. Photo by Mario Tama/Getty Images.

As the COVID-19 pandemic presents the greatest threat to human health in over a century, people turn to their states to resolve the crisis and protect their health, their livelihoods and their future well-being.

How leaders perform and respond to the pandemic is likely to define their premiership - and this therefore presents a tremendous opportunity to write themselves into the history books as a great leader, rescuing their people from a crisis. Just as Winston Churchill did in World War Two.

Following Churchill’s advice to “never let a good crisis go to waste”, if leaders take decisive action now, they may emerge from the COVID-19 crisis as a national hero. What leaders must do quickly is to mitigate the crisis in a way which has a demonstrable impact on people’s lives.

Given the massive shock caused by the pandemic to economies across the world, it is not surprising that heads of state and treasury ministers have implemented enormous economic stimulus packages to protect businesses and jobs – this was to be expected and has been welcome.

National heroes can be made

But, in essence, this remains primarily a health crisis. And one obvious area for leaders to act rapidly is strengthening their nation’s health system to stop the spread of the virus and successfully treat those who have fallen sick. It is perhaps here that leaders have the most to gain - or lose - and where national heroes can be made.

This is particularly the case in countries with weak and inequitable health systems, where the poor and vulnerable often fail to access the services they need. One major practical action that leaders can implement immediately is to launch truly universal, publicly-financed health reforms to cover their entire population – not only for COVID-19 services but for all services.

This would cost around 1-2% GDP in the short-term but is perfectly affordable in the current economic climate, given some of the massive fiscal stimuluses already being planned (for example, the UK is spending 15% GDP to tackle COVID-19).

Within one to two years, this financing would enable governments to implement radical supply side reforms including scaling up health workforces, increasing the supply of essential medicines, diagnostics and vaccines and building new infrastructure. It would also enable them to remove health service user fees which currently exclude hundreds of millions of people worldwide from essential healthcare. Worldwide these policies have proven to be effective, efficient, equitable and extremely popular.

And there is plenty of precedent for such a move. Universal health reform is exactly what political leaders did in the UK, France and Japan as post-conflict states emerging from World War Two. It is also the policy President Kagame launched in the aftermath of the genocide in Rwanda, as did Prime Minister Thaksin in Thailand after the Asian Financial Crisis in 2002, and the Chinese leadership did following the SARS crisis, also in 2003.

In China’s case, reform involved re-socialising the health financing system using around 2% GDP in tax financing to increase health insurance coverage from a low level of one-third right up to 96% of the population.

All these universal health coverage (UHC) reforms delivered massive health and economic benefits to the people - just what is needed now to tackle COVID-19 - and tremendous political benefits to the leaders that implemented them.

When considering the current COVID-19 crisis, this strategy would be particularly relevant for countries underperforming on health coverage and whose health systems are more likely to be overwhelmed if flooded with a surge of patients, such as India, Pakistan, Bangladesh, Myanmar, Indonesia and most of sub-Saharan Africa, where many governments spend less than 1% of their GDP on health and most people have to buy services over the counter.

But also the two OECD countries without a universal health system – the United States and Ireland – are seeing the threat of COVID-19 already fuelling the debate about the need to create national, publicly-financed health system. And the presidents of South Africa, Kenya and Indonesia have already committed their governments to eventually reach full population coverage anyway, and so may use this crisis to accelerate their own universal reforms. 

Although difficult to predict which leaders are likely to grasp the opportunity, if some of these countries now fast-track nationwide UHC, at least something good will be coming from the crisis, something which will benefit their people forever. And ensuring everyone accesses the services they need, including public health and preventive services, also provides the best protection against any future outbreaks becoming epidemics.

Every night large audiences are tuning in to press briefings fronted by their heads of state hungry for the latest update on the crisis and to get reassurance that their government’s strategy will bring the salvation they desperately need. To truly improve health security for people across the world, becoming UHC heroes could be the best strategic decision political leaders ever make.




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Emerging Lessons From COVID-19

2 April 2020

Jim O'Neill

Chair, Chatham House
Exploring what lessons can be learned from the crisis to improve society and the functioning of our economic model going forward.

2020-04-02-COVID-Italy

A man with a protective mask by the Coliseum in Rome during the height of Italy's COVID-19 epidemic. Photo by ALBERTO PIZZOLI/AFP via Getty Images.

As tentative evidence emerges that Italy and Spain may have reached - or are close to - the peak of the curve, this could demonstrate that not only can Asian countries get to grips with COVID-19, but so can western democracies. And, if so, this offers a path for the rest of us.

The last few weeks does demonstrate there is a role for governments to intervene in society, whether it be health, finance or any walk of life, as they have had to implement social distancing. Some have been forced, and the interventions are almost definitely only temporary, but perhaps some others may be less so.

Governments of all kinds now realise there is a connection between our health system quality and our economic capability. On an index of global economic sustainability that I presided over creating when I was at Goldman Sachs, the top ten best performing countries on growth environment scores includes eight of the best performing ten countries - so far- in handling the crisis in terms of deaths relative to their population.

Health system quality

The top three on the index (last calculated in 2014) were Singapore, Hong Kong and South Korea, all of which are exemplary to the rest of us on how to deal with this mess. This suggests that once we are through this crisis, a number of larger populated countries - and their international advisors such as the IMF - might treat the quality of countries' health systems just as importantly as many of the other more standard indicators in assessing ability to deal with shocks.

Policymakers have also been given a rather stark warning about other looming health disasters, especially antimicrobial resistance, of which antibiotic resistance lies at the heart. An independent review I chaired recommended 29 interventions, requiring $42 bn worth of investment, essentially peanuts compared to the costs of no solution, and the current economic collapse from COVID-19. It would seem highly likely to me that policymakers are going to treat this more seriously now.

As a clear consequence of the - hopefully, temporary - global economic collapse, our environment suddenly seems to be cleaner and fresher and, in this regard, we have bought some time in the battle against climate change. Surely governments are going to be able to have a bigger influence on fossil fuel extractors and intense users as we emerge from this crisis?

For any industries requiring government support, the government can make it clear this is dependent on certain criteria. And surely the days of excessive use of share buy backs and extreme maximisation of profit at the expense of other goals, are over?

It seems to me an era of 'optimisation' of a number of business goals is likely to be the mantra, including profits but other things too such as national equality especially as it relates to income. Here in the UK, the government has offered its strongest fiscal support to the lower end of the income earning range group and, in a single swoop, has presided over its most dramatic step towards narrowing income inequality for a long time.

This comes on top of a period of strong initiatives to support higher levels of minimum earnings, meaning we will emerge later in 2020, into 2021, and beyond, with lower levels of income inequality.

The geographic issue of rural versus urban is also key. COVID-19 has spread more easily in more tightly packed cities such as London, New York and many others. More geographically remote places, by definition, are better protected. Perhaps now there will be some more thought given by policymakers to the quality and purpose of life outside our big metropolitan areas.

Lastly, will China emerge from this crisis by offering a mammoth genuine gesture to the rest of the world, and come up, with, unlike, in 2008, a fiscal stimulus to its own consumers, that is geared towards importing a lot of things from the rest of the world? Now that would be good way of bringing the world back together again.

This is a version of an article originally published in The Article




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The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation [DNA and Chromosomes]

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.




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Proteomics of the Chloroplast Envelope Membranes from Arabidopsis thaliana

Myriam Ferro
May 1, 2003; 2:325-345
Research




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Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research




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Analysis of the Subunit Composition of Complex I from Bovine Heart Mitochondria

Joe Carroll
Feb 1, 2003; 2:117-126
Research




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In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy

Ivan Matic
Jan 1, 2008; 7:132-144
Research




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Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




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Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research




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Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research




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Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae

Sean R. Collins
Mar 1, 2007; 6:439-450
Research




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A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology




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Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research




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Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology




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Parts per Million Mass Accuracy on an Orbitrap Mass Spectrometer via Lock Mass Injection into a C-trap

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology




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Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research




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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.




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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.




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What Europe Can Learn From the Law and Justice Party’s Victory in Poland

15 October 2019

Dr Angelos Chryssogelos

Associate Fellow, Europe Programme
The EU must remain vigilant about threats to liberal democracy in Poland, but European leaders must also accept that PiS’s electoral success is reflective of its ability to deliver on things that other political parties in Europe have long neglected.

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The button of a PiS supporter on election day. Photo: Getty Images.

The Polish election on 13 October resulted, as expected, in a victory for of the ruling Law and Justice party (PiS).

But despite again securing a slim majority in parliament, it has not been wholly a triumph for PiS. And though there continue to be concerns about the party’s authoritarian tendencies, the election has illuminated some important nuances to its support and appeal, which hold lessons for politics across Europe.

Even though some opinion polls had suggested PiS were close to winning a supermajority in parliament that would have allowed it to pursue constitutional changes, the party fell short of that target, while it lost its majority in the Senate. Thus, while PiS may well renew its efforts to consolidate its control over the state apparatus and the media or meddle with the justice system, it becomes much more difficult with the opposition controlling the Senate and being able to scrutinize laws or have a say in the appointment of public officials.

Most importantly, the election result has shown that while Polish citizens were willing to reward a party that delivered on promises of economic growth and redistribution, they were not ready to hand a blank cheque for full-blown institutional realignment to PiS. Tellingly, many moderate candidates in PiS lists performed quite well among the party’s voters. 

Even though they rewarded a party that at times employed harsh rhetoric against Brussels, Polish voters have long expressed some of the strongest rates of support for EU membership, according to Eurobarometer surveys. The government has also faced massive protests against its most radical initiatives, such as reform of the judicial system and a law to almost completely ban abortion that was ultimately scrapped. It is therefore more likely that the party’s radicalism kept it from increasing its share, rather than helping it to secure victory.

This is not to say that the threat of illiberalism does not remain alive in Poland. But it shows that the degree of PiS dominance in Poland has never been comparable to that of Fidesz in Hungary, with which it is often compared.

This was reflected in the party’s own rhetoric. In the election campaign the government mostly focused on its economic record, recognizing that much of its support is conditional on conventional measures of political success like voter welfare. PiS may not give up on its ambition to establish a ‘new Polish republic’, but the elections have made it clear that economic stability rather than political radicalism will ensure its longevity in power – with the latter perhaps even being a liability as the party experiences fatigue in office.

Similarly, despite the government’s antagonistic stance towards the EU on various issues, PiS never entertained ideas of withdrawing from the EU, as some of its critics feared earlier in its term. With the Polish economy deeply entwined with the European market and Poland expecting – probably for the last time – to receive substantial subsidies from the next EU budget, EU membership is a necessary precondition for the economic success for which PiS is claiming credit.

With the pro-European left returning to parliament but also an extreme party of the right winning representation, the next government will have a difficult balancing act as it tries to draw on the benefits of EU membership while maintaining its defiant image towards Brussels.

Ultimately, beneath the rhetoric and the posturing, PiS is a party that has shrewdly combined popular policies from the left and right, fulfilling promises of both cultural sovereignty and economic redistribution. Its reelection should not come as a surprise given that it fulfilled its electoral pledges by delivering some of the things that many voters in western Europe also crave but that mainstream parties there have largely failed to provide.




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Virtual Breakfast: Engaging with the EU From the Outside: A Perspective From Norway

Invitation Only Research Event

24 April 2020 - 8:30am to 9:30am

Event participants

Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign Affairs
Chair: Dr Robin Niblett, Director; Chief Executive, Chatham House

Please note this an online-only event.

Norway is one of the few European countries that remains outside of the European Union. After the country’s population rejected the prospect of joining the EU twice, Norway’s relationship with the Union has been based on its membership of the European Economic Area (EEA), alongside Iceland and Liechtenstein.

The ‘Norway Model’ was often mentioned in the run up to the Brexit vote as a possible basis for Britain’s future relationship with the bloc, not least because it offers the least disruption to the current arrangement. Equally, Norway is not subject to the EU fisheries policy - an anticipated major issue in the next phase of Brexit talks. Nor is it part of the EU Customs Union.

Even though Prime Minister Johnson has now ruled out the type of deep economic and regulatory integration with the EU that Norway enjoys through its EEA membership, the country’s experience can still offer valuable lessons for the UK as it prepares to exit the transition period at the end of 2020.

In this session, the speaker will share Norway’s experience as a long-standing EEA member and discuss the challenges of engaging with the EU from the outside. What lessons can Norway offer the UK ahead of the negotiations on the future of UK-EU relations? What are the limits of its current arrangement with the EU? And is there any appetite among the Norwegian population to revisit it?

Alina Lyadova

Europe Programme Coordinator




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An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1 [Enzymology]

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.




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Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology]

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.




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Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability [Enzymology]

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.




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Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin [Computational Biology]

In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency.




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.




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Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics]

Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases.




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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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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




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The Crisis in Syria from the Perspective of Syrian Kurds

Research Event

20 May 2014 - 10:00am to 2:00pm

Chatham House, London

Event participants

Salih Muslim, Chairman, Democratic Union Party (PYD), Syria

This expert-level meeting will bring together policy-makers, analysts and Chatham House experts to discuss the crisis in Syria from the perspective of Syrian Kurds. 

Salih Muslim is a prominent member of the Kurdish opposition in Syria and chairman of the Democratic Union Party (PYD), which controls Rojava, an autonomous administration area in northern Syria. He is also the deputy coordinator of the National Coordination Committee for Democratic Change. At this roundtable he will discuss the movement for a political settlement and prospects for a Kurdish democratic model in Syria.

To enable as open a debate as possible, the question and answer session will be held under the Chatham House Rule.

Event attributes

Chatham House Rule




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Promoting a Culture of Development and Investment: Lessons from the Post-War Era

Research Event

5 December 2014 - 1:00pm to 2:00pm

Chatham House, London

Event participants

Giovanni Farese, Assistant Professor of Economic History, European University of Rome
Chair: Dr Paola Subacchi, Research Director, International Economics, Chatham House

This event will discuss the rise of the culture of world development. It will examine the post-war reconstruction and development projects of the 1940s through to the 1960s, including those devised at Chatham House. The speaker will argue that these projects hold valuable lessons that still apply to the current economic environment. The speaker will also discuss the key role played by Eugene R Black (1898-1992), the third president of the International Bank for Reconstruction and Development (the World Bank), who was one of the main architects of post-war reconstruction and development projects and a promoter of a ‘culture of development’.

Effie Theodoridou

+44 (0)20 7314 2760




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Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




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Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions

M. Burstein
Nov 1, 1970; 11:583-595
Articles




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Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells

JL Dixon
Feb 1, 1993; 34:167-179
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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Reflections from the Munich Security Conference on America’s Role in the World

Invitation Only Research Event

17 February 2020 - 8:00am to 9:15am

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

Event participants

Senator Chris Coons, United States Senator, Delaware
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

In the aftermath of World War II, the United States cemented its role as the leader of a new global order, characterized by the creation of international institutions and treaties like the United Nations and North Atlantic Treaty Organization. More recently, however, the United States has appeared to take an inward turn, a trend which has been mirrored across the globe and has led to the international order being challenged more now than ever before.

As the Trump administration and US members of Congress attempt to address multiple challenges from a rising China and a disruptive Russia to a nuclear North Korea and shifting Middle East, Senator Chris Coons will offer his vision for restoring American leadership on the world stage.What is the role of Congress in setting and shaping US foreign policy?  How will the outcome of the consequential 2020 elections shape the future of America’s global role? Would a change in administration necessarily increase prospects of American reengagement, and if so, across which international spheres?

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




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{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.




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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




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Planning for Africa's Future: Youth Perspectives from Kenya and South Africa




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Reforming the EU: A View From Poland




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Mainstreaming Human Rights: From Humanitarian Response to Funding Reconstruction in Syria




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The Reconstruction of Iraq: Lessons from Mosul




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Undercurrents - Episode 16: Cybercrime in the GCC States, and Fiction from Refugee Camps