National security and transatlantic unity top Biden’s agenda Expert comment NCapeling 1 February 2023

The timing of the State of the Union address is significant as Joe Biden tries to maintain focus on Ukraine and China while navigating partisanship at home.

Although primarily a domestic affair, the president’s remarks in the annual State of the Union (SOTU) telegraph the US’s foreign policy priorities to the rest of the world. They reveal the prism through which the US understands its national security and its role in the world.

The 2023 address comes as the first anniversary of the Ukraine invasion rapidly approaches, and the US is also trying to build international support for tough economic measures towards China. Domestically, Republican control of the House of Representatives will exert new pressure on US foreign policy choices. Electoral pressures are also around the corner and Joe Biden should announce soon whether he plans to run for president in 2024.

Alliances and partnerships are a driving force for Biden. As pressure to end the war in Ukraine intensifies, maintaining transatlantic unity on Ukraine will be a key priority for the president. And as US electoral politics rise to the fore, ensuring the visibility of Europe’s role as a security provider in its own backyard will be essential.

For a US president who sees China and the Indo-Pacific as America’s most significant long-term geopolitical challenge – and the only peer competitor to the US – transatlantic unity on China will also come under pressure.

Ukraine, China, and controlling domestic division

Republican leaders who now chair key committees in the House of Representatives continue to signal support for Ukraine, and polling shows a majority of US public opinion (54 per cent) favours sending either weapons or air defence systems.

But recent polls also reveal a growing gap between Democrat and Republican supporters with a slight majority of Republicans (52 per cent) now opposing further support for Ukraine.

Biden’s ability to demonstrate that America and its European partners remain unified in their policy towards Ukraine and Russia will help him ward off partisanship at home. Congressional approval of $45 billion for Ukraine in its end of year spending budget will help the president remain above the fray of partisan politics for now. But if there is an absence of clear signs Ukraine is succeeding in its war aims, the challenge of maintaining domestic support could become more difficult.

A greater US focus on China, India, and on the Indo-Pacific in 2023 is also likely. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures. At a time of war in Europe, the president will place great emphasis on the need to maintain transatlantic unity and to work with a broader coalition of partners in the Indo-Pacific.

The groundwork for focus on China has already been laid. Throughout 2022, the Biden administration worked steadily, but quietly, to set out its China policy. Just before Russia’s invasion of Ukraine in February 2022, the US released its new US-Indo Pacific Strategy stressing regional partnerships – especially the Quad and ASEAN – and it’s determination to shape essential norms for the region.

It stated boldly – albeit in a document which was largely unnoticed – that the objective is not to change China but to ‘shape the strategic environment in which it operates’, a policy which signifies a clear departure from the more ideological approach pursued by the US during Donald Trump’s final year in office. And in May, the US announced its economic strategy for the region, the Indo-Pacific Economic Framework.

Now the terrain for competition with China and alignment with US partners and allies is heavily focused on technology and the daylight between national security and economic strategy in US China policy is rapidly disappearing. Biden’s policy focus of ‘invest (at home), align (with allies and partners), and compete (with China)’ has overshadowed earlier talk of cooperation between the US and China.

But as China opens its doors and Europe looks to bolster its economies, the US will have to work far harder to maintain transatlantic unity. Japan and the Netherlands embracing the US adoption of export controls on semiconductor chips is a positive sign, but the US’s economic strategy towards China may present harder choices to come for Europe. If China leans into its diplomacy, the pressure on transatlantic unity will also grow.

The new US Congress will only sharpen the president’s tough stance on China. Some Republican leaders still deny climate change and have demonstrated little interest in cooperating with China on debt relief for developing countries. The prospects for addressing critical global challenges appear dim without China’s collaboration, and the UK and Europe should work with the US president and Congress to correct this.

President Biden has clearly recognized that diplomacy will be critical in the months ahead. At a time of growing tensions, the potential for misperceptions or misunderstandings to create conflict will also increase, and so a US – and also European – commitment to broadening and deepening diplomacy with China is urgent but it also needs to be patient and sustained.

A new American industrial policy?

Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing. The American state appeared to be disturbingly absent in the early months of the US pandemic response – but now it is back and, in a surprising turn of events, is being cast as a solution not a problem.

US and Europe Strategic Security Cooperation: The View from Washington 27 March 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 9 March 2023 Chatham House

As the US prepares to enter the next presidential election cycle, can the transatlantic alliance stay the course, especially against a deepening Russia-China partnership?

Thank you for your interest in joining our event. Please plan to arrive at Chatham House from 08:45 GMT as the event will begin promptly at 09:00.

The Biden administration’s response to Russia’s war in Ukraine and the rise of a globally assertive China, as articulated in the 2022 US national strategy, is to ‘constrain Russia and out-compete China’. It needs Europe as a partner and ally for both – yet Europe is also an object and a battleground in this era of strategic competition.

As the US prepares to enter the next presidential election cycle, can the transatlantic alliance stay the course, especially against a deepening Russia-China partnership? Can Europeans, in particular, move from deepening dependency to greater agency and self-reliance? What is the role for Germany – and for the UK?

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Space security 2025 5 March 2025 — 8:00AM TO 5:00PM Anonymous (not verified) 10 October 2024 Chatham House and Online

Join senior policymakers, space security experts and industry leaders for this unique conference, examining how space actors are tackling conflict and competition and enhancing cooperation in a fracturing world.

We’re pleased to offer you a 30% discount for our Security and Defence Conference on 6 March 2025. Simply use code SECDEF25SAVER at checkout.

Conflict, competition and cooperation in outer space

Space is a crucial domain of conflict, competition and cooperation. Recent years have seen the emergence of new actors in the ecosystem, as more countries seek to grow their presence in outer space, accompanied by the explosive growth of the space industry. Extraterrestrial exploration offers great opportunities, from the benefits of the space economy and technological developments to national security advantages. But with increasing activity and the diverging interests of state actors, governments, international organizations and the private sector are confronting fierce competition and the potential for conflict in space.

Alongside intensified competition, stakeholders are managing the growing role that space plays in modern military and defence strategies. Increased extraterrestrial activity has also created sustainability issues with serious security implications, demanding long-term solutions. At the same time, a fracturing global order poses major challenges to cooperation on space governance efforts and attempts to uphold international law.  

The 2025 Space Security Conference convenes policymakers and leaders from the private sector, multilateral organizations, academia and NGOs for a day of high-level interactive discussions examining conflict, competition and cooperation in outer space. Ahead of the 2025 Chatham House Security and Defence Conference, this event explores how the public and private sectors are addressing space security challenges and fostering a secure environment whilst harnessing the benefits of space for defence and economic growth.

Why attend?

• Gain unique insights into the many and varied threats to space security and how governments, international organizations and the private sector are tackling them.  
• Understand how key leaders in the domain are viewing the 21st century space race and what countries and space organizations are doing to mitigate conflict whilst keeping up in this competitive landscape.
• Network with senior leaders from across government, international organizations and industry in-person at Chatham House and access exclusive ‘under the Rule’ discussions. 

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.

In conversation with Julien Harneis, UN Assistant Secretary-General 18 November 2024 — 2:30PM TO 3:30PM Anonymous (not verified) 11 November 2024 Chatham House and Online

In this discussion, Julien Harneis will give critical insights into the UN’s humanitarian response in Yemen and the importance of maintaining independent humanitarian assistance.

According to the United Nations, Yemen has faced the world’s worst humanitarian crisis in the last decade, with over 20 million people in need of assistance. Years of ongoing conflict have devastated infrastructure, displaced millions, and caused widespread food insecurity and health emergencies. Access to essential services remains a daily struggle, and the escalating economic collapse has left vulnerable communities facing critical shortages in food, water, and medical supplies.

However, humanitarian actors are continually facing challenges in delivering aid to Yemen due to security threats and supply chain barriers, highlighting the urgent need for coordinated and sustainable international assistance.

UN Assistant Secretary-General and Humanitarian Coordinator for Yemen, Julien Harneis, will provide an account of the humanitarian mission and evolving strategies in Yemen, the impact of regional conflicts in the delivery of aid and discuss other key questions including:

JL Dixon
Feb 1, 1993; 34:167-179
Reviews

JP Segrest
Feb 1, 1992; 33:141-166
Reviews

Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security News Release sysadmin 27 June 2019

Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security.

Supporting Civic Space: The Role and Impact of the Private Sector 23 September 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online

The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism.

A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.

However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.

This roundtable brings together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space.

The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.

This meeting is the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. 

Supporting Civic Space: The Role and Impact of the Tech Sector 13 October 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online

This event brings together a diverse and international group of stakeholders to exchange perspectives and experiences on the role that tech actors can play in supporting civic space.

In a deteriorating environment for civic freedoms, tech sector actors are increasingly engaging, publicly or otherwise, on issues of civic space.

In the US, for example, a number of tech companies have cancelled contracts with the Pentagon and stopped censoring search results in China as a result of protests by employees. The Asia Internet Coalition recently wrote to Pakistan’s Prime Minister expressing human rights concerns about new rules regulating social media.

While we have recently seen technology companies show support for the social movements, including through substantial pledges, in some cases these have elicited criticism of hypocrisy, and the interventions of social media platforms on freedom of expression and privacy issues have been closely linked to the preservation of their own business models.

The COVID-19 crisis has also posed new dilemmas for the tech sector with the pervasiveness of disinformation, as well as new tools for tracking individuals which raise privacy issues.

This roundtable provides an opportunity to explore the drivers of (and barriers to) corporate activism, develop a better understanding of existing initiatives, identify good practice and routes to effective collaboration with other actors, and discuss practical strategies that could be adopted by the tech community.

It is the second of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space.

Why the private sector should protect civic society Explainer Video NCapeling 10 December 2021

A short animation explaining the crucial role that the private sector can play in protecting and defending civic space.

This video explainer introduces a synthesis paper which analyses how the private sector can support the protection of civic society space.

The private sector is in a unique position to work with civil society organizations to uphold and defend civic freedoms and support sustainable and profitable business environments. Companies have the capacity, resources and expertise to enhance the protection of civic space.

By doing so, this helps create a society in which fundamental rights and the rule of law are respected and exercised by governments, private citizens, and all organizations which, in turn, is critical to a sustainable and profitable business environment.  

For more information, download the report.

How are war crimes prosecuted? Explainer Video NCapeling 26 April 2022

Explaining what war crimes are and how, in the circumstances of Ukraine, could war crimes be prosecuted.

The Geneva Conventions and Protocol 1 describe what they call ‘grave breaches’ of international humanitarian law, and both Ukraine and Russia are parties to these treaties.

Grave breaches include directly attacking civilians and launching an indiscriminate attack affecting the civilian population or civilian property.

Many states and the International Criminal Court (ICC) also have the possibility to prosecute a wider set of war crimes although, in the past, states have not prosecuted many such crimes committed outside their own territory.

Neither Russia nor Ukraine is a party to the ICC Statute, but Ukraine did declared it accepted the Court’s jurisdiction for crimes on its territory, and and investigations have now started.

But there are several problems to be overcome to achieve successful prosecutions, such as the collection and preservation of evidence, proof of the intent of the suspects in the heat of war, how to be arrest suspects, and the issue of immunity.

Expert

Power Sector Transformation, New Market Dynamics and Geopolitical Implications 7 November 2018 — 8:00AM TO 9:30AM Anonymous (not verified) 6 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The global electricity sector is experiencing profound change due to a confluence of technological innovation, environmental policies and regulatory reform. The effect is most obvious in the EU28, Australia and parts of North America.

However, this is just the beginning and the success of the next phase of electricity sector transformations hinges on enhancing system flexibility to facilitate unhindered low-cost deployment of renewables. It remains to be seen how utilities will seek to navigate this second phase of electricity transformations.

This session starts with a presentation and discussion that focuses on:

• Public and private sector risks of the transformation of the power sector, changes in generation mix and their implications for supply chain, employments and investment patterns.
• The role of government and the regulatory framework in light of changing market structure, new entrants and big data.
• Wider geopolitical issues including the implication for fossil fuel producers and the rise in demand for new materials and changes in land use.
• The possible implications on the power sector on the electrification of heat and transport.

The discussion then moves to the speed of transformation and what this means for existing and new market actors.

Plant-based 'Meat' and Cultured Meat: Revolutionizing the Livestock Sector 10 April 2019 — 4:00PM TO 5:30PM Anonymous (not verified) 14 March 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Consensus is building across the scientific, environmental and public health communities that a radical shift away from excessive meat-eating patterns is urgently needed to tackle the unsustainability of the livestock sector. Recognizing the scale of the challenge ahead, public policymakers, civil society and innovators have increasingly sought to prompt shifts in consumer food choices – away from the most resource-intensive meat products and towards more sustainable alternatives.

Meat analogues – plant-based ‘meat’ and cultured meat also known as ‘lab-grown’ meat – mark a departure from traditional meat alternatives. Both are intended to be indistinguishable from – and in the case of cultured meat biologically equivalent to – animal-derived meat and are marketed principally at meat-eaters. Innovation and investment in meat analogues have increased significantly, but the direction and pace of growth in the meat analogue industry will depend upon a multitude of factors, including public acceptance, civil society support and incumbent industry responses.

This event will explore the challenges of scaling up production and generating demand for meat alternatives. It will also look at the ways policymakers in the UK and EU can impact the direction of the industry while examining what factors will influence consumer acceptance of plant-based ‘meat’ and cultured meat as substitutes for animal-derived meat.

COVID-19 and food security in southern Africa 16 July 2021 — 10:00AM TO 11:30AM Anonymous (not verified) 10 June 2021 Online

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa.

Developing climate smart agri-food systems in sub-Saharan Africa is a precondition for achieving the Sustainable Development Goals. Over the years household food security has been affected by different shocks including climate change and the recent COVID-19 pandemic.

The impact on rural households in southern Africa, in particular, has been significant due to the structure of food systems in the region.

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa and consider how practitioners and policymakers can build more equitable, resilient and better food systems. 

The Ukraine war and threats to food and energy security 13 April 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 6 April 2022 Online

What are the potential impacts on food and energy markets emerging from the situation in Ukraine?

Russia and Ukraine are key players in global energy, food, fertilizer and mineral markets. In the first few days after Russia’s invasion, both the threat and reality of resource flows being reduced drove up global prices, and has impacted the day-to-day life of people and businesses around the world.

Developing and nutrition-fragile countries across Africa and the Middle East will be hit the hardest – Somalia, for example, is reliant on Russia and Ukraine for 100 per cent of its wheat imports and is currently experiencing its worst drought in years.

The potential scale of disruption to food and energy markets increases with every week the war continues. This event launches the Environment and Society programme’s latest briefing paper The Ukraine war and threats to food and energy security: Cascading risks from rising prices and supply disruptions.

The panel discusses:

• The political, socio-economic and resource pressures already faced by the international community prior to Russia’s invasion of Ukraine.
• Direct and cascading impacts on the complex and interconnected energy, minerals, food and fertilizer markets, and policy or market responses that may exacerbate these impacts.
• Geopolitical ramifications that will affect the evolution of the conflict, as well as longer-term international cooperation and security.
• Measures that governments can take to build resilience, both to the ongoing impacts of the situation in Ukraine and to future risks of market disruption and geopolitical upheaval.

Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
Abstract, references and article information

Angela Robinson explains the math behind the next generation of cryptographic algorithms. Whenever you log in to a website, send an email, or make an online purchase, you're counting on your data being sent securely, without hackers being able to crack the code. Our standard cryptographic systems hinge on mathematical problems that stump present-day computers, like finding the prime factors of a very large number. But in the coming decades, powerful quantum computers are expected to be able to rapidly solve some such problems, threatening the security of our online communications. To develop new methods that can withstand even the most sophisticated quantum computer, cryptographers are using a wide range of mathematical tools, many of which were originally developed without any real-life applications in mind.

Switzerland-based reggae and dancehall recording artiste Cali P has expressed gratitude to the public for supporting his music, following the release of his latest single ' Secret Hater'. The song, which was produced jointly by himself and Suku...

Staff at the Secrets and Breathless resorts in Montego Bay, St James, walked off the job this morning complaining of overwork, low wages, lack of overtime pay and disrespect.

α1-antitrypsin (AAT) regulates the activity of multiple proteases in the lungs and liver. A mutant of AAT (E342K) called ATZ forms polymers that are present at only low levels in the serum and induce intracellular protein inclusions, causing lung emphysema and liver cirrhosis. An understanding of factors that can reduce the intracellular accumulation of ATZ is of great interest. We now show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media:cell ratio. This effect is more pronounced for ATZ than with AAT and is only partially dependent on the glycan-binding site of CRT, which is generally relevant to substrate recruitment and folding by CRT. The CRT-related chaperone calnexin does not enhance ATZ secretory trafficking, despite the higher cellular abundance of calnexin-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions with components required for ER-Golgi trafficking, coincident with reduced levels of the protein transport protein Sec31A in CRT-deficient cells. These findings indicate a novel role for CRT in promoting the secretory trafficking of a protein that forms polymers and large intracellular inclusions. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ inclusion bodies. Further understanding of the factors that control the secretory trafficking of ATZ and their regulation by CRT could lead to new therapies for lung and liver diseases linked to AAT deficiency.

A booming tech sector can unleash pan-African trade The World Today mhiggins.drupal 31 July 2022

The new African Continental Free Trade Area must embrace hyperscale data centres, cross-border digital payments and other innovations to realise its potential.

The Africa Continental Free Trade Area (AfCFTA) not only lays the groundwork for a single market across the continent, it can act as a driving force to unleash the full potential of the technology revolution that is under way across the African continent. 

To help achieve this, the AfCFTA must go beyond simply lowering barriers to the movement of goods and services, to what the World Bank calls an ‘FDI [foreign direct investment] deep scenario’. This requires harmonizing policies on investment, competition, intellectual property rights and e-commerce to encourage FDI at a greater scale. 

The World Bank estimates that the AfCFTA could increase income across the continent by 7 per cent by 2035 (an additional $445 billion), mainly by boosting intra-regional trade in manufactured goods and lifting approximately 40 million people from extreme poverty. Under an FDI deep scenario, the projected income growth jumps to 9 per cent by 2035, supporting 50 million people out of extreme poverty. 

The initial focus of the AfCFTA is on movement of goods and services and the associated financial flows through the establishment of the Pan-African Payment and Settlement System (PAPSS), a technology that enables instant local currency payment across Africa without first converting to a hard currency. In addition, harmonizing policies and easing the movement of data could enable technology to accelerate the anticipated AfCFTA income growth.

Global venture capital is pouring in

There is no doubt the African tech industry is growing. In 2021, 681 African technology companies raised $5.2 billion in equity venture funding, up from $2 billion in 2019, according to Partech Partners’ annual Africa Tech Venture Capital report. 

It is understandable why the industry has attracted global venture capital. While tech businesses are often initially focused on meeting needs in their home markets, most have a strong desire to tap into the pan-African market, with its 1.3 billion consumers across 54 countries and a combined GDP of $3.4 trillion. This in turn should attract global venture capital to invest in Africa. 

The AfCFTA has created a framework for technology-led companies to scale across the continent in a way that will impact digital infrastructure, logistics, energy and much else. For example, Africa’s hyperscale data centre capacity would benefit from the ability to locate centres in the lowest cost jurisdiction with the best energy availability and to use that to power cloud storage across the continent.

Yet various regulatory constraints, including the desire for each state to own its population’s data on local servers, prevent that. As a result, African data centres are less competitive than those in America and China. 

Similarly, logistics and other sectors would be transformed if the information on goods in transit, such as digital customs documentation, could move easily across borders while being tracked across all 54 countries. Financial services would also benefit from the ability to pay across borders in a low-cost, frictionless way.

Fintech companies should be encouraged to build technology solutions linking to PAPSS and other initiatives to accelerate the adoption-of-use cases that PAPSS supports – such as intra-Africa instant payment, embedded finance and remittances services.

AfCFTA may also unlock mergers and acquisitions (M&A) activity among African and international firms. Technology companies are using M&A to enter new markets, as the international payments platform Stripe did when it acquired the Nigerian business Paystack, and the payments business MFS Africa did when it took over the fintech start-up Baxi. 

Governments and regulators must support innovation

Given the difficulty of a country-by-country organic growth strategy across Africa, M&A is likely to increase in various technology sectors over the next few years. With the anticipated ease of doing business that the AfCFTA could facilitate, we are likely to witness further welcome consolidation, creating larger corporates that create more jobs and increase tax revenues. 

To unlock the benefits that technology will bring, governments and regulators need to play a supportive role in encouraging innovation. They will need to ensure the appropriate consumer protections are in place without stifling creativity through regulation, inefficiencies or rent-seeking. 

At the same time, governments and regulators should not permit themselves to be held to ransom by dominant incumbents, such as banks and mobile operators in the fintech space, at the expense of stifling technology companies looking to disrupt their respective industries. 

Only then will the AfCFTA allow Africa to benefit from its tech potential. 

Risana Zitha writes this article in a personal capacity

The Climate Briefing: The nexus of water security and climate policy Audio NCapeling 22 August 2022

Examining the crossover between water security and climate change with the next two COPs taking place in regions with a history of being water stressed.

What should policymakers and negotiators from the Middle East and Africa working on water security focus on at COP27?

What does it mean to achieve water security? What are the main barriers or challenges? How is water security relevant to climate change?

This podcast was produced in collaboration with the UK Aid-funded Knowledge, Evidence and Learning for Development (K4D) programme which facilitates the use of evidence and learning in international development policy and programming.

On October 24 and 25, SophosAI presents ideas on how to use models large and small—and defend against malignant ones.

Felicia Grasso
Dec 1, 2020; 19:1986-1996
Research

Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2–AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)–dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. In contrast, glucose stimulation induces cell spreading, actin remodeling, and point-like adhesions that contain phospho-FAK and phosphopaxillin, located in small protrusions. Rat primary β-cells and mouse insulinomas showed an adhesion remodeling during GSIS resulting from autocrine insulin/IGF2 and AKT1 signaling. However, under starving conditions, the maintenance of stress fibers and the large adhesion phenotype required autocrine IGF2-IGF1 receptor signaling mediated by AKT2 and elevated FAK-kinase activity and ROCK-RhoA levels but low levels of paxillin phosphorylation. This starved adhesion phenotype prevented excessive insulin granule release to maintain low insulin secretion during fasting. Thus, deregulation of the IGF2 and adhesion-mediated signaling may explain dysfunctions observed in diabetes.