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Central & Eastern Europe and Africa Engagement: Labour Mobility and Policy in East Africa

Research Event

15 January 2020 - 10:00am to 12:30pm

Nairobi, Kenya

Strengthened links between the states of sub-Saharan Africa (SSA) and Central and Eastern Europe (CEE) are emerging marked by growth in diplomatic representation, trade and economic ties and supporting networks.

Against this backdrop, labour migration within and from the CEE and East Africa sub-regions are a key policy area with significant potential for shared learning and cooperation. For both regions, migration trends in recent years have evolved as a result of a diverse range of interactions among public, private and civil society actors and at local, national, regional and international levels. Unpacking such interactions and their political and geographical specificities is essential to effective engagement and cooperation within and between the regions on issues of labour migration and their management.

This roundtable brainstorming workshop will provide a platform for stakeholders based in East Africa to discuss the way in which different actors and agencies in the region influence and shape labour migration processes and policy responses.

This event is supported by the Robert Bosch Stiftung.

Event attributes

Chatham House Rule

Fergus Kell

Projects Assistant, Africa Programme
+ 44 (0) 20 7314 3671




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Nkirote Laiboni

Robert Bosch Stiftung Academy Fellow (Central & Eastern Europe and Africa), Europe Programme

Biography

Nkirote Laiboni is a Kenyan international development and human rights practitioner with over 10 years of experience in managing humanitarian, human rights and international development programmes and coordinating research projects in Sub-Saharan Africa.

She has worked with international nongovernmental organisations on a wide range of sectors and issues including migration, humanitarian support, media development, democracy and governance, education and health.

Having previously worked on projects benefiting refugees, internally displaced persons, migrant workers, and trafficked persons in Kenya, Uganda, South Sudan and other African countries, Nkirote’s professional interest in migration has grown in recent years. Her research at Chatham House will explore and compare labour migration trends and patterns in Eastern Africa and Central and Eastern Europe.

She holds an MA in International Law and International Human Rights from the University of Peace, Costa Rica.

Areas of expertise

  • Non-profit management
  • Programme and project management
  • Participatory action research
  • Migration and human rights
  • International development
  • Humanitarian support




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Côte d'Ivoire’s 2020 Elections and Beyond: Ensuring Stability and Inclusion

Research Event

21 January 2020 - 11:30am to 12:30pm

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

Event participants

HE Alassane Ouattara, President, Republic of Côte d'Ivoire
Chair: Bob Dewar CMG, Associate Fellow, Africa Programme, Chatham House

Please note, the second video on this page is from an interview with the president outside the event.

HE Alassane Ouattara, president of Côte d'Ivoire, discusses governance and domestic priorities ahead of and beyond elections, as well as efforts to sustain stability and support an inclusive electoral process.

Presidential elections in Côte d'Ivoire, the world’s top cocoa producer and the largest economy in the West African Economic and Monetary Union (WAEMU), will be held ‪on 31st October 2020 against a backdrop of marked political dynamism in the country and wider region.

Possible constitutional amendments and a newly announced major reform of the currency regime are among significant issues drawing focus.

A credible and inclusive electoral process is critical for the improvement of socio-development outcomes and for the maintenance of a positive investment environment.

But instability remains a serious risk and the stakes are high for Côte d'Ivoire and the wider region.




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Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms

Research Event

21 January 2020 - 2:30pm to 3:30pm

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

Event participants

Hon. Manuel José Nunes Júnior, Minister of State for Economic Coordination, Republic of Angola
Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Minister Nunes Júnior will discuss the progress of the Angolan government’s economic stabilization plans and business reform agenda including the privatization of some state-owned enterprises. These reforms could expand Angola’s exports beyond oil and stimulate new industries and more inclusive economic growth.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ

Invitation Only Research Event

30 January 2020 - 8:15am to 9:15am

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

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. 

In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.

Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents.  

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




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Innovative Funding for Humanitarian Impact in Africa

Research Event

3 February 2020 - 5:00pm to 6:15pm

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

Event participants

Helen Alderson, Head of Regional Delegation to UK and Ireland, International Committee of the Red Cross
Paul van Zyl, Co-Founder and Chief Creative Officer, The Conduit
Maya Marissa Malek, Chief Executive Officer, Amanie Advisors Global Office
Chair: Maram Ahmed, Senior Teaching Fellow, SOAS, University of London

The cost of humanitarian assistance is forecast to rise to $50 billion per year by 2030 as a result of long-running, complex conflicts as well as natural disasters. Requirements are particularly acute in fragile contexts in sub-Saharan Africa that have lacked the fiscal and technical capacity for crisis prevention and response. As a result, traditional humanitarian actors are increasingly collaborating with the private sector and utilizing tools such as impact bonds, faith-based finance and other innovative financial products and services to mobilize greater funding to address humanitarian needs.

At this event, a panel of speakers will assess the challenges for sustainable financing in the humanitarian sector and prospects for multi-stakeholder collaboration and innovative funding tools to fill the widening deficit in assistance needs.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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The Central African Republic: Security, Development and Responding to the Humanitarian Situation

Invitation Only Research Event

3 February 2020 - 2:00pm to 3:00pm

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

Event participants

Denise Brown, United Nations Deputy Special Representative of the Secretary-General, Resident and Humanitarian Coordinator in the Central African Republic
Chair: Ben Shepherd, Consulting Fellow, Africa Programme, Chatham House

With two-thirds of the country’s population estimated to be in need of humanitarian aid and one-quarter either internally displaced or living as refugees in neighbouring countries, the Central African Republic (CAR) continues to face serious and complex humanitarian challenges. The country’s forthcoming presidential elections scheduled for December 2020 risk inflaming CAR’s volatile security situation particularly with the return of former leader, François Bozizé, ousted by the Séléka rebel coalition leader, Michel Djotodia, who has also returned from exile.

At this event, Denise Brown will discuss CAR’s current security, humanitarian and development situations and the role of actors such as the United Nations Multidimensional Integrated Stabilization Mission in the Central African Republic (MINUSCA). She will also discuss prospects for much-needed governance reform and reconciliation.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Hanna Desta

Programme Assistant, Africa Programme




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Equatorial Guinea in 2020: Prospects for Economic and Governance Reforms

Research Event

31 January 2020 - 2:00pm to 3:00pm

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

Event participants

Tutu Alicante, Executive Director, EG Justice
Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Despite boasting one of Africa’s highest GDP per capita rates, much of Equatorial Guinea’s population remain in poverty, with the world’s largest gap between its GDP per capita rates and human development index score. Equatorial Guinea’s economy is highly dependent on oil exports but production is in decline. In December 2019, the IMF Executive Board approved a US$282.8 million three-year Extended Fund Facility loan for Equatorial Guinea with provisions for promoting economic diversification, good governance, increasing transparency and fighting corruption. The country is also seeking to join the Extractive Industries Transparency Initiative.

At this event, Tutu Alicante will discuss prospects for meaningful reforms in Equatorial Guinea to improve economic governance, human rights and achieve sustainable and inclusive economic growth.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Decentralization and Cross-border Integration in the Horn of Africa

Research Event

4 February 2020 - 5:00pm to 6:15pm

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

Event participants

Mohamed Guleid, Chief Executive Officer, Frontier Counties Development Council
Nuradin Dirie, Chair, Puntland Presidential Advisory Council
Aden Abdi, Horn of Africa Programme Director, Conciliation Resources
Chair: Dr Zahbia Yousuf, Senior Research Advisor, Saferworld 

The interdependence of communities across the Horn of Africa results from social, familial, linguistic and cultural ties that cross territorial borders. Such linkages are reinforced by established patterns of movement and trade, often leading to stronger political and social connections between communities on either side of borders, than with their respective national capitals. States in the region are increasingly being challenged by demands for decentralization and more effective local governance. Improved understanding of the complexity of sub-national and cross-border political and economic contexts will be required to meet these demands and support enhanced governance so that challenges such as marginalization, intercommunal conflict and more equitable sharing of resources can be effectively addressed.

At this event, speakers will examine some of the key subnational and cross-border relations in the Horn of Africa. They will also discuss initiatives and stakeholders needed to support common solutions to building peace, furthering development and bolstering inclusive growth and integration. 

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Deepening Economic Ties? The Future of Africa-UK Trade and Investment

Corporate Members Event

25 February 2020 - 6:00pm to 7:00pm

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

Event participants

Raj Kulasingam, Senior Counsel, Dentons

Megan McDonald, Head of Investment Banking (International), Standard Bank Group

Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Theresa May’s announcement in 2018 on the UK’s ambition to become the G7’s largest investor in Africa by 2022 has been followed by similar stated ambitions at the recent UK-Africa Investment Summit, which saw the attendance of 16 African heads of states. Such ambitions mirror overtures from various international players including a call for a ‘comprehensive strategy for Africa’ by the EU in 2019. While the UK’s recent expansion of its diplomatic networks in Africa and the signing of the Economic Partnership Agreement with the Southern African Customs Union and Mozambique appear promising, there are significant challenges to deepening partnerships including visa restrictions and complex business environments.
 
At this event, the panellists will assess the future of trade and investment relations between the UK and Africa. Amid a proliferation of new trading partners including Asia’s emerging economies, Russia and the Gulf states, what are the points of change and continuity in the long-standing relationship between Africa and the UK? And what are the challenges and opportunities facing governments and businesses in Africa and the UK in efforts to build long-lasting economic ties?
 
This event will be followed by a drinks reception.

This event is open to Chatham House Corporate Members and corporate contacts of Chatham House's Africa Programme only.

Not a member? Find out moreFor further information on the different types of Chatham House events, visit Our Events Explained.

 

 

Members Events Team




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Financing for Sustainable Development in Africa

Research Event

27 February 2020 - 6:30pm to 7:30pm

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

Event participants

HE Nana Akufo-Addo, President of the Republic of Ghana
Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Please note, the second video on this page is from an interview carried out alongside the main event.

HE Nana Akufo-Addo, the president of Ghana, discusses his government’s approach to sustainable development, and how different stakeholders can be involved in achieving long-term goals in Ghana and beyond.

The government of Ghana has actively embedded sustainable development into its global and domestic policies. Ghana is signatory to international agreements including the 2030 UN Agenda for Sustainable Development, the African Union’s Agenda 2063, and the Paris Agreement on Climate Change; as well as including these goals into its domestic 2017-2024 economic and social development programme.

Private sector engagement has been central to Ghana’s approach to sustainable development. The government is also collaborating through the Private Enterprise Foundation on the implementation of the SDGs and is working with an Advisory Group of chief executives to establish a $100 million fund for the delivery of the SDGs and a further $200 million ‘Green Fund’ to help tackle climate change.

Event attributes

Livestream

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Realizing South Sudan's Peace Deal

Invitation Only Research Event

24 February 2020 - 5:00pm to 6:15pm

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

Event participants

Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee Council
Matthew F. Pritchard, Research and Policy Specialist, McGill University
Joshua Craze, Writer and Researcher
Teohna Williams, CEO, Business Plan for Peace

South Sudan’s new power sharing government must be formed by 22 February 2020, as specified in the Revitalized Agreement on the Resolution of the Conflict in the Republic of South Sudan (R-ARCSS). There have been two extensions to this process already, reflecting the continued distrust among leaders and the complexity of the conflict.

The lack of progress in several contentious areas has delayed the formation of the Revitalized Transitional Government of National Unity (R-TGoNU) for nine months, but the recent decision taken by President Salva Kiir Mayardit to re-establish 10 states has been welcomed by opposition groups, regional mediators and international partners.

It is seen as the breakthrough needed for an agreement to be reached, despite some outstanding concerns. Further meaningful compromises and difficult decisions will be needed to implement a lasting peace agreement.

At this event, a panel of speakers will examine the status of the peace deal following the February deadline and the steps needed to progress the key issues underlying implementation.

Event attributes

Chatham House Rule

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Freedom in the World 2020: Political Rights and Civil Liberties in Africa

Research Event

5 March 2020 - 3:30pm to 4:30pm

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

Event participants

Jon Temin, Director, Africa Programs, Freedom House
Chair: Rachael Jolley, Editor-in-chief, Index on Censorship 

Freedom House’s annual report,  Freedom in the World, assesses the condition of political rights and civil liberties around the world. Its next report, to be published on 4 March, will examine trends and changes since its previous assessment which found that political rights and civil liberties have declined globally over 13 consecutive years. This event will launch the Africa findings of its forthcoming report, highlighting positive and negative changes, and why different regions are diverging.

Jon Temin, Director of Africa Programs at Freedom House, will examine trends in political freedoms in Africa in the global context, discussing the causes and potential consequences of the shifts being seen, and what needs to be done to protect positive shifts and prevent further decline elsewhere.

Please note that this event is at capacity and registration is now closed. 

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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POSTPONED: UN Peacekeeping in Africa: Insights from Successes and Failures of the Past

Research Event

10 March 2020 - 3:00pm to 4:00pm

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

Event participants

Alan Doss, President, Kofi Annan Foundation
 

With Africa hosting half of the UN peacekeeping missions currently in operation and more than 80 per cent of the UN’s peacekeepers, it is clear that crisis management and conflict resolution on the continent remain key priorities. However, traditional international supporters, notably Canada and the United States, have reduced their financial support for peacekeeping in recent years. Together with frequent reports on peacekeeping abuse, declining support is proving disruptive for the maintenance and predictability of UN missions.

At this event, which will launch the book A Peacekeeper in Africa: Learning from UN Interventions in Other People’s Wars, Alan Doss will reflect on past UN peacekeeping missions in Africa and will consider how lessons learned might help to improve future UN peace operations.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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POSTPONED: Africa, Japan and the UK: Emerging Partnerships Beyond Summits

Research Event

17 March 2020 - 9:30am to 1:15pm

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

Event participants

HE Nabil Ben Khedher, Ambassador of Tunisia to the United Kingdom
Professor Naohiro Kitano, Visiting Fellow, Japan International Cooperation Agency Research Institute (JICA-RI); Professor, Waseda University
Taku Miyazaki, Deputy Director General, Japan External Trade Organisation (JETRO) London
Serge Mouangue, Founder and Art Director, WAfrica
Norio Suzuki, Senior Strategist, BBOXX
HE Professor Mohammed Gana Yisa, Ambassador of the Federal Republic of Nigeria to Japan; Chairman, African Diplomatic Corps in Tokyo (ADC) TICAD Committee

Chairs:
Dr Champa Patel
, Director, Asia-Pacific Programme, Chatham House
Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme

Since Japan established its Tokyo International Conference on African Development (TICAD) in 1993, an increasing number of summits for African engagement have appeared across the Asia-Pacific region. TICAD VII, held on 28-30 August 2019 in Yokohama, sought to strengthen partnerships between Japan and Africa in three main areas: technical cooperation; business and women’s entrepreneurship; and next generation and people-to-people connectivity.

The UK-Africa Investment Summit held in January 2020 highlighted similar themes, with an emphasis on investing to generate sustainable growth and create jobs.  Common interests and goals among different African countries, Japan and the UK bring opportunities for trilateral cooperation.

This event will examine how collaboration between African countries, Japan and the UK can help to more effectively achieve sustainable growth, business development and job creation.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Hanna Desta

Programme Assistant, Africa Programme




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POSTPONED: Pursuing Economic Reform and Growth in South Africa: the view from the African National Congress

Research Event

18 March 2020 - 10:30am to 11:30am

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

Event participants

Paul Mashatile, Treasurer General, African National Congress (ANC)

The government of South Africa is pursuing a programme of reform to revitalize the economy, strengthen institutions and combat corruption. The State of the Nation Address (SONA) on 13 February and the budget speech of 26 February represent the most significant articulation of the government’s economic strategy. Central to this is the government’s plans for the energy sector, which is fundamental for reviving the economy, and the reform of State Owned Enterprises (SOEs). But questions remain about possible divergence of the approach taken by government ministers from the policy position of the ruling party, the African National Congress (ANC), and what this might mean for the sustainability and progress of reform.  

At this event, Paul Mashatile, Treasurer General of the ANC, will discuss the party’s assessment of reform efforts to date and priorities for delivering on inclusive growth.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Children 'born of war': a role for fathers?

4 March 2020 , Volume 96, Number 2

Camile Oliviera, Erin Baines

In this article, we examine exceptional circumstances in which men who father children born as the result of conflict-related sexual violence assume full or partial responsibility for their child's well-being. Children ‘born of war’ are increasingly recognized as a particular victim group in relevant international policy frameworks. Their social status falls somewhere between the victimization of their mother and perpetration of their father. Given the circumstances of their birth, they often experience social rejection and loss of identity with a long-term impact on their well-being. Previous scholarship has primarily documented the challenges faced by their mothers as caregivers and as victims of wartime sexual violence. A discussion on fathers to children ‘born of war’ is absent, attributable not only to their perpetrator status, but also to the assumption that their identity is unknown or that a relationship between father and child is undesired. The article demonstrates this is not always the case. Based on research in northern Uganda between 2016 and 2019 which included interviews and focus group discussions with former male combatants in the rebel group the Lord's Resistance Army, we explore how some fathers seek to maintain a relationship with children born as the result of ‘forced marriage’ and assume partial or full responsibility for their well-being and care.




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Why The Insurgency in Northern Mozambique Has Got Worse

1 April 2020

Dr Alex Vines OBE

Managing Director, Ethics, Risk & Resilience; Director, Africa Programme
Two attacks on towns in northern Mozambique by suspected jihadists point to a rapidly deteriorating security crisis.

2020-04-01-Mozambique

Macomia, Cabo Delgado, Northern Mozambique. Photo by EMIDIO JOSINE/AFP via Getty Images.

On March 23 to 24, the centre of Mocimboa da Praia in Cabo Delgado province was occupied by up to 40 “jihadists”, who targeted government facilities, including a barracks, and brandished banners of affiliation to the so-called Islamic State.

On March 25, suspected jihadists raided the town of Quissanga and destroyed the district police headquarters. They too carried an Islamic State flag. Twenty to 30 members of Mozambique’s security forces were killed in both attacks.

Mocimboa da Praia is just south of the Afungi Peninsula, the location of gas projects worth $60- billion. Mocimboa was briefly occupied in late 2017, during attacks claimed by a group known as Ahlu Sunnah Wa-Jama (or al-Sunnah) that marked the start of a brutal low-intensity conflict, with widespread human rights abuses and attacks on civilians.

Up to 1,000 people have now been killed and 100,000 displaced. More recently, The Islamic State Central Africa Province (Iscap), affiliated with the Islamic State group, has claimed responsibility for the attacks. Video and photos of these most recent events, along with the testimony of frightened residents and overstretched government officials, suggest a shift of strategy by the insurgents.

There seems to have been an effort to avoid harming civilians, to win hearts and minds by redistributing stolen food, medicine and fuel to “loyal” residents, and to direct attacks on the state and its symbols, such as police stations and military barracks. It is difficult from a distance to assess if there was any genuine pleasure over these attacks among local people; while residents in both towns that did not flee seemed to welcome the attackers, this may well have been out of fear that the government is currently unable to guarantee their security.

These attacks also indicate that the jihadist-linked insurgents are growing in confidence. They are confronting government security forces with little appetite for fighting. The Mozambican government has been expecting setbacks like those of Mocimboa and Quissanga — its forces are demoralised and many commanders exhausted or corrupted by an emerging war economy. Jihadists are also taking tactical advantage before a reformed and more effective government counterinsurgency effort is introduced in response.

President Filipe Nyusi, inaugurated in January for his second term, has made this crisis his prime focus and has become the de-facto minister of defence.

Military reform and the role of private military companies

But there is no quick fix. Most importantly, the Mozambican military and security forces need to be restructured. They were unable to win the Mozambican civil war (1977-1992), even with international support, and have not improved in capacity or conduct since. They now face a complex, multilayered and asymmetrical conflict, mostly drawing upon local and regional grievances and networks but increasingly also attracting some limited encouragement and advice from further afield.

Nyusi will need to build-up trusted relationships in the military in the way he has successfully done with parts of the intelligence community. The Mozambican government has already reached out to international expertise — though not necessarily the right kind. The founder of the Blackwater private military company, Erik Prince, supplied two helicopters and support crew for the Mozambican military in mid-2019, before being replaced by some 170 Russian privateers linked to the Wagner Group.

The Wagner contingent arrived in September 2019 at Nacala airport with trucks, drones and a Mi-17 helicopter gunship, then deployed into the combat zone of northern Cabo Delgado. Setbacks, including at least two dead Russians, forced a tactical fallback to Nacala, though a new effort is reported to have been underway since late February 2020.

The Mozambican government is also considering a number of proposals from other private military companies. Maputo needs to consider these carefully; Israeli or Gulf State involvement in any form might exasperate rather than alleviate this crisis.

The Tanzanian connection

But market-led security and military providers will not end this insurgency. Nor will the engagement of states such as the United States, France, the United Kingdom or Angola, all of which have made their own offers of support. What would significantly make a difference is much closer to home: serious Tanzanian engagement.

This insurgency is concentrated in districts bordering Tanzania and there is clear-cut intelligence of connections into Tanzania and beyond. Swahili is also a lingua franca for the jihadists, connecting them up the East African coast, and into eastern Congo and elsewhere.

It is puzzling, given the deep shared history between Tanzania and Mozambique, that the bilateral relationship is as patchy as it is today: during the liberation struggle (1965-1974) against the Portuguese, Mozambique’s ruling party Frelimo maintained rear bases in Tanzania, and Nyusi was educated there.

Conspiracy theories circulate that Tanzania has encouraged the Cabo Delgado insurgency to weaken its neighbour, or at least displace radicalised individuals from Tanzanian soil into Mozambique.

President John Magafuli of Tanzania did not attend the January inauguration of Nyusi. It has become urgent that Magafuli (who is also the current chair of the regional body, the Southern African Development Community) and Nyusi meet face-to-face to map out improved intelligence sharing and a joint strategy to respond to an emerging regional threat.

Southern Africa is locking down because of Covid-19, which will distract the government’s ability to focus fully on this crisis and create a perfect moment for the infant insurgency in Cabo Delgado to grow. More military setbacks should be expected in coming months.

But the Mozambican government can still contain and prevail if it seriously reforms its military, builds strong alliances with its regional neighbours (especially Tanzania), chooses its private security contractors and international partnerships wisely, and backs military efforts with better intelligence and developmental interventions that offer alternative pathways to potential recruits.

But despite Maputo’s hope that significant progress will be made over the coming year, and the setting up of a presidential task force to evaluate progress and intelligence, it is likely that Mozambique and its partners will need to prepare themselves for a drawn-out struggle.

This article originally appeared in the Mail & Guardian




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Webinar: Implications of the COVID-19 Pandemic for African Economies and Development

Research Event

21 April 2020 - 4:30pm to 5:30pm

Event participants

Dr Hafez Ghanem, Vice President for Africa, World Bank
Chair: Elizabeth Donnelly, Deputy Director, Africa Programme, Chatham House

Dr Hafez Ghanem discusses the implications of the COVID-19 pandemic for African economies and their development and poverty reduction efforts, and assesses the priorities and obstacles for establishing a comprehensive response to the crisis.
 
While the acute strain placed on health systems by the COVID-19 pandemic is already in evidence, the long-term economic fallout from the crisis is yet to fully manifest.
 
For Africa it is the economic impact that may leave the most enduring legacy: from the direct expense of measures to treat, detect and reduce the spread of the virus; to the indirect costs of domestic lockdown measures, global supply chain disruptions and plummeting commodity prices.
 
As decision-makers globally start to plan for the scale of this economic shock, strategizing in and on Africa to meet the challenge will require unprecedented planning and commitment - and will need to be matched by support from international partners to enable long-term recovery.
 

Hanna Desta

Programme Assistant, Africa Programme




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Webinar: Implications of the COVID-19 Pandemic for Food Security and Resilience in Africa

Research Event

23 April 2020 - 1:00pm to 2:00pm

Event participants

Dr Arif Husain, Chief Economist and Director of Research, Assessment and Monitoring, United Nations World Food Programme
Respondent: Dr Leena Koni Hoffmann, Associate Fellow, Africa Programme, Chatham House
Chair: Professor Tim Benton, Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme, Chatham House
Dr Arif Husain gives his assessment of the potential impact that the COVID-19 pandemic will have on food security in Africa and what can be done to prevent a food security emergency.
 
Linked to the immediate public health consequences of the COVID-19 pandemic are those of economic and food security, particularly significant for low- and middle-income countries. Currently more than 821 million people globally go hungry, with 100 million of those suffering acute hunger, and this will worsen if the evolving economic emergency becomes a food security emergency.
 
Sub-Saharan African countries rely on trade for food security and for revenue; they imported more than 40 million tons of cereal from around the world in 2018, according to the World Food Programme (WFP). The region faces stark new challenges due to the pandemic.

This event launches the WFP paper COVID-19: Potential impact on the world’s poorest people.

Department/project

Hanna Desta

Programme Assistant, Africa Programme




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Beyond Lockdown: Africa’s Options for Responding to COVID-19

21 April 2020

Ben Shepherd

Consulting Fellow, Africa Programme

Nina van der Mark

Research Analyst, Global Health Programme
The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right.

2020-04-22-Africa-COVID-Dakar

Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images.

African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.

But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.

It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.

Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.

Complex and unknown

Ultimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.

What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.

And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.

Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.

The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.

Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.

So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.

Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.

A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.

How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.

The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long.




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Nigeria’s Political Leaders Need to Win Trust to Tackle COVID-19

23 April 2020

Elizabeth Donnelly

Deputy Director, Africa Programme

Idayat Hassan

Director, Centre for Democracy and Development
COVID-19 will require Nigeria's government to rely on already stretched communities and informal institutions. But there is a yawning gap in trust and accountability between citizens and the state in Nigeria – the crisis will force the state to attempt to bridge this divide.

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News stand in Lagos, Nigeria on April 12, 2020. Photo by PIUS UTOMI EKPEI/AFP via Getty Images.

Nigeria is better placed than many to respond to the arrival of the coronavirus disease. In 2014, it successfully contained a deadly Ebola virus outbreak and the country’s current score on the Epidemic Preparedness Index (38.9 per cent) is higher than the African and global averages.

But the outbreak is compounding Nigeria’s numerous pre-existing crises. It was already grappling with a Lassa fever outbreak that has claimed more than one hundred lives in 2020, the aftermath of recession, and conflict and insecurity within its borders.

Effective leadership to build confidence will be vital. However, President Muhammadu Buhari has made few appearances, delivering his first speech on Nigeria’s response more than one month after the country’s first recorded case. And the indefinite suspension of meetings of the Federal Executive Council has raised questions on the efficacy of the response.

Extended lockdown imposed

The recent loss of President Buhari’s steadfast chief of staff Abba Kyari as a result of contracting COVID-19 is a further significant setback for the presidency. But the administration has established a presidential task force to develop a national strategy and an extended lockdown has been imposed on the most affected states  Lagos, Ogun and the Federal Capital Territory of Abuja. The country has also closed national borders and is expanding testing capacity to 1,500 per day.

However, when Nigeria’s first case was recorded on February 27 it was state governments that initially took action  shutting schools, closing state borders and imposing lockdowns. Going forwards, the 36 state governments will have a key role to play although their governance capacity and commitment varies widely.

The federal government has released $2.7 million to support the Nigeria Centre for Disease Control (NCDC), and promised an additional $18 million  but this falls well short of the estimated $330 million needed to tackle the coronavirus disease in Nigeria. The government is looking to its private sector to help make up the difference. The country’s finances are under severe pressure with Nigerian crude oil  the main source of government revenue and foreign exchange reserves  selling for as low as $12 or $13 a barrel (with production costs of around $22 per barrel), and a debt servicing to revenue ratio of more than 50 per cent even before the oil price crash.

Facing its second recession in four years, with -3.4 per cent GDP growth forecast by the IMF, the country has little economic resilience. Nigeria will not be able to sustain restrictions on its 81.15 million-strong workforce, 83.2 per cent of which operate in the informal sector. One area at particular risk is food security, as the pandemic is disrupting farming, supply chains and trade. By building on past benefit programmes, the federal government is providing cash and distributing food to vulnerable households, but this important effort is being hampered by poor communication, inefficiencies and a lack of transparency  longstanding challenges in many aspects of public service delivery in Nigeria.

In the absence of a reliable social safety net, Nigerians trust and rely on their families, communities and the informal economy to see them through difficult times. It is these informal mechanisms that lend Nigeria its oft-referenced resilience, which has enabled society to function and continue while a largely disconnected political class has focused on self-enrichment.

It is through these traditional channels that the government will need to deliver information, support, testing and treatment. But without high levels of trust, the administration may find it difficult to do so. Many Nigerians initially considered the pandemic a hoax, some describing it as a ‘rich man’s disease’, while others see it as another conspiracy by politicians to loot the treasury.

Lockdown measures have also heightened tensions across the country. Some citizens are rebelling and in one instance burned down a police station in response to the closure of mosques in Katsina state. Marking a further breakdown in the relationship between the population and its leaders, the Nigerian National Human Rights Commission (NHRC) recently reported security services enforcing the lockdown have extrajudicially killed 18 people, while, so far, COVID-19 has killed 25 people in Nigeria.

Mitigating the spread and worst consequences of the virus will depend on the state rebuilding trust with its citizens through effective communication and action. It is particularly important that the community mechanisms of support are protected as they come under growing pressure as communities become increasingly affected by the virus.

The stark choice facing most Nigerians  between risking starvation and risking contagion  means a sustained lockdown is not a tenable option. People will choose to go to work. This will especially be the case as people grow weary of measures imposed upon them by a state that the vast majority of the population believe does not serve or care for them.

Having largely ignored the needs of Nigeria’s citizens for decades, the political class face an uphill battle in building trust with the population. Earning this trust is not only crucial for the struggle against COVID-19 but also for Nigeria’s longer-term progress and system of political governance.




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Coronavirus Risks Worsening a Food Crisis in the Sahel and West Africa

1 May 2020

Dr Leena Koni Hoffmann

Associate Fellow, Africa Programme

Paul Melly

Consulting Fellow, Africa Programme
In responding to the spread of the coronavirus, the governments of the Sahel and West Africa will need to draw on their collective experience of strategic coordination in emergency planning, and work together to prioritize the flow of food across borders.

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An informal market in the Anyama district of Abidjan, Côte d’Ivoire, is sanitized against the coronavirus. Photo by SIA KAMBOU/AFP via Getty Images.

The COVID-19 pandemic has struck the Sahel and West Africa at a time when the region is already under severe pressure from violent insecurity and the effects of climate change on its land, food and water resources.

By the end of April, there had been 9,513 confirmed coronavirus cases across the 17 countries of the region, and some 231 deaths, with the highest overall numbers recorded in Nigeria, Ghana, Guinea, Côte d’Ivoire, Senegal, Niger and Burkina Faso. Low testing rates mean than these numbers give only a partial picture.

The Food Crisis Prevention Network (RPCA) forecast in early April that almost 17 million people in the Sahel and West Africa (7.1 million in Nigeria alone) will need food and nutritional assistance during the coming lean season in June–August, more than double the number in an average year. The combined impact of violent insecurity and COVID-19 could put more than 50 million other people across the region at risk of food and nutrition crisis.

Rippling across the region

The effects of the collapse in global commodity prices, currency depreciations, rising costs of consumer goods and disruptions to supply chains are rippling across the region. And for major oil-exporting countries such as Nigeria, Ghana, Chad and Cameroon, the wipe-out of foreign currency earnings will hammer government revenues just as the cost of food and other critical imports goes up. It is likely that the number of people who suffer the direct health impact of the coronavirus will be far outstripped by the number for whom there will be harsh social and economic costs.

In recent years, valuable protocols and capacities have been put in place by governments in West and Central Africa in response to Ebola and other infectious disease outbreaks.

But inadequate healthcare funding and infrastructure across this region compound the challenge of responding to the spread of the COVID-19 infection – which is testing the resources of even the world’s best-funded public health systems.

Over many years, however, the region has steadily built up structures to tackle humanitarian and development challenges, particularly as regards food security. It has an established system for assessing the risk of food crisis annually and coordinating emergency support to vulnerable communities. Each country monitors climate and weather patterns, transhumance, market systems and agricultural statistics, and terrorist disruption of agricultural productivity, from local community to national and regional level.

The system is coordinated and quality-controlled, using common technical data standards, by the Permanent Interstate Committee for Drought Control in the Sahel (CILSS), a regional intergovernmental body established in 1973 in response to a devastating drought. Collective risk assessments allow emergency support to be mobilized through the RPCA.

For almost three months already, countries in Sahelian West Africa have been working with the World Health Organization to prepare national COVID-19 response strategies and strengthen health controls at their borders. Almost all governments have also opted for domestic curfews, and variations of lockdown and market restrictions.

Senegal has been a leader in rapidly developing Africa’s diagnostic capacity, and plans are under way to speed up production of test kits. Niger was swift to develop a national response strategy, to which donors have pledged €194.5 million. While the IMF has agreed emergency financial assistance to help countries address the urgent balance-of-payments, health and social programme needs linked to the COVID-19 pandemic, signing off $3.4 billion for Nigeria, $442 million for Senegal and $130 million for Mauritania.

Steps are also now being taken towards the formulation of a more joined-up regional approach. Notably, Nigeria’s President Muhammadu Buhari has been chosen by an extraordinary session of the Economic Community of West African States to coordinate the regional response to COVID-19. As Africa’s biggest economy and home to its largest population, Nigeria is a critical hub for transnational flows of goods and people. Its controversial August 2019 land border closure, in a bid to address smuggling, has already painfully disrupted regional agri-food trade and value chains. The active engagement of the Buhari administration will thus be crucial to the success of a multifaceted regional response.

One of the first tough questions the region’s governments must collectively address is how long to maintain the border shutdowns that were imposed as an initial measure to curb the spread of the virus. Closed borders are detrimental to food security, and disruptive to supply chains and the livelihoods of micro, small and medium-sized entrepreneurs that rely on cross-border trade. The impact of prolonged closures will be all the more profound in a region where welfare systems are largely non-existent or, at best, highly precarious.

Nigeria, in particular, with more than 95 million people already living in extreme poverty, might do well to explore measures to avoid putting food further beyond the reach of people who are seeing their purchasing power evaporate.

In taking further actions to control the spread of the coronavirus, the region’s governments will need to show faith in the system that they have painstakingly developed to monitor and respond to the annual risk of food crisis across the Sahel. This system, and the critical data it offers, will be vital to informing interventions to strengthen the four components of food security – availability, access, stability and utilization – in the context of COVID-19, and for charting a post-pandemic path of recovery.

Above all, careful steps will need to be put in place to ensure that preventing the spread of the coronavirus does not come at the cost of even greater food insecurity for the people of the Sahel and West Africa. The region’s governments must prioritize the flow of food across borders and renew their commitment to strategic coordination and alignment.




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Webinar: Implications of the COVID-19 Pandemic for African Elections and Democracy

Research Event

6 May 2020 - 2:30pm to 3:30pm

Event participants

Dr Christopher Fomunyoh, Senior Associate and Regional Director for Central and West Africa, National Democratic Institute (NDI)
Chair: Elizabeth Donnelly, Deputy Director, Africa Programme, Chatham House
2020 was anticipated to be a year of landmark elections across Africa, including general elections scheduled in Somalia and Ethiopia – countries at critical junctures in their transitions to electoral democracy – as well as a re-run of annulled presidential elections in Malawi.
 
The COVID-19 pandemic has created new challenges for African countries seeking to hold elections or further democratization – including the practicalities of adapting containment measures to electoral processes in the context of strained financial and logistical resources. It may also be used as a pretext for the pursuit of repressive legislation and constitutional amendments to preclude elections or bolster authoritarianism, compounded by new constraints on accountability mechanisms such as election observation missions.
 
At this event, Dr Christopher Fomunyoh discusses the likely impact of the COVID-19 pandemic on elections and democracy in various African countries, as well as responses and measures to meet the multifaceted challenges posed.

Hanna Desta

Programme Assistant, Africa Programme




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Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya

Research Event

12 May 2020 - 1:00pm to 2:00pm
Add to Calendar
Natasha Kimani, Academy Associate, Chatham House; Head of Partnerships and Programmes, Shujaaz Inc.
Chair: Tighisti Amare, Assistant Director, Africa Programme, Chatham House
While gender equality was enshrined in Kenyan law under the 2010 constitution, gender-based marginalization remains a significant issue across all levels of society. The advent of devolution in 2013 raised hopes of enhanced gender awareness in policymaking and budgeting, with the 47 newly instituted county governments expected to tackle the dynamics of inequality close to home, but implementation has so far failed to match this initial promise. As Kenya approaches the tenth anniversary of the constitution, and with the COVID-19 pandemic throwing the challenges of gender inequality into sharper relief, it is critical to ensure that constitutional pathways are followed with the requisite level of urgency, commitment and investment to address entrenched gender issues.
 
This event, which will launch the report, Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya, will assess the current status of efforts to devolve and adopt gender-responsive budgeting and decision-making in Kenya, and the priorities and potential future avenues to tackle the implementation gap.
 
This event will be held on the record.

To express your interest in attending, please follow this link. You will receive a Zoom confirmation email should your registration be successful.

Hanna Desta

Programme Assistant, Africa Programme




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How images frame China's role in African development

7 May 2020 , Volume 96, Number 3

George Karavas

Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’.




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COVID-19 in South Africa: Leadership, Resilience and Inequality

7 May 2020

Christopher Vandome

Research Fellow, Africa Programme
In a world looking for leadership, South Africa’s president Cyril Ramaphosa has been remarkable. One year after he carried the time-worn ANC through a national election, South Africans are crying out for more.

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Cyril Ramaphosa at NASREC Expo Centre in Johannesburg where facilities are in place to treat coronavirus patients. Photo by JEROME DELAY/POOL/AFP via Getty Images.

In the COVID-19 crisis so far, Cyril Ramaphosa has been widely praised for displaying the decisive leadership so many hoped for when they cast their ballot for him in May 2019. Buttressed by others such as health minister Dr Zweli Mkhize, and on a simple objective to prevent transmission, South Africa has been a lesson to the world. Act fast. Act hard.

Former president Thabo Mbeki’s disastrous response to the HIV crisis cast a long shadow over his legacy, and Ramaphosa has taken note. South Africa has had one of the tightest lockdowns in the world. No exercise. No cigarettes. No alcohol.

The lockdown was imposed when the country had only around 1,000 recorded cases and just two deaths. As a result, transmission from returning travellers has not yet led to an exponential infection rate within the community. The government’s swift reaction has bought much needed time with the peak now seemingly delayed to September or October.

Continental and national leadership

Ramaphosa has also emerged as a key focal point for Africa-wide responses. As current chair of the African Union (AU) he leads the continental engagement with the World Health Organization (WHO), and the various international finance institutions, while South African officials are working with the AU and the United Nations Economic Commission for Africa (UNECA) on a push for African debt restructuring.

He has also been active in trouble shooting to unlock external assistance to the continent, including from China and Russia. Appointing special envoys is typical of his boardroom-honed leadership style.

International and regional partnerships are vital for resilience and the arrival of 217 Cuban doctors to South Africa is strongly reminiscent of the liberationist solidarity of the Cold War era. And regional economies remain dependent on South Africa to protect their own vulnerable citizens. Following the 2008 financial crisis, it was South Africa’s regional trading relationships that remained robust, while trade with its main global partners in China and the US dropped.

Despite the plaudits, Ramaphosa remains vulnerable to challenge at home, notably around his failure to stimulate South Africa’s moribund economy. On the eve of lockdown, Moody’s joined its peers Standard and Poor’s and Fitch in giving South Africa a below investment grade credit rating. The move was a long time coming. Long mooted economic reforms were slow to materialise, and South Africa had fallen into recession.

Ramaphosa depends on a small core of close advisors and allies, initially united in apparent opposition to the kleptocratic rule of President Jacob Zuma and the deep patronage networks he created within both the party and the state. But this allegiance is being tested by economic reality. Support within the party was already drifting prior to the crisis.

Disagreements are not just technocratic – there are big ideological questions in play around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. Energy minister and former union stalwart Gwede Mantashe is wary of job losses, and minister of public enterprises Pravin Gordhan protective of state-owned enterprises (SOEs). Before coronavirus hit, Ramaphosa seemed content to allow these policy disputes to play themselves out with little decisive intervention.

Slow progress on reform, against worsening economic performance, left Ramaphosa and his allies exposed. In January the president missed the UK’s African Investment Summit in order to assert control over a party meeting at which it was expected his detractors would seek to remove Gordhan.

COVID-19 has sharpened thinking

As the independently assertive - and eminently quotable - pro-market reformist finance minister Tito Mboweni stated, ‘you can’t eat ideology’. Accelerated reform and restructuring is required if the government turns to the International Monetary Fund (IMF) for assistance.

For the first time, Gordhan has been forced to deny a bailout to beleaguered state airline South African Airways (SAA), and the government’s lockdown bailout of R300 billion has been applauded by business. Much like the fiscal stimulus and recovery plan of 2018, it relies on smart spending, targeting sectors with high multiplier effects. It also includes significant reserve bank loans.

But it has been criticised for not doing enough to help the most vulnerable. There is considerable fear of what could happen when the virus takes hold in South Africa’s townships and informal settlements where social distancing is almost impossible, basic toilet facilities are shared, and HIV and TB rates high.

There are mounting concerns of the humanitarian cost of a prolonged lockdown, and the government has been faster than others in implementing a tiered lockdown system, trying to get people back to work and keep the economy afloat.

South Africa has been criticized by the UN for the use of lethal force by security forces in enforcing lockdown and, in a society plagued by corruption, there are fears legislation to stop the spread of false information could be used to restrict legitimate reporting on the virus response or other issues.

COVID-19 shines a spotlight on societies’ fault-lines worldwide. South Africa is often touted as having one of the highest levels of inequality in the world but, in a globalized economy, these divisions are international as much as they are local.

Resilience comes from within, but also depends on regional and global trading and financial systems. South Africans and international partners have long recognised Ramaphosa’s leadership qualities as an impressive voice for the global south.

But he must also be an advocate for South Africa’s poor. This crisis could accelerate implementation of his landmark pro-poor National Health Insurance and Universal Health Care programmes. Or the hit of COVID-19 on top of South Africa’s existing economic woes could see them derailed entirely. Ramaphosa must push through economic reforms at the same time as managing COVID-19 and rebuilding trust in his government.




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Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids]

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.




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Phosphoproteomic characterization of the signaling network resulting from activation of the chemokine receptor CCR2 [Genomics and Proteomics]

Leukocyte recruitment is a universal feature of tissue inflammation and regulated by the interactions of chemokines with their G protein–coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CC chemokine ligand 2 (CCL2), plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to conduct an unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition MS analysis, we quantified both the proteome and phosphoproteome in FlpIn-HEK293T cells stably expressing CCR2 at six time points after activation with CCL2. Differential expression analysis identified 699 significantly regulated phosphorylation sites on 441 proteins. As expected, many of these proteins are known to participate in canonical signal transduction pathways and in the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors and GTPase-activating proteins. Moreover, we identified regulated phosphorylation sites in numerous proteins that function in the nucleus, including several constituents of the nuclear pore complex. The results of this study provide an unprecedented level of detail of CCR2 signaling and identify potential targets for regulation of CCR2 function.




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Correction: Graph Algorithms for Condensing and Consolidating Gene Set Analysis Results. [Additions and Corrections]




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Combining Precursor and Fragment Information for Improved Detection of Differential Abundance in Data Independent Acquisition [Technological Innovation and Resources]

In bottom-up, label-free discovery proteomics, biological samples are acquired in a data-dependent (DDA) or data-independent (DIA) manner, with peptide signals recorded in an intact (MS1) and fragmented (MS2) form. While DDA has only the MS1 space for quantification, DIA contains both MS1 and MS2 at high quantitative quality. DIA profiles of complex biological matrices such as tissues or cells can contain quantitative interferences, and the interferences at the MS1 and the MS2 signals are often independent. When comparing biological conditions, the interferences can compromise the detection of differential peptide or protein abundance and lead to false positive or false negative conclusions.

We hypothesized that the combined use of MS1 and MS2 quantitative signals could improve our ability to detect differentially abundant proteins. Therefore, we developed a statistical procedure incorporating both MS1 and MS2 quantitative information of DIA. We benchmarked the performance of the MS1-MS2-combined method to the individual use of MS1 or MS2 in DIA using four previously published controlled mixtures, as well as in two previously unpublished controlled mixtures. In the majority of the comparisons, the combined method outperformed the individual use of MS1 or MS2. This was particularly true for comparisons with low fold changes, few replicates, and situations where MS1 and MS2 were of similar quality. When applied to a previously unpublished investigation of lung cancer, the MS1-MS2-combined method increased the coverage of known activated pathways.

Since recent technological developments continue to increase the quality of MS1 signals (e.g. using the BoxCar scan mode for Orbitrap instruments), the combination of the MS1 and MS2 information has a high potential for future statistical analysis of DIA data.




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Thorough Performance Evaluation of 213 nm Ultraviolet Photodissociation for Top-down Proteomics [Technological Innovation and Resources]

Top-down proteomics studies intact proteoform mixtures and offers important advantages over more common bottom-up proteomics technologies, as it avoids the protein inference problem. However, achieving complete molecular characterization of investigated proteoforms using existing technologies remains a fundamental challenge for top-down proteomics. Here, we benchmark the performance of ultraviolet photodissociation (UVPD) using 213 nm photons generated by a solid-state laser applied to the study of intact proteoforms from three organisms. Notably, the described UVPD setup applies multiple laser pulses to induce ion dissociation, and this feature can be used to optimize the fragmentation outcome based on the molecular weight of the analyzed biomolecule. When applied to complex proteoform mixtures in high-throughput top-down proteomics, 213 nm UVPD demonstrated a high degree of complementarity with the most employed fragmentation method in proteomics studies, higher-energy collisional dissociation (HCD). UVPD at 213 nm offered higher average proteoform sequence coverage and degree of proteoform characterization (including localization of post-translational modifications) than HCD. However, previous studies have shown limitations in applying database search strategies developed for HCD fragmentation to UVPD spectra which contains up to nine fragment ion types. We therefore performed an analysis of the different UVPD product ion type frequencies. From these data, we developed an ad hoc fragment matching strategy and determined the influence of each possible ion type on search outcomes. By paring down the number of ion types considered in high-throughput UVPD searches from all types down to the four most abundant, we were ultimately able to achieve deeper proteome characterization with UVPD. Lastly, our detailed product ion analysis also revealed UVPD cleavage propensities and determined the presence of a product ion produced specifically by 213 nm photons. All together, these observations could be used to better elucidate UVPD dissociation mechanisms and improve the utility of the technique for proteomic applications.




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Mass Spectrometry Based Immunopeptidomics Leads to Robust Predictions of Phosphorylated HLA Class I Ligands [Technological Innovation and Resources]

The presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition of infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing or aberrant post-translational modifications. Identifying HLA-I ligands remains a challenging task that requires either heavy experimental work for in vivo identification or optimized bioinformatics tools for accurate predictions. To date, no HLA-I ligand predictor includes post-translational modifications. To fill this gap, we curated phosphorylated HLA-I ligands from several immunopeptidomics studies (including six newly measured samples) covering 72 HLA-I alleles and retrieved a total of 2,066 unique phosphorylated peptides. We then expanded our motif deconvolution tool to identify precise binding motifs of phosphorylated HLA-I ligands. Our results reveal a clear enrichment of phosphorylated peptides among HLA-C ligands and demonstrate a prevalent role of both HLA-I motifs and kinase motifs on the presentation of phosphorylated peptides. These data further enabled us to develop and validate the first predictor of interactions between HLA-I molecules and phosphorylated peptides.




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Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State [Research]

The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5'-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.




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Site-specific N-glycan Analysis of Antibody-binding Fc {gamma} Receptors from Primary Human Monocytes [Research]

FcRIIIa (CD16a) and FcRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ~20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145).




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Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion [Research]

The blue mold fungus, Penicillium expansum, is a postharvest apple pathogen that contributes to food waste by rotting fruit and by producing harmful mycotoxins (e.g. patulin). To identify genes controlling pathogen virulence, a random T-DNA insertional library was created from wild-type P. expansum strain R19. One transformant, T625, had reduced virulence in apples, blistered mycelial hyphae, and a T-DNA insertion that abolished transcription of the single copy locus in which it was inserted. The gene, Blistering1, encodes a protein with a DnaJ domain, but otherwise has little homology outside the Aspergillaceae, a family of fungi known for producing antibiotics, mycotoxins, and cheese. Because protein secretion is critical for these processes and for host infection, mass spectrometry was used to monitor proteins secreted into liquid media during fungal growth. T625 failed to secrete a set of enzymes that degrade plant cell walls, along with ones that synthesize the three final biosynthetic steps of patulin. Consequently, the culture broth of T625 had significantly reduced capacity to degrade apple tissue and contained 30 times less patulin. Quantitative mass spectrometry of 3,282 mycelial proteins revealed that T625 had altered cellular networks controlling protein processing in the endoplasmic reticulum, protein export, vesicle-mediated transport, and endocytosis. T625 also had reduced proteins controlling mRNA surveillance and RNA processing. Transmission electron microscopy of hyphal cross sections confirmed that T625 formed abnormally enlarged endosomes or vacuoles. These data reveal that Blistering1 affects internal and external protein processing involving vesicle-mediated transport in a family of fungi with medical, commercial, and agricultural importance.




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Molecular Basis of the Mechanisms Controlling MASTL [Research]

The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, whereas the N-lobe is dynamic and the NCMR and C-tail contain few localized regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a possible link with truncated mutations observed in cancer-related databases.




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Multi-omic Characterization of the Mode of Action of a Potent New Antimalarial Compound, JPC-3210, Against Plasmodium falciparum [Research]

The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favorable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on biochemical pathways within P. falciparum-infected red blood cells, we have applied a "multi-omics" workflow based on high resolution orbitrap mass spectrometry combined with biochemical approaches. Metabolomics, peptidomics and hemoglobin fractionation analyses revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a specific depletion of short hemoglobin-derived peptides, peptidomics analysis revealed a depletion of longer hemoglobin-derived peptides, and the hemoglobin fractionation assay demonstrated decreases in hemoglobin, heme and hemozoin levels. To further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerization assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerization, about 10-fold less potent then the quinoline antimalarials, such as chloroquine and mefloquine. Further, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature compared with other known antimalarials. While JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. These studies revealed that the mode of action for JPC-3210 involves inhibition of the hemoglobin digestion pathway and elevation of regulators of protein translation. Importantly, JPC-3210 demonstrated rapid parasite killing kinetics compared with other quinolones, suggesting that JPC-3210 warrants further investigation as a potentially long acting partner drug for malaria treatment.




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Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling [Research]

Aberrantly high mTORC1 signaling is a known driver of many cancers and human disorders, yet pharmacological inhibition of mTORC1 rarely confers durable clinical responses. To explore alternative therapeutic strategies, herein we conducted a proteomics survey to identify cell surface proteins upregulated by mTORC1. A comparison of the surfaceome from Tsc1–/– versus Tsc1+/+ mouse embryonic fibroblasts revealed 59 proteins predicted to be significantly overexpressed in Tsc1–/– cells. Further validation of the data in multiple mouse and human cell lines showed that mTORC1 signaling most dramatically induced the expression of the proteases neprilysin (NEP/CD10) and aminopeptidase N (APN/CD13). Functional studies showed that constitutive mTORC1 signaling sensitized cells to genetic ablation of NEP and APN, as well as the biochemical inhibition of APN. In summary, these data show that mTORC1 signaling plays a significant role in the constitution of the surfaceome, which in turn may present novel therapeutic strategies.




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Deep Characterization of the Human Antibody Response to Natural Infection Using Longitudinal Immune Repertoire Sequencing [Research]

Human antibody response studies are largely restricted to periods of high immune activity (e.g. vaccination). To comprehensively understand the healthy B cell immune repertoire and how this changes over time and through natural infection, we conducted immune repertoire RNA sequencing on flow cytometry-sorted B cell subsets to profile a single individual's antibodies over 11 months through two periods of natural viral infection. We found that 1) a baseline of healthy variable (V) gene usage in antibodies exists and is stable over time, but antibodies in memory cells consistently have a different usage profile relative to earlier B cell stages; 2) a single complementarity-determining region 3 (CDR3) is potentially generated from more than one VJ gene combination; and 3) IgG and IgA antibody transcripts are found at low levels in early human B cell development, suggesting that class switching may occur earlier than previously realized. These findings provide insight into immune repertoire stability, response to natural infections, and human B cell development.




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Combined EGFR and ROCK Inhibition in Triple-negative Breast Cancer Leads to Cell Death Via Impaired Autophagic Flux [Research]

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell death, however, the underlying mechanisms remain unclear. To investigate this, here we applied a mass spectrometry-based proteomic approach to identify proteins altered on single and combination treatments. Our proteomic data revealed autophagy as the major molecular mechanism implicated in the cells' response to combinatorial treatment. We here show that EGFR inhibition by gefitinib treatment alone induces autophagy, a cellular recycling process that acts as a cytoprotective response for TNBC cells. However, combined inhibition of EGFR and ROCK leads to autophagy blockade and accumulation of autophagic vacuoles. Our data show impaired autophagosome clearance as a likely cause of antitumor activity. We propose that the inhibition of the autophagic flux on combinatorial treatment is attributed to the major cytoskeletal changes induced on ROCK inhibition, given the essential role the cytoskeleton plays throughout the various steps of the autophagy process.




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Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer [Research]

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.




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Phosphoproteomic Approaches to Discover Novel Substrates of Mycobacterial Ser/Thr Protein Kinases [Reviews]

Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive. Recently developed mass spectrometry (MS)-based phosphoproteomic approaches have expanded the list of potential STPK substrate identifications, yet further investigation is required to define the most functionally significant phosphosites and their physiological importance. Prior to the application of MS workflows, for instance, GarA was the only known and validated physiological substrate for protein kinase G (PknG) from pathogenic mycobacteria. A subsequent list of at least 28 candidate PknG substrates has since been reported with the use of MS-based analyses. Herein, we integrate and critically review MS-generated datasets available on novel STPK substrates and report new functional and subcellular localization enrichment analyses on novel candidate protein kinase A (PknA), protein kinase B (PknB) and PknG substrates to deduce the possible physiological roles of these kinases. In addition, we assess substrate specificity patterns across different mycobacterial STPKs by analyzing reported sets of phosphopeptides, in order to determine whether novel motifs or consensus regions exist for mycobacterial Ser/Thr phosphorylation sites. This review focuses on MS-based techniques employed for STPK substrate identification in mycobacteria, while highlighting the advantages and challenges of the various applications.




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Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies [Reviews]

Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field.




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MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity [Technological Innovation and Resources]

Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry (XL-MS) has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. The inception of MS-cleavable cross-linkers enabled the MS2-MS3 XL-MS acquisition strategy that provides cross-link information from both MS2 and MS3 level. However, the current cross-link search algorithm available for MS2-MS3 strategy follows a "MS2-centric" approach and suffers from a high rate of mis-identified cross-links. We demonstrate the problem using two new quality assessment metrics ["fraction of mis-identifications" (FMI) and "fraction of interprotein cross-links from known interactions" (FKI)]. We then address this problem, by designing a novel "MS3-centric" approach for cross-link identification and implementing it as a search engine named MaXLinker. MaXLinker outperforms the currently popular search engine with a lower mis-identification rate, and higher sensitivity and specificity. Moreover, we performed human proteome-wide cross-linking mass spectrometry using K562 cells. Employing MaXLinker, we identified a comprehensive set of 9319 unique cross-links at 1% false discovery rate, comprising 8051 intraprotein and 1268 interprotein cross-links. Finally, we experimentally validated the quality of a large number of novel interactions identified in our study, providing a conclusive evidence for MaXLinker's robust performance.




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Concentration Determination of >200 Proteins in Dried Blood Spots for Biomarker Discovery and Validation [Technological Innovation and Resources]

The use of protein biomarkers as surrogates for clinical endpoints requires extensive multilevel validation including development of robust and sensitive assays for precise measurement of protein concentration. Multiple reaction monitoring (MRM) is a well-established mass-spectrometric method that can be used for reproducible protein-concentration measurements in biological specimens collected via microsampling. The dried blood spot (DBS) microsampling technique can be performed non-invasively without the expertise of a phlebotomist, and can enhance analyte stability which facilitate the application of this technique in retrospective studies while providing lower storage and shipping costs, because cold-chain logistics can be eliminated. Thus, precise, sensitive, and multiplexed methods for measuring protein concentrations in DBSs can be used for de novo biomarker discovery and for biomarker quantification or verification experiments. To achieve this goal, MRM assays were developed for multiplexed concentration measurement of proteins in DBSs.

The lower limit of quantification (LLOQ) was found to have a median total coefficient of variation (CV) of 18% for 245 proteins, whereas the median LLOQ was 5 fmol of peptide injected on column, and the median inter-day CV over 4 days for measuring endogenous protein concentration was 8%. The majority (88%) of the assays displayed parallelism, whereas the peptide standards remained stable throughout the assay workflow and after exposure to multiple freeze-thaw cycles. For 190 proteins, the measured protein concentrations remained stable in DBS stored at ambient laboratory temperature for up to 2 months. Finally, the developed assays were used to measure the concentration ranges for 200 proteins in twenty same sex, same race and age matched individuals.




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N-glycosylation Site Analysis Reveals Sex-related Differences in Protein N-glycosylation in the Rice Brown Planthopper (Nilaparvata lugens) [Research]

Glycosylation is a common modification of proteins and critical for a wide range of biological processes. Differences in protein glycosylation between sexes have already been observed in humans, nematodes and trematodes, and have recently also been reported in the rice pest insect Nilaparvata lugens. Although protein N-glycosylation in insects is nowadays of high interest because of its potential for exploitation in pest control strategies, the functionality of differential N-glycosylation between sexes is yet unknown. In this study, therefore, the occurrence and role of sex-related protein N-glycosylation in insects were examined. A comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes at the glycopeptide level. N-glycopeptide enrichment via lectin capturing using the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans, resulted in the identification of over 1300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosylation sites were shown to be derived from proteins with a putative role in insect reproduction. In addition, differential glycan composition between males and females was observed for proteins shared across sexes. Both lectin blotting experiments as well as transcript expression analyses with complete insects and insect tissues confirmed the observed differences in N-glycosylation of proteins between sexes. In conclusion, this study provides further evidence for protein N-glycosylation to be sex-related in insects. Furthermore, original data on N-glycosylation sites of N. lugens adults are presented, providing novel insights into planthopper's biology and information for future biological pest control strategies.




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Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping [Research]

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.




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Peptidomic Analysis of Urine from Youths with Early Type 1 Diabetes Reveals Novel Bioactivity of Uromodulin Peptides In Vitro [Research]

Chronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis are captured by the urinary peptidome. To elucidate the early kidney response to chronic hyperglycemia, we conducted a peptidomic investigation into urines from otherwise healthy youths with type 1 diabetes and their non-diabetic peers using unbiased and targeted mass spectrometry-based techniques. This cross-sectional study included two separate cohorts for the discovery (n = 30) and internal validation (n = 30) of differential peptide excretion. Peptide bioactivity was predicted using PeptideRanker and subsequently verified in vitro. Proteasix and the Nephroseq database were used to identify putative proteases responsible for peptide generation and examine their expression in diabetic nephropathy. A total of 6550 urinary peptides were identified in the discovery analysis. We further examined the subset of 162 peptides, which were quantified across all thirty samples. Of the 15 differentially excreted peptides (p < 0.05), seven derived from a C-terminal region (589SGSVIDQSRVLNLGPITRK607) of uromodulin, a kidney-specific protein. Increased excretion of five uromodulin peptides was replicated in the validation cohort using parallel reaction monitoring (p < 0.05). One of the validated peptides (SGSVIDQSRVLNLGPI) activated NFB and AP-1 signaling, stimulated cytokine release, and enhanced neutrophil migration in vitro. In silico analyses highlighted several potential proteases such as hepsin, meprin A, and cathepsin B to be responsible for generating these peptides. In summary, we identified a urinary signature of uromodulin peptides associated with early type 1 diabetes before clinical manifestations of kidney disease and discovered novel bioactivity of uromodulin peptides in vitro. Our present findings lay the groundwork for future studies to validate peptide excretion in larger and broader populations, to investigate the role of bioactive uromodulin peptides in high glucose conditions, and to examine proteases that cleave uromodulin.




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Integration of IgA and IgG Autoantigens Improves Performance of Biomarker Panels for Early Diagnosis of Lung Cancer [Research]

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.