in Democratize Trade Policymaking to Better Protect Human Rights By feedproxy.google.com Published On :: Thu, 06 Jun 2019 12:11:18 +0000 12 June 2019 Dr Jennifer Ann Zerk Associate Fellow, International Law Programme There is growing interest in the use of human rights impact assessment to screen proposed trade agreements for human rights risks, and to ensure appropriate risk mitigation steps are taken. 2019-02-15-HumanRightsTradeAgreements-Smaller.jpg Tea pickers walk at dawn through the tea plantations of Munnar, Kerala, on 7 May 2017. Copyright: Pardeep Singh Gill/Getty Images With international trade discourse taking an increasingly transactional and sometimes belligerent tone, it would be easy to overlook the quiet revolution currently under way to bring new voices into trade policy development and monitoring. The traditional division of responsibilities between the executive and legislature – whereby treaties are negotiated and signed by the executive, and the legislature does what is necessary to implement them – may be undergoing some change.Growing awareness of the implications of trade and investment treaties for many aspects of day-to-day life – food standards, employment opportunities, environmental quality, availability of medicines and data protection, just to name a few – is fuelling demands by people and businesses for more of a say in the way these rules are formulated and developed.Various options for enhancing public and parliamentary scrutiny of trading proposals have recently been examined by two UK parliamentary select committees.[1] The reason for this interest is obviously Brexit, which has presented UK civil servants and parliamentarians with the unusual (some would say exciting) opportunity to design an approval and scrutiny process for trade agreements from scratch.Doubtless, EU authorization, liaison and approval procedures (which include a scrutinizing role for the European Parliament) will be influential,[2] as will the European Commission’s experience with stakeholder engagement on trade issues.[3] The recommendations of both UK select committees to include human rights impact assessment processes as part of pre-negotiation preparations[4] echo calls from UN agencies and NGOs for more rigorous and timely analysis of the human rights risks that may be posed by new trading relationships.[5] Again, EU practice with what it terms ‘sustainability impact assessment’ of future trade agreements provides a potential model to draw from.[6] However, process is no substitute for action. Human rights impact assessment is never an end in itself; rather, it is a means to a positive end, in this case a trade agreement which is aligned with the trading partners’ respective human rights obligations and aspirations. It bears remembering, though, that the idea of assessing trade proposals for future human rights risks is a relatively recent one. Do we have the tools and resources to make sure that this is a meaningful compliance and risk management exercise?Thus far there is little evidence that human rights impact assessment and stakeholder engagement exercises are having any real impact on the content of trade agreements.[7] This is the case even in the EU, where practice in these areas is the most advanced and systematic.[8]There are several possible reasons for this. First, the methodological challenges are enormous. Aside from the crystal-ball gazing needed to forecast the social, economic and environmental effects of a trade intervention well into the future, demonstrating causal links between a trade agreement and a predicted adverse impact is often highly problematic given the number of other economic and political factors that may be in play.[9]Secondly, there are many challenges around the need to engage with affected people and listen to their views.[10] The sheer number of possible impacts of a trade agreement on different individuals and communities, as well as the range of rights potentially engaged, makes this a difficult (some would say impossible) task. Some prioritization is always necessary.This makes for difficult decisions about who to engage with and how. Perceived bias or an apparent lack of even-handedness – favouring business compared to civil society, for instance – can sow mistrust about the true aims of such a process, undermining its future effectiveness as participants begin to question whether it is genuine or worthwhile.[11]The challenges are even more acute where impact assessment practitioners are tasked with investigating potential human rights impacts in other countries. Even if it is possible to get past the inevitable political sensitivities,[12] the sort of in-depth consultations required will be beyond the budget and time constraints of most assignments.[13]There are good reasons why trade policy should be subject to greater public and parliamentary scrutiny, and why there should be more opportunities for public participation in the formation of new trading regimes. By building more opportunities for stakeholder consultation at these stages, we can acquire perspectives on trade that are not available from other forms of assessment and analysis.However, policymakers should be wary of overstating the benefits of existing procedural models. Human rights impact assessment processes are still struggling to provide compelling analyses of the relationships between trade agreements and the enjoyment of human rights, let alone a roadmap for policymakers and trade negotiators as to what should be done.[14]And financial and practical barriers to participation in stakeholder engagement exercises mean that, at best, these will provide only a partial picture of stakeholder impacts and views.Experiences with human rights impact assessment of trade agreements so far demonstrate the need for realism about two things: first, the extent to which one can sensibly anticipate and analyse human rights-related risks and opportunities in the preparation stages for a new trading agreement; and, second, the extent to which problems identified in this way can be headed off with the right form of words in the treaty itself.Both recent UK select committee reports place considerable faith in the ability of pre-project transparency and scrutiny processes to flush out potential problems and prescribe solutions. Of course, there may be cases where frontloading the analysis in this way could be useful, for instance where the human rights implications are so clear that they can readily be addressed through upfront commitments by the parties concerned, whether by bespoke or standardized approaches.More often, though, for a trade agreement running many years into the future, human rights impacts and implications will take time to emerge, suggesting the need for robust monitoring and mitigation frameworks designed with longevity in mind. Ideally, pre-signing approval and assessment processes would lay the groundwork for future action by both trading partners, either jointly or separately (though preferably both).To this end, as well as developing ideas for more robust substantive provisions on human rights, policymakers should consider the institutional arrangements required – whether pursuant to the trade agreement or by complementary processes – to ensure that human rights-related risks identified during the planning stages are properly and proactively followed up, that emerging risks are tackled in a timely fashion, and that there are opportunities for meaningful stakeholder contributions to these processes.What needs to happenTrade policymakers can use human rights impact assessment to screen proposed trade treaties for human rights-related risks and to identify possible ways of mitigating those risks, whether through the terms of the agreement itself, domestic law reform or flanking measures.Building more opportunities for stakeholder consultations can enable perspectives on trade to be highlighted that are not available from other forms of assessment.Assessment is complicated, however, by methodological challenges and the difficulties of forecasting a trade agreement’s future impacts. Policymakers need to be realistic about the risks that can be anticipated, and the extent to which many of those identified can be addressed upfront in trade agreements’ terms.These inherent limitations may be overcome to some extent by better ongoing monitoring. Future trade agreements should include more robust human rights risk monitoring and mitigation frameworks, designed with longevity in mind.Notes[1] UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements, Seventeenth Report of Session 2017–19’, HC 1833 HL paper 310, 12 March 2019, https://publications.parliament.uk/pa/jt201719/jtselect/jtrights/1833/1833.pdf; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny, Sixth Report of Session 2017-2019’, HC 1043, 29 December 2018.[2] European Parliament and Directorate General for External Policies (2019), Parliamentary scrutiny of trade policies across the western world, study paper, March 2019, http://www.europarl.europa.eu/RegData/etudes/STUD/2019/603477/EXPO_STU(2019)603477_EN.pdf.[3] European Commission (2019), ‘Trade policy and you’, http://ec.europa.eu/trade/trade-policy-and-you/index_en.htm.[4] See UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements’, para 12; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny’, paras 124–34.[5] OHCHR (2003), Report of the High Commissioner for Human Rights on Human Rights, Trade and Investment, 2 July 2003, E/CN.4/Sub.2/2003/9, Annex, at para 63; UN Economic and Social Council (2017), ‘General Comment No 24 (2017) of the Committee on Economic, Social and Cultural Rights on State obligations under the International Covenant on Economic, Social and Cultural Rights in the context of business activities’, UN Doc. E/C.12/GC/24, 10 August 2017, para 13; and UN General Assembly (2011), ‘Guiding principles on human rights impact assessment of trade and investment agreements’, Report of the Special Rapporteur on the Right to Food, Olivier De Schutter, UN Doc. A/HRC/19/59/Add.5, 19 December 2011.[6] European Commission (2016), Handbook for Sustainability Impact Assessment (2nd ed.), Brussels: European Union, http://trade.ec.europa.eu/doclib/docs/2016/april/tradoc_154464.PDF.[7] Zerk, J. (2019), Human Rights Impact Assessment of Trade Agreements, Chatham House Research Paper, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/human-rights-impact-assessment-trade-agreements.[8] Ibid., pp. 11–13. For a detailed explanation of the EU’s approach to human rights impact assessment, see European Commission (2016), Handbook for Sustainability Impact Assessment.[9] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 14–21.[10] Ibid., pp. 21–22.[11] Ergon Associates (2011), Trade and Labour: Making effective use of trade sustainability impact assessments and monitoring mechanisms, Final Report to DG Employment, Social Affairs and Inclusion European Commission, September 2011; and Gammage, C. (2010), ‘A Sustainability Impact Assessment of the Economic Partnership Agreements: Challenging the Participatory Process’, Law and Development Review, 3(1): pp. 107–34. For a civil society view, see Trade Justice Movement (undated), ‘Trade Justice Movement submission to the International Trade Committee inquiry into UK Trade Policy Transparency and Scrutiny’, https://www.tjm.org.uk/resources/briefings/tjm-submission-to-the-international-trade-committee-inquiry-into-uk-trade-policy-transparency-and-scrutiny, esp. paras 23–32.[12] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 20–21.[13] Ibid., pp. 21–22.[14] Ibid.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
in 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
in Sieges, the Law and Protecting Civilians By feedproxy.google.com Published On :: Thu, 27 Jun 2019 10:35:30 +0000 27 June 2019 Siege warfare has been employed throughout the ages and remains dramatically relevant today. Questions of the compatibility of this practice with international humanitarian law (IHL) arise when besieged areas contain civilians as well as enemy forces. This briefing addresses those rules of IHL that are particularly relevant to sieges. Read online Download PDF Emanuela-Chiara Gillard Associate Fellow, International Law Programme 2019-06-27-Syrian-Family.jpg A Syrian family gather to eat a plate of corn and cabbage in Saqba, in the besieged rebel-held Eastern Ghouta area near Damascus on 6 November 2017. Photo: Getty Images SummaryAlthough sieges may conjure up images of medieval warfare, they are still used by armed forces today, in international and non-international armed conflicts.International law does not define sieges, but their essence is the isolation of enemy forces from reinforcements and supplies. Sieges typically combine two elements: ‘encirclement’ of an area for the purpose of isolating it, and bombardment.Questions of the compatibility of sieges with modern rules of international humanitarian law (IHL) arise when besieged areas contain civilians as well as enemy forces.Sieges are not prohibited as such by either IHL or other areas of public international law.Three sets of rules of IHL are relevant to sieges. The first comprises the rules regulating the conduct of hostilities. The second is the prohibition of starvation of civilians as a method of warfare, along with the rules regulating humanitarian relief operations. The third comprises the rules on evacuation of civilians.The application of IHL to sieges is unsettled in some respects. This briefing does not purport to resolve all the difficulties or address all the issues in detail.While it may go too far to say that it is now impossible to conduct a siege that complies with IHL, the significant vulnerability of civilians caught up in sieges puts particular emphasis on the need for both besieging and besieged forces to comply scrupulously with the legal provisions for the protection of civilians and to conclude agreements for their evacuation. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
in Tackling Cyber Disinformation in Elections: Applying International Human Rights Law By feedproxy.google.com Published On :: Wed, 18 Sep 2019 10:30:02 +0000 Research Event Tackling Cyber Disinformation in Elections: Applying International Human Rights Law 6 November 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Susie Alegre, Barrister and Associate Tenant, Doughty Street ChambersEvelyn Aswad, Professor of Law and the Herman G. Kaiser Chair in International Law, University of OklahomaBarbora Bukovská, Senior Director for Law and Policy, Article 19Kate Jones, Director, Diplomatic Studies Programme, University of OxfordChair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House Register Interest Cyber operations are increasingly used by political parties, their supporters and foreign states to influence electorates – from algorithms promoting specific messages to micro-targeting based on personal data and the creation of filter bubbles. The risks of digital tools spreading disinformation and polarizing debate, as opposed to deepening democratic engagement, have been highlighted by concerns over cyber interference in the UK’s Brexit referendum, the 2016 US presidential elections and in Ukraine. While some governments are adopting legislation in an attempt to address some of these issues, for example Germany’s ‘NetzDG’ law and France’s ‘Law against the manipulation of information’, other countries have proposed an independent regulator as in the case of the UK’s Online Harms white paper. Meanwhile, the digital platforms, as the curators of content, are under increasing pressure to take their own measures to address data mining and manipulation in the context of elections. How do international human rights standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context? What practical steps can governments and technology actors take to ensure policies, laws and practices are in line with these fundamental standards? And with a general election looming in the UK, will these steps come soon enough? This event brings together a wide range of stakeholders including civil society, the tech sector, legal experts and government, coincides with the publication of a Chatham House research paper on disinformation, elections and the human rights framework. Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Department/project International Law Programme, Cyber, Sovereignty and Human Rights, Rights, Accountability and Justice Full Article
in In Judging Prorogation, UK Supreme Court Marks Evolution, Not Revolution, in Law By feedproxy.google.com Published On :: Thu, 03 Oct 2019 07:49:48 +0000 3 October 2019 Ruma Mandal Director, International Law Programme @RumaCHLaw Despite the political significance, last week’s judgment does not signal a newly activist court. 2019-10-03-UKSC.jpg The Supreme Court building in Westminster. Photo: Getty Images. The UK Supreme Court’s ruling last Wednesday has, at least temporarily, scuppered the prime minister’s plans to limit parliamentary debate before the looming Brexit deadline. Some of the prime minister’s allies have attacked the ruling as a ‘constitutional coup’. But a close reading reveals that the court has stayed within its remit to interpret, rather than make, the law.In a carefully reasoned judgment, the court emphasized that the case was not about Brexit. But the judges certainly did not shy away from the extraordinary nature of the matters before it, noting that such factual situations have ‘never arisen before and are unlikely ever to arise again… But our law is used to rising to such challenges and supplies us with the legal tools to enable us to reason to a solution.’The key question before the court was whether the prime minister’s decision to seek prorogation was ‘justiciable’ – i.e. amenable to being reviewed by a court. The English and Scottish courts earlier on in these proceedings had come, dramatically, to opposing views on this.The Supreme Court was not dissuaded by the inherently political considerations involved in the prime minister’s decision, stating that while ‘courts cannot decide political questions, the fact that a legal dispute concerns the conduct of politicians, or arises from a matter of political controversy, has never been sufficient reason for the courts to refuse to consider it’.The court went on to emphasize that the Crown’s remaining prerogative powers (exercised on the advice of the government or directly by ministers) have long been subject to judicial scrutiny; such oversight is essential to guarding the separation of powers underpinning the UK’s constitution.So far, so conventional. The full bench of the Supreme Court was required to grapple, though, with a prerogative power that had never been tested before in the courts. And so they delved back to the 1611 Case of Proclamations: ‘the King hath no prerogative, but that which the law of the land allow him’. In the court’s view, the legal issue to be resolved was the scope of the power to prorogue (the existence of this particular prerogative not being in dispute).With no case law available to provide direct guidance on this question, the court, instead, relied on two fundamental principles of the UK’s constitution – parliamentary sovereignty and parliamentary accountability. What would be the logical consequence of an unlimited power to prorogue? The ability to shut parliament permanently.The conclusion: this particular prerogative power had limits. The court held that:‘A decision to prorogue Parliament (or to advise the monarch to prorogue Parliament) will be unlawful if the prorogation has the effect of frustrating or preventing, without reasonable justification, the ability of Parliament to carry out its constitutional functions as a legislature and as the body responsible for the supervision of the executive. In such a situation, the court will intervene if the effect is sufficiently serious to justify such an exceptional course.’Having come to this conclusion, the court was left to examine what justification had in fact been given, noting that the prime minister’s motives were irrelevant. It noted that no clear reason had been given – the relevant documents were all concerned with preparing for the Queen’s speech.Noting evidence on normal practice for such preparations, including from a former prime minister, the court found it ‘impossible… to conclude…that there was any reason – let alone a good reason – to advise Her Majesty to prorogue Parliament for five weeks’.The court’s decision was neither inevitable nor a radical departure from legal tradition. It represents the gradual evolution of the long-established legal principle that the crown’s powers are set by the law and supervised by the courts.Courts have traditionally been reticent to rule on prerogative powers which are ‘high politics’ by nature – classic examples include declaring war and negotiating treaties. In recent years, though, the judiciary has shown a growing confidence to grapple with the contours of those prerogative powers that remain. Deference is still shown when looking at how those powers have been used as opposed to the limits of the prerogative in question.The Supreme Court ruling won’t reassure those who worry about the emergence of an activist court willing to wade (improperly) into the political arena. Nor will it necessarily bring comfort to those anxious about an unwritten constitution in an era where political conventions are fast unravelling.But divisive court rulings are nothing new, nor are ministerial outbursts about inconvenient judgments. In the current environment, politicians should take particular care not to send mixed messages which undermine the independence of the UK’s judiciary. Public trust in British institutions is dangerously low and the UK can ill-afford further damage to its reputation as a country steeped in democracy and the rule of law. Full Article
in 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
in Security and Prosperity in Asia: The Role of International Law By feedproxy.google.com Published On :: Fri, 01 Nov 2019 11:38:35 +0000 1 November 2019 The 'Security and Prosperity in Asia' conference looked at the impact of international law in the Asia-Pacific with a focus on regional economic and security issues such as the South China Sea disputes. Read online Download PDF Security and Prosperity in Asia Cover Image.jpg Singapore skyline at sunset, 2016. Photo: Getty Images. About the ConferenceAt a time of geopolitical uncertainty and with multilateralism under pressure, this conference brought together diverse actors to explore the evolving role of international law on critical security and economic issues in the Asia-Pacific. From trade agreements to deep-sea mining, cyberwarfare to territorial disputes, the breadth of the discussion illustrated the growing reach of international law in the region.Hosted by the International Law Programme and the Asia-Pacific Programme at Chatham House on 27 March 2019, the conference focused on three themes: trade and investment, maritime security and governance, and emerging security challenges. What trends are emerging in terms of engagement with international law in the region, and how can international standards play a greater role in encouraging collaboration and reducing tensions? And, with the eastward shift in geopolitical power, how will Asia-Pacific states shape the future of international law? Department/project International Law Programme, Global Governance and the Rule of Law, Asia-Pacific Programme, Geopolitics and Governance, Trade, Investment and Economics Full Article
in Online Disinformation and Political Discourse: Applying a Human Rights Framework By feedproxy.google.com Published On :: Tue, 05 Nov 2019 11:03:02 +0000 6 November 2019 Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law. This paper examines how human rights frameworks should guide digital technology. Download PDF Kate Jones Associate Fellow, International Law Programme @katejones77 LinkedIn 2019-11-05-Disinformation.jpg A man votes in Manhattan, New York City, during the US elections on 8 November 2016. Photo: Getty Images. SummaryOnline political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse. Department/project International Law Programme, Cyber, Sovereignty and Human Rights, Rights, Accountability and Justice Full Article
in Investigating Violations of International Humanitarian Law By feedproxy.google.com Published On :: Wed, 13 Nov 2019 13:25:01 +0000 Research Event 21 January 2020 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Andrew Cayley, Director, Service Prosecuting Authority, UK Ministry of DefenceLarry Lewis, Vice President and Director, Center for Autonomy and Artificial Intelligence, CNAJelena Pejic, Senior Legal Adviser, International Committee of the Red CrossChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House Countries should have adequate systems in place for investigating violations of international humanitarian law, for launching criminal prosecutions for war crimes and for inquiring into responsibility for unlawful actions of national armed forces. There also needs to be proper counting and recording of the civilian casualties of military operations. This event, which will be introduced by the director of the UK Service Prosecuting Authority, Andrew Cayley, will discuss the new report by the International Committee of the Red Cross and the Geneva Academy of International Humanitarian Law, Guidelines on Investigating Violations of International Humanitarian Law: Law, Policy and Good Practice, as well as the problems and challenges associated with recording civilian casualties of armed conflict. This meeting is the third in a series of three commemorating the 70th anniversary of the 1949 Geneva Conventions supported by the British Red Cross. It will be followed by a drinks reception. Department/project International Law Programme, The Limits on War and Preserving the Peace Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
in 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
in Madeleine Forster By feedproxy.google.com Published On :: Wed, 11 Dec 2019 11:22:45 +0000 Richard and Susan Hayden Academy Fellow, International Law Programme Biography Madeleine is the Richard and Susan Hayden Academy Fellow, hosted in the International Law Programme.Prior to joining Chatham House, she provided specialist legal services to United Nations humanitarian operations in the Middle East. She brings particular expertise in applied international human rights law across complex political, security and operational environments. She has also acted on internal United Nations boards of inquiry and system efforts to combat sexual exploitation and abuse.Her current research interests are at the intersection of international law, ethics and technology, including the potential and pitfalls of innovative solutions to refugee and migrant crises.Madeleine began her career as an employment lawyer with global law firm DLA Piper, has been an Australian Youth Ambassador for Development in Cambodia, and holds a Master of Laws from the University of Melbourne, where she was awarded the Edward Walter Outhwaite Prize for academic achievement in human rights. Areas of expertise International lawEthics & technologyRefugee law and policyMiddle East & North Africa region experienceCombatting sexual exploitation and harassment in organisations Past experience 2015-19Legal officer (Protection), United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA)2015Lawyer, Victorian Department of Education2014-15Australian Youth Ambassador for Development (Cambodia)2013DLA Piper Secondee Lawyer, Human Rights Law Centre2010-13Lawyer, DLA Piper Australia +44(0)2073143616 Email @maddiefors LinkedIn Full Article
in POSTPONED: Supporting Civic Space: The Role and Impact of the Private Sector By feedproxy.google.com Published On :: Wed, 22 Jan 2020 17:05:01 +0000 Invitation Only Research Event 16 March 2020 - 11:00am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.This roundtable will bring together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting will provide an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.This meeting will be the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Attendance at this event is by invitation only. PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project International Law Programme, Global Governance and the Rule of Law, Rights, Accountability and Justice Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
in COVID-19 Brings Human Rights into Focus By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:59:58 +0000 9 April 2020 Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats With a reawakened sense of our shared humanity and vulnerability, and the benefits of collective action, this crisis may translate into a comeback for human rights as a popular idea. 2020-04-09-US-COVID-homeless A previously homeless family in the backyard of their newly reclaimed home in Los Angeles, where officials are trying to find homes to protect the state's huge homeless population from COVID-19. Photo by FREDERIC J. BROWN/AFP via Getty Images. During this extraordinary global public health emergency, governments must strike the right balance between assertive measures to slow the spread of the virus and protect lives on the one hand, and respect for human autonomy, dignity and equality on the other.International law already recognises the grave impact of pandemics and other catastrophic events on social order and provides criteria to guide states in their emergency action. The International Covenant on Civil and Political Rights permits curbs on the right to ‘liberty of movement’ so long as restrictions are provided by law, deemed necessary to protect public health, and consistent with other rights in that treaty.Freedom of expression and association, and the rights to privacy and family life are also qualified in these terms under international and regional human rights treaties. But, as emphasised in the Siracusa Principles, any limitations must not be applied in an arbitrary or discriminatory way, and must be of limited duration and subject to review.International law also guarantees the right to the highest attainable standard of health, while states are specifically required to take steps to prevent, treat and control epidemics under the International Covenant on Economic, Social and Cultural Rights. Even in health emergencies, access to health services must be ensured on a non-discriminatory basis, especially for vulnerable or marginalised groups.Abuse of coronavirus emergency measuresMany governments have taken pains to craft emergency laws that respect human rights, such as permitting reasonable exceptions to lockdowns for essential shopping and exercise, and making them subject to ongoing parliamentary review and sunset clauses. But even laws that appear to be human rights compliant can still easily be misapplied, as the recent debates about over-zealous policing of people walking and travelling in the UK illustrate.And disturbing stories are emerging from states where police brutality is entrenched. In Kenya, a 13-year-old boy was reportedly shot on the balcony of his home by police enforcing a coronavirus curfew. Authorities in the Philippines' are allegedly locking those caught defying the curfew in dog cages.As the recent history of counterterrorism demonstrates, emergency laws tend to be sticky, remaining on the statute books far longer than desirable.The virus is also proving a powerful accelerant for the current global authoritarian drift which is so detrimental to progress on human rights. Many authoritarian leaders have seized the opportunity to further reduce constraints on their power.Hungary's prime minister Viktor Orbán has used the pandemic as a pretext for new laws enabling him to rule by decree, completing the country's transition to an elected dictatorship. In Brazil, president Jair Bolsonaro has suspended deadlines for public bodies to reply to freedom of information requests. Iran is the latest of many repressive states in the Middle East to ban the printing and distribution of all newspapers. In China, the government brushed off criticism over ‘disappearances’ of whistleblowers and citizen journalists who questioned its response to the crisis.Others have exploited the turmoil to undermine justice for human rights abuses - Sri Lanka's president Gotabaya Rajapaksa pardoned one of the only soldiers held accountable for crimes during the country's brutal civil war.Coronavirus also places liberal values under further strain. Fear is a major driver in the appeal of populist authoritarians and the virus is stoking it. One poll showed 73% of British citizens agreed coronavirus is just the latest sign that the world we live in is increasingly dangerous. Extremists are exploiting these fears to spread hate by blaming the outbreak on ethnic or religious groups, and encouraging those infected to spread it to these groups.The closure of borders helps reinforce xenophobic tendencies, and high public tolerance of emergency measures could easily spill into normalisation of intrusive digital surveillance and restrictions on liberty for other reasons well into the future.Disadvantaged groups face a higher level of risk from the crisis. The health of aboriginal Australians is so poor that those aged 50 and above are being urged to stay home, advice otherwise given to those over 70 in the general population. The Moria refugee camp on Lesbos is reporting no soap and just one water tap for 1,300 refugees. In the UK, asylum seekers struggle to self-isolate in shared accommodation and have a daily allowance of just £5.40 for food, medicine and toiletries. Women's rights groups are reporting a spike in domestic violence.For countries racked by war and extreme poverty, the impact is catastrophic. The virus is set to run rampant in slums, refugee camps and informal settlements where public health systems - if they exist at all - will struggle to cope. And detainees are among the most at risk, with the UN calling for release of political prisoners and anyone detained without sufficient legal basis.But the crisis has galvanised debate around the right to health and universal health coverage. Many governments have quickly bankrolled generous relief packages which will actually safeguard the socio-economic rights of many, even if they are not being justified in those terms. Portugal and Ireland have rolled back barriers to accessing healthcare for asylum seekers and other marginalised migrants.The pandemic strikes as many powerful governments have become increasingly nationalistic, undermining or retreating from international rules and institutions on human rights. But as the crisis spreads, the role of well-established international human rights standards in shaping and implementing effective - but also legitimate - measures is becoming ever clearer.The virus has reminded us of our interconnectedness as human beings and the need for global cooperation to protect our lives and health. This may help to revive popular support for human rights, creating momentum for the efforts to tackle inequality and repression - factors which have made the global impact of coronavirus so much worse than it might have been. Full Article
in Bulletin updated at 19:45 HKT - 03/05/2020 By www.weather.gov.hk Published On :: Sun, 03 May 2020 11:45:05 GMT There is no warning in force. Full Article W
in 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
in 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
in 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
in Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease. Full Article
in MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae. Full Article
in 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
in 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
in 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
in 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
in 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
in Bulletin updated at 00:00 HKT 10/May/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:00:00 GMT General Situation:A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. With the anticyclone aloft strengthening in the middle and latter parts of this week, the weather over southern China will improve and it will be hot. Date/Month: 10/05 (Sunday) Wind: South force 3. Weather: Sunny intervals and a few showers. Isolated thunderstorms later. Temp range: 28 - 32 C R.H. range: 65 - 95 per Cent Date/Month: 11/05 (Monday) Wind: South force 2 to 3. Weather: Mainly cloudy with occasional showers and a few squally thunderstorms. Temp range: 26 - 30 C R.H. range: 70 - 95 per Cent Date/Month: 12/05 (Tuesday) Wind: Light winds force 2. Weather: Mainly cloudy with a few showers and thunderstorms. Temp range: 25 - 29 C R.H. range: 70 - 95 per Cent Date/Month: 13/05 (Wednesday) Wind: Southeast force 3. Weather: Sunny intervals and one or two showers. Temp range: 26 - 30 C R.H. range: 65 - 90 per Cent Date/Month: 14/05 (Thursday) Wind: Southeast force 3. Weather: Sunny periods. Temp range: 26 - 31 C R.H. range: 60 - 85 per Cent Date/Month: 15/05 (Friday) Wind: South to southeast force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 16/05 (Saturday) Wind: South force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 17/05 (Sunday) Wind: South force 3 to 4. Weather: Sunny periods. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Date/Month: 18/05 (Monday) Wind: South force 3 to 4. Weather: Sunny periods and isolated showers. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Sea surface temperature at 2 P.M. 09/05/2020 at North Point was 25 degrees C.Soil temperatures at 7 A.M. 09/05/2020 at Hong Kong Observatory :0.5 M below surface was 27.6 degrees C 1.0 M below surface was 26.4 degrees C Full Article F
in Bulletin updated at 00:45 HKT 10/05/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:45:00 GMT An anticyclone aloft brought hot weather to southern China yesterday. Locally, it was hot with sunny periods and isolated showers. A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. Weather forecast for Hong Kong:Mainly cloudy with a few showers. Sunny intervals during the day. There will be isolated thunderstorms later. Hot with temperatures ranging between 28 and 32 degrees. Moderate southerly winds. Outlook: There will be showers and thunderstorms on Monday and Tuesday. The weather will improve gradually in the following couple of days. Full Article F
in 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
in 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
in 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
in Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome By feedproxy.google.com Published On :: 2020-04-01 Xien Yu ChuaApr 1, 2020; 19:730-743Technological Innovation and Resources Full Article
in Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis By feedproxy.google.com Published On :: 2020-04-01 Beatriz RochaApr 1, 2020; 19:574-588Research Full Article
in Organellar maps through proteomic profiling - a conceptual guide By feedproxy.google.com Published On :: 2020-04-28 Georg H H BornerApr 28, 2020; 0:R120.001971v1-mcp.R120.001971Review Full Article
in Peptide-based interaction proteomics By feedproxy.google.com Published On :: 2020-04-28 Katrina MeyerApr 28, 2020; 0:R120.002034v1-mcp.R120.002034Review Full Article
in 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
in 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
in 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
in 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
in 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
in Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility By feedproxy.google.com Published On :: 2020-04-20 Yunlei LiApr 20, 2020; 0:RA120.002017v1-mcp.RA120.002017Research Full Article
in Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics By feedproxy.google.com Published On :: 2020-04-01 Patrick HerrApr 1, 2020; 19:608-623Research Full Article
in 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
in 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
in 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
in 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
in 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
in 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
in 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
in Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation By feedproxy.google.com Published On :: 2020-04-14 Nora LinscheidApr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878Research Full Article
in Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity By feedproxy.google.com Published On :: 2020-04-01 Mona RadwanApr 1, 2020; 19:640-654Research Full Article
in Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC By feedproxy.google.com Published On :: 2020-03-31 Yan Zhou TranMar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036Research Full Article