is Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome By spectrum.diabetesjournals.org Published On :: 2002-01-01 Guillermo E. UmpierrezJan 1, 2002; 15:Articles Full Article
is Motivational Interviewing and Diabetes: What Is It, How Is It Used, and Does It Work? By spectrum.diabetesjournals.org Published On :: 2006-01-01 Garry WelchJan 1, 2006; 19:5-11Lifestyle and Behavior Full Article
is Blood Glucose Awareness Training: What Is It, Where Is It, and Where Is It Going? By spectrum.diabetesjournals.org Published On :: 2006-01-01 Daniel J. CoxJan 1, 2006; 19:43-49Feature Articles Full Article
is Glucose Metabolism and Regulation: Beyond Insulin and Glucagon By spectrum.diabetesjournals.org Published On :: 2004-07-01 Stephen L. AronoffJul 1, 2004; 17:183-190Feature Articles Full Article
is The Diabetes Attitudes, Wishes, and Needs (DAWN) Program: A New Approach to Improving Outcomes of Diabetes Care By spectrum.diabetesjournals.org Published On :: 2005-07-01 Soren E. SkovlundJul 1, 2005; 18:136-142Lifestyle and Behavior Full Article
is Autonomous Vehicles: Futurist Technologies in Markets and Society By www8.gsb.columbia.edu Published On :: Mon, 13 Jan 2020 17:00:21 +0000 What are the ethical, logistical and legal complexities that accompany Autonomous Vehicle technology—and what role should business strategists play in guiding AVs integration into business and society? Full Article
is Kohl & Frisch: A Prescription for Competition By www8.gsb.columbia.edu Published On :: Mon, 04 May 2020 13:48:24 +0000 How can Canadian pharmaceutical wholesaler Kohl & Frisch deploy its new market clout after acquiring a key competitor? Full Article
is D’Angel raises J$225,000 from online charity concert By jamaica-star.com Published On :: Tue, 05 May 2020 05:01:17 -0500 The Lady of Dancehall, D'Angel, says although her COVID-19 Relief Concert did not meet its US$200,000 target, she is overwhelmed by the support. The event, held via Instagram Live last Friday, saw performances from the likes of Beenie Man, G... Full Article
is Kaay Jones: The Jamaican who joins region in singing ‘We Got This’ By jamaica-star.com Published On :: Wed, 06 May 2020 05:01:07 -0500 Up-and-coming recording artiste Kaay Jones says she did not know she was becoming part of a transformational music project that would connect her to a wide cross section of talent in the Caribbean. Jones carries Jamaica's flag in a unified... Full Article
is Violence is not the answer - Dexta Daps’ new single spurs conversation on domestic abuse By jamaica-star.com Published On :: Wed, 06 May 2020 05:01:37 -0500 Hours after he was released from police lock-up last week, dancehall artiste Dexta Daps dropped some new music on his eager fans. The track, Breaking News, explores an all-too-familiar domestic violence storyline, but incorporates a controversial... Full Article
is Dancers' Paradise: Devon Unruly working hard to expand dance group By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:38 -0500 He's celebrating 10 years of dancing both competitively and in the street, and the co-founder of Unruly Skankaz, Devon Brown, says he is looking to expand the brand. The once three-member male dance group has grown to five, he told THE WEEKEND... Full Article
is JCF distribute PSOJ COVID-19 food packages By jamaica-star.com Published On :: Thu, 07 May 2020 17:32:28 -0500 Members of the Jamaica Constabulary Force on Thursday, distributed more than 300 food packages to individuals and families impacted by COVID-19 in St. James, under the Private Sector Organisation of Jamaica (PSOJ)-led COVID-19 Response Fund... Full Article
is ‘Rise together’ By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:41 -0500 The COVID-19 pandemic has created a disruptive new normal for all of us, including thousands of urban and rural poor. Let's emerge into a place where the vulnerable are not so affected by social inequality, and rise together to create a world that'... Full Article
is It felt like prison - Cruise ship worker happy to be home By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:43 -0500 "It felt like prison." Those are the exact words of Jermaine who returned to the island yesterday after he was stranded on a cruise ship for 56 days in South Hampton, United Kingdom. "Bwoy we are out of prison ... it was rough mentally. They... Full Article
is Chic on Sticks going the extra mile for persons with disabilities By jamaica-star.com Published On :: Fri, 08 May 2020 05:01:59 -0500 Her voice cracked as she related the story of a man with disabilities who lost his wife and whose child has had to drop out of school because he has no money. All he has is Bridgette Johnson, a fellow disabled person who has dedicated her life... Full Article
is Leading Through a Protracted Crisis: How to Drive, Survive, and Thrive in a Crisis By www8.gsb.columbia.edu Published On :: Fri, 01 May 2020 00:00:00 -0400 Management professors Adam Galinksy and Paul Ingram, together with Jonathan Laor ’21, CEO of Applicaster, advise on leadership during a crisis. Full Article
is Quick Earthquake Messages M6.7 [7.0S, 130.0E] in Tanimbar Islands Region, Indonesia (21:54 HKT 06/05/2020) By openstreetmap.org Published On :: Wed, 06 May 2020 22:01:16 +0800 Earthquake: 2020-05-06 21:54HKT M6.7 [7.0S, 130.0E] in Tanimbar Islands Region, Indonesia http://openstreetmap.org/?mlat=-7&mlon=130. Full Article
is Fashion Brands Repurpose Resources to Offer Aid in the COVID-19 Crisis By www8.gsb.columbia.edu Published On :: Wed, 22 Apr 2020 00:00:00 -0400 Retail giants like Yoox Net-a-Porter Group and Brooks Brothers quickly pivoted to offer life-saving services. Full Article
is 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
is 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
is Migration Deals Risk Undermining Global Refugee Protection By feedproxy.google.com Published On :: Fri, 13 Apr 2018 09:53:48 +0000 13 April 2018 Amanda Gray Meral Associate Fellow, International Law Programme @AmandaLouGray While some aspects of agreements like that between the EU and Turkey reflect a genuine effort to cooperate in addressing the needs of refugees, other elements risk undermining the very essence of the global refugee protection regime. 2018-04-13-Lesbos.jpg A boat carrying migrants approaches shore after making the crossing from Turkey to the Greek island of Lesbos in November 2015. Photo: Getty Images. Last month the European Commission proposed that the EU should mobilize the next tranche of funding for Turkey (€3 billion) under the EU–Turkey deal agreed in 2016. The deal is part of a rapidly developing strategy on the part of the EU to improve cooperation on migration issues with countries of origin as well as those through which migrants and refugees transit en route to Europe. Since 2015, the EU has ramped up negotiations, with the New Partnership Framework underpinning arrangements with countries such as Niger, Mali and Ethiopia, and endorsing a memorandum of understanding between Italy and Libya in February 2017.A common thread that runs across all of these deals is their focus on containment in exchange for funding, rather than a principled approach to refugee protection. For example, the EU has committed around €6 billion to Turkey as a contribution towards the cost of humanitarian assistance for the over 3 million Syrian refugees residing there. This funding also operates as an incentive for Turkey to take back all refugees and migrants who have irregularly arrived in Greece via Turkey since the deal entered effect.Similarly, the EU is providing financial support to Libya in exchange for its cooperation in reducing the flow of migrants and refugees towards Europe, while the New Partnership Framework aims to reduce the number of migrants and refugees departing for Europe in exchange for EU aid. While financial incentives geared towards containment do not amount to new policy, with the increasing number of deals being negotiated, the use of such a strategy appears to be both accelerating and becoming more explicit.An effective investment?Implementation of these deals has been hindered by obligations under international law, raising questions not only as to their legality but also their value for money.Under the EU–Turkey deal, refugees arriving in Greece irregularly were to be returned to Turkey, with an equal number of Syrian refugees resettled to Europe in exchange. However, implementation of this aspect of the deal has been limited.Under EU asylum law, Greece is obliged to provide access to asylum procedures for those arriving on its shores. Given that most arrivals from Turkey came from refugee-producing countries (including Syria, Afghanistan and Iraq), an individualized assessment of ‘safe third country’ is required before any possible return to Turkey can take place. This requires a finding that Turkey can guarantee effective access to protection for the individual in question, including protection against refoulement (i.e. forced return to a country where he or she is at risk of serious harm or persecution). By the end March 2018, only 2,164 people had been returned to Turkey.As for Italy, with EU support, under the MOU with Libya it has been training as well as providing funding and logistical support to the Libyan coastguard – including an Italian naval presence in Libyan waters – to intercept boats in the Mediterranean. Given the mounting evidence of abuse of migrants and refugees, whether by Libyan coastguards or inside Libyan detention centres, this raises questions as to whether the support being provided by Italy and the EU amounts to a breach of international law.Despite concerns about the protection risks for refugees, advocates of such deals claim they have the potential to prevent dangerous journeys, saving lives and interrupting the business model of smugglers. Numbers crossing the Mediterranean have indeed dropped since the deals were agreed. However, in Libya it has created an ‘anti-smuggling’ market which, despite leading to a reduction of migration in the short term, may not be sustainable in the long term if it drives conflict between various non-state actors.In the case of the EU–Turkey deal, while it has led to a fall in arrivals to the Greek islands in the first six months of 2017, there is also evidence that smugglers were already adapting their routes, forcing refugees and migrants to travel on the more dangerous central Mediterranean route.For now, at least, these deals appear to have gained significant popular support within the EU. Italy’s approaches in Libya, for example, have been broadly backed by the Italian public – unsurprising given that some polls indicate 50 percent of the Italian population believe migrants to be a threat to public security. However, the drivers of public attitudes towards refugees and migration are complex and, as noted in a policy brief published under the Chatham House–ODI Forum on Refugee and Migration Policy, influenced in part by narratives driven by politicians and the media.What some of these deals have achieved is the significant flow of aid money towards job creation and economic opportunities for refugees, incentivizing policy change in some contexts and producing real benefits for the refugees concerned (while reducing pressures on them to move onwards via dangerous journeys).A prominent example is the Jordan Compact, a 2016 agreement between Jordan, the EU and international financial institutions including the World Bank to improve the livelihoods and education of Syrian refugees inside Jordan. While challenges in its implementation remain, including concerns about labour rights, the Jordan Compact has resulted in real improvements in education and access to the labour market for Syrian refugees. The Jordanian government has made policy concessions on access to work permits for Syrian refugees, removing some of the barriers that prevented refugees accessing jobs, while the EU has committed to ease trade barriers for goods produced in Jordanian factories on condition they hire a percentage of Syrian refugees.Likewise, the EU–Turkey deal’s most successful component has been its financial contribution of €3 billion of aid under the EU Facility for Refugees towards support for the 3.7 million Syrian refugees currently being hosted by Turkey. This includes €1 billion allocated to the Emergency Social Safety Net, described by the European Commission as the ‘largest single humanitarian project in the history of the EU’, directly impacting the livelihoods of some 1.1 million vulnerable refugees.Moving aheadWhile some aspects of these deals reflect a genuine effort to cooperate in addressing the needs of refugees, other elements risk undermining the very essence of the global refugee protection regime.The diplomatic squabble over a proposed refugee ‘swap’ of 1,250 refugees between the US and Australia in February 2017 highlights the danger of refugees becoming bargaining chips. Similarly, the Kenyan government’s announcement that it would close Dadaab refugee camp in late November 2016 cited the EU-Turkey deal as justification. Migration partnerships which emphasise the securing of EU borders against refugee arrivals may diminish the willingness of states in the Global South to continue to host large numbers of refugees.While the positive aspects of such deals deserve acknowledgement, understanding their impact on refugee protection must be given greater attention. This is vital not only to ensure their workability but also to ensure that those countries who spearheaded the creation of the global refugee protection regime do not end up undermining its existence. Full Article
is 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
is Exploring Public International Law Issues with Chinese Scholars – Part Four By feedproxy.google.com Published On :: Tue, 30 Oct 2018 09:01:59 +0000 3 June 2018 As part of a roundtable series, Chatham House and the China University of Political Science and Law (CUPL) held a two-day roundtable in Beijing on emerging issues of public international law. Download PDF Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting was co-hosted with CUPL and involved 28 participants, consisting of 19 Chinese participants (from six leading research institutions in Beijing and Shanghai) and nine nonChinese participants (from eight leading research institutions in Australia, the Netherlands, the UK, Switzerland, Canada and Singapore).To ensure continuity while also expanding the expert network being built, the fifth meeting included a mix of participants from the previous meetings and some new participants.All discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
is 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
is How Human Rights Law Is Evolving to Address Inequality By feedproxy.google.com Published On :: Mon, 10 Dec 2018 13:15:42 +0000 10 December 2018 Chanu Peiris Programme Manager, International Law Programme @chanupeiris On the 70th anniversary of the Universal Declaration of Human Rights, Chanu Peiris examines how its principles apply to one of today’s burning political issues. 2018-12-10-UDHR.jpg Copies of the Universal Declaration of Human Rights in a variety of languages. Photo: Getty Images. There is growing attention to human rights in debates on economic inequality. In the UK, concerns about the disproportionate impact of economic policy on vulnerable groups have been raised recently by the UN special rapporteur on extreme poverty and human rights – who issued a statement criticizing the Conservative government’s austerity policies – as well as in a report from the UK government’s independent Equality and Human Rights Commission. These reports echo global concerns about fiscal policies, poverty and extreme economic inequality.The Universal Declaration of Human Rights – which celebrates its 70th anniversary today – and the human rights treaties it inspired do not expressly address income and wealth gaps. But international human rights law is playing an increasing role in addressing economic polarization. Those concerned about inequality should consider how, especially over the past 25 years, the principles of socioeconomic rights have been clarified by courts and other human rights mechanisms. While the focus in the Global North has historically been on civil and political rights, such as the prohibition on torture or the right to fair trial, international human rights law does set out economic and social rights. For example, Article 23(4) of the Declaration – which is replicated in the International Covenant on Economic, Social and Cultural Rights and other treaties – calls for the right to collective bargaining in employment. Weakening protection in this area has been raised as a partial cause of the current escalation in income inequality. Human rights law also guarantees rights, including to education, healthcare and social security, that have redistributive potential and so have the potential to mitigate inequality.Human rights law recognizes that fulfilment of economic and social rights, unlike civil and political rights, can be limited by the resources available to different states, and this conditionality – along with a lack of guidelines to assist with implementation and monitoring – has historically shielded fiscal policies from human rights scrutiny. However, attitudes have shifted.For example, international human rights law has come to embody a commitment to tackling substantive inequalities which impair human dignity. This requires the state regulate markets, and redistribute resources, in order to prevent discrimination against disadvantaged groups such as the poor. The UN Committee on Economic, Social and Cultural Rights and other human rights bodies assert that states have an immediate obligation, even during times of resource constraint, to ensure the fulfilment, without discrimination, of the minimum essential levels of socioeconomic rights, for example essential subsistence and basic shelter. Thus, austerity measures that scale back the enjoyment of rights may breach human rights standards. In order to justify such measures, governments need to first demonstrate they have considered ‘less restrictive’ avenues, including taxation options.Although the application of human rights standards to economic policy is an emerging area, human rights campaigners have been successfully leveraging these protections to address the causes and consequences of the inequality crisis. For example, in case No. 66/2011 the European Committee of Social Rights overturned austerity measures that would have brought wages under the poverty level, citing breaches of labour rights and protections against discrimination. In Brazil, a coalition of civil society actors successfully used human rights standards to legitimize their critiques of a 2008 tax reform bill that would have given additional tax breaks to the wealthy while withdrawing resources for social services.Beyond legal enforcement, framing concerns within the architecture of human rights can shift power to rights-bearers and move debates on tackling extreme inequality from the policy sphere into one where the state has a duty for which it is accountable. While the state bears primary responsibility for realizing human rights, non-state actors such as businesses have responsibilities to respect human rights. Thus, human rights can also help communities to recast the scope of the crisis to one of shared responsibility.While human rights have seen many normative developments and advocacy successes since the adoption of the Universal Declaration of Human Rights, the last 70 years also offer several lessons and strategies to adopt going forward. As highlighted at a recent Chatham House event, the continued emphasis on civil and political rights in the discussion about human rights is at odds with the lived experience of individuals and communities worldwide, who may not feel their economic and material concerns are reflected in campaigns for human rights.There will need to be a greater emphasis on adapting messaging to be more inclusive and to build alliances between disparate groups. Human rights analysis will also need to move beyond documenting the impact of systemic issues towards tackling root causes and creating a positive vision for economic inclusion and governance. Full Article
is Protection of the Wounded and Medical Care-Givers in Armed Conflict: Is the Law Up to the Job? By feedproxy.google.com Published On :: Wed, 27 Feb 2019 10:21:55 +0000 Research Event 16 May 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Françoise Bouchet-Saulnier, Legal Director, Médecins Sans FrontièresEzequiel Heffes, Thematic Legal Adviser, Geneva CallRain Liivoja, Associate Professor, University of QueenslandMaciej Polkowski, Head, Health Care in Danger Initiative, International Committee of the Red CrossChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House This meeting, supported by the British Red Cross, is the first in a series of three to commemorate the 70th anniversary of the 1949 Geneva Conventions. The meeting will focus on the protection of the wounded and sick in armed conflict and will also include discussion of challenges to the protection of medical care and of health providers.Attacks on health care personnel and facilities have increased in recent years, as have the instances in which proceedings have been brought against those providing medical care to wounded fighters, including under counter-terrorism measures.The Geneva Conventions and their Protocols give protection to the wounded and sick and to healthcare providers, but is the law adequate? Is the law sufficiently widely known? How can the law be more fully implemented? What particular challenges arise in non-international armed conflicts?This event will be followed by a drinks reception. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
is 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
is 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
is 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
is The Use of Sanctions to Protect Journalists By feedproxy.google.com Published On :: Wed, 29 Jan 2020 15:00:02 +0000 Members Event 13 February 2020 - 12:30pm to 1:45pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Sarah Cleveland, Louis Henkin Professor of Human and Constitutional Rights; Faculty Co-Director, Human Rights Institute, Columbia Law SchoolAmal Clooney, Barrister, Doughty Street ChambersThe Honourable Irwin Cotler, Chair, Raoul Wallenberg Centre for Human Rights; Minister of Justice and Attorney-General of Canada (2003-06)Baroness Helena Kennedy QC, Director, International Bar Association’s Human Rights InstituteLord Neuberger, President, Supreme Court of the United Kingdom (2012-17)Maria Ressa, CEO, Rappler Online News NetworkChair: Elizabeth Wilmshurst CMG, Distinguished Fellow, International Law Programme, Chatham House Attacks against journalists and challenges to media freedom are urgent and global. The sharp decline globally of democratic values which are underpinned in international values highlights the need for a free press and the necessity for states to take concerted action to protect media freedom.The High-Level Panel of Legal Experts on Media Freedom is an independent body convened at the request of the UK and Canadian governments in July 2019.The remit of the panel is to provide recommendations to governments on how to better protect journalists and address abuses of media freedom in line with international human rights law.Drawing on the panel’s new report, the speakers will discuss the use of targeted sanctions to protect journalists and a free press. Can the threat of targeted sanctions help curb the trend of increasing abuses against journalists?And what legal frameworks and mechanisms will be necessary to ensure targeted sanctions achieve their goal of identifying, preventing and punishing abuses against journalists? This event is organized in collaboration with the International Bar Association’s Human Rights Institute which acts as the secretariat to the High-Level Panel of Legal Experts on Media Freedom. Department/project International Law Programme, Rights, Accountability and Justice Members Events Team Email Full Article
is 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
is 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
is 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
is 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
is 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
is 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
is 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
is 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
is 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
is 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
is HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV By feedproxy.google.com Published On :: 2020-04-21 Daniella H HockApr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076Research Full Article
is 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
is 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
is 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
is 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
is 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
is 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
is 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
is Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue By feedproxy.google.com Published On :: 2020-05-01 Eva GriesserMay 1, 2020; 19:839-851Research Full Article
is 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