en NYC Silkscreen Studio Swaps Fine Art Prints for Safety Signage By www8.gsb.columbia.edu Published On :: Wed, 22 Apr 2020 00:00:00 -0400 Gary Lichtenstein Editions has partnered with Urban Pathways to increase awareness and safety in the homeless community. Full Article
en Columbia-Harlem Small Business Development Center Is a Lifeline for Business Owners By www8.gsb.columbia.edu Published On :: Tue, 28 Apr 2020 00:00:00 -0400 The SBDC offers resources and guidance to Harlem’s small businesses amidst the COVID-19 crisis. Full Article
en Alumni Food Entrepreneurs Team Up to Feed NYC Healthcare Workers By www8.gsb.columbia.edu Published On :: Wed, 29 Apr 2020 00:00:00 -0400 Fundraising efforts, along with a generous donation from Beyond Meat, founded by Ethan Brown ’08, helps restaurant P.S. Kitchen, owned by April Tam Smith ’10 and Graham Smith ’21, provide meals to healthcare workers. Full Article
en Beyond CARES: Economist Glenn Hubbard on Government Response to COVID-19 By www8.gsb.columbia.edu Published On :: Fri, 08 May 2020 00:00:00 -0400 Hubbard asks: Can we design a more effective plan, in case of a next time? Full Article
en Cyber and International Law in the 21st Century By feedproxy.google.com Published On :: Mon, 30 Apr 2018 10:00:00 +0000 Research Event 23 May 2018 - 9:00am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Rt Hon Jeremy Wright QC MP, Attorney General, UKChair: Elizabeth Wilmshurst CMG, Distinguished Fellow, Chatham House Cyber intrusions do not respect international borders. At this event, the attorney general will discuss how to apply and shape international law in order to ensure the rules-based international system can adapt to the threats – and opportunities – posed by cyber into the future. Department/project International Law Programme, International Law Discussion Group Full Article
en Geneva Launch: Protecting Civilians — When is ‘Incidental Harm’ Excessive? By feedproxy.google.com Published On :: Tue, 02 Oct 2018 13:45:01 +0000 Research Event 14 December 2018 - 10:00am to 11:30am Graduate Institute | Chemin Eugène-Rigot 2 | 1202 Geneva | Switzerland Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseEzequiel Heffes, Thematic Legal Adviser, Geneva CallSigrid Redse Johansen, Judge Advocate General, The Norwegian Armed ForcesChair: Elizabeth Wilmshurst, Distinguished Fellow, Chatham HouseFurther speakers to be announced. PLEASE NOTE THIS EVENT IS BEING HELD IN GENEVA.There have been large numbers of civilian deaths in the armed conflicts in Yemen and Syria. Is international humanitarian law being ignored? This meeting coincides with the launch of a Chatham House research paper on the incidental harm side of the proportionality assessment which belligerents are legally required to make. The panel at the meeting will consider the types of harm that fall within the scope of proportionality assessments, what constitutes ‘excessive’ harm and measures that belligerents can take to give effect to the rule on proportionality.This event will be followed by a reception. Department/project International Law Programme Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
en London Launch: Protecting Civilians — When is ‘Incidental Harm’ Excessive? By feedproxy.google.com Published On :: Tue, 06 Nov 2018 18:25:01 +0000 Research Event 14 January 2019 - 5:30pm to 7:00pm Chatham House, London Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseEzequiel Heffes, Thematic Legal Adviser, Geneva CallSigrid Redse Johansen, Judge Advocate General, Norwegian Armed ForcesAndrew Murdoch, Legal Director, UK Foreign & Commonwealth OfficeChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House There have been large numbers of civilian deaths in the armed conflicts in Yemen and Syria. Is international humanitarian law being ignored?This meeting marks the London launch of a Chatham House research paper on the incidental harm side of the proportionality assessment which belligerents are legally required to make. The panel at the meeting will consider the types of harm that fall within the scope of proportionality assessments, what constitutes ‘excessive’ harm and measures that belligerents can take to give effect to the rule on proportionality.This event will be followed by a reception. Department/project International Law Programme, Rights, Accountability and Justice Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
en Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment By feedproxy.google.com Published On :: Thu, 06 Dec 2018 14:56:29 +0000 10 December 2018 Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial. Download PDF Emanuela-Chiara Gillard Associate Fellow, International Law Programme 2018-12-10-ilp-proportionality-paper.jpg Members of civil right defence conduct a search and rescue operation on destroyed buildings after an airstrike was carried out over the city of Jisr al-Shughur in Idlib province in Syria, on 6 May 2018. Photo: Hadi Harrat/Anadolu Agency/Getty Images. SummaryMilitary operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality.The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm.Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable).For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment.Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive.In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard.Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered.If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended.Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
en Human Rights Impact Assessment of Trade Agreements By feedproxy.google.com Published On :: Thu, 07 Feb 2019 14:35:02 +0000 Research Event 26 February 2019 - 6:00pm to 7:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants James Harrison, Reader and Associate Professor, University of Warwick School of LawRichard James, Evaluation Co-ordinator, Directorate-General for Trade European CommissionJennifer Zerk, Associate Fellow, International Law Programme, Chatham HouseChair: Andrea Shemberg, Chair, Global Business Initiative on Human Rights The idea that trade agreements should be subject to human rights impact assessment has been gathering momentum in recent years. This idea springs from concern – particularly on the part of trade unions and civil society organizations – that states are not presently doing enough to anticipate and address the human rights-related issues that arise from their trading arrangements with other countries.This meeting will coincide with the launch of a research paper on human rights impact assessment by Dr Jennifer Zerk. It will bring together experts from law, trade policy, human rights impact assessment practice and civil society to take stock of progress so far and consider the future prospects for human rights impact assessment as a risk-analysis and policymaking tool in the trade context. The meeting will explore the key risks and benefits of the human rights impact assessment of trade agreements. What legal, political and practical challenges have been encountered so far? In what ways could communication, stakeholder consultation and follow-up of findings be improved? And what is needed to build political and stakeholder support for these kinds of processes? This meeting will be followed by a reception. Department/project International Law Programme, Rights, Accountability and Justice Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
en China’s Growing Military Presence Abroad Brings New Challenges By feedproxy.google.com Published On :: Mon, 18 Feb 2019 08:22:32 +0000 18 February 2019 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 Dr Wim Muller Associate Fellow, International Law Programme @wimclmuller Increasing contributions to UN peacekeeping and the rising presence of Chinese security forces abroad are pushing Beijing to engage with questions of international law it has not previously had to consider. 2019-02-18-ChinaDjibouti.jpg Soldiers stand in line as the frigate Xuzhou arrives at the port of Djibouti in May 2018. In 2017, China established its first foreign naval base in Djibouti. Photo via Getty Images. China’s involvement in UN peacekeeping contributions has been on the rise for some time. China is also stepping up its own military and security operations abroad to protect its commercial and strategic interests, particularly in Africa. In doing so, China is exposing itself to a more complex set of issues – including international legal issues – with which it is only just starting to grapple.China’s contribution to UN peacekeeping over the last 10 years has expanded dramatically. In September 2016, it pledged $1 billion to help fund UN peace, security and development activities, while in 2018 it supplied 10.3 per cent of the UN peacekeeping budget, up from 3.93 per cent in 2012. China is also the largest contributor of peacekeeping forces among the five permanent members of the Security Council. As well as its regular troop contributions, it has also established a stand-by rapid deployment force of 8,000 peacekeeping troops.For China, increased involvement in UN peacekeeping offers what it likes to refer to as a ‘win-win’ situation. China’s contribution is very valuable at a time when peacekeeping is in need of resources, given the cutbacks from the other four permanent members of the Security Council in both financial and personnel contributions, waning US support for the UN and pressures on the UN budget.Embed this image <img src="https://www.chathamhouse.org/sites/default/files/images/2019-02-18-P5Peace.jpg" alt="" title="" />At the same time, the increased role in UN peacekeeping helps to cement China’s image as a ‘responsible stakeholder’ in the international order. China’s contributions to peacekeeping missions also help to promote stability in countries in which China has significant strategic and commercial interests, such as Senegal, South Sudan and Mali. China’s increased involvement in UN peacekeeping has coincided with the adoption of a more pragmatic position in relation to its traditionally staunch adherence to the principles of state sovereignty and non-intervention.China was initially sceptical of the UN’s Responsibility to Protect (R2P) doctrine, endorsed by member states in 2005, which seeks to protect populations from gross human rights violations, and which can include recourse to use of force by the international community, if authorized by the Security Council under Chapter VII of the UN Charter. Over time, though, Beijing has softened its stance to intervention and has gradually acknowledged the ability to respond to humanitarian catastrophes in certain circumstances, for example voting in favour of the Intervention Brigade in the Democratic Republic of the Congo in 2013. The softening of China’s stance on non-intervention is also evident in the significant rise not only in the involvement of Chinese troops in UN peacekeeping, but also in the deployment of Chinese military and security forces in a number of African states in order to protect China’s investment and infrastructure projects located there. China and the Future of the International Order – Peace and Security In this podcast, Roderic Wye and Professor Rosemary Foot explore how China’s engagement with the UN is evolving in the areas of peace and security, looking in particular at the rise in China’s involvement in peacekeeping. In 2017, China established its first foreign naval base in Djibouti, and in 2018 it held military drills in several African countries. The significant increase in China’s military presence in Africa since 2015 gives rise to a number of more complex issues for both China and the local communities involved. According to a recent report, China’s growing military and security presence in Africa is leading to concern in some local constituencies. The fact that China’s state-centric perception of security and development downplays the importance of human rights is likely to compound these tensions on the ground.New international law implicationsThe growing presence of Chinese peacekeeping, police and security forces abroad also carries implications for China in a number of different areas of international law with which it has only recently started to grapple. These include the law on the use of force and, given that many Chinese infrastructure projects are situated in fragile states, the law of armed conflict.The mushrooming presence of Chinese companies and investments abroad also carries implications for the Chinese state, and for the companies concerned, under international human rights law (particularly the UN Guiding Principles on Business and Human Rights). The international law on state responsibility could also be relevant if security companies owned or employed by the Chinese government, where their actions are attributable to China, become complicit in breaches of international law by other governments (such as human rights abuses).Compared to other areas of international law, such as international economic law and the law of the sea, China has not invested much to date in education in these areas, which may leave it exposed as it increases its global footprint. It was clear from a recent Chatham House roundtable at Columbia Law School in New York that China is now seeking to rapidly upskill in these areas.China’s global economic and security ambitions appear to be tilting China towards a more interventionist approach, which is extending beyond UN peacekeeping contributions towards security and military missions of its own. Time will tell how China will respond to the challenge of burnishing its image as a good global citizen while maintaining an approach to peacekeeping, security and development which is closely informed by its own economic and security interests. Full Article
en State Cyber Interventions Below the Threshold of the Use of Force: Challenges in the Application of International Law By feedproxy.google.com Published On :: Wed, 17 Apr 2019 10:45:01 +0000 Invitation Only Research Event 30 April 2019 - 10:00am to 4:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House Under what circumstances will a state-sponsored cyberattack on another state that falls below the threshold of the use of force be a breach of international law – for example, hacking into another state’s electoral databases, usurping inherently governmental functions such as parliamentary processes or an attack on another state’s financial system? In the dynamic field of state cyber operations, persistent, low-level cyberattacks are increasing, as are multilateral attempts to attribute the attacks to the states responsible. There is general agreement that international law applies to cyberspace but the question is how it applies and with what consequences. This meeting will bring together a small group of academics and practitioners to explore the application of international law to states’ cyber operations that interfere in the internal affairs of another state and which fall below the threshold of the use of force. What is the law on non-intervention in international law and how does it apply to states’ cyber activities? Does the Nicaragua case represent the best expression of the law in this area including the requirement of coercion? And are there any other principles of international law that are relevant? The meeting will also consider processes and procedures for agreeing on the law and best practices. The purpose of the meeting will be to inform a research paper by Chatham House. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project International Law Programme Full Article
en Cyber Interference in Elections: Applying a Human Rights Framework By feedproxy.google.com Published On :: Thu, 25 Apr 2019 13:55:01 +0000 Invitation Only Research Event 7 May 2019 - 10:00am to 4:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE The use of social media, including algorithms, bots and micro-targeted advertising, has developed rapidly while there has been a policy lag in identifying and addressing the challenges posed to democracy by the manipulation of voters through cyber activity. What role should international human rights law play in developing a normative framework to address potential harms caused by such cyber activity including the closing down of democratic space, the spread of disinformation and hate speech? This meeting will bring together a small group of academics and practitioners to explore the implications of applying a human rights framework to both the activities of social media companies and the activities of governments and international organizations in seeking to regulate their activity. The purpose of the meeting will be to inform a report that will provide an overview of the applicable law and recommendations for how that law might inform future policy and regulation. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project International Law Programme, Rights, Accountability and Justice Full Article
en Engage China to Uphold Multilateralism – But Not at Any Cost By feedproxy.google.com Published On :: Thu, 23 May 2019 11:14:05 +0000 12 June 2019 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 Where China’s interests align with those of the international community, there are opportunities for the country’s influence and economic power to strengthen the rules-based international order. Where they do not, states that traditionally support that order should join together to push back. 2019-02-01-China.jpg Students holding Chinese national flags watch the live broadcast of the 40th anniversary celebration of China's reform and opening-up at Huaibei Normal University on 18 December. Photo: Getty Images. China’s adherence to the rules-based international system is selective, prioritizing certain rules in favour of others. States supportive of that ‘system’ – or, as some argue, systems[1] – should identify areas of mutual strategic interest so that they can draw China further into the global rules-based order and leverage China as a constructive player that potentially also contributes to improvements in such areas. This is particularly apposite at a time when the US is in retreat from multilateralism and Russia seems bent on disrupting the rules-based international order.Supportive playerThere are many reasons for actively engaging with China on mutual areas of interest. China is a committed multilateralist in many areas, recognizing that often international cooperation and frameworks hold the key to its domestic problems, for example in the fields of environmental sustainability and financial regulation.China’s economic power is valuable in upholding international institutions: China is the UN’s third-largest donor (after the US and Japan) at a time when the UN is facing budgetary shortfalls. China is also the second-highest contributor to the UN peacekeeping budget, and the largest contributor of peacekeeping forces among the five permanent members of the UN Security Council.China also has a valuable role to play in the settlement of international disputes over trade and investment. China is a big supporter of the World Trade Organization (WTO)’s dispute settlement mechanism, and one of its most active participants;[2] China is currently playing an active role in negotiations to save the WTO’s appellate mechanism from folding in the wake of the US’s refusal to nominate new judges.The last 15 years have also seen a major shift in Chinese attitudes to investment arbitration, from a general suspicion and limitation of arbitration rights to broad acceptance and incorporation of such rights in China’s trade and investment treaties. China is actively engaged in multilateral negotiations through the UN Commission on International Trade Law (UNCITRAL) on reforms to investor–state dispute settlement.China has shown leadership on global climate change diplomacy, urging nations to remain committed to the Paris Agreement in the wake of the US decision to pull out, and has been an important interlocutor with the UK and the EU on these issues. As a strong supporter of the Paris Agreement, but also as the world’s top emitter of carbon dioxide, China has a crucial role to play in pushing forward implementation of the Paris targets. Despite its high emissions, China remains one of the few major economies on track to meet its targets,[3] giving it greater leverage to peer review other parties’ efforts.A recent report by the UK parliament’s Foreign Affairs Committee (FAC), on China and the rules-based international order, noted that where a body of trust and goodwill is developed with China, there is the possibility of discovering interests that coincide and the ability to work together on issues mutually regarded as of global importance. The report refers to a number of success stories from UK partnership with China in multilateral forums, including in counterproliferation and global health.[4]Developing areas of global governanceAs well as working with the current system, China is increasingly involved in the shaping of newer areas of international law – whether it be submissions to the International Tribunal for the Law of the Sea (ITLOS) on procedural rules for the emerging deep-sea mining regime or pitching for a greater role in Arctic governance.[5]This enthusiasm should be harnessed to promote the international rule of law, but at the same time there needs to be recognition of the strategic goals that drive China’s engagement. China’s interest in the Arctic, while including the desire to protect its ecology and environment, is also about access to marine resources, as well as about the Arctic’s strategic potential for China’s military.China’s submissions to ITLOS on the rules of procedure for deep-sea mining are constructive, but also reflect an ambition to secure first-mover advantage when commercial mining eventually takes place. Like other major powers working in this policy area, China’s actions are guided by self-interest, but that doesn’t mean its goals can’t be pursued through multilateral rules.China is also interested in creating new international structures and instruments that further its strategic aims. For example, with Russia (through the Shanghai Cooperation Organisation) it has proposed an International Code of Conduct for Information Security in the UN.[6]China is also pondering an array of options for dispute-resolution mechanisms for its Belt and Road projects, including the possibility of an Asian version of the international Convention on the Settlement of Investment Disputes, which might sit under the auspices of the Asian Infrastructure Investment Bank (AIIB).[7]The creation of new instruments and institutions need not be a threat to the rules-based international order in itself. We have already seen a combination of the creation of parallel complementary regimes alongside the reform of existing institutions, for example in development financing through the AIIB or the New Development Bank (often referred to as the ‘BRICS Bank’); these two banks are relatively conventionally structured along the lines of Western-dominated institutions, albeit with greater Chinese control. Based on these examples, selective adaptation seems more likely than a hostile ‘Eastphalian’ takeover.[8]RisksThere is, however, a real risk that in certain areas China may promote a rival authoritarian model of governance, assisted by an opportunistic convergence with Russia on issues such as human rights, development and internet governance. In areas where China’s core interests clash with those of the rules-based international order, China has shown itself to be unbending, as in its refusal to abide by the July 2016 decision of the Permanent Court of Arbitration in its dispute with the Philippines over the South China Sea.[9]China is becoming more assertive at the UN, but while it seeks to project itself there as a responsible emerging global leader, it is promoting a vision that weakens international norms of human rights, transparency and accountability,[10] while also carrying out practices domestically that raise serious human rights concerns (not least the detention of hundreds of thousands of Uighurs in re-education camps in Xinjiang).[11]China’s increased dominance geographically and geopolitically through its Belt and Road infrastructure projects carries with it a number of social and economic risks, including smaller states becoming trapped in unsustainable financial debts to China.But at a recent Chatham House conference on Asia and international law, participants highlighted the limitations on how far China can shape an alternative governance model.[12] China currently lacks soft power, cultural power and language power, all of which are needed in order to embed an alternative model abroad. China also currently lacks capacity and confidence to build coalitions with other states in the UN.Where it has tried to get buy-in from the international community for its new institutions, such as the China International Commercial Court (CICC) announced in July 2018, there has been scepticism about the standards to be applied.[13] Unless the court can demonstrate sufficient due process, international parties are likely to prefer other centres with a strong reputation for upholding the rule of law, such as those in London, Dubai and Singapore.Where China does promote its own governance model at the expense of the rules-based international order, states are starting to push back, often in concert. EU member states so far have adopted a joined-up approach to the Belt and Road Initiative. With the exception of Italy, they have refused to sign a Memorandum of Understanding on participation unless China provides much greater transparency on its compliance with international standards.The EU also recently presented a coordinated response to China on the situation in Xinjiang.[14] Similarly, members of the so-called ‘Five Eyes’ intelligence-sharing alliance (comprising Australia, Canada, New Zealand, the UK and the US) have acted together in relation to certain incidents of cyber interference attributed to China.[15]There are also signs of pushback from smaller states closer to home in relation to challenges to national sovereignty, debt diplomacy and financial viability arising from Belt and Road projects. The Sri Lankan government recently reversed the award of a $300 million housing deal to China, instead opting for a joint venture with an Indian company.China has been downscaling its investments as a way to counter some of the backlash it has received: the most recent Belt and Road summit put forward a more modest set of aspirations. This suggests that there is some scope for states to stand up to China and use leverage to secure better deals.Many international institutions have been Western-dominated for years;[16] China, together with many emerging and middle powers, has felt for some time that the international architecture does not reflect the world we live in. Given that context, states that champion the rules-based international order should acknowledge China’s desire to update the international order to reflect greater multipolarity, globalization and technological change, while being clear-eyed about their engagement with China. This involves investing in a proper understanding of China and how it works.[17]Where possible, cooperation with China should lead to outcomes that are backed up by international standards and transparency. The above-mentioned FAC report cites evidence that the UK’s support, and that of other developed countries, had a positive impact in shaping the governance and standards of the AIIB.[18] China has brought in international experts to advise on disputes before the CIIC, which may reassure would-be litigants.China’s relationship with the rules-based international order needs to be assessed pragmatically and dynamically. China can be a valuable partner in many areas where its objectives are closely aligned with those of the international community – from trade to climate change to peacekeeping.But where the country’s core interests are at odds with those of the wider international community, an increasingly confident China will strongly resist pressure, including on the South China Sea and human rights. In these areas, states supportive of international law can most powerfully push back through alliances and by ensuring that their own core values are not compromised in the interests of economic benefits.What needs to happenChina’s rising power and selective commitment to multilateralism make it a potentially influential ally in modernizing international governance.China is increasingly involved in shaping newer areas of international law. This enthusiasm could be harnessed in the service of institutional development and reform.Other states should identify areas of mutual strategic interest where China may offer a constructive role, including dispute settlement, health and climate change.However, engagement must not ignore the strategic calculations that drive China’s agenda, or its poor record on civil and political rights, transparency and accountability.Cooperation with China should lead to outcomes that are backed up by international standards and transparency.Where China’s actions undermine the rules-based international order, coordinated action by states supportive of that order is likely to be more effective than acting individually.Notes[1] Chalmers, M. (2019), Which Rules? Why There is No Single ‘Rules-Based International System’, RUSI Occasional Paper, April 2019, London: Royal United Services Institute, https://rusi.org/occasional-papers/Which-Rules-Why-There-Is-No-Single-Rules-Based-International-System.[2] See, for example, Moynihan, H. (2017), China’s Evolving Approach to International Dispute Settlement, Briefing, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/chinas-evolving-approach-international-dispute-settlement.[3] UN Environment (2018), Emissions Gap Report 2018, p. XVII, https://www.unenvironment.org/resources/emissions-gap-report-2018.[4] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System: Sixteenth Report of Session 2017–19, p. 32, https://publications.parliament.uk/pa/cm201719/cmselect/cmfaff/612/612.pdf.[5] Moynihan, H. (2018), ‘China Expands Its Global Governance Ambitions in the Arctic’, Expert Comment, 15 October 2018, https://www.chathamhouse.org/expert/comment/china-expands-its-global-governance-ambitions-arctic.[6] Updated version proposed 9 January 2015.[7] Moynihan, H. (2018), ‘Exploring Public International Law Issues with Chinese Scholars – Part Four’, Meeting Summary, 3 June 2018, https://www.chathamhouse.org/publication/exploring-public-international-law-issues-chinese-scholars-part-four.[8] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’, conference summary, https://www.chathamhouse.org/event/security-and-prosperity-asia-pacific-role-international-law.[9] Permanent Court of Arbitration Case No. 2013-19 (Philippines v China), Award of 12 July 2016, https://pca-cpa.org/wp-content/uploads/sites/6/2016/07/PH-CN-20160712-Award.pdf.[10] Piccone, T. (2018), China’s Long Game on Human Rights at the United Nations, Washington, DC: Brookings Institution, https://www.brookings.edu/wp-content/uploads/2018/09/FP_20181009_china_human_rights.pdf.[11] Wye, R. (2018), ‘‘The entire Uyghur population is seemingly being treated as suspect’: China’s persecution of its Muslim minority’, LSE Religion and Global Society blog, 18 September 2018, https://blogs.lse.ac.uk/religionglobalsociety/2018/09/the-entire-uyghur-population-is-seemingly-being-treated-as-suspect-chinas-persecution-of-its-muslim-minority/.[12] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’.[13] Walters, M. (2018), ‘Jury is out over China’s new commercial court, say lawyers’, Law Society Gazette, 1 November 2018, https://www.lawgazette.co.uk/law/jury-is-out-over-chinas-new-commercial-court-say-lawyers/5068125.article.[14] The Economist (2019), ‘Hope remains for Western solidarity. Look at embassies in Beijing’, 17 April 2019, https://www.economist.com/china/2019/04/20/hope-remains-for-western-solidarity-look-at-embassies-in-beijing.[15] In December 2018, the Five Eyes attributed the activities of a Chinese cyber espionage group targeting intellectual property and sensitive commercial property to China’s Ministry of State Security.[16] Roberts, A. (2017), Is International Law International?, Oxford: Oxford University Press.[17] Parton, C. (2019), China–UK Relations: Where to Draw the Border Between Influence and Interference?, RUSI Occasional Paper, February 2019, London: Royal United Services Institute, p. 30, https://rusi.org/publication/occasional-papers/china-uk-relations-where-draw-border-between-influence-and.[18] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System, p. 15.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
en Strengthen the International Criminal Court By feedproxy.google.com Published On :: Fri, 31 May 2019 10:54:53 +0000 12 June 2019 Elizabeth Wilmshurst CMG Distinguished Fellow, International Law Programme The ICC has been criticized for slow proceedings, weak management and ineffective prosecutions. The good news is that pragmatic reform need not entail fundamental treaty amendment; a culture change and more realistic expectations would go a long way. 2016-02-22-Gbagbo2.jpg Laurent Gbagbo looks on next to his lawyer Emmanuel Altit before the start of his trial at the ICC on 28 January 2016. Photo by Getty Images. The 1998 treaty which established the International Criminal Court (ICC) was adopted at a time when the world (or most of it) was willing to reach multilateral agreements on a variety of topics and was encouraging the development of international criminal justice. The two tribunals, set up by the UN Security Council, for the former Yugoslavia and for Rwanda had been relatively successful. The time was ripe for states to agree together to set up a permanent international court with wider scope than the two tribunals.So the ICC was created, with jurisdiction over the international crimes of genocide, crimes against humanity and war crimes; its jurisdiction for the crime of aggression developed later. The court was given the power to prosecute nationals of states that were parties to the ICC Statute, and also to prosecute where the crime was committed in the territory of a state party, whatever the nationality of the alleged criminals. The court had further jurisdiction when the Security Council referred a situation to it.That was some 20 years ago. There is now a perception in many quarters that the ICC has not fulfilled the expectations of its founders. The court’s proceedings are cumbersome and lengthy. Many of the accused are still at large, including Omar al-Bashir, the former president of Sudan. Some €1.5 billion has been spent, and there have been only three convictions for the core international crimes.There have been criticisms of the judges, the former Prosecutor and other officials, as well as concern over particular decisions of the court. The allegation that the court is only interested in crimes in Africa[1] is perhaps heard less frequently now than it once was (most of the African governments concerned referred the situations in their countries to the ICC themselves), and there has not been the mass walk-out of African states that was once predicted. Our Shared Humanity: The Arc of Intervention From Bosnia to the Brahimi Report and from Rwanda to R2P, Annan played a significant role in many critical moments that shaped approaches to peacekeeping and to the protection of civilians. What was the impact? But in other quarters there is serious unease about the situation in the court. As the UK representative said at a meeting last year, ‘We cannot bury our heads in the sand and pretend everything is fine when it isn’t.’[2]The negative assessment of the ICC’s work may be countered by the fact that it is the failure of states to cooperate with the court that causes many of the problems. Further, the expectations of states and civil society about the possibilities of international criminal justice have been so high that no court would be able to meet them. It is not possible for one court actually to ‘end impunity’ for international crimes,[3] nor to prevent war-related violence and mass atrocities, nor to satisfy all victims.Moreover, the criticisms of the ICC come against the background of the global crisis for multilateralism more generally. The present US administration is notoriously hostile towards this international institution.[4]On the plus side, the establishment of the court has encouraged states to revise their own laws on international crimes and to institute their own prosecutions where it is possible to do so. It is also claimed that the very existence of the court can be a deterrent to potential perpetrators of international crimes. The court has begun to add to the body of international criminal law and has increased the possibility that mass atrocities will be investigated.But there is indeed some truth in the criticisms made of the internal workings of the court. One problem is that the particular combination of the civil and common law systems that has developed has produced cumbersome procedures regarding the representation of victims at most stages of the proceedings. It has also resulted in endless appeals from huge numbers of small decisions made by one chamber or another.Then there are the management failures which have led to officials of the court being awarded compensation by the administrative tribunal of the International Labour Organization (ILO) because of the way they were treated by the court, and finally the decision of a few of the judges to take proceedings themselves at the ILO to have their salaries increased. Some ICC decisions have been met with surprise. For example, a former vice-president of the Democratic Republic of the Congo, Jean-Pierre Bemba, who was in the custody of the ICC for 10 years, was convicted by a unanimous trial chamber of various crimes and then succeeded on his appeal. Following this and the acquittal of former Côte d’Ivoire president Laurent Gbagbo,[5] there are concerns about the ability of the prosecution to succeed in cases against high-level alleged perpetrators.Most recently, there has been criticism of the reasoning behind the appeal court decision regarding the immunity – or, rather, lack of immunity – of former president Bashir. And a decision of a chamber of the ICC not to authorize the opening of an investigation in Afghanistan has been seen as shielding the US from possible proceedings (though it has been welcomed by others as a pragmatic approach).The message that certain problems with the ICC need fixing is coming not just from the writings of academics and the legal blogs,[6] but from governments too, including those, like the UK, which are among the foremost supporters of the court.The former presidents of the ICC’s Assembly of States Parties (which comprises the representatives of all states parties) say that they ‘are disappointed by the quality of some of [the court’s] judicial proceedings, frustrated by some of the results, and exasperated by the management deficiencies that prevent the Court from living up to its full potential’.[7] Changes to remove the worst excesses of the procedures that have evolved could be effected without amendments to the treaty incorporating the ICC Statute. It may be that a change in culture is also needed. More modesty by the court, along with more realism from governments and civil society, is needed.And, attractive as it might seem to push at the boundaries of the law, the court should be realistic in what it can achieve. It is next to impossible to prosecute a case effectively where there is no cooperation from the state on whose territory the crimes were committed.What is needed is a court that can undertake efficient and effective criminal proceedings, delivering fair and impartial justice in the small number of cases which it is reasonable to expect it to address, in the light of the evidential challenges, limited resources and limited state cooperation.Governments should decide together at the Assembly of States Parties to set in hand a review of the ICC’s operations. It has been suggested that a group of experts might be mandated to assess the management of the court;[8] on the basis of their report, governments could agree on the necessary improvements.Not everything, however, can come within the remit of such a group. Governments should adopt new rules and practices to address matters such as the election process for judges and their training; governments might consider reaching their own understandings on how some provisions of the ICC Statute should be interpreted in practice. Governments should reach out to the many civil society organizations which have supported the court over the years, to ensure that they are involved in the process.Measures of this kind cannot detract from the fact that the ICC is fundamentally sound and that its role is as necessary as when it was first established. As Richard Goldstone, former chief prosecutor of the United Nations International Criminal Tribunals for the former Yugoslavia and Rwanda, has said, ‘If there were no ICC in existence today, many people in many countries would be agitating for and demanding one. That we have one is a singular achievement. It behoves us to make it the best possible and to assist it, as States, civil society, and individuals, in the best and most productive way possible.’[9]What needs to happenCumbersome procedures, ineffective prosecutions against high-level alleged perpetrators, and weak internal management are among current criticisms of the ICC.Improvements to the court’s effectiveness and credibility may be possible without amending the treaty incorporating the ICC Statute.The Assembly of States Parties should review the ICC’s operations, whether or not with a group of experts, and governments should agree on improvements.New rules and practices should address matters such as the election process for judges and their training.Better management of expectations of the ICC among governments, civil society and the court itself is needed.Governments might consider reaching their own understandings on how some provisions of the ICC Statute should be interpreted in practice.Civil society organizations should be involved in any procedures for reform.Notes[1] See, for example, du Plessis, M., Maluwa, T. and O’Reilly, A. (2013), Africa and the International Criminal Court, London: Royal Institute of International Affairs, July 2013, https://www.chathamhouse.org/publications/papers/view/193415.[2] GOV.UK (2018), ‘UK statement to ICC Assembly of States Parties 17th session’, 5 December 2018, https://www.gov.uk/government/speeches/uk-statement-to-icc-assembly-of-states-parties-17th-session.[3] As the preamble to the ICC Statute desires. See ICC (2011), Rome Statute of the International Criminal Court, p. 1, https://www.icc-cpi.int/resource-library/Documents/RS-Eng.pdf.[4] See the speech of John Bolton, US National Security Advisor. Just Security (2018), ‘Bolton’s Remarks on the International Criminal Court’, 10 September 2018, https://www.justsecurity.org/60674/national-security-adviser-john-bolton-remarks-international-criminal-court/.[5] Gbagbo was accused of various crimes which took place after Côte d’Ivoire’s election in 2010, in which Gbagbo lost power to Alassane Ouattara. The case was terminated by the court following a year’s hearings in which the prosecution put forward its evidence.[6] See, for example, Guilfoyle, D. (2019), ‘Reforming the International Criminal Court: Is it Time for the Assembly of State Parties to be the adults in the room?’, EJIL:Talk! blog post, 8 May 2019, https://www.ejiltalk.org/reforming-the-international-criminal-court-is-it-time-for-the-assembly-of-state-parties-to-be-the-adults-in-the-room/.[7] Al Hussein, Z. R., Stagno Ugarte, B., Wenaweser, C. and Intelman, T. (2019), ‘The International Criminal Court Needs Fixing’, Atlantic Council, 24 April 2019, https://www.atlanticcouncil.org/blogs/new-atlanticist/the-international-criminal-court-needs-fixing.[8] Ibid.[9] Goldstone, R. (2019), ‘Acquittals by the International Criminal Court’, EJIL:Talk! blog post, 18 January 2019, https://www.ejiltalk.org/acquittals-by-the-international-criminal-court/. Richard Goldstone is also a former justice of the Constitutional Court of South Africa.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
en The Protection of Children in Armed Conflict By feedproxy.google.com Published On :: Tue, 25 Jun 2019 18:10:01 +0000 Research Event 25 September 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseJoanne Neenan, Legal Adviser, UK Foreign and Commonwealth OfficeDarren Stewart, Head of Operational Law, UK Army HeadquartersChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House With more protracted and urbanized conflicts, the character of warfare is changing in a manner that is having a greater impact on children. Aside from physical harm, they face the trauma of family separation and displacement, are vulnerable to sexual abuse and recruitment as soldiers and suffer severe disruption to their education. This event will discuss how international humanitarian law applies to the protection of children. Are offences against children in armed conflict being prosecuted adequately? Are there better ways of ensuring compliance with the law?This meeting is the second in a series of three commemorating the 70th anniversary of the 1949 Geneva Conventions.This event, which is supported by the British Red Cross, will be followed by a drinks reception.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project International Law Programme, The Limits on War and Preserving the Peace Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
en Human Rights Priorities: An Agenda for Equality and Social Justice By feedproxy.google.com Published On :: Wed, 23 Oct 2019 13:50:01 +0000 Members Event 19 November 2019 - 6:00pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Michelle Bachelet, United Nations High Commissioner for Human RightsChair: Ruma Mandal, Head, International Law Programme, Chatham House Following just over one year in office, UN High Commissioner for Human Rights, Michelle Bachelet, outlines her ongoing priorities at a tumultuous time for fundamental rights protections worldwide.She discusses the rights implications of climate change, gender inequality including the advancement of sexual and reproductive rights, the protection of vulnerable groups and the need to work closely with states, civil society and business to protect and advance human rights. Department/project International Law Programme Members Events Team Email Full Article
en Sovereignty and Non-Intervention: The Application of International Law to State Cyberattacks By feedproxy.google.com Published On :: Fri, 01 Nov 2019 10:55:01 +0000 Research Event 4 December 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Douglas, Legal Director, GCHQZhixiong Huang, Luojia Chair of International Law, Wuhan UniversityNemanja Malisevic, Director of Digital Diplomacy, MicrosoftHarriet Moynihan, Associate Fellow, International Law Programme, Chatham HouseChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House International law applies to cyber operations – but views differ on exactly how. Does state-sponsored interference in another state's affairs using cyber means – for example, disinformation campaigns in elections, disabling government websites, or disrupting transport systems – breach international law? If so, on what basis and how are the principles of sovereignty and non-intervention relevant? States are increasingly attributing cyber operations to other states and engaging in the debate on how international law applies, including circumstances that would justify countermeasures.As states meet to debate these issues at the UN, the panel will explore how international law regulates cyberoperations by states, consider the prospects of progress at the UN, and assess the value of other initiatives.This event coincides with the launch of a Chatham House research paper which analyses how the principles of sovereignty and intervention apply in the context of cyberoperations, and considers a way forward for agreeing a common understanding of cyber norms.This event will bring together a broad group of actors, including policymakers, the private sector, legal experts and civil society, and will be followed by a drinks reception. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
en The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention By feedproxy.google.com Published On :: Fri, 29 Nov 2019 16:56:12 +0000 2 December 2019 Hostile cyber operations by one state against another state are increasingly common. This paper analyzes the application of the sovereignty and non-intervention principles in relation to states’ cyber operations in another state below the threshold of the use of force. Read online Download PDF Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 2019-11-29-Intl-Law-Cyberattacks.jpg A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images. SummaryThe vast majority of state-to-state cyberattacks consist of persistent, low-level intrusions that take place below the threshold of use of force. International law, including the principle of non-intervention in another state’s internal affairs and the principle of sovereignty, applies to these cyber operations.It is not clear whether any unauthorized cyber intrusion would violate the target state’s sovereignty, or whether there is a threshold in operation. While some would like to set limits by reference to effects of the cyber activity, at this time such limits are not reflected in customary international law. The assessment of whether sovereignty has been violated therefore has to be made on a case by case basis, if no other more specific rules of international law apply.In due course, further state practice and opinio iuris may give rise to an emerging cyber-specific understanding of sovereignty, just as specific rules deriving from the sovereignty principle have crystallized in other areas of international law.Before a principle of due diligence can be invoked in the cyber context, further work is needed by states to agree upon rules as to what might be expected of a state in this context.The principle of non-intervention applies to a state’s cyber operations as it does to other state activities. It consists of coercive behaviour by one state that deprives the target state of its free will in relation to the exercise of its sovereign functions in order to compel an outcome in, or conduct with respect to, a matter reserved to the target state.In practice, activities that contravene the non-intervention principle and activities that violates sovereignty will often overlap.In order to reach agreement on how international law applies to states’ cyber operations below the level of use of force, states should put their views on record, where possible giving examples of when they consider that an obligation may be breached, as states such as the UK, Australia, France and the Netherlands have done.Further discussion between states should focus on how the rules apply to practical examples of state-sponsored cyber operations. There is likely to be more commonality about specific applications of the law than there is about abstract principles.The prospects of a general treaty in this area are still far off. In due course, there may be benefit in considering limited rules, for example on due diligence and a prohibition on attacking critical infrastructure, before tackling broad principles. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Full Article
en Seventy Years of the Geneva Conventions: What of the Future? By feedproxy.google.com Published On :: Tue, 24 Mar 2020 12:19:34 +0000 24 March 2020 Seventy years after the adoption of the Geneva Conventions, there are challenges that remain to be addressed. This briefing takes three pertinent examples, and discusses possibilities for addressing them. Read online Download PDF Emanuela-Chiara Gillard Associate Fellow, International Law Programme GettyImages-913468402.jpg Rescue of the wounded in Duma city by Syrian Red Crescent paramedics, 2 February 2018. Photo: Samer Bouidani/NurPhoto/Getty Summary The 70th anniversary of the adoption of the 1949 Geneva Conventions was commemorated in 2019. But violations of the Conventions and of the 1977 Additional Protocols are widespread.Contemporary conflicts have been marked by violations of some of the foundational rules of international humanitarian law (IHL) relating to the protection of the wounded and sick and of providers of medical assistance.A further area of IHL that has come under strain and scrutiny are the rules regulating humanitarian relief operations and their application to sieges and blockades.War has a huge impact on children, and the treatment of children in armed conflict is another area of the law that requires further attention.In the current political climate, it is unlikely that new treaties will be negotiated to address emerging issues or uncertainties in the law.Other measures must be explored, including the adoption of domestic measures to implement existing law; support for processes that interpret the law; and initiatives to promote compliance with the law by organized armed groups.One overarching challenge is the interplay between IHL and counterterrorism measures. It can undermine the protections set out in IHL, and hinder principled humanitarian action and activities to promote compliance with the law by organized armed groups. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
en 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions. Full Article
en Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain. Full Article
en 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] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 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. Full Article
en COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism. Full Article
en AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease. Full Article
en The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis. Full Article
en Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance. Full Article
en The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype. Full Article
en Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification By feedproxy.google.com Published On :: 2020-04-01 Lucía Trilla-FuertesApr 1, 2020; 19:690-700Research Full Article
en A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities By feedproxy.google.com Published On :: 2020-04-01 David CluetApr 1, 2020; 19:701-715Technological Innovation and Resources Full Article
en Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms By feedproxy.google.com Published On :: 2020-04-01 Quentin PerraudApr 1, 2020; 19:589-607Research Full Article
en The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling By feedproxy.google.com Published On :: 2020-04-28 Bokai SongApr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981Research Full Article
en Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2) By feedproxy.google.com Published On :: 2020-04-07 Elena LorenteApr 7, 2020; 0:RA120.002014v1-mcp.RA120.002014Research Full Article
en Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 By feedproxy.google.com Published On :: 2020-04-01 Michael PlankApr 1, 2020; 19:655-671Research Full Article
en Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS By feedproxy.google.com Published On :: 2020-04-13 James A. WilkinsApr 13, 2020; 0:RA120.001944v1-mcp.RA120.001944Research Full Article
en Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics By feedproxy.google.com Published On :: 2020-04-24 Eelke P. BéguinApr 24, 2020; 0:RA120.001964v1-mcp.RA120.001964Research Full Article
en Proteaphagy in mammalian cells can function independent of ATG5/ATG7 By feedproxy.google.com Published On :: 2020-04-16 Tatjana GoebelApr 16, 2020; 0:RA120.001983v1-mcp.RA120.001983Research Full Article
en Robust summarization and inference in proteome-wide label-free quantification By feedproxy.google.com Published On :: 2020-04-22 Adriaan StickerApr 22, 2020; 0:RA119.001624v1-mcp.RA119.001624Research Full Article
en Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS By feedproxy.google.com Published On :: 2020-04-06 Samvel K GularyanApr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986Research Full Article
en Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses By feedproxy.google.com Published On :: 2020-04-15 Sonia PodvinApr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079Research Full Article
en Developments and Applications of Functional Protein Microarrays By feedproxy.google.com Published On :: 2020-04-17 Guan-Da SyuApr 17, 2020; 0:R120.001936v1-mcp.R120.001936Review Full Article
en Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) By feedproxy.google.com Published On :: 2020-05-01 Liye ChenMay 1, 2020; 19:871-883Research Full Article
en Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions By feedproxy.google.com Published On :: 2020-05-01 Élie LambertMay 1, 2020; 19:808-827Research Full Article
en Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice By feedproxy.google.com Published On :: 2020-04-07 Taewook KangApr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882Research Full Article
en Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism By feedproxy.google.com Published On :: 2020-05-01 Xing-Huang GaoMay 1, 2020; 19:852-870Research Full Article
en Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling By feedproxy.google.com Published On :: 2020-04-06 Samuel W EntwisleApr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946Research Full Article
en Large-scale Identification of N-linked Intact Glycopeptides in Human Serum using HILIC Enrichment and Spectral Library Search By feedproxy.google.com Published On :: 2020-04-01 Qingbo ShuApr 1, 2020; 19:672-689Research Full Article
en Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments By feedproxy.google.com Published On :: 2020-03-31 Tsung-Heng TsaiMar 31, 2020; 0:RA119.001792v1-mcp.RA119.001792Research Full Article
en DEqMS: a method for accurate variance estimation in differential protein expression analysis By feedproxy.google.com Published On :: 2020-03-23 Yafeng ZhuMar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646Technological Innovation and Resources Full Article
en Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker By feedproxy.google.com Published On :: 2020-04-01 Karl A. T. MakepeaceApr 1, 2020; 19:624-639Research Full Article
en MaxQuant software for ion mobility enhanced shotgun proteomics By feedproxy.google.com Published On :: 2020-03-10 Nikita PrianichnikovMar 10, 2020; 0:TIR119.001720v1-mcp.TIR119.001720Technological Innovation and Resources Full Article