Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: Report 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.

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.

President-elect Donald Trump is reportedly considering lawyer Alina Habba to be the White House press secretary. Habba often spoke to the media while she was on the legal team representing […]

The post Report Shows New Front-Runner for Trump's Press Secretary Spot: The Media Should Be Terrified appeared first on The Western Journal.

Springbok team doctor Jerome Mampane says that injured utility back Sacha Feinberg-Mngomezulu is recovering well.

By JEAN-PIERRE LLEDO MABATIM Oct. 16, 2022 Toutes les informations qui nous parviennent d’Iran nous disent que cette nouvelle révolte est totalement inédite. Elle se distingue de toutes les précédentes parce que ce sont les femmes qui en ont pris l’initiative et plus encore parce que ce qui est ciblé n’est pas seulement le pouvoir, […]

Mekka Newspaper, Mecca, Saudi Arabia: Oct. 28, 2022 It was my distinct honor to Arabic receive a wonderful review by Mecca Newspaper, one of the oldest newspapers in the Middle East. I am deeply grateful and humbled to be part of the historic reformation and renaissance taking place in the Middle East. When Mecca newspaper […]

Cairo, Egypt Oct. 28, 2022 On Egyptian TV show, “Headlines,” Dr. Hossam Farouk dedicated an episode to discussing national and international coverage of the Secret Apparatus: The Muslim Brotherhood’s Industry of Death. It was a great honor having the book featured on this great show.

Presented by the Middle East Forum on Nov. 18, 2022 Panel discussion with Daniel Pipes, Cynthia Farahat, and Jonathan Schanzer:

Originally published in Gatestone Institute on Nov. 25, 2022 By Cynthia Farahat Bahgat Saber, a member of the Muslim Brotherhood, operates from his New York apartment and often streams live videos from Times Square. During his multi-hour videos, Saber routinely incites terrorism, assassinations, kidnapping and torture in an extremely graphic manner. The calls for violence […]

Carvana is America’s fastest-growing e-tailer   February 23, 2022 (New York, NY) – Americans have taken to buying cars online, so much so that ecommerce car dealer Carvana is now […]

Amazon’s share declines for first time; Apple surpasses eBay in online sales June 14, 2022 (New York, NY) – This year will mark a major US retail milestone, as ecommerce […]

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

Alexander Kupers and Oscar Randal-Williams
J. Amer. Math. Soc. 38 (), 63-178.
Abstract, references and article information

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

Beijing briefing: China bets on warmer EU relations The World Today mhiggins.drupal 30 January 2023

With the Sino-US Xi relationship cooling, Xi Jinping is sending a new diplomatic team to Europe – but his ties to Putin may mean slow progress, writes Yu Jie.

It has been a momentous year for Beijing. Twelve months after Russia’s invasion of Ukraine, its relations with the West have become more strained than ever. And after President Xi Jinping secured an unprecedented third term in office at the 20th Party Congress, the country has embarked on a chaotic exit from the Covid lockdown amid hopes the economy will rebound quickly.

Some are already asking if Beijing will set a course correction in its diplomatic priorities to spare itself some of the setbacks it incurred in 2022. But when it comes to foreign affairs, China’s priorities rarely change. 

The Chinese leadership seeks to create a stable external environment to allow its domestic economic development. This conservative maxim was adopted in the 1980s by Deng Xiaoping, and President Xi is likely to follow it as a time-honoured recipe for diplomatic reconciliation.

China’s awkward position

Beijing’s close relationship with Moscow and its failure to oppose Russia’s invasion of Ukraine have put China in an awkward position. Xi and his colleagues have begun to realize that cooperation with Russia comes with substantial limits to avoid undermining China’s own political priorities and longer-term economic interests.

Interestingly, pundits interpreted the omission of ‘pursuing new types of great power relations’ in the 20th Party Congress report as an acceptance by the party leadership that its fraught relationship with advanced developed nations is likely to remain, with little prospect of improvement in the short term.

Chinese diplomatic literature has always presented Russia as a great power, but the abandonment of such terms signals that Beijing is keen to put clear daylight between itself and Vladimir Putin, although international commentators may argue this is not enough and nothing has changed.

There has been little sign of China using its influence to help resolve the Ukraine conflict. Facing, as it feels it now does, a ‘collective West’ and not the Americans alone, Beijing has concluded there are few reasons not to move closer to Russia.

But a reset would appear necessary if China is to tackle its domestic economic woes. So far, Beijing’s main political tactic has been to reassure European countries that it is willing to use its ties with Russia to restrain Putin from entertaining the deployment of nuclear weapons. That was the message conveyed during the visit of Olaf Scholz, the German Chancellor, and it will be said again when both President Emmanuel Macron of France and Giorgia Meloni, Italy’s prime minister, each visit later this year.

Economically, China has traditionally relied on its relationships with the European Union and the United States to support innovation and growth. So, a perceived isolation from ‘a collective West’ is not an attractive option given Xi’s hopes of achieving a robust economic rebound after dropping the country’s ‘zero-covid’ policy. A precarious bilateral tie with the US has already reduced Beijing’s choice of partners and consumers. Worsening Sino-US relations and a tightening of access to overseas markets for Chinese companies have prompted Beijing not only to reconsider the country’s sources of economic growth but to reconfigure its approach to foreign affairs.

China is making a renewed push to strengthen ties with the Global South, which does not see the war in Ukraine as black and white as the West does. Such a move is only possible because five decades of engagement with the ‘collective West’ has allowed China to emerge from poverty and become a global economic powerhouse.

A new diplomatic team

In an attempt to reset the tone of China’s relations with the EU, its largest trading partner, Xi has formed a new diplomatic team headed by Qin Gang, as Minister of Foreign Affairs, who is returning from his post in Washington as ambassador to the US and who has a background in European affairs. Achieving warmer relations will be easier said than done, however, as China has maintained its ‘neutrality’ at Russia’s aggression since February 2022.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

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?

Sustainability Accelerator Summer Drinks 2024 6 September 2024 — 5:30PM TO 7:30PM Anonymous (not verified) 19 August 2024 Chatham House

Join us for the Sustainability Accelerator’s annual summer drinks reception.

This event brings together a diverse group of thinkers and changemakers from our network, as well as our collaboration partners, to reflect on our successes over the past year and give an opportunity to meet new people.

The reception will follow the Sustainability Accelerator’s annual UnConference, but is a separate event. Unless you have received confirmation of your place at UnConference, you must register for the summer drinks reception via this webpage to secure your place.

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. 

Member’s question time: Is Russia losing the South Caucasus? 22 October 2024 — 1:00PM TO 1:30PM Anonymous (not verified) 2 September 2024 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.

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) 5 September 2024 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.

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?

In conversation with Speaker Emerita Nancy Pelosi 14 October 2024 — 12:00PM TO 1:00PM Anonymous (not verified) 19 September 2024 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.

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?

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).

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.

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.

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.

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.

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.

Development Prospects in the Asia-Pacific: The Role of the Asian Development Bank 25 September 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 4 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The speaker will discuss development prospects in the Asia-Pacific and their implications for Europe and the UK. He will outline prospects for the region’s growth, the impact of the current US-China trade conflict as well as other challenges faced by the region. He will also discuss the future role of the Asian Development Bank and how it plans to support the further development of the region.

What are the lasting impacts of the AUKUS agreement? Interview LJefferson 15 August 2022

Drawing on their International Affairs article, Jamal Barnes and Samuel Makinda outline the effect of AUKUS on Australia-France relations and the liberal order.

Almost a year after the surprise announcement of the AUKUS treaty, its full diplomatic implications are still being understood. The security cooperation agreement between Australia, the US and the UK caused outrage in France and was a notable source of discord between states that see themselves as defenders of the liberal international order.

In this interview Jamal Barnes and Samuel Makinda discuss their recent article in International Affairs and assess the effect of the agreement on relationships between its signatories and France and the EU, the potential for reconciliation in the treaty’s aftermath, as well as the implications it has for trust in world politics.  

What was the AUKUS treaty and why did Australia sign it?

The AUKUS treaty is an agreement between Australia, the US and the UK. Signed in 2021, it facilitates cooperation on security issues in the Indo-Pacific between the three countries – specifically, it concerns the sharing of ‘military capabilities and critical technologies, such as cyber, artificial intelligence, quantum technologies, and undersea domains’.

A key aspect is that Australia will purchase nuclear-fuelled submarines from either the US or UK. Australia decided to purchase nuclear-powered submarines – and reneged on its 2016 agreement to purchase French-built diesel-propelled submarines – because it believed that the French-made submarines were no longer fit for purpose.

However, the agreement is about more than submarines. Although Australia, the UK and US argue that AUKUS is designed to defend the rules-based international order and help ‘preserve security and stability in the Indo-Pacific’, AUKUS has been largely seen as a response to the rise of China and its military activities in the region. The AUKUS agreement reflects the increased attention that the US, UK and Australia are paying to the Indo-Pacific and their commitment to constraining China’s exercise of power in the region.

What were the effects of the AUKUS treaty on relations between Australia and France?

It led to a serious diplomatic rift. Australian officials, including former Prime Minister Morrison, had visited President Macron in France and told him nothing about AUKUS. Morrison had assured Macron in June 2021 while former Australian foreign and defence ministers had assured their French counterparts that Australia was fully committed to the purchase of French submarines just two weeks before the announcement of AUKUS.

When French officials found out about AUKUS on the day it was announced on 15 September 2021, they declared publicly that they had been betrayed and stabbed in the back. Not only had France built its relationship with Australia on trust, but its relationship was more than just about submarines. It was designed to be central to France’s 50-year engagement strategy in the Indo-Pacific. However, France was not only left out of talks but was also betrayed by a country it considered a close ally.

France responded by temporarily recalling its ambassador and stated that it would ‘redefine’ its relationship with Australia. It did not say that it would not work with Australia, but rather downgraded its relationship to one where it would only do so on a case-by-case basis.

In your article you mention that the AUKUS treaty was seen as a betrayal of trust by France in particular. Why use the word ‘betrayal’?

The word betrayal is accurate because Australia’s actions went beyond simply cancelling a business contract. Australia breached France’s trust. Not all agreements involve trust. Some are driven by self-interest while others are simply legal contracts. When these agreements are broken, the usual response is feelings of disappointment and a belief that one party is unreliable and has not lived up to its end of the agreement.

However, when diplomatic partnerships involve trust, they often contain an emotional element. A key element of trust is that one party makes itself vulnerable to another in the expectation that neither party will take advantage. When that trust is breached, the response is different from a breach of contract.

It involves feelings of betrayal as deeper emotional factors are involved. This could be seen in President Macron’s anger, and his and other French officials’ willingness to publicly call Prime Minister Morrison a liar who had stabbed France in the back. If the previous France-Australia agreement was simply a legal contract, it would have been difficult to explain the emotional element of this diplomatic fallout.

How did the signing of the AUKUS treaty affect wider relations between members of AUKUS and EU member states?

The EU, like France, felt betrayed by the AUKUS announcement. Despite being a key ally of the US, Australia, and the UK, it was left out of AUKUS discussions, and was not aware of the agreement until it was announced in the media.

What made this worse was that the EU was in the process of announcing its Indo-Pacific strategy, which was characterized as ‘maybe one of the [EU’s] most important geopolitical documents’ by High Representative for Foreign and Security Affairs, Josep Borrell. For the EU, this was the latest in a long line of recent policy betrayals that had left it uncertain if it could trust key allies on important issues. The result was greater calls from within the EU to more forcefully pursue ‘strategic autonomy’, meaning a more assertive and independent EU foreign policy.

Do betrayals of trust affect the health of the liberal international order?

Yes, they can. While it is common for leaders in liberal democracies to lie to their own people, lying to the leaders of other countries can have serious repercussions for the norms, rules and institutions of international society. A key aspect of international society is the ‘presumption of trust’ that facilitates legal compliance and diplomatic cooperation.

Without this presumption it is difficult for states to engage in long term partnerships or have confidence that diplomatic agreements will be upheld. In our article, we highlight how Australia’s violation of a particular norm, that agreements must be kept, has undermined this presumption of trust. This norm not only helps build trust between states, but also contributes to the maintenance of international order by helping to support the presumption of trust in international society.

Nuclear proliferation in a fragmenting world 13 September 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 5 September 2022 Online

Where does the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) stand in 2022?

With the war in Ukraine and China–US tensions rising, the threat of a nuclear arms race has never been as high since the Cold War.

Global efforts to control the appropriation and use of nuclear weapons are strained with the war in Ukraine, US–Russia and US–China tension, Iran on the nuclear threshold, instability in Pakistan and the ongoing threat from North Korea.

The Review Conference of the NPT that took place in New York this August sought to deal with the multiple nuclear threats, but new missile technology such as hypersonic glide vehicles and torpedoes are not covered by a treaty.

Russia and the US are in a development phase for a host of new technologies and delivery systems, especially after both withdrew from various arms-control treaties in the 2000s and 2010s. Now the nuclear stockpile is growing again and major superpowers are adopting confrontational geostrategic positions.

As the world’s established orders and system fragment, there is a possibility the nine countries with confirmed nuclear weapons could grow. Events in Ukraine highlight the need for a new, modern agreement on nuclear weapons control, needed today more than ever.

The panel of experts discuss key questions including:

• What did ‘RevCon’ in New York tell us about the adoption or update to the NPT?

• Will the war in Ukraine deter or prevent any agreement between nations or does nuclear weapons control represent an area of potential multilateral harmony?

• Are we likely to see a new arms race akin to the Cold War? Where does China fit into this race?

• How has technology changed the arms control landscape?

 As with all Chatham House member events, questions from members drive the conversation.

Interview: Nicole Hemmer The World Today rescobales.drupal 27 September 2022

The political historian talks to Mike Higgins about how Donald Trump has transformed the US midterm elections and the Republican party’s lurch further right.

Partisans: The Conservative Revolutionaries Who Remade American Politics in the 1990s
Nicole Hemmer, Basic Books, $18.99

In Partisans, you argue that the American political far right had been preparing the conditions for Donald Trump for 25 years and ‘the puzzle pieces snapped into place’ when he was nominated in 2016. What did you mean by that?

There were changes happening in plain sight over a quarter of a century. Such as the rise of presidential candidates who had never held elected office but who had a following in conservative media and cable news more broadly. There was also a turn towards pessimism, to connections with extreme groups and to procedural extremism in the Republican Party, such as the impeachment of Bill Clinton over what most Americans agreed was a small indiscretion.

All that accelerates in the 2000s and 2010s to the point where if you look back from Trump’s election, he suddenly seems eligible in a way that I don’t think he was in 2015 during his ascendancy.

 How did the end of the Cold War open the door for the hard right in the early 1990s?

The Cold War is so important to making sense of conservative politics in the United States because it sat at the core of American conservatism for 50 years. Opposition to Soviet communism held together the conservative coalition. It brought together religious conservatives who talked about the atheistic Soviet Union with the libertarians who were fearful of a big state.

The Cold War forced conservatives to talk in a language of freedom and democracy because that was the way that the US was different from the Soviet Union. Ronald Reagan, in particular, was a master of this. It had real implications for domestic policy. Reagan embraced free trade and talked about immigration and diversity as things that were great for America.

And then the Cold War ends, and you have politicians like Pat Buchanan [a former White House Communications Director] who had been beating the Reagan line for years, coming out and saying: ‘You know what? Immigration is bad and immigrants are bad. They are harmful for the United States. Free Trade is bad. We need to have more protectionist economy and build Fortress America. And, by the way, democracy might not actually be the best form of government for our country. The Marine Corps and IBM are better run than the federal government, and those are autocratic governed institutions.’

It allowed a resurgence of a right-wing politics that the US hadn’t seen since the 1930s and 1940s. It would become a powerful political movement within conservatism that we ultimately see taking over the Republican Party by the 2010s.

 What was it that allowed far-right figures such as Rush Limbaugh to take advantage of the transformation of the media in the 1990s?

Part of what they saw in it was interactivity. We tend to associate that with the internet and with the rise of social media, but call-in national radio and cable TV gave people an opportunity to have their voices heard.

The most popular TV show on CNN was Larry King Live, a call-in show. That interactivity fed into this idea that a frustrated populace suddenly had a voice, and it was easy to play on that sense of frustration. Also, the right was innovative because they had been focused on alternative media for decades.

So, as you get new formats in the 1990s like political talk radio and cable news, conservatives were already in that space looking for ways to get their message across.

Also, journalistic objectivity in the 1990s became getting a voice from the right and a voice from the left, which opened the door for a new generation of conservative pundits such as TV hosts Laura Ingraham and Ann Coulter. You have these incentives drawing the right into this new media and all of these conservatives in the base who are looking for right-wing voices.

There are hearings into the January 6, 2021, Capitol invasion and an FBI investigation into the alleged presence of confidential papers at Trump’s residence Mar-a-Lago. Are we about to witness the insurgent far right within the Republican Party being brought to account legally?

There has been more accountability than I anticipated at the beginning of the Trump presidency. Some innovative legal techniques are being used successfully, such as sedition and conspiracy charges against some of the Capitol rioters.

Steve Bannon, one of Trump’s chief advisers in the 2016 campaign, has been charged with money laundering, conspiracy and fraud during the Trump presidency. Will that accountability lead to a fundamental transformation of right-wing politics in the US? I wouldn’t bet on that.

How is the radicalism of the Republican party shaping the upcoming mid-term elections?

The real radicalism in the Republican Party now is its willingness to use both procedural mechanisms but also mob violence to get the electoral outcomes that it wants – something that we saw with the insurrection on January 6, 2021.

That makes the mid-terms an existential election if Republicans are able to vote in candidates who are running on a platform of throwing out election results if Republicans don’t win. That is a real challenge to the future of American democracy.

As long as the political system is organized around one party that respects the rules of democracy and one party that fights against them, each election is going to be existential. It will make mid-term elections have the weight that the 2016 and 2020 presidential elections had.

Did the far right misunderstand the electorate when it comes to abortion, considering the strong reaction to the Dobbs ruling?

I think that is exactly right, and it’s fascinating. A major turn happens in American politics between the 1980s and the 1990s, especially on the right. Ronald Reagan built these broad coalitions. He was winning landslide elections, and building this ‘big tent’ party that would bring in people who didn’t identify as Republicans or conservatives.

By the time you get to the 1990s, you have this idea of the Rino – politicians who are ‘Republican in name only’. You had to be purer and purer when it came to your right-wing politics. And the Republican Party grew a lot more unpopular. It has lost elections because of the extremism of its candidates, but it has still been able to win democratic elections without majorities, something we saw in 2000 and 2016.

The outcome of it all is exactly what you are seeing right now, that in many ways the conservative movement has got something it wanted for half a century, which is the overturning of Roe v Wade – something that energized its space for a very long time. Now that the dog has caught the fire truck, it is looking around and saying: ‘Oh, people do not like this.’

August’s referendum in Kansas that upheld the right to abortion mobilized lots of voters who normally wouldn’t have come out for an off-year election.

As you get more stories of 10-year-old rape victims who have to go to a different state to get an abortion, or stories of women who have high-risk pregnancies not able to get medical care because of these new extremist laws, that really does mobilize a population who understand what is at stake.

It is not just their access to abortion, but to reproductive healthcare more broadly. Not everywhere, but in some places that is going to change the dynamics of these mid-term races.

Why America’s midterm elections matter for the world The World Today mhiggins.drupal 28 September 2022

The outcome could threaten the fight against climate change and the future of democracy itself, warns Leslie Vinjamuri.

As the November 8 midterm elections in the United States approach, the sense of urgency among the Democrats and Republicans is escalating. Early voter turnout is on track to surpass the 2018 midterms, when a record 122 million Americans voted ahead of election day. The midterms – when congressional, state and local seats are determined – used to pass almost unnoticed, especially outside the US.

Since 2018, though, they have become a matter of global concern. The 2022 midterm elections will be the first major elections in the US since the January 6 insurrection at the US Capitol. As such, they will be the first real litmus test for the continued relevance of Donald Trump and Trumpism.

For both parties, winning is more important than ever and it is not only a matter of policy. Today, a majority of members of both parties – 72 per cent of Republicans and 63 per cent of Democrats – see those belonging to the opposing party as immoral, according to a Pew Research Center poll in September, representing a significant rise since 2016.

In many states, the midterms will have a direct impact on the 2024 presidential elections, influencing who decides how voting takes place, how votes are counted and, especially, who controls the certification of election results.

Given this context, the stakes in elections are especially high. The winners will have the upper hand not only in defining many procedural rules but also the values that constitute the nation, such as on abortion rights, education and healthcare.

Republicans and Democrats align on most key foreign policy

Though foreign policy will bear a strong resemblance to its former self even if Republicans gain a majority in the House of Representatives, as many anticipate, the outcome of the elections on US global influence could impact efforts to combat climate change and to support the defence of Ukraine.

The Republican Party has become known for its embrace of climate deniers and the radicalized anti-immigrant rhetoric of many of its party’s most established figures. The failure to address rampant gun violence – and, instead, to defend a historically suspect interpretation of the right to bear arms – and the push for a national abortion ban mean that the party is imposing a version of America onto itself that is out-of-step with virtually all other rich democratic countries.

The choices voters make in November are likely to shape the values that come to the fore in the US, and with this the affinity that America’s closest partners feel for it.

Domestic policy is likely to be more heavily affected by the elections. A Republican majority in the House would stall progress on President Joe Biden’s domestic agenda and undercut his ability to raise the taxes he needs to pay for his spending plans. The drive to hold the former President Trump accountable will also be affected by the choices voters make in November.

A Republican majority in the House would spell an end to congressional investigations of Donald Trump. Instead, Republicans would use their electoral gains to launch their investigations into the Democrats.

One anti-Trump Republican on the January 6 committee investigating the storming of the Capitol building last year warned of a vengeful and obstructive turn against Biden from his Republican colleagues if they took the House. ‘They’re going to demand an impeachment vote on President Biden every week,’ said congressman Adam Kinzinger. It is under this shadow that the January 6 Committee is pressing ahead to finish its proceedings and publish its report.

On foreign policy, the parties are more aligned than divided on most of the key issues. Their differences are a matter of diplomacy, which matters, and degree. Support for Ukraine has had bipartisan backing, but in recent weeks the issue has become politicized. Some congressional Republicans are more hawkish than their Democratic counterparts in their ambition to support Ukraine. Yet, the congressman set to be Speaker of the House if Republicans gain a majority, Kevin McCarthy, is leading an effort to exercise far stronger oversight of any additional funds for Ukraine.

Ultimately, though, the president and his advisers maintain considerable control over foreign policy.  

Bipartisan support for a tougher stance on China was consolidated under Trump. He mobilized US voters by blaming China for the loss of manufacturing jobs. Later he held China responsible for the outbreak of Covid and for covering it up. China’s crackdown on democracy in Hong Kong, its assertiveness in the South China Seas, tensions over Taiwan and reports of human rights abuse against the Uighur in Xinjiang have cemented a bipartisan consensus on America’s China policy. But a more empowered Republican base looks likely to lead to a more ideologically driven anti-China rhetoric. 

The ground has also shifted over Russia. During President Trump’s tenure, Republican attitudes towards Vladimir Putin softened. But the Russian president’s aggressive invasion of Ukraine has entrenched American opposition to him and bolstered support for NATO.

Democrats and Republicans are also more aligned on policy towards Iran today than they were before Trump abandoned the Iran Deal negotiating the Middle Eastern country’s nuclear programme. On some contentious issues, such as immigration reform, progress is already stalled and that is unlikely to change.

US climate change policy may depend on the results

The upshot of all this is that the president is unlikely to make radical changes to US foreign policy regardless of the results of the midterms. The most important exception to this is climate change, which continues to be the unwanted stepchild of the Republican Party. Domestic infighting in the US would inevitably detract even further from the bold policy that is needed.

Republicans are unlikely to get the two-thirds majority needed to pass legislation that would undermine President Biden’s climate bill. Republican control of House committees, however, would add more politically driven oversight of any climate spending, including what has already been authorized by the Inflation Reduction Act. 

Policy convergence and clear executive authority cannot mitigate the sheer disruption that would be unleashed if the Republicans were to gain majorities in both the Senate and the House, however. For the rest of the world, and especially within Europe, this would send warning signs about the future trajectory of US foreign policy commitments and set off alarm bells that an ‘America First’ president might return to the White House after 2024.

A Republican majority in the House with a Democratic majority in the Senate would be disruptive, if less so, but would probably spell the end of business as usual, unsettling people, states and markets. All of this is unfolding at a time when many of the world’s rich democracies face internal divisions, rising inequality and populist challenges at home and so are ill-equipped to lead.

Democracies face a trust deficit. This is especially apparent in the US where only 43 per cent of Americans have trust in US institutions, according to the 2022 Edelman Trust Barometer.

Internal threats to democracy also unsettle the promise of US global leadership at a time when concerted and determined leadership is needed to maintain a strong and united response to Russia, and to tackle global food insecurity and the energy, climate and debt crises. In addition, the failure to lead a global response that can help developing countries is feeding a trust deficit between rich and poor countries.

The midterms will reveal a greater truth about the future of the Republican Party. Even more so, it will reveal the values held by the American electorate. In the run-up to the 2020 US presidential elections, Europeans frequently said that they would not give Americans a pass if they voted for Donald Trump twice – and indeed only 17 per cent of those in European Union countries would have cast a vote for Trump if they could.

A Republican midterm victory in both the Senate and the House of Representatives would have ripple effects across the Atlantic at a time when the threat from Russia has intensified.

The US is judged around the world for what it does, but also for who it is. The perception that democracy is failing in America creates a permissive environment for aspiring autocrats. At a time when democracy has been in decline around the world for more than 15 years, it is essential that the US fix its own democracy and that it demonstrates to the rest of the world that democracy can deliver.

The midterms will signal to the world what Americans value, sending a message about what it can expect from the US.

This article was updated on October 31, 2022 to reflect developments such as early voting turnout, and the impact of the midterms on the 2024 presidential election, support for Ukraine and climate change spending.

Director's briefing: What next for America? 17 November 2022 — 8:00AM TO 9:15AM Anonymous (not verified) 7 November 2022 Chatham House

Chatham House’s Director of the US and America’s Programme discusses what is next for America following one of the most contentious midterms races to date.

Hosted by Bronwen Maddox, Director, Chatham House, this Director’s Briefing is an opportunity to digest the outcomes of the US Midterm elections with Chatham House’s Director of the US and Americas Programme, Dr Leslie Vinjamuri. 

Arguably one of the most contentious midterm races to date, this election has key implications for the rest of the world also. At this event, Dr Leslie Vinjamuri and Bronwen Maddox will discuss the crucial themes coming out of the election and the key issues on voters’ minds. What impact will the results have on US foreign policy more broadly? What might the outcome of the election signal about Trumpism? And how confident can we be about the strength of US democracy?

This event is only open to Chatham House Partners and Major Corporate Members as well as selected giving circles of Chatham House. If you would like to attend, please RSVP to Linda Bedford at RSVP@chathamhouse.org.

America’s vote shows a desire for stability and calm Expert comment NCapeling 11 November 2022

Joe Biden has presided over the best midterm election results by a party in power in two decades, but the future for the Republican Party leadership is now uncertain.

For a president continually struggling with low approval ratings, the midterms provided a stunning result as the widely anticipated Republican red wave failed to materialize.

Although Democrats look set to lose their majority in the House, it is by a much smaller margin than either history or today’s pollsters anticipated. Democrats have maintained their majority in the Senate, a result that was confirmed four days after election day when Senator Catherine Cortez Masto won reelection. The final Senate seat will be decided by a 6 December run-off in the state of Georgia. 

The midterm elections were not good for the Republican party but were especially bad for Donald Trump who has until now managed to defy expectations and maintain his grip on the party even after his 2020 defeat at the polls.

Trump managed to win the presidency once but he lost the popular vote twice and at no stage during his time in office did his approval ratings go above 40 per cent. Now, after six years of the most divisive and disruptive leadership the US has ever seen, he has presided over the worst midterm results a party out of power has suffered in two decades.

Trump’s influence is on the wane

Many of the candidates endorsed by the former president – including in battleground states such as Pennsylvania and Arizona – lost. In Georgia, the Republican governor and Trump GOP rival won, despite Trump’s opposition, and the candidate he endorsed for the US Senate has come up short of the 50 per cent needed to get over the line in the first round.

Trump’s nemesis, Ron DeSantis, the Republican governor of Florida, won a second four-year term in a landslide. Trump is suffering attacks from his own party and many loyal media supporters, such as Fox News, the New York Post, and the Wall Street Journal. None of this bodes well for the prospect of Trump leading the party through the 2024 presidential election.

After six years of chaos, this upset has been delivered with remarkably little chaos and, so far, no violence in a win for democracy and stability in the US which will reverberate beyond the US shores.

The system has worked, with multiple elections held across all 50 states. Hotly contested seats were decided peacefully even when the margins were thin. The midterm elections were also a win for democracy. In every battleground state, election deniers that were nominated to run for offices that would control state election systems, including in the 2024 presidential elections, have been defeated.

For a country with a polarized electorate and a radical Republican leader who has continued to spread disinformation and sought to rile his base, this election has been surprisingly normal.

This means the debate about the future of America’s international leadership is postponed. Biden is still in the saddle and, instead of a battle for control inside the Democratic party, it is the Republicans who look set to descend into internal conflict and recrimination.

The unofficial contest to win the Republican nomination for president has already begun. Donald Trump has signalled loudly that he plans to run. If he does, it could impact Republican prospects in the 6 December runoff for the final seat in the Senate. DeSantis may also run and could be followed by several aspiring Republican candidates. A disrupted party facing a period of significant change seems likely. 

Inflation and the economy proved key factors

As always, foreign policy barely featured in the elections but the result promises a period of continuity. Instead of facing dangerous sniping on Ukraine from an emboldened Republican House leadership, the Biden administration looks set to hold to its Ukraine policy.

Biden’s increasingly hard-line policy on China will continue to be qualified by a clear-headed determination – however hard – to cooperate on climate. Trade policy will remain stuck, as will US policy in the developing world.

Exit polls show Democrats were motivated to vote by the reversal of Roe vs Wade and the restrictions on abortion rights that followed, while Republicans voted against inflation.

But Democrats at the national level continually failed to effectively communicate the positive impacts of Biden’s legislative agenda for ordinary Americans, or to deliver a clear economic message.

The national leadership veered from abortion rights to the Inflation Reduction Act, to the future of democracy in the US – all of which proved too complicated to cut through.

The state level shows a more complex picture because inflation and the economy – which could have swept Republicans to victory – were blunted by dogged local campaigning from Democrats who knew their voters and spoke to the cost-of-living concerns which were top of their minds.

Critical elections and the future of American politics 14 December 2022 — 9:00AM TO 10:15AM Anonymous (not verified) 8 December 2022 Chatham House

This event explores whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Drawing on current and historical events, Paul E. Peterson joins us to examine whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Key questions to consider include:

• What factors might be driving such an evolution within both parties?

• How could these dynamics affect the balance of power in Washington and in states?

This event is co-hosted with the Centre on US Politics at UCL, and the US and Americas programme at Chatham House would like to thank the British Association for American Studies for their generous support of this event.