There is a reason Joe Rogan became the world's largest podcaster. He doesn't take his audience -- or his guests -- for granted. He wants MEANINGFUL conversations.

The post Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet appeared first on Clash Daily.

The usual talking heads in the media are freaking out and making all kinds of wild claims. Those are the rage-y emotional reactions. What's a more sensible take on all of this?

The post Why Did Trump Win And What Happens Now? appeared first on Clash Daily.

Kamala was right about one thing: this election really DID deliver 'joy'... just not the way she expected.

The post EPIC: The ‘Songify’ Trend Of Clipping Speeches To Music Is Back… And AWESOME! appeared first on Clash Daily.

A.F. Branco Cartoon – Compare and contrast. Fight, Fight, Fight against Kamala’s Marxist tyrannical government. It’s what’s at stake in..

Bob Moesta is a dear friend, mentor, and all around original thinker. He’s helped me see around corners, shine lights on things I didn’t know were there, and approach product development from unusual angles. Every time we talk, I come away inspired and full of optimism. So when he asked me to help him with… keep reading

Chairman Klein and members of the Senate Industry, Business and Labor Committee- My name is David Heinemeier Hansson, and I’m the CTO and co-founder of Basecamp, a small internet company from Chicago that sells project-management software and email services. I first testified on the topic of big tech monopolies at the House Antitrust Subcommittee’s field… keep reading

There appeared to be a definite frost between first lady Jill Biden and Vice President Kamala Harris during a Veterans Day event at Arlington National Cemetery on Monday. A close-up […]

The post Footage of Jill Biden and Kamala Harris Sitting Side-by-Side at Veterans Day Event Goes Viral appeared first on The Western Journal.

Republicans have solidified their control of Washington by retaining control of the House of Representatives. President-elect Donald Trump’s overwhelming victory in the presidential race, coupled with GOP control of the […]

The post Breaking: Republicans Retain Control Over House of Representatives, Handing Trump the Keys to His Agenda appeared first on The Western Journal.

In a surprise move that broke in the early hours of Tuesday morning, President-elect Donald Trump has reportedly picked South Dakota Gov. Kristi Noem as his nominee to head the […]

The post Trump Makes His Pick for Secretary of the Department of Homeland Security Secretary: Report appeared first on The Western Journal.

Left-wing networks had plenty of bad news for their viewers as former President Donald Trump stormed to victory in the Nov. 5 election. Now, they’re getting plenty of bad news […]

The post Insult to Injury: MSNBC and CNN Suffer Staggering Ratings Plunge Following Trump Victory appeared first on The Western Journal.

To a large extent, President-elect Donald Trump’s winning coalition came together around one absolute truth. In sum, Americans do not have a self-governing constitutional republic if we also have a […]

The post Trump Shares His 10-Step Plan to 'Shatter the Deep State' and It Will Give You Chills appeared first on The Western Journal.

New York Judge Juan Merchan — who is overseeing President-elect Donald Trump’s business records case — agreed to freeze the case until Nov. 19. There was to be a hearing […]

The post Judge Juan Merchan Grants Request from Trump's Legal Team and DA in NY Hush Money Case appeared first on The Western Journal.

Legendary Christian writer C.S. Lewis gave us an analogy to help explain otherwise inexplicable moments such as this. Tolerance, Lewis once wrote, “parodies love as flippancy parodies merriment.” In a […]

The post Biden Asked If He'll Get a Hostage Deal by the End of His Term, and His Response Is Telling appeared first on The Western Journal.

A Louisiana law that sought to post the Ten Commandments in every schoolroom in the state has been shelved by a federal judge. U.S. District Court Judge John W. deGravelles, […]

The post Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law appeared first on The Western Journal.

Canan Moodie used his start against Scotland to show that he is about far more than just pace out wide and aerial ability.

In his latest Rucking with Rob newsletter, Rob Houwing argues that for England to have any hopes of beating the Springboks, they'll have to be on the ball in the final stages.

Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

The first battle cry has sounded ahead of the showdown at Twickenham on Saturday, with English winger Tommy Freeman reckoning that the Springboks are 'still human' and 'still playing the same game'.

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.

Originally posted on Oct 28, 2022 It was an honor to be interviewed by the beautiful and patriotic Sandy Rios about my book and my journey writing it on her show, “Sandy Rios In the Morning.” https://afr.net/podcasts/sandy-rios-in-the-morning/2022/october/cynthia-farahat-discusses-her-new-book-the-secret-apparatus-the-muslim-brotherhood-s-industry-of-death/

Spotify still No. 1 by wide margin February 24, 2022 (New York, NY) – Pandora, once the dominant player in terms of digital music streaming, will be eclipsed by Amazon […]

Total media ad spend in Russia to drop nearly 50%   March 30, 2022 (New York, NY) – Insider Intelligence expects the ongoing war in Ukraine to have a significant […]

Worldwide revenues will triple in 2022   April 11, 2022 (New York, NY) – TikTok’s worldwide ad revenues will triple this year and surpass that of two competitors combined, according […]

Toni Annala, Marc Hoyois and Ryomei Iwasa
J. Amer. Math. Soc. 38 (), 243-289.
Abstract, references and article information

Marcelo Campos, Matthew Jenssen, Marcus Michelen and Julian Sahasrabudhe
J. Amer. Math. Soc. 38 (), 179-224.
Abstract, references and article information

A feminist and postcolonial approach to nuclear politics Expert comment NCapeling 20 July 2022

The July issue of International Affairs includes eight articles on the global nuclear order and eight more covering Chinese lending, abortion rights, and global security.

Disarmament and arms control has been a consistent area of debate in this journal for the past century, as underscored in our recent archive collection of research on a century of war and conflict.

The July edition moves this debate forward with a collection of papers guest-edited by Shine Choi and Catherine Eschle. The section ‘Feminist interrogations of global nuclear politics’ includes work by nine authors exploring seven global case-studies that help rethink nuclear politics and feminism.

As the guest editors note in their introduction, the section brings together research on nuclear power and nuclear weaponry to ‘begin the process of decentring 1980s white, western experiences of the global nuclear order in feminist IR’.

The articles speak to three core themes: they provide evidence of the ongoing destructive nature of nuclear technologies, extend understanding of the gendered, racialized, and colonial dimensions of nuclear discourses, and unearth the impact of colonialism on the global nuclear order.

Global nuclear politics

Anne Sisson Runyan examines the gendered effects of uranium mining and nuclear waste dumping on North American Indigenous women, showing how the nuclear cycle tends to have a disproportionate effect on certain communities but also that the area of disposal remains problematic.

This is a global problem – for example, the Royal Navy has yet to successfully dispose of a single redundant nuclear-powered submarine and is rapidly running out of space to store further vessels.

Hebatalla Taha goes back to the early years of nuclear development and, using Egypt as a case-study, her article argues the early visualizations of the atomic age were fluid and ambivalent. She concludes – perhaps controversially – that feminizing nuclear politics and nuclear images will not lead to disarmament but rather reinforce the nuclearized world. The piece is a welcome addition to the emerging field of visuality within international relations.

Anand Sreekumar brings together feminist and Gandhian thinking to suggest a way for Narendra Modi’s government to move beyond the possession of nuclear weapons as symbols of power. In doing so, he also critiques the binary labels of ‘West’ and ‘non-West’ that often frame our understanding of the world.

Lorraine Bayard de Volo revisits the Cuban missile crisis – a point in time where nuclear war looked likely. She compares the actions of Khrushchev, Castro, and Kennedy and finds the pursuit of masculinity led to the rejection of approaches considered more feminine, such as diplomacy and negotiation – the crisis was exacerbated by what might be referred to now as toxic masculinity.

Sweden’s and Finland’s recent application to join the nuclear alliance NATO lends a particular urgency to Emma Rosengren’s article on the original Swedish decision to renounce the development of nuclear weapons during the Cold War. Her article concludes much of the emphasis on power in international relations has contributed to a gendered and racialized nuclear order.

Similarly, Laura Rose Brown and Laura Considine’s article on the Non-Proliferation Treaty finds that ‘gender-sensitive’ approaches focus almost exclusively on women’s inclusion as opposed to feminist policy analysis. They end by making recommendations for future policymaking.

Finally, Rebecca Hogue and Anais Maurer look at the anti-nuclear poetry of Pacific women. This article raises fundamental questions about what is currently considered to constitute evidence. They point to the role of oral history in many communities and the tendency of policymakers and social scientists to ignore this source of understanding.

National politics with international implications

This edition’s ‘Editor’s Choice’ is Jeffrey A. Friedman’s article which questions whether US grand strategy is dead in a post-Trump world. Running counter to much of the existing literature, he suggests there is a strong bilateral commitment to existing partnerships and alliances within the US political establishment.

Following the US Supreme Court decision over Roe vs Wade, it is important to note the issue of abortion rights can have an international dimension. Megan Daigle, Deirdre N. Duffy, and Diana López Castañeda reveal that, although Colombia now has the most progressive legal framework for abortion in Latin America, intense backlash persists as legacies of the civil war overshadow the issue and lead to barriers to safe abortion care.

China

Ric Neo and Chen Xiang look at Chinese public opinion and finds that citizens can be upset by foreign policies of other states even when they have no impact on their daily lives. It reminds us of the potency of nationalism and the importance of who controls the prevailing narrative.

Deborah Brautigam examines China’s role in creating Zambia’s debt crisis, arguing this has not been brought about by a centralized master plan which would give China control over Zambia. Instead, the crisis has been caused by the failure of Chinese bureaucracy with too many state organs offering funding in an uncoordinated fashion.

Security and defence

Using Iran as a case-study, Henrik Stålhane Hiim argues the development of nuclear-capable ballistic missiles is a key indicator when looking for potential nuclear proliferators.

Eray Alim demonstrates the impact of an external great power interacting with local states. Russia’s involvement in the Syrian civil war has allowed it – sometimes through restrictive and punitive measures – to ensure Turkey and Israel do not harm its interests in the region.

Nina Wilén draws on fieldwork in Niger to study how Security Force Assistance (SFA) impacts on Niger’s security sector and compares this to global trends in security. She finds these developments contribute to blurred borders and confusion regarding labour division in the security sector and points to wider questions for intervenors in developing local units.

Beijing briefing: is the Belt and Road going nowhere? The World Today mhiggins.drupal 29 July 2022

Scaling back infrastructure plans and investment in the Global South could cause China problems, says Yu Jie.

Over the past two decades, China specialists around the world have tried to analyze Beijing’s approach to developing countries in the Global South, including Africa, Latin America, parts of Asia and the Pacific islands.
 
China’s relationships with nations in these regions vary considerably. In some, ideology or geography are the biggest influencing factors; for others, economic and commercial gains matter most. However, many of Beijing’s recent engagements have attracted more criticism than praise. A domestic economic downturn means that Beijing has tightened its belt, spending less on overseas development.

When President Xi Jinping came to power, he was keen to highlight how China’s power could shape and dictate the global agenda across multilateral platforms. His vision was for China to project discursive power and become an agenda-setter rather than a rule-follower. The Global South is the route to fulfilling his proposal.

To this end, China’s Belt and Road Initiative (BRI) and the latest Global Development Initiative are the means to Beijing’s ends. The former, launched in 2013, focuses on building physical infrastructure linking Global South countries; the latter aims to allow development through grants and capacity-building in line with the UN’s Sustainable Development Goals.

China’s engagements with Africa and Latin America seem characterized by the rapid extension of Chinese finance to resource-rich African states, particularly oil producers, since the early 2000s. From 2003, for example, oil-backed infrastructure loans were made to the Angolan government for reconstruction after decades of civil conflict. By 2016, they totalled some $15 billion. 

However, Beijing’s appetite for offering cheap loans in exchange for natural resources has shrunk. It faces a dilemma between protecting the value of its investments while also defending its strategic interests and maintaining its self-image as a partner, not a predator, of Africa.

Beijing has historically preferred bilateral relationships for its development finance and investments over multilateral ones. This allows China control over the terms and conditions, while demonstrating its unwillingness to accept without question rules and frameworks devised years ago by western countries.

China has already realized that some elements of its engagements with the Global South are no longer the flavour of the day, partly because some of its programmes include serious climate and financial risks without proper third-party due diligence in place. 

Growth through gigantic infrastructure investments of the sort that drove China’s own economic miracle is not a panacea applicable everywhere. Nor is relentlessly seeking endorsements from its neighbours and other countries from afar.

China wants to be a ‘brother’ to the Global South

Ideologically, China wants to be seen and respected as a leader of the Global South. Since its founding in 1949, the People’s Republic has maintained a ‘brotherly’ relationship with developing countries, notably in the UN context, where it remains a member of the G77 group of developing nations. 

The West has responded to China’s development agenda with its own infrastructure programmes, such as Washington’s Build Back Better World and the European Union’s Global Gateway. 

Great power rivalry should not be ignored, but it shouldn’t blind world powers to the need for collaboration in tackling global poverty and sustainable development. Nor should Beijing’s efforts to adjust its diplomatic and aid programmes to become a likeable partner of choice in search of a better economic future, be disregarded.

Since launching BRI, China has poured hundreds of billions of dollars into building infrastructure in the Global South. And many developing countries hope that advanced economies and China can continue to act to alleviate poverty. But the brakes have been applied to Beijing’s spree as a result of China’s domestic economic slowdown. It has no wish to continue spending its foreign reserves.

To go forward, China must remain open to what others want – or fear – from Beijing’s development initiatives and infrastructure investments. Many developing countries, facing insurmountable costs and damage exacerbated by the Covid pandemic, crave meaningful assistance rather than diplomatic rhetoric. 

The ultimate test of Beijing’s economic statecraft is whether it can engage with the Global South beyond relationships built on financial resources and political capital. It must also become more self-aware of how its words and deeds are received – and then act accordingly. Showering dollars and renminbi is not always guaranteed to win hearts and minds. In this respect, Beijing has more bridges to build.

Russia–China defence and security relations: Insights from the expert community 13 September 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 31 August 2022 Online

Experts share insights on Russia–China military, defence, and security relations. 

In the defence and security realms, Russia–China relations resemble more pragmatic cooperation based on shared, calculated interests than an alliance.

This event presents and discusses key findings from a recent expert survey conducted by Chatham House with the aim to gather insights on Russia–China military, defence, and security relations.

Survey responses helped identify areas of bilateral cooperation but also crucial friction points and obstacles that prevent the relationship from developing further, as well as policy pathways for the West.

Russia-China Defence and Security Relations

This project explores the military and security linkages between Russia and China.

The project seeks to provide a nuanced understanding of Russia-China relations in the defence and security realms.

It also seeks to understand Russian political and security perceptions regarding Chinese inroads into what Russia considers its ‘near abroad’, as well as other sources of irritation and tension in the bilateral relationship. It offers recommendations to guide NATO policy responses.

Russia and China in Antarctica: Implications for the Five Eyes 15 December 2022 — 11:00AM TO 12:00PM Anonymous (not verified) 2 December 2022 Online

This event explores Russia’s and China’s postions on the Antarctic and offers a critical assessment of their actions in the region.

Ever since the 1959 Antarctic Treaty System (ATS), signed at the height of Cold War, Antarctica has remained a demilitarized continent.

Today, even though the ATS is not in immediate danger of collapse, Antarctica and the Southern Ocean are no longer insulated from wider geopolitical tension, with China and Russia posing challenges to regional governance. 
 
This event also discusses key recommendations for the Five Eyes regarding Russian and Chinese current and future efforts at undermining the ATS and Antarctic governance. 

The discussion is informed by Mathieu Boulègue’s paper ‘Russia and China in Antarctica and the Southern Ocean: Implications for the Five Eyes’ published by the Sea Power Centre of the Royal Australian Navy.

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.

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) 15 August 2024 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?

A world in transition and the future of the global workforce 15 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 22 August 2024 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.

How can young people in MENA thrive despite economic and political insecurity? 24 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 30 August 2024 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. 

US domestic polarization and implications for the presidential election 30 September 2024 — 5:00PM TO 6:00PM Anonymous (not verified) 19 September 2024 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?

Business Briefing: US election geopolitical and economic risk scenarios 10 October 2024 — 11:45AM TO 1:00PM Anonymous (not verified) 23 September 2024 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?

Security and defence 2025 6 March 2025 — 8:00AM TO 6:00PM Anonymous (not verified) 26 September 2024 Chatham House and Online

Join senior policymakers, business leaders and international security experts at Chatham House for a day of thought-provoking discussions exploring the tools needed to equip military forces with for an increasingly insecure future.

You will receive further instructions regarding your registration soon.

Future-proofing a fracturing world

The security and defence landscape is characterised by rapid change and evolving threats to global stability. The uncertainties of a complex geopolitical environment, with war on multiple fronts, are exacerbated by the array of threats presented across the domains of conflict - from land, sea and air through to space and technology. From drone swarm attacks in the Donbas, utilising the latest battlefield technology to gain advantages on the land and in the air, through to the battle for primacy in the space domain above the strategically important, yet inhospitable Arctic shipping lanes, the domains of conflict are becoming increasingly intertwined. A holistic strategy fit to tackle the threats of a fracturing world will rely on effective collaboration between the public and private sectors.

The 2025 Security and Defence conference brings together global policymakers, senior military and armed forces figures, business leaders and civil society experts. An insightful day of keynotes, high-level panel dialogues, and ‘under-the-Rule’ spotlights will explore how advanced technology is shaping the battlefield, examine how security architectures can be redesigned to support the end goal of peace, and address the future of arms control measures. Discussions will also unpack how forward-thinking defence actors might unlock fresh opportunities alongside current challenges. Forging stronger ties with partners to future-proof institutions and develop the architecture that will sustain security and defence ecosystems into the future will be crucial to ensuring that fighting forces are equipped, not just for the conflicts of today, but the security challenges of tomorrow.

Why attend?

• Learn more about the areas that leaders across the security and defence ecosystem are prioritizing and how they aim to counter emerging threats in order to foster resilience in this environment.
• Gain an understanding of the array of threats that are present, both across the domains of conflict and also the different regions of the world.
• In-person networking opportunities with senior leaders from across the government, international militaries and global business, as well as access to exclusive ‘under-the-Rule’ sessions.

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.

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

Shaping modern Britain: the role of African and Caribbean communities 24 October 2024 — 5:00PM TO 6:00PM Anonymous (not verified) 3 October 2024 Chatham House and Online

As part of Black History Month, this event celebrates the enduring contributions of African and Caribbean communities to the UK.

When British colonial rule ended, newly independent countries in Africa and the Caribbean retained influences such as the English language and governance systems modelled on that of the UK. Initially, these post-independence relations were largely marked by the UK’s soft power, shaping the nation-building processes in these regions.

Over time, however, this influence has become a two-way exchange. African and Caribbean cultures have profoundly shaped modern Britain – from music and food to sports, arts, literature and beyond. These evolving dynamics have not only enriched the UK’s cultural landscape but also provided significant benefits for diaspora communities, fostering a sense of belonging and promoting cultural exchange. Diaspora groups and civil society organizations have adeptly utilised these connections to advocate for their communities and advance their interests.

At this event, speakers will explore how African and Caribbean influences rose to prominence in the UK and how this cultural momentum can be harnessed to build stronger, forward-looking partnerships. By highlighting the shared histories and more vibrant present-day exchanges, this event will explore how these ties can be used to break down stereotypes, promote social cohesion, and contribute to a more inclusive future.

This event forms part of our series of events celebrating Black History Month, including a photo exhibition and drinks reception.

Is the world ready for the next pandemic? 29 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 9 October 2024 Chatham House and Online

In a joint event with The Elders, Helen Clark, Ban Ki-moon and other experts discuss the policies needed to prevent the next health catastrophe. A drinks reception will follow this event.

The world faces multiple interlinked existential threats such as pandemics and the climate crisis, exacerbated by conflict and extreme poverty. However, the multilateral system is failing to respond with sufficient urgency or impact. As the fifth anniversary of the COVID-19 pandemic approaches, Chatham House and The Elders will discuss the risk of a general slide into complacency. 

Amid the expanding outbreak of mpox in Africa, rich countries continue to withhold stockpiled mpox vaccines. The failure to release the required amount is contributing to the diseases spread across the continent. 

Meanwhile, the Pandemic Accord negotiations are in overtime, with nations unable to reach agreement over concerns around sovereignty and resource distribution in any future pandemic. Similarly, a proposal to include a UN Emergency Platform in the recent Summit of the Future to strengthen the multilateral response to complex global shocks was shelved due to political deadlock.

Can the world learn from past mistakes and break the cycle of panic and neglect? In today’s fractious and polarized geopolitical context, what would it take for leaders to do what’s necessary? And why is it so critical to have equity at the heart of any sustainable global response?

Join Chatham House for this event in which the panel discuss key questions including:

• Five years on from COVID-19, who is showing global leadership today in preparing for future pandemics?
• Are international organizations and institutions fit for purpose to respond to pandemics in a multipolar geopolitical environment? How can they best adapt?
• What can be done to clarify and detoxify current debates around sovereignty to improve global pandemic prevention, preparedness and response?

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.

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.

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.

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.

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,...

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).

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.

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.

• 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.