mini

Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




mini

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3 [Cell Biology]

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.




mini

Five Foreign Policy Questions for the UK’s Next Prime Minister

18 June 2019

Thomas Raines

Director, Europe Programme
Even if most don’t get to vote in the Conservative leadership election, the public deserves serious answers on the foreign policy plans of those who want to lead the country.

2019-06-18-10D.jpg

10 Downing Street. Photo: Getty Images.

In a month’s time, the UK will have a new prime minister. The campaign has been dominated by candidates’ views on how to deliver Britain’s withdrawal from the EU by October, alongside some discussion of domestic issues.

But relatively little has been said about international affairs, despite the fact that foreign policy questions are becoming a more partisan issue and Britain is facing crucial questions around Brexit and the wider international context. These will be waiting for whoever finds themselves in Number 10 on 22 July. 

1. How can Britain influence Europe from outside the EU?

Theresa May was fond of saying that Britain is leaving the EU but not leaving Europe. Britain cannot change its geography. It will continue to share many strategic and security interests with the rest of the continent, but it will be outside of Europe’s central political and economic project. A new PM will not only have to negotiate Britain’s new relationship with the EU, but also think about how to influence it as a third country.

An aspect of this will be finding a new way to work with the EU on foreign, security and defence policy that meets the need for autonomy on both sides. How deep this relationship is or how institutionalized it will be is yet to be negotiated and can be shaped by the next PM.

The UK needs to decide how ambitiously it wants to engage with the new defence agenda in the EU (particularly its industrial components), and how to balance these with key bilateral relationships like France and Germany. Amid uncertainty about American security guarantees and Russian aggression, the next PM must also consider what Britain’s security role in Europe should be and NATO’s place within that.

Beyond conventional foreign policy issues, Britain is also going to be heavily shaped and influenced by the rule-making power of the EU, and how the world’s largest market regulates itself, from energy to financial services, consumer products and the environment.

The UK will need a strategy to influence the EU from the outside – something Swiss, Norwegians and Americans will acknowledge is no easy feat. This could include significantly increasing its diplomatic footprint across Europe, working closely with the UK’s private and non-profit sectors, utilizing Britain’s technical expertise in areas like sanctions, and creating new ad hoc groupings to share perspectives and ideas, building on examples like the Northern Future Forum

2. Should Britain do business with President Trump?

President Trump represents a fundamental challenge to Britain: an American president whose belligerent unilateralism runs counter to many of Britain’s foreign policy objectives. His frequent and often shameless diplomatic faux pas – from proposing Nigel Farage be the British ambassador to his dog-whistle attacks on the mayor of London – are compounded by real differences of substance on issues like trade, climate change and nuclear non-proliferation.

A new prime minister must decide how to manage relations with the US administration, whether to challenge or condemn a US president when he acts against Britain’s interests, or use flattery or quieter diplomacy to seek to influence him. Theresa May’s strategy of staying politically close to the president and playing to his ego has yielded little in policy terms, though other world leaders have fared little better.

A new PM will face some uncomfortable choices. Will they continue to defend the Iran nuclear deal alongside European allies while the US continues to undermine it? Do they believe a trade deal with America is desirable or achievable with the current administration, and what are they willing to sacrifice to achieve it? Is the American security guarantee for Europe secure with Donald Trump as president? Judgements on these questions should inform Britain's wider strategy, and its objectives for a future relationship with the European Union.

3. Should Britain prioritize economics or security in its relations with China?

Britain faces its own version of the challenge that many countries face – how to balance the economic and investment benefits of a positive relationship with China with concerns about repressive domestic politics and a more assertive Chinese role regionally and globally. This tension has become more acute for two reasons.

First, the economic dislocation of leaving the EU may create a greater reliance on Chinese trade and investment. China is already a major investor in the UK. If Brexit proves to be disorderly, Britain’s need may be all the greater (though China faces economic headwinds as well). Some in Brussels even fear that the economic difficulties of Brexit may make the UK a soft touch for emerging powers from which it seeks inward investment and market access.

Second, the deterioration in US–China relations means the UK may come under increasing pressure from the United States to take a tough line with China. The controversy over Huawei’s role in delivering 5G networks may become a more regular feature of transatlantic debates, with Britain facing Chinese economic pressure on one side and a squeeze from America over security issues on the other, without the weight of the EU behind it.  

A new prime minister should consider whether the UK’s interests are served by a security role in east Asia, and whether it has the capability to play one.

The UK remains a party to the Five Power Defence Arrangements. The Royal Navy has conducted freedom of navigation exercises in the South China Sea, prompting a rebuke from Beijing. It has also taken steps to deepen security ties with Japan.

But the UK government has struggled to present a coherent position. Some cabinet ministers have sought to open doors to the Chinese market at the same time as others announced their intentions to send aircraft carriers to the Pacific. The next PM will need to find a balance between China and the US, or accept the consequences of more directly taking sides on disputes about trade, technology, and security.

4. How can the contradictions between UK foreign and domestic policy be reconciled?

One of the many problems with the vague and unhelpful slogan ‘Global Britain’ is how it jars with many aspects of domestic policy. This incoherence reduces Britain’s foreign policy credibility and effectiveness.

Britain has actively supported the UN-led Yemen peace process while continuing to support Saudi Arabia’s military campaign through arms sales. Britain wants to build a new ambitious independent trade policy while restricting the migration that is crucial for services trade. British foreign secretaries trumpet the UK’s soft power while the Home Office deports members of the Windrush generation, bungles EU citizenship applications and sets unreasonable burdens for many people seeking visas simply to visit the country.

Global universities are celebrated while international students had their post-study visas cut (a policy that sensibly is likely to be reversed). Britain advocates international tax compliance and transparency while not taking robust steps to regulate the tax haven role played by crown dependencies and overseas territories.

A new prime minister has the chance to get to grips with these inconsistencies and develop foreign and domestic policies which are more coherent and self-re-enforcing.

5. At what level should Britain’s international ambitions be funded?

Successive governments have celebrated the fact the UK is the only Western country to spend 2% of GDP on defence and 0.7% on development. However, this masks some real pressures in the system.

There are significant problems in the defence budget and a growing gap between commitments and committed funds. Meanwhile, the funding of Britain’s diplomacy has been cut by successive governments – Labour, Conservative and coalition – for much of the last 20 years. Numerous bodies have highlighted the problems facing the overstretched and underfunded Foreign Office. Where would defence and diplomacy sit in the new prime minister’s hierarchy of priorities?

The problem is not purely one of funding, but the gap between ambitions, rhetoric and resources. It is not sustainable for British ministers to trumpet Britain’s global ambitions while not properly funding the tools of its influence abroad.

It would be reasonable and understandable for a new prime minister to adjust that ambition and tone down the rhetoric, or alternatively to address resource pressures by investing in diplomacy and defence. But that choice should be informed by a sober reflection on Britain’s international position and interests as it leaves the EU. Brexit offers a chance to revisit assumptions that have guided British policy for a generation. A new prime minister should seize this opportunity.

A realistic vision for the future

All these issues will be more pronounced if the UK leaves the EU with no deal at the end of October. ‘No deal’ would be not simply an economic shock but a diplomatic rupture that will colour the UK’s capacity to negotiate a new relationship with the EU, which will be the first order of business after a ‘no deal’ exit. Trust will be in short supply.

Even if they don’t get to vote on the new prime minister, the public deserves serious answers to these and other questions from the men who want to lead the country. Not the platitudes of ‘Global Britain’ or a reflexive and unexamined British exceptionalism, but a serious, realistic assessment of how Britain will cope with the disruptions of leaving the EU and how it might thrive outside the regional bloc it has been a part of for more than 45 years.




mini

Brexit, Party Politics and the Next Prime Minister

Invitation Only Research Event

15 July 2019 - 8:30am to 9:30am

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

Event participants

Daniel Finkelstein OBE, Associate Editor, The Times; Conservative Member of the House of Lords; Chairman, Onward 
Chair: Thomas Raines, Head, Europe Programme, Chatham House

With the new leader of the Conservative party due to be announced on 23 July, what are the prospects for the party and the country?

On Brexit, the new prime minister faces most of the same challenges and constraints as Theresa May. The leadership contenders have outlined their ambitions for a revised deal, but with the EU insisting negotiations are over, their room for manoeuvre appears to be limited. Furthermore, even with a new leader at the helm, important divisions remain among voters about what shape Brexit and the future UK-EU relationship should take. If the EU won’t change the deal, and parliament won’t accept it, how can the deadlock be broken? Is a 'No Deal' Brexit politically deliverable? Or could there be a general election later in 2019? Can the Conservative party survive a pre-Brexit election intact?

Beyond Brexit, what are the other choices, in both domestic and foreign policy, facing the next prime minister? How might the decisions he makes affect the future of the party and British politics more broadly?

In this session, the speaker will share his reflections on the likely result of the leadership election, and what lies beyond it.

Attendance at this event is by invitation only.

Event attributes

Chatham House Rule

Alina Lyadova

Europe Programme Coordinator




mini

Year Two of the Abe Administration: Prospects for the Future of Japanese Foreign Policy and UK-Japan Relations

Research Event

11 February 2014 - 3:00pm to 5:00pm

Chatham House, London

Event participants

Kiichi Fujiwara, Professor of International Politics, Graduate School for Law and Politics, Tokyo University
Yuichi Hosoya, Professor of International Politics, Faculty of Law, Keio University
Akiko Yamanaka, Senior Visiting Research Fellow, Churchill College, University of Cambridge; Vice Minister for Foreign Affairs of Japan (2005-2006)
Chair: John Swenson-Wright, Senior Consulting Fellow, Asia Programme, Chatham House 

As Prime Minster Abe enters his second year in office, the speakers will consider future prospects for Japanese foreign policy and UK-Japan relations. 

This event is funded by the Nippon Foundation. It is held in partnership with the Nippon Foundation and the Great Britain Sasakawa Foundation.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Department/project




mini

Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles




mini

Podcast: Examining The Post-Brexit Japan-UK Partnership




mini

Biosafety Protocol News Issue 9 - National Administrative Systems for Biosafety /Feedback Questionnaire




mini

55th edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (October-December 2011)




mini

56th edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (January to March 2012)




mini

57th, 58th and 59th edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (April to June 2012) (July to December 2012) is now available.




mini

The Biannual Report on the Administration of the Convention on Biological Diversity for January to June 2013 is now available (page 27).




mini

The Biannual Report on the Administration of the Convention on Biological Diversity for July to December 2013 is now available (page 36).




mini

Will Prime Minister Boris Johnson be good for the UK tech sector?

Here's what we expect from the new government's IT policies




mini

Housing minister announces plans to boost UK proptech sector with data

Esther McVey said the government will release local data on properties and land to help the proptech sector thrive




mini

CBD News: Message from Ahmed Djoghlaf, Executive Secretary, to the G8 Environment Ministers Meeting, Kobe, Japan, 24-26 May 2008.




mini

CBD News: Biodiversity added to the agenda of Hokkaido Toyako G8 Summit. G8 Environmental Ministers issue the "Kobe Call for Action for Biodiversity".




mini

CBD News: 3 Heads of State, 87 Ministers to Open Biodiversity High Level Conference.




mini

CBD News: Statement from Dr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Twelfth Regular Session of the African Ministerial Conference on the Environment, Johannesburg, South Africa, 7-12 June 2008




mini

CBD News: Statement by the Executive Secretary, Ahmed Djoghlaf, at the Annual Ministerial Review of the High-level Segment of the 2008 Substantive Session of the Economic and Social Council, United Nations, New York, 1 July 2008




mini

CBD News: Intervention du Dr. Ahmed Djoghlaf lors du Cycles de Conférences 2008 « Relever le défi de la Biodiversité » organisés par l'Institut de Formation de l'Environnement et le Ministère français de l&#




mini

CBD News: Director of the Biodiversity and Policy Division, Ministry of the Environment, Japan, visits the Secretariat.




mini

CBD News: Syracuse Charter on Biodiversity and Chair's Summary - G8 Environment Ministerial Meeting, Castello Maniace, Siracusa, 22-24 April, 2009.




mini

CBD News: Statement by Mr Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity on the occasion of the G8 Environment Ministers Meeting Opening Working Session on Biodiversity, 23 April 2009, Syracuse, Italy.




mini

CBD News: Statement by Ahmed Djoghlaf, CBD Executive Secretary, at the Interactive Dialogue with Heads of Agencies at the Ministerial Segment of the Seventeenth Session of the Commission on Sustainable Development, New York City, 13 May 2009.




mini

CBD Communiqué: G-77 Ministers Pay Special Tribute to CBD Secretariat's Leading Role in South-South Cooperation.




mini

CBD News: Statement by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of at the Ministerial Round Table of the Ninth Conference of the Parties to the United Nations Convention to Combat Desertification,




mini

CBD News: Quarterly Report on the Administration of the Convention on Biological Diversity (July-September 2009)




mini

CBD News: The 47th Edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (October-December 2009).




mini

CBD News: Statement by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the African Ministerial Conference on Access And Benefit-Sharing, Windhoek, 8 March 2010.




mini

CBD Communiqué: President Pohamba of Namibia Opens the African Ministerial Conference on Access and Benefit-sharing.




mini

CBD News: Statement on the International Year on Biodiversity by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of Information Session with the Canadian Diplomatic Corps, Ministry of Foreign Affairs and




mini

CBD News: The 48th edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (January-March 2010).




mini

CBD News: Message by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Ministerial Segment of the XVII Meeting of the Forum of Ministers of Environment of Latin America and the Caribbean, 29 April 20




mini

CBD News: Statement by Mr Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Third Ministerial Symposium on Natural Resources And Environment: "Many Species, One Planet, One Future", 21 July 201




mini

CBD News: Quarterly Report on the Administration of the Convention on Biological Diversity (April-June 2010).




mini

CBD Notification: To Minimize Waste During MOP5 and COP10, Complete Sets of Pre-Session Documents Upon Request Only




mini

CBD Press Release: Ministerial forum calls for leadership for a new biodiversity vision for the twenty first century




mini

CBD Communiqué: The Ministers of Foreign Affairs of the Group of 77 and China support the adoption of the Multi-Year Plan of Action on South-South Cooperation on Biodiversity for Development at the tenth meeting of the Conference of the Parties to th




mini

CBD News: Statement by Mr Ahmed Djoghlaf, CBD Executive Secretary, on the occasion of the International Ministerial Conference of Mountain Countries on Climate Change, 4 October 2010, Kathmandu, Nepal




mini

CBD News: Statement by Mr Ahmed Djoghlaf, CBD Executive Secretary, on the occasion of the Second Inter-American Meeting of Ministers and High Level Authorities on Sustainable Development, 17 November 2010, Santo Domingo, Dominican Republic




mini

CBD News: 50th-51st edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (July-December 2010)




mini

CBD News: Statement by Mr. Ahmed Djoghlaf, CBD Executive Secretary, on the occasion of The Ministerial Conference on the occasion of the Fourth Regular Session of the Governing Body of the International Treaty on Plant Genetic Resources for Food and Agric




mini

CBD News: 52nd edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (January-March 2011).




mini

CBD News: The new Indian Minister of Environment and Forests, HE Jayanthi Natarajan, invites all Parties to the high-level segment of COP-11 at Hyderabad International Convention Centre from 17 to 19 October 2012 highlighting five key issues for discussio




mini

CBD News: 53rd edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (April-June 2011)




mini

CBD Communiqué: The 132 Ministers for Foreign Affairs of the Group of 77 and China call for implementation of Aichi Biodiversity Targets




mini

CBD News: 54th edition of the Quarterly Report on the Administration of the Convention on Biological Diversity (July-September 2011)




mini

CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary, on the occasion of the 14th Session of the African Ministerial Conference on the Environment (AMCEN), 10 - 14 September 2012, Rusha, Tanzania




mini

CBD News: The New Delhi ASEAN-India Ministerial Statement on Biodiversity: Ministers responsible for the environment and their representatives of India and ASEAN countries have agreed to enhance awareness among all stakeholders, strive towards mainstreami