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Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the {alpha}/{beta}-fold epoxide hydrolase Alp1U [Enzymology]

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.




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Structure, mechanism, and regulation of mitochondrial DNA transcription initiation [Enzymology]

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.




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The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2 [Computational Biology]

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.




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Business Briefing: Assessing the geopolitical implications of EU AI regulation

Business Briefing: Assessing the geopolitical implications of EU AI regulation 17 September 2024 — 4:00PM TO 5:00PM Anonymous (not verified) Chatham House

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology.

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology

Governments, technology companies and civil society groups across the world are now advocating firmer AI regulation. Machine learning algorithms have changed the way we interact with technology and powered much of our online lives for decades: why has this pendulum swung back so far toward greater control, and why now?

In 2023 the UK government seized the initiative with its Bletchley AI Safety Summit. The event attempted to address the so called ‘frontier risks’ associated with AI development. Global competition on AI is reflected in AI governance efforts in China, US, the Gulf and beyond. But to date, it is the EU that has led the West in passing AI legislation. The EU AI Act, has separated AI systems into graded risk categories carrying different regulatory requirements, and it remains to be seen whether global AI will feel the Brussels effect.

This conversation will cover the following questions:

  • Critics have painted regulation including the AI Act as anti-innovation. Is this a fair assessment?
  • What lessons can we learn from the successes and shortcomings of GDPR?
  • How do we tackle the challenge of low public trust in AI and low public trust in government technology projects, particularly in Western democracies?
  • Does the proliferation of safety institutes, and the AI office, point to the emergence of a new type of technical governance institution? What is its future?




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30 Years of Non-Maghreb: What next for Algeria-Morocco relations?

30 Years of Non-Maghreb: What next for Algeria-Morocco relations? 10 September 2024 — 2:00PM TO 3:15PM Anonymous (not verified) Online

Experts discuss Algeria-Morocco relations and implications for regional actors.

In 1989, the establishment of the Arab Maghreb Union (UMA) brought a promise of economic integration and strengthening of ties between Algeria, Libya, Mauritania, Morocco and Tunisia for the benefit and prosperity of their societies.

Decades on, very little has been accomplished in developing the Maghreb project, and the region remains one of the least integrated in the world, despite significant social and cultural similarities between member countries. The last time the full UMA leadership met was back in 1994, with August 2024 marking 30 years of closed borders between Algeria and Morocco.

Relations between the two largest Maghreb countries have deteriorated further since 2020 due to disagreements over issues of Western Sahara, and, most recently, the Abraham Accords, with Algeria cutting diplomatic ties with Morocco in 2021.

In this webinar, experts will discuss:

  • Which primary obstacles are hindering Maghreb integration and Algeria-Morocco relations?
  • What are the costs and implications for regional countries?
  • What are the positions of Libya, Tunisia, and Mauritania?
  • What is required for a rapprochement and how can external partners support this? 




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In conversation with David Miliband: Finding a new approach to tackle conflict, climate and extreme poverty

In conversation with David Miliband: Finding a new approach to tackle conflict, climate and extreme poverty 11 September 2024 — 5:00PM TO 5:45PM Anonymous (not verified) Chatham House and Online

David Miliband discusses how the climate crisis, extreme poverty and conflict are becoming inextricably linked and how the global community must respond.

Combatting the climate crisis, ending protracted conflicts, and alleviating poverty are three of the greatest priorities for international action. However, these three challenges become increasingly concentrated in a handful of countries. The subsequent feedback loop makes addressing these challenges even more complex.

The International Rescue Committee’s (IRC’s) work in crisis-affected communities highlights this new geography of crisis. Just 16 countries, which are both climate-vulnerable and conflict-affected. This represents 43% of all people living in extreme poverty, 44% of all people affected by natural disasters and 79% of all people in humanitarian need. This trend towards the concentration of crisis is only deepening. In three decades, the number of conflict-affected, climate-vulnerable states has increased from 44% to more than two-thirds.

Affected countries - like Sudan, Myanmar, and Syria - are also among the least supported financially. Debt burdens are siphoning away critical resources needed for adaptation and resilience. Humanitarian aid budgets are being slashed by donor governments. The private sector refuses to invest in these communities they view as too risky. And the international financial institutions meant to alleviate poverty and spur climate action are not well-designed to work with crisis-affected states or local communities. With the upcoming COP29 Summit in Azerbaijan focused on the New Collective Quantified Goal for climate finance, vulnerable communities will be watching closely whether they will get support in their fight against the worst impacts of the climate crisis.

Conflict, the climate crisis, and extreme poverty are taking their toll. But how can the world best respond?

Key questions to be discussed during the session include:

  • At a time of political disruption, how does the West engage with vulnerable countries? What actions should be prioritised in providing support to such countries?
  • Can global institutions evolve to better protect vulnerable and displaced people from conflict and climate-risk, particularly as geopolitical rivalries reduce space for cooperation?
  • What is the UK’s role in supporting climate action in fragile states and how does this align with its agenda on the Sustainable Development Goals and extreme poverty?




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In conversation with HRH Prince Turki AlFaisal

In conversation with HRH Prince Turki AlFaisal 13 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) Chatham House and Online

This event will discuss how the ongoing Gaza war is impacting the region and the role external actors can play to support de-escalation.

The Gaza war, now in its tenth month, continues with ever-worsening consequences for Palestinians and no end in sight. The Israeli-Palestinian conflict has also heightened tensions across the Middle East with fears of a broader regional war that would include Iran and aligned groups from the ‘axis of resistance’.

Against this backdrop, ceasefire negotiations supported by regional and international mediators, have not amounted to an agreement nor have there been any concrete proposals for a way forward out of the crisis by key actors such as the United States, Gulf countries or other key stakeholders.

In this event, His Royal Highness Prince Turki AlFaisal will discuss how the Gaza war and related developments are impacting the Middle East, and will share his views on the role of regional and external actors in supporting de-escalation efforts.

The addresses:

  • How are Middle Eastern countries managing regional security and heightened tensions with Iran and aligned groups in Iraq, Lebanon and Yemen?
  • What role are Gulf countries playing in efforts to de-escalate tensions?
  • How can they support short- and long-term planning for a way forward in the Israeli-Palestinian conflict?
  • How are relationships between Middle East countries and external powers such as the United States changing as a result of the Gaza war?

In person places for this event are balloted. Confirmations will be sent by email on Monday 9 September at 3pm or a placed on the waiting list. Virtual registrations are confirmed immediately.

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.




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Islamic radicalisation in Central Asia

Islamic radicalisation in Central Asia 18 September 2024 — 10:00AM TO 11:30AM Anonymous (not verified) Chatham House and Online

Experts analyse rising foreign recruitment, current counter-radicalisation efforts and challenge past Chatham House predictions made of the Central Asia region.

In 2014, Chatham House released a report titled The Myth of Post-Soviet Muslim Radicalisation in the Central Asian Republics. At that time, a significant, Western-funded counter-radicalisation industry was addressing what was believed to be a major issue of Islamic violent extremism in the region.

Over the past decade, two key developments have occurred. First, Western interest in the region has declined in favour of traditional geopolitical concerns. Second, while violent extremism incidents within Central Asia remain rare, there has been a notable recruitment of Central Asians by foreign groups, with several attacks carried out by Central Asians overseas.

In this event, the original report’s authors, John Heathershaw and David Montgomery, will discuss whether the report’s arguments are still valid and how we might answer these questions today.

This raises several questions:

  • What did the report accurately predict, and where did it fall short?
  • How can we explain the lack of violent extremist organisations (VEOs) within Central Asia but the presence of Central Asians in VEOs abroad?
  • Could repression by Central Asian states both domestically and transnationally have contributed to this issue?
  • What, if anything, can the counter-radicalisation industry do today to address this problem more effectively?

Please note that in-person places are limited. Please wait for confirmation before participating. 




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A world in transition and the future of the global workforce

A world in transition and the future of the global workforce 15 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) Chatham House and Online

How are migration and global megatrends shaping international labour?

As the fallout of 2024’s ‘Election Super-Year’ becomes clearer, international policymakers and business leaders must now equip themselves to face the challenges and opportunities of the three key transitions that will dominate the next few decades: the journey toward a greener and healthier world; the transition to a more technologically adept society; and the development of a secure and productive economy for all.

The adaption and evolution of the global workforce is an essential component of all three of these transitions and therefore a prescient analysis of how migration, workforce policies and modern technology trends will impact this ecosystem is essential.

Upskilling the workforce will no doubt remain a key focus for stakeholders. But the question remains, how do these plans move beyond the ‘ideas-phase’ and become policies that will keep pace in the fast-paced, modern and digital workplace?

It may prove harder than ever for these ideas to come to fruition, with the rise of populist and nationalist political thinking fragmenting the balance between local and international labour. Indeed, this often leads to reduced attractiveness of skilled foreign labour in domestic markets.

This puts global business in a very powerful position though, as companies can play an important role in readdressing these narratives, shaping the future of workforce policies and using examples of best practice to improve access, mobility and ultimately economic productivity, for the benefit of all.

Through this event, in partnership with EY, the panel analyses how migration, skills development agendas and global megatrends, such as technology, sustainability and the global economy, will shape developments in the years to come.

A networking breakfast precedes this event, served between 0800 and 0900 BST.

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.




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How can young people in MENA thrive despite economic and political insecurity?

How can young people in MENA thrive despite economic and political insecurity? 24 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) Online

Experts share insights on how young people navigate challenges and find opportunities in a changing domestic and regional landscape.

Across the Middle East and North Africa young people between the ages of 15 and 29 comprise around 24 per cent of the population in the region. As the complex regional geopolitical developments unfold, the majority of these young people are living in a time of economic and political insecurity, with many, such as Iraqis and Libyans, also growing up during conflict and uncertainty.

Enhanced education and employment programs are key opportunities for development and stability in the region. Despite this, limited resources and competing priorities have meant that governments often struggle to deliver competitive educational and employment opportunities and lack the capacity and funding for education reform and active labour market policy development. Key tensions that pit modernity and autonomy against tradition and control continue to frame the education and skills development landscape.

This webinar will address:

  • The challenges young people within the MENA region face in different contexts;
  • The role education and employment play in developing skills for 21st century challenges;
  • Spaces for young people to practice citizenship and participate in political processes;
  • Youth’s economic prospects while navigating the tumultuous backdrop of enduring conflict and authoritarianism. 




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Member’s question time: Is Russia losing the South Caucasus?

Member’s question time: Is Russia losing the South Caucasus? 22 October 2024 — 1:00PM TO 1:30PM Anonymous (not verified) Online

Join us and ask Chatham House Senior Research Fellow, Natalie Sabanadze anything about the situation in the Caucasus. Submit your questions in advance.

Whilst Russia focuses on its illegal invasion of Ukraine, the situation at its southern border is evolving. Relations between the three states in the South Caucasus and Moscow have never been easy as Russia tried to maintain its dominance by leveraging vulnerabilities, playing one side against another to keep conflicts simmering and even engaging in open military aggression.  Although the violence seen in the 1990s and early 2000s has abated, the war in Ukraine has had an indirect impact on the region, bringing a change to the status quo.

Russia abandoned its long-standing support for Armenia, allowing for the collapse of Nagorny-Karabakh and the restoration of the territorial integrity of Azerbaijan with the backing of Turkey. As a result, Azerbaijan has emerged as a dominant regional player with Baku recently declaring its interest to join BRICS.  Turkey’s influence has grown, while Armenia frustrated by Russia’s change of heart has been turning cautiously towards the EU and the US.

In Georgia, meanwhile, the ruling party has been consolidating its grasp on power, rolling back democratic reforms and pivoting away from the West. Georgia’s long-awaited European integration process has been suspended, following the adoption of the Russian-style foreign agents legislation.

Join us as our Senior Research Fellow in the Russia and Eurasia Programme answers your questions in this quick-fire session assessing the extent to which the Russian influence has changed since the start of the invasion of Ukraine and who is there to fill the vacuum; how geopolitical contestation in the region is going to impact aspirations of Armenia, Azerbaijan and Georgia; and much more.

Submit your questions to Natalie Sabanadze in advance of the event. Your questions will drive the conversation.




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Making the circular economy work for global development: how the UN Summit of the Future can deliver

Making the circular economy work for global development: how the UN Summit of the Future can deliver 23 September 2024 — 6:15PM TO 9:00PM Anonymous (not verified) Online

This policy roundtable focusses on how to advance implementation of a global approach and collaboration to an inclusive circular economy for an updated post-2030 SDG framework.

As the world looks beyond the Sustainable Development Goals (SDGs) towards the post-2030 era, integrating the principles of the circular economy into the future global development agenda becomes imperative.  

A new Chatham House research paper about the role of the circular economy for the SDGs and their possible extension into the post-2030 development agenda will be launched in September 2024 during the UN Summit of the Future and the New York Climate Week. The paper outlines the rationale for the integration of circular economy goals into for the next crucial phase of international development and how to meet net-zero 2050 targets. It provides actionable recommendations on international cooperation mechanisms for policymakers and stakeholders at the UN Summit for the Future in 2024 and beyond.

The aim of the roundtable is to bring together stakeholders and leaders from intergovernmental organisations, business, governments and civil society. The focus of the roundtable meeting is: 

  • Reflections on the Summit of the Future and the role of circularity for an updated post-2030 SDG framework.
  • Discussion on key aspects of the institutional arrangements and international coordination that are needed for a globally coordinated approach to achieve an inclusive circular economy that supports SDG implementation. 
  • Development of joint strategies on how to advance implementation of a global approach and collaboration to an inclusive circular economy as a follow-up from the Summit of the Future.

The objective is to emerge from the roundtable with a clearer roadmap for translating the recommendations for international coordination into concrete actions, with a shared commitment to driving meaningful change on the international level.

The event is co-hosted by Chatham House and partners from the Global Circular Economy Roadmap initiative including the African Circular Economy Network, the African Development Bank, Circular Change, Circular Innovation Lab, Circle Economy, EU CE Stakeholder Platform, Hanns Seidel Foundation, Institute of Global Environmental Strategies, Sitra, UNIDO, World Business Council on Sustainable Development, World Economic Forum and the Wyss Academy for Nature.

Further background information is available on the initiative website.

More speakers to be announced.




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Labour Party Conference – International affairs networking brunch

Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) Labour – Grace 1 Suite, Hilton Hotel, Liverpool

Hosted by Sir Simon Fraser, Chairman of Chatham House.

This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool.

You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.

Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.

This event will be taking place outside of the secure zone.




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In conversation with Valerii Zaluzhnyi, Ukrainian Ambassador to the UK

In conversation with Valerii Zaluzhnyi, Ukrainian Ambassador to the UK 17 October 2024 — 10:00AM TO 11:00AM Anonymous (not verified) Chatham House and Online

The former Commander-in-Chief of the Armed Forces of Ukraine offers insight into the evolution of Russia’s war against his country, and what to expect next.

More than two and a half years since Russia launched its full-scale invasion, Ukraine has consistently adapted to Moscow’s advances by implementing new strategies.

Ukraine’s recent incursion into Russia’s Kursk region demonstrated operational tactical ingenuity, surprising both Russia and Ukraine’s Western supporters. Success against the Russian Black Sea Fleet has already showcased how Ukraine can skilfully beat back Russian aggression. And increasing numbers of targeted strikes on Russian supply depots and airfields are disrupting Russian operations behind the front lines.

Critical Western supplies continue to resource Ukraine’s military. But questions linger over the quantity and sustainability of these supplies. Kyiv will be watching the US presidential election in November as its biggest backer goes to the polls with the possibility of an outcome that could seriously affect the war. Meanwhile, Russian forces continue to edge forward in Donbas, despite heavy casualties, and strike at Ukrainian towns and cities from the air, demonstrating that President Putin has no intention of relinquishing the fight.

Amid these complexities, Ambassador Zaluzhnyi will discuss how the war is changing both sides, advances on the battlefield, and what dangers lie ahead for Ukraine in the coming months. Other key questions include:

  • What kind of enemy is Russia today and how to secure its strategic defeat in Ukraine;
  • How have new strategies, such as the recent incursion into the Kursk region, affected the state of play on the battlefield?
  • What technologies and armaments does Ukraine need from its Western allies in both the short and long term?

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.




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In conversation with Martin Griffiths: How can a divided world address conflict?

In conversation with Martin Griffiths: How can a divided world address conflict? 1 October 2024 — 10:00AM TO 11:00AM Anonymous (not verified) Chatham House and Online

The former United Nations Under-Secretary-General describes how a weakening multilateralism system and dysfunctional political diplomacy can be revitalized by a humanitarian approach.

The international community is failing to stop conflict. Despite efforts by international organisations and state actors to resolve or prevent it from breaking out, wars around the world have left millions of people suffering. Unstable governments and global insecurity are contributing to an age of poly-crisis, compounded by growing inequity and impunity.

How can a divided world work better to prevent and resolve conflict and reduce the suffering of the civilians affected?

Martin Griffiths has spent decades working within the United Nations system and other institutions on conflict resolution and humanitarian action, most recently as Under-Secretary General for Humanitarian Affairs and the Emergency Relief Coordinator. He worked on peace deals in Indonesia, Spain, Thailand, Myanmar, Darfur, Syria and Yemen and responded to emergencies in Ethiopia, Haiti, Afghanistan, Syria, Ukraine, Sudan, Turkiye  and Gaza and elsewhere. In this discussion, he casts his expertise over the biggest challenges in the world today and assess the prospects for international cooperation on conflict resolution in the future.

Key questions to be discussed include:

  • How can a lasting peace be secured in the conflict between Israel and Palestine ?
  • Is the world too fragmented to prevent or resolve conflicts around the world?
  • What role can the United Nations play in today’s geopolitical environment?
  • How can the West and Global South better engage to limit conflict ?

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.




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The 2024 US Election: Global Consequences

The 2024 US Election: Global Consequences 26 September 2024 — 5:30PM TO 6:45PM Anonymous (not verified) Online

This webinar explores what is at stake for US policy in key regions around the globe.

In the lead up to the 2024 US presidential election, Chatham House experts discuss:

  • What is at stake for US policy towards China, Europe, and Latin America and what challenges will confront the next US president?

  • Can the US lead when its partners and allies are continually dissatisfied by the new turn in its trade and economic policy?

  • What are the core humanitarian challenges and how can they be addressed?




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US domestic polarization and implications for the presidential election

US domestic polarization and implications for the presidential election 30 September 2024 — 5:00PM TO 6:00PM Anonymous (not verified) Online

This webinar explores the rise of polarization amongst the US public and implications for the upcoming election.

Domestic polarization has been on the rise in the US in recent years, with Democrats and Republicans moving further away from the centre on key policy issues. As polarization increases, so too do concerns about the state of US democracy and prospects of political violence surrounding the upcoming presidential election. 

This expert panel discusses key questions including:

  • What are the driving forces of the growing political divide in the US?
  • How far apart are voters on key election issues, from healthcare to immigration to national security?
  • How is partisan polarisation altering the effectiveness of US foreign policy and influencing America’s role in the world?




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In conversation with Speaker Emerita Nancy Pelosi

In conversation with Speaker Emerita Nancy Pelosi 14 October 2024 — 12:00PM TO 1:00PM Anonymous (not verified) Chatham House and Online

The former Speaker of the House of Representatives discusses challenges to American democracy and the importance of leadership in an election year.

As the US gears up for the 2024 Presidential election, the importance of leadership in politics has come to the fore. As the Harris and Trump campaigns move towards election day, the heightened sense of strong leadership is central to the position of both candidates.

Following her first election to the House in 1987, Speaker Emerita Nancy Pelosi has been central to American political leadership for over two decades. Serving as the 52nd Speaker of the House of Representative, Speaker Pelosi rose to become one of the most powerful and consequential Speakers in American political history.

Following the release of her recent book The Art of Power, Speaker Pelosi will discuss how she became a master legislator, working with numerous presidents, her political legacy in the house and her leadership during a contentious time in US politics.




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Business Briefing: US election geopolitical and economic risk scenarios

Business Briefing: US election geopolitical and economic risk scenarios 10 October 2024 — 11:45AM TO 1:00PM Anonymous (not verified) Chatham House

Please join us for this critical discussion of the US Election related global business risks.

The outcome of the US presidential election will have significant, intersecting implications for global as well as American business. At stake will be the degree of continuity and stability on both the domestic and international fronts, with a Harris presidency pursuing policies building broadly on the Biden Administration and a second Trump Administration departing sharply from them—with both shaped and limited by control of Congress.

An already volatile geopolitical environment and global economy may become even more unpredictable in the face of potential American political instability and uncertain leadership in the international community.

Please join us for this critical session to discuss:

  • How might trade policy differ between a Harris and Trump presidency? Will national security pressures, especially over China, lead to greater policy commonalities than expected?

  • What might differing approaches to decarbonization and the energy transition mean for the future of policy toward EVs, critical mineral supply chains, and ‘green’ industrial subsidy?

  • How might each Administration approach fiscal policy? Will either push for a tightening to the current loose policy—and what may be implications for US debt and the dollar?

  • What economic effects can we expect in the case of a disputed election result or non-peaceful transfer of power—and will Corporate America be compelled to make public statements?




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Looking ahead to the 2024 US Presidential Election

Looking ahead to the 2024 US Presidential Election 2 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) Chatham House and Online

This panel explores the state of the US presidential election following the vice presidential debate.

With only weeks to go, this panel looks at the state of the 2024 US presidential election.

Harris and Trump are campaigning to drive up voter enthusiasm and bring undecided voters to their side.

What are the key issues shaping voter’s preferences and how may this impact voter turnout? What can we expect in the weeks ahead?




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What are MENA countries’ priorities for climate action and COP?

What are MENA countries’ priorities for climate action and COP? 24 October 2024 — 1:00PM TO 2:00PM Anonymous (not verified) Online

Experts discuss the impacts of COP27 and 28 on the region and priorities for COP29.

In November this year, all eyes will be on Azerbaijan as Baku hosts the 29th UN Climate Conference (COP). Hosting COP offers an opportunity to push for climate action that reflects the host country’s unique circumstances, as well as regional interests. COP28 in the United Arab Emirates and COP27 in Egypt highlighted the climate priorities for the Middle East and North Africa (MENA), one of the world’s most vulnerable regions to the impacts of climate change.

From rising temperatures and deadly heatwaves, to extreme weather events such as heavy rainstorms, sandstorms, and cyclones, climate change exacerbates existing vulnerabilities. These vulnerabilities include water scarcity, food security, and the preservation of livelihoods increasingly threatening the region’s social and economic stability.

While there has been some progress in advancing formal negotiations on key issues, the gap between COP agreements and tangible actions to address the increasingly severe effects of climate change in the MENA region remains vast. 

This webinar aims to assess:

  • What are the key tangible impacts of COP27 and COP28 in Egypt and the UAE respectively on driving climate action in the region?
  • How do MENA countries balance COP28’s landmark agreement to transition away from fossil fuels with their unique national circumstances?
  • How will the region benefit from COP28 breakthrough in integrating the issues of climate, peace and security in climate action through the ‘Declaration of Climate, Relief, Recovery and Peace’?
  • What are the priorities for COP29 and how do they align with the climate agenda in the MENA region?




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Celebrating Black History Month at Chatham House

Celebrating Black History Month at Chatham House 24 October 2024 — 6:00PM TO 8:00PM Anonymous (not verified) Chatham House

Join us for the ‘Beyond expectations: The impact and legacy of migration exhibition 2024’ exhibition and drinks reception.

About the Photographer  

Neil Kenlock, a photographer and media professional, has lived in London since arriving from Jamaica in 1963 to join his parents. He spent the early years of his career as a professional photographer, specialising in fashion, beauty, celebrities, and the cultural lifestyles of Black people in the UK. In the late 1960s and 1970s, he captured images of the UK Black Panther movement and documented demonstrations and anti-racism protests across the country.

“Neil Kenlock helps us to better understand the story of London’s Black communities and to appreciate the huge artistic and cultural impact they have had on all our lives. He is a significant photographer whose work documents a key chapter in London’s post-war history.” — Mike Seaborne, former curator of photographs at the Museum of London.

About the exhibition

This exhibition unveils a collection of photographs by Neil Kenlock, capturing Black British individuals who migrated from their homelands and settled in the UK. Curated by his daughter Emelia Kenlock, the series explores the theme of ‘expectations’ and its enduring legacy, featuring African and Caribbean subjects who brought their skills, passions, and dreams—contributions that have profoundly shaped British culture today.

Reflecting on the work, Kenlock stated: “Over 50 years since the concept of ‘black excellence’ first manifested, and more than 70 years since the Windrush, I truly hope this exhibition will add to the national cultural narrative and resonate with new audiences.” 




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Iraq Initiative Conference 2024

Iraq Initiative Conference 2024 20 November 2024 — 9:30AM TO 5:00PM Anonymous (not verified) Chatham House and Online

Our sixth annual Iraq Initiative conference will convene Iraqi and international policymakers, experts and civil society in London to discuss the critical questions for Iraq’s future, and the country’s trajectory in the year ahead.

Over two decades following regime change, Iraq appears to be on a path to recovery and growth. With the support of high oil prices, Prime Minister Mohammed Shia’ al-Sudani’s government is implementing an ambitious plan to develop critical infrastructure, enhance ties with neighbouring countries, and renegotiate relationships with international partners like the US and UN. The political system has rebounded from a series of shocks and is in the process of consolidating and centralising power in Baghdad under the governing Shia Coordination Framework.

However, underlying political, economic, security, and regional challenges, if not addressed, threaten this apparent stability and frustrate longer-term hope for a better future. Despite the country’s wealth, many young Iraqis struggle to find jobs while the space for civic activism shrinks. Meanwhile, the escalation of violence across the region threatens to engulf Iraq in further conflict. With the 2025 parliamentary election approaching, infighting within the governing coalition also suggests political turmoil in the year ahead.

The key questions explored through each session include:

  • How can the Sudani government tackle the roots of these obstacles to ensure that development can be sustained over time?
  • What are the key steps to coherent and effective state-building?
  • And how can regional and international actors support this process?

This conference is part of Chatham House’s Iraq Initiative.

This year’s conference features RE-PLAY – a video art exhibition curated by Dr Tamara Chalabi of the Ruya Foundation. The artists featured in this exhibition, spanning multiple generations both within Iraq and in the Iraqi diaspora, use their work to grapple with complex notions of Iraqi identity through the thematic issues of heritage, exile, disconnection, freedom of expression, and other persistent issues explored in this show.

Simultaneous English-Arabic interpretation will be available for all conference sessions. This event is part of Chatham House’s Iraq Initiative.

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.




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[4Fe-4S] cluster trafficking mediated by Arabidopsis mitochondrial ISCA and NFU proteins [Enzymology]

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.




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Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways [Molecular Bases of Disease]

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.




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Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources]

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.




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Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography [Enzymology]

The main protease (3CL Mpro) from SARS–CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL Mpro possesses an unusual catalytic dyad composed of Cys145 and His41 residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL Mpro, which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterionic reactive form in which Cys145 is in the negatively charged thiolate state and His41 is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment.




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M8R tropomyosin mutation disrupts actin binding and filament regulation: The beginning affects the middle and end [Molecular Bases of Disease]

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.




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Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...




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Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).




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Naturally occurring hotspot cancer mutations in G{alpha}13 promote oncogenic signaling [Molecular Bases of Disease]

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.




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Allosteric activation of proto-oncogene kinase Src by GPCR-beta-arrestin complexes [Enzymology]

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.




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Hdac3 regulates bone modeling by suppressing osteoclast responsiveness to RANKL [Signal Transduction]

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.




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Ligand bias in receptor tyrosine kinase signaling [Signal Transduction]

Ligand bias is the ability of ligands to differentially activate certain receptor signaling responses compared with others. It reflects differences in the responses of a receptor to specific ligands and has implications for the development of highly specific therapeutics. Whereas ligand bias has been studied primarily for G protein–coupled receptors (GPCRs), there are also reports of ligand bias for receptor tyrosine kinases (RTKs). However, the understanding of RTK ligand bias is lagging behind the knowledge of GPCR ligand bias. In this review, we highlight how protocols that were developed to study GPCR signaling can be used to identify and quantify RTK ligand bias. We also introduce an operational model that can provide insights into the biophysical basis of RTK activation and ligand bias. Finally, we discuss possible mechanisms underpinning RTK ligand bias. Thus, this review serves as a primer for researchers interested in investigating ligand bias in RTK signaling.




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FUS contributes to mTOR-dependent inhibition of translation [Signal Transduction]

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes.




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Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of Disease]

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases.




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Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function [Signal Transduction]

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phosphorylated on IQGAP1 when phosphotyrosine phosphatase activity was inhibited in cells. IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. To investigate the biological sequelae of phosphorylation, we generated a nonphosphorylatable IQGAP1 construct by replacing Tyr-1510 with alanine. The ability of hepatocyte growth factor, the ligand for MET, to promote AKT activation and cell migration was significantly greater when IQGAP1-null cells were reconstituted with IQGAP1 Y1510A than when cells were reconstituted with WT IQGAP1. Collectively, our data suggest that phosphorylation of Tyr-1510 of IQGAP1 alters cell function. Because increased MET signaling is implicated in the development and progression of several types of carcinoma, IQGAP1 may be a potential therapeutic target in selected malignancies.




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Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work Research paper sysadmin 29 June 2016

A new paper sets out the factors that have made previous cross-border projects in South Asia successful, arguing that cooperation around water is feasible despite the region’s political differences and economic assymetries.

Indian people walk in the Ganga riverbed in Allahabad on 1 September 2015. Photo: Getty images.

  • The countries of South Asia share some of the world’s major river basins – the Ganga (or Ganges), the Brahmaputra and the Indus. These rivers and their tributaries flow through seven countries, support more than 1 billion people, irrigate millions of hectares of land and are of cultural importance to many of those who rely on them.
  • River management presents common challenges across the region. These include physical factors such as droughts, flooding, cyclones and climate change, as well political and institutional factors impeding the development of solutions and policies to improve resource management and reduce vulnerability. Water is increasingly seen as a source of competition, with population growth, industrialization and urbanization exacerbating the pressures on supply.
  • Although South Asian examples of regional cooperation in general are limited, there is a clear positive trend. In areas such as disaster response and cross-border power trading, regional and bilateral engagement is beginning to take place. Multilateral official arrangements exist for trade and other economic issues, but there is none on water or ecosystems. However, as the benefits from cooperation become proven, its desirability is likely to gradually enter mainstream policy thinking on water issues.
  • This research paper sets out the factors that have enabled cooperation, and the processes adopted, in previous successful cross-border projects. It focuses on four categories of cooperation: development of early-warning systems for natural disasters, in particular floods; protection of cross-border ecosystems; sharing of learning, through the showcasing of innovative approaches in one country that can be adopted by others; and power trading, in particular the development of hydropower in Bhutan and its export to India.
  • The paper argues that cooperation around water in South Asia is feasible despite political differences and economic asymmetries. Different forms of collective action, and common understanding of both the threats and the shared benefits from cooperation, are required to foster more partnerships within the river basin states.




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The Critical Transition: China’s Priorities for 2021

The Critical Transition: China’s Priorities for 2021 Research paper sysadmin 31 January 2017

This paper sets out the core issues for the Xi leadership, and focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president.

The Great Hall of the People during the closing ceremony of China’s National People’s Congress on 15 March 2015 in Beijing, China. Photo via Getty Images.

In 2017 Xi Jinping will complete his first full five-year term as China’s leader. Towards the end of the year, in autumn, the country is due to hold its 19th Party Congress. This major meeting usually marks the moment when the Communist Party of China (CPC) assesses its performance over the previous five years, sets out political goals for the coming five-year period and makes new appointments.

Xi Jinping’s leadership has been characterized by a number of significant domestic and international policy strategies. China’s economic growth rate is slowing, and the country’s economy is undergoing major restructuring. Export-led manufacturing growth and capital investment in fixed assets are now being replaced by consumer-led and service-dominated expansion. Meanwhile, the role of the CPC has been rearticulated with a major anti-corruption struggle since 2013 that has sought to clear away a raft of different networks and senior officials and connected business people. Xi has proved a more communicative, more populist and more nationalistic leader than his predecessors. He is also crafting an image of himself as a more visionary leader.

Internationally, China is striving for a relevance and role that it has never had before. Its reach is felt in international organizations, regionally, and through its economic and resource needs. It has a role in global affairs that embraces places once considered on its periphery, such as Latin America, the Arctic and Antarctic Circles, and the Middle East. Its impact in Asia is particularly striking, marked by activity in the South China Sea, and a new kind of relationship with Russia, India and the US. The major Belt and Road Initiative, in particular, has started to outline a new expansiveness in China’s relations with the outside world, despite the largely abstract nature of its overall shape and form at the moment.

The themes and viewpoints in this collection of essays are particularly geared towards those with an interest in policy engagement with China. While setting out the core issues for the Xi leadership, it also focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president. As the UK seeks a new kind of relationship with a rapidly changing China, this group of expert opinions maps out the key markers in the run up to 2021, when China is due to celebrate achieving the first of its centennial goals: the delivery of middle-income status and a moderately prosperous society.




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Brexit: Implications for EU–China Relations

Brexit: Implications for EU–China Relations Research paper sysadmin 10 May 2017

For Beijing, the EU–China relationship will take priority over UK–China ties – with China’s relative focus on Germany becoming even more significant.

Containers are loaded onto a freight train at a depot in Corringham, east of London, en route to Yiwu, China, on 10 April 2017. Photo: Getty Images.

Summary

  • The extent of current UK relations with China means that Brexit will notably reduce the scale and diversity of overall EU–China economic and commercial interactions. But the impact will vary across different areas.
  • In policy terms, liberal voices on economic policy towards China will be somewhat weaker among the post-Brexit EU27. Brexit will not be the most important factor determining the future level of strategic coherence in EU policy towards China.
  • The impact on post-Brexit EU27 trade with China will be felt both in the volume of trade and its composition. Following Brexit the EU will no longer be China’s largest trading partner.
  • There will be some relative shift in Chinese investment in Europe away from the UK, though over time the impact of Europe-wide policy approaches to Chinese investment will have more impact than Brexit per se.
  • EU–China educational exchanges will be weakened after Brexit, but inbound Chinese tourism will be less affected by Brexit.
  • By 2025, the EU will have compensated for Brexit’s impact in some areas, but much depends on the EU’s own trajectory over the next decade.
  • For Beijing, the EU–China relationship will take priority over UK–China ties. Within the EU, China’s relative focus on Germany will be even more significant.




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A Digital India Must Embrace the Circular Economy

A Digital India Must Embrace the Circular Economy Expert comment sysadmin 15 January 2018

A growing amount of e-waste should draw attention to the broader sustainability of a digital society.

Workers dismantle old computers at an e-waste recycling factory near Bangalore. Photo: Getty Images.

The latest Global E-Waste Monitor places India as one of the highest contributors to global e-waste, generating over 2 million metric tonnes in 2016. Posing serious health and environmental risks, growing e-waste represents the hidden cost of increasingly digital lives in an information society.

With just 33 per cent of the population owning a smart phone, India already has the second largest number of smart phone users in the world, nearly 4 times that of the United States. The amount of e-waste generated will exponentially increase in the coming decade as the cost of consumer electronics decline, middle-class incomes rise, and the frequency at which devices are discarded increases.

As governance instruments are increasingly digitized and industry re-repositions itself to leverage Industry 4.0 solutions, the generation of e-waste will become a byproduct of institutional choices rather than consumer consumption and behaviour alone.

India is already a leader in the management and recycling of e-waste. But over 90 per cent is managed in the unorganized sector by small businesses and individual entrepreneurs, typically from low-income marginalized communities, and often women. E-waste contains various toxic substances such as mercury and lead, prolonged exposure to which can lead to major health problems.

Almost 80 per cent of e-waste workers in India suffer from respiratory ailments due to improper standards and nearly 500,000 children are engaged in e-waste collection without adequate protection and safeguards. The bulk of the dirty and dangerous work supporting India’s march towards an increasingly digital society is done by those who have the least access to technology gains. Government regulations for the management of e-waste, on the other hand, are becoming more relaxed, presumably as a result of industry pressure. To streamline e-waste management, the government notified Electronic Waste Rules in 2011, based on the concept of extended producer responsibility (EPR).

EPR makes manufacturers of electronic products responsible for the end-of-life management of their products, including setting up collection centres. By shifting the burden to manufacturers, the EPR framework, in theory, creates incentives for more environmentally friendly design. But the impact of EPR rules on manufacturers has been minimal, at best. The recently released Draft Notification (2017) by the Ministry of Environment, Forest and Climate Change further relaxes the EPR rule by reducing the e-waste collection targets for industries.

While the efficiency and productivity gains of Digital India are to be welcomed, growing e-waste should draw attention to the broader sustainability of a digital society. Data centres, for example, are one the largest contributors to global warming, contributing a similar amount to global greenhouse emissions as the aviation industry.

This amount is expected to triple in the next decade. In many ways, the sustainability challenge is a ‘wicked problem’ – where possible solutions create a new set of additional challenges and the choice between available alternatives is largely about competing values.

For example, data centres powered by renewable sources of energy such as solar provide a greener alternative, but will also create new forms of e-waste in the form of photovoltaic cells and panels. An unverified estimate suggests that India’s projected solar capacity of 100 gigawatts by 2022 will create 7.76 million tonnes of e-waste. Without adequate and preemptive consideration of how this waste should be disposed and recycled, renewable energy solutions can create new negative externalities.

For Digital India to be sustainable, we need to develop anticipatory knowledge for preemptive solutions. It is an opportune moment to think of the broader architecture of a digital society, one that avoids getting locked into unsustainable models of production and consumption, as is the case with many industrialized economies.

The argument that such considerations are premature for India, given high levels of poverty and unemployment, are misplaced. Enquiries into the sustainability of Digital India are no less urgent than the need for sustained job-creating economic growth. These issues should not be addressed in a sequential or linear manner, but in parallel, or else we will be only partially aware of available choices and their consequences, creating new forms of technological and economic lock-ins.

The value-based choice demanded by the ‘wicked problem’ at hand is one that embraces the idea of a circular economy — one that departs from the linear economic growth model predicated on ‘take, make, dispose’ to embrace a growth model based on creating closed loops of production, consumption and re-use. A circular economy model is built on the idea of designing out waste and pollution; keeping products and materials in use; and regenerating natural systems. In many ways, India is already a leader in the circular economy.

Alongside, the management of e-waste and other forms of recycling, high levels of repair and reuse are distinctly observable. A number of reports note that the informal waste management sector in India works better than systems in many industrialized economies.

A circular economy vision for Digital India would include organizing informal waste management systems, including safety and social protection initiatives for workers; revising and tightening existent e-waste rules for increased accountability by manufacturers both in terms of durable design and responsible disposal; green data centres; and building future smart cities with a view towards energy and water efficiency, among others.

A recent report by the Ellen McArthur Foundation and the World Economic Forum also estimates that a circular economy path to development could bring India annual benefits of $624 billion by 2050. Greenhouse gas emissions could also be 44 per cent lower in 2050, compared with current development path.

Unsurprisingly, Nordic countries are leading the way in promoting the idea of a circular economy. Sweden recently announced tax breaks for repair related activities and Finland hosted the first global conference on the circular economy earlier this year. The circular economy provides an opportunity for India to capitalize and leverage an already existing culture of circular activities, and promote it as a policy agenda that will create new forms of employment while facilitating sustainable environmental management.

This article was originally published in the Indian Express.




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Managing Risks Along the Belt and Road

Managing Risks Along the Belt and Road 27 March 2018 — 8:30AM TO 11:30AM Anonymous (not verified) 5 March 2018 Chatham House, London

China’s ‘Belt and Road Initiative’ offers potential benefits in connectivity, infrastructure and trade, through significantly increased Chinese engagement across many different countries. However, many of these countries face internal tensions and have relatively underdeveloped market structures, legal systems and governance frameworks. While Belt and Road investments can make positive contributions in host countries, there is also the potential for these investments to exacerbate tensions and risks.

This roundtable, held in partnership with the Security & Crisis Management International Centre (Shanghai Academy of Social Sciences-UNITO), will seek to examine risk management along the Belt and Road, differentiating between roles that can be played by public sector and private sector actors.

Attendance at this event is by invitation only.




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Arguments Over Innovation Capacity Miss How Much the US and China Are Intertwined

Arguments Over Innovation Capacity Miss How Much the US and China Are Intertwined Expert comment sysadmin 30 May 2018

Most discussions of current US–China trade tensions fundamentally misrepresent the globalized nature of innovation.

The C919 aircraft, China’s first modern passenger jet, is a flagship project of President Xi Jinping’s ambition to build the country’s domestic manufacturing capabilities. Photo: Getty Images.

Among the many issues at play in the ongoing economic and trade tensions between the US and China are questions of technological capability and innovation.

Two of the main complaints in the US Section 301 report were that American companies have been forced to transfer technology to China and been the subject of cyber espionage. The presentation of the issues in this report has been disputed, but behind it lies concern in the US that Chinese innovative and technological capability is catching up with that in the US, thanks partly to the support of state policies set out in the Made in China 2025 initiative.

One important feature of the package of measures announced by the US last month is that it was designed to contain China’s technological development as much as to reduce the trade deficit, even though the latter has been the focus of President Donald Trump’s rhetoric.

(Some have cast doubt on this picture of Chinese innovation, suggesting that China is more of a ‘fat tech dragon’ whose massive inputs into research and development do not translate into real innovative capacity.)

The problem with the debate comparing Chinese and American technological capability is that it misunderstands or misrepresents the globalized nature of innovation in today’s world.

Contrary to the economic nationalist rhetoric emanating mainly from Washington, and to a lesser extent from Beijing, the US and China are not two separate economies competing for economic hegemony. As part of the globalization of manufacturing and production over the last 40 years and the more recent globalization of consumption, the shape and structure of innovation has also changed.

As we argue in a new paper, the key to understanding this is to think of innovation as being carried out through global or transnational networks linking economic actors, not within separated economies. What the recent phase of globalization has demonstrated is that innovation is achieved most effectively and efficiently when those engaged in innovation are connected not just within national borders but across them.

China has become integrated into these global innovation networks in ways which reflect its relative strengths and weaknesses in research and development. China’s extensive manufacturing ecosystem has enabled its companies to perform well in production-related and efficiency-driven innovation. Moreover the rapid growth in its large and dynamic consumer market provides fertile ground for consumer-related innovation by Chinese and foreign-invested enterprises alike. The rapidly increasing talent pool in China also provides additional human capital for innovation and technology.

Apart from the increased emphasis by Chinese enterprises on innovation, multinationals have also been stepping up their research and development (R&D) efforts in China. These now consitute a significant part of China’s R&D landscape, and are an increasingly important part of the global innovation by multinationals.

Things are of course changing. China’s overall innovation capacity is improving, and there are concerns in both in the US and Europe that Chinese policy is moving backwards towards the promotion of ‘indigenous innovation’ – or self-reliant innovation – and away from openness. In other words, we may be seeing a more ‘techno-nationalist’ China as well as a protectionist US.

China has also been criticized for inadequate protection of intellectual property rights, though the establishment of special courts for such disputes marks a commitment to improve – and the rights of Chinese companies increasingly need protection too.

As the benefits of globalization increasingly come under question, and with some degree of nationalist political pressure in both the West and China, it is not going to be possible – or politically desirable – to do away with national borders when it comes to innovation. But at the same time, the extent to which businesses and consumers have globalized means that fully ‘indigenous’ innovation is not possible, even if it were politically desirable.

EU-China innovation relations, as well as those between Washington and Beijing, therefore need careful management. But both Americans and Europeans should have more confidence in their innovation capability, given the relative strengths and weaknesses of Chinese innovation.

Americans and Europeans should acknowledge and promote the opportunities that come from globally networked innovation processes. Taking advantage of the comparative advantage of all the players in these networks means working with China as an innovation partner.




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Mobile Ecosystems as a Driver of Innovation and Growth in the Asia-Pacific

Mobile Ecosystems as a Driver of Innovation and Growth in the Asia-Pacific 19 September 2018 — 12:30PM TO 3:00PM Anonymous (not verified) 18 September 2018 Chatham House, London

This meeting, held in partnership with Digital Asia Hub, will analyze the role of mobile platforms in catalyzing socioeconomic transformation in the Asia-Pacific region. Contributing to mobility in every sense - through untethering information from knowledge centres, helping women overcome socio-cultural divides and transforming financial services - communications ecosystems have driven innovation and change.
Despite significant gains, challenges of access to mobile platforms and of digital literacy remain. This meeting will explore the current opportunities for market players, the ways in which inclusive growth can be addressed as well as the ways young people can engage and learn through their devices. It will also analyze the role of apps, tools and design choices in enhancing civic participation, safety and knowledge sharing.
Attendance at this event is by invitation only.




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How Women are Transforming Indonesia

How Women are Transforming Indonesia Interview sysadmin 20 May 2019

In a series exploring women in international affairs, Isabel Dunstan speaks to Gitika Bhardwaj about the rise of the women’s movement in Indonesia.

Southeast Asia has one of the highest records of gender-based violence in the world and Indonesia was recently ranked as the second most dangerous place for women in the Asia-Pacific. What is the state of women’s rights and gender equality in Indonesia?

It is true that Indonesia has high rates of violence against women, however, it’s difficult to know the realities of women’s experiences because in the past the data has been somewhat unreliable. This has been due to reasons such as a lack of reporting mechanisms available to survivors of violence and the fact that discussing sexual violence is a taboo and, if reported, can result in stigmatization which limits the number of survivors who have come forward.

However, the first reliable nationwide survey on gendered violence in Indonesia was conducted in 2017 by the Indonesian Ministry of Women and Child Protection and the United Nations Population Fund. Interestingly, it showed that Indonesia’s rates of violence against women are on par with the global rate which is that 1 in 3 women are affected by sexual violence in their lifetime.

It’s therefore difficult to generalize that Indonesia is an unsafe place for women because it’s an extremely diverse country. There is a growing middle class while there is pervasive poverty. There is religious diversity where the eastern-most province of Aceh is the only province in the country where Sharia law is enforced, whereas in the western-most province of West Papua, the dominant religion is Christianity and the ways of life are completely different.

Nevertheless, violence against women is high in Indonesia and can happen in all places – rich or poor, east or west – and has different manifestations from street harassment and trafficking to domestic violence and workplace harassment.

In some parts of the country there are high rates of child marriage too and, according to UNICEF, 14 per cent of girls in Indonesia are married by the time they turn 18 which is shocking when we think about how child marriage limits girls’ access to education and makes them more vulnerable to sexual violence and therefore restricts their futures.

Child marriage is high in Indonesia in part due to rooted gender norms, low levels of education and discriminating legislation, such as the marriage law, which states that, although it is legal to marry at 21, girls can marry at 16 and boys can marry at 19 with parental consent. But this can be even lower meaning parents could get their daughters married at as young as 13. So the law is fundamentally unfair between girls and boys and the women’s movement in Indonesia has been fighting extremely hard to reform legislation that discriminates against women and girls.

From the country’s first female president, Megawati Sukarnoputri​, to incumbent finance minister Sri Mulyani Indrawati – who was voted ‘Best Minister in the World’ in 2018 – and maritime​ and fisheries minister Susi Pudjiastuti – who has become notorious for her tough stance against illegal fishing activities – how are women progressing in Indonesian politics?

Indonesia has come a long way since becoming a democracy in 1998. Before that, the second president and dictator, Suharto, ruled the country for almost 32 years and increased the inequality gap between men and women during his reign.

Since the fall of Suharto, however, gender equality is explicitly enshrined in Indonesia’s constitution and the country has ratified the Convention on the Elimination of Violence Against Women.

The country has also been undergoing a process of democratization which has involved slowly decentralizing its power. This means that greater authority has been distributed to the 34 provincial governments outside of the capital of Jakarta.

Furthermore, to aid gender equality, a quota system requiring political parties to be made up of 30 per cent women has been put in place, although remnants of Suharto’s old system of cronyism remain, limiting the impact of the quotas translating to more women in provincial parliaments.

But the defining approach to furthering gender equality in Indonesia has been through gender mainstreaming and gender-responsive budgeting which can be seen throughout provincial administrations in the country.

This means there is the intention to ensure infrastructure, health and education outcomes include results that address specific gender equality gaps. The challenge for effective gender mainstreaming, however, is the political will to translate the approach into well-resourced programmes from one province to another.

Indonesia has come a long way since becoming a democracy in 1998. Before that, Suharto, ruled the country for almost 32 years and increased the inequality gap between men and women.

Nevertheless, we have just seen Indonesia go through the most incredible presidential and legislative elections last month – won by the current president, Joko Widodo, who has often been called the ‘Barack Obama of Southeast Asia’ and whose existing cabinet has the highest number of women in the country’s history. This is not simply a matter of filling seats in the cabinet with women – such as the wives and sisters of male politicians – because it’s required by law. But, rather, there are some incredible female political figures who are there because they are strong, smart and capable.

You’ve rightly mentioned Minister of Maritime Affairs and Fisheries, Susi Pudjiastuti, who is a fabulous role model for a lot of women particularly women who have not had tertiary education because she entered politics through an unorthodox route.

Then there’s Minister of Finance, Sri Mulyani Indrawati, who is also the former leader of the World Bank and is such an inspiration to a lot of women who are looking to work in public life because of her experience as well as her work to include gender mainstreaming in state budgets.

There is also Minister of Women’s Empowerment and Child Protection, Yohana Susana Yembise, who is a Papuan woman, as well as many more female public figures.




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International Arbitration: Exploring India’s Potential

International Arbitration: Exploring India’s Potential 15 November 2019 — 9:30AM TO 5:30PM Anonymous (not verified) 17 October 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

As India’s economic clout grows, so does its aspiration to become a favoured arbitration destination in a globalized world dominated by foreign investments flows and cross border transactions. India’s bid to enhance its status as an arbitration destination depends largely on the suitability of its legal environment in meeting the demands of an increasingly sophisticated approach to disputed resolution. This conference will assess these, and other related, issues.

To register your interest in attending this event, please contact Nisha Ramdas by phone +91 9650977833 or by e-mail nisha@globaldialoguereview.com.




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Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.




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Virtual Roundtable: The Economic Implications of COVID-19 on Asia

Virtual Roundtable: The Economic Implications of COVID-19 on Asia 2 April 2020 — 11:00AM TO 12:00PM Anonymous (not verified) 27 March 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The COVID-19 pandemic is likely to have a damaging economic impact on Asia, potentially the most serious since the financial crisis two decades ago. While early estimates suggest that a recession is inevitable, differing countries in Asia are generally deploying modest fiscal and monetary measures. This is true even in China, compared with the ‘whatever it takes’ approach pursued by Europe and America.

How effective will these measures be in reviving growth and in easing the pain, particularly on the poor in developing countries in Asia? Is Asia witnessing a sudden but temporary halt in economic activity rather than a prolonged slowdown? At this virtual roundtable, the speakers will consider the likelihood of a recovery for trade in the region and will explore what lessons can be learned from countries like Singapore, who seem to be successfully managing the health and economic aspects of COVID-19.

This event is online only. After registering, you will receive a follow-up confirmation email with details of how to join the webinar.




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Webinar: Is It All Over For Globalization?

Webinar: Is It All Over For Globalization? 15 April 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 8 April 2020

 

The coronavirus pandemic has led many to predict the end of globalization. Confronted with unprecedented social and economic challenges, countries are prioritizing their own citizens. Now, more than ever, international cooperation is necessary but, amidst the rise of nationalist-populist governments, global partnerships are absent or faltering. And as economies grind to a halt, so does international commerce — particularly in trade-dependent Asia, a region whose rise drove the period of ‘hyper-globalization’ which preceded the global financial crisis.

Yet there are other possible futures too. The level of scientific collaboration and information-sharing now underway in search of a vaccine is unprecedented, and after a hesitant beginning the major powers have woken up to the importance of concerted economic stimuli. The virus may in some ways have the paradoxical result of bringing countries together, not driving them apart. Rather than causing its demise, it could help begin a new period in which globalization is not as deep, but at least is better managed and more equitable? Could this be the catalyst for a new coming together at home and abroad?

In this webinar, speakers debate what impact the COVID-19 pandemic will have on the future of globalization, both in Asia and around the world.




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China's Evolving Economic Relations with North Africa: Before and After COVID-19

China's Evolving Economic Relations with North Africa: Before and After COVID-19 10 September 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 20 August 2020 Online

China’s economic presence across North Africa has grown in recent years. The global power has forged close economic relationships with Egypt and Algeria, while also continuing to develop ties with Morocco and Tunisia.

Beijing, which views the region as a geostrategic intersection between Mediterranean, Middle East, and Africa, has primarily focused its efforts on developing bilateral relations, while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF).

All countries of the region have agreed to participate in China’s Belt and Road initiative (BRI), which has raised concerns among Western powers. As North African countries grapple with fiscal constraints as part of the fallout from COVID-19 (and the oil price drop for hydrocarbon exporters such as Algeria), it is yet to be seen whether China’s ambitions and relations within the region will continue to develop at the same pace going forward.

In this webinar, organized by Chatham House’s MENA and Asia-Pacific Programmes, experts will discuss the evolving economic relationship between China and North African states, and explore the impact of China’s pandemic diplomacy across the region.

How asymmetric are economic relations between China and North African states? Which sectors are most important, and what are the prospects for China to develop the region’s digital and healthcare infrastructure? Will China’s increasing economic interests necessitate an increasing political and security engagement? Should North African states be wary of Chinese loans? What is the public opinion of China’s economic presence in North Africa? Have Chinese ‘soft power’ efforts helped to bolster economic (and political) ties? What will be the likely fallout of COVID-19 on BRI and infrastructure projects in the region?

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.