cli Insights from Climate Policy: Engaging Subnational Governments in Global Platforms By www.chathamhouse.org Published On :: Tue, 09 Feb 2021 12:54:17 +0000 Insights from Climate Policy: Engaging Subnational Governments in Global Platforms 10 June 2020 — 2:45PM TO 6:00PM Anonymous (not verified) 9 February 2021 Online How have subnational governments shaped the global agenda and created momentum on climate change where national and international governance processes could not? Can these advances be converted into meaningful collaboration channels for policy development? What works, or does not, when it comes to engagement with multilateral negotiation processes? What ingredients are necessary for success? What are the broader implications of these trends for inclusivity and innovation in international governance? This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world. Full Article
cli The trickle-up effect of rights-based climate litigation By www.chathamhouse.org Published On :: Tue, 16 Nov 2021 13:07:28 +0000 The trickle-up effect of rights-based climate litigation Expert comment NCapeling 16 November 2021 With governments failing in their pledges and companies accused of ‘green-washing’, human rights-based litigation is increasingly important for accountability. Tuvalu’s foreign minister addressing COP26 while standing knee-deep in seawater was a stark illustration of how the climate emergency directly and imminently threatens the most basic human rights protected under international law – including to the right to life, self-determination and cultural rights. Human rights are now a fundamental component of more than 90 per cent of the climate litigation currently taking place outside the US, highlighting the international reach of human rights law and how its emphasis on protecting the most vulnerable helps diverse communities find common arguments for shared goals. Cases are set to continue and to evolve but three types of claim are emerging, each of which is examined in a new Chatham House briefing paper. 1. Enforcing commitments One category of cases seeks to hold states accountable for pledges they have made on climate change, such as emission reduction targets made under the framework of the 2015 Paris Agreement. Drawing on human rights obligations, governments can be charged with not taking sufficient steps to implement these pledges. Human rights are now a fundamental component of more than 90 per cent of the climate litigation currently taking place outside the US The case of Leghari v Pakistan (2015) concerned the government’s failure to carry out the National Climate Change Policy of 2012 and the Framework for Implementation of Climate Change Policy (2014-2030). The Lahore High Court held that several of the human rights enshrined in Pakistan’s constitution cover climate change and ‘provide the necessary judicial toolkit to address the government’s response to climate change’. The court ordered the government to carry out measures such as publishing an adaptation action plan realizable within a few months of the order and establishing a Climate Change Commission to monitor progress. 2. Positive duties to mitigate risks Many rights-based climate cases are being brought to clarify the scope of states’ positive duties under human rights law to take meaningful steps to protect their citizens against foreseeable risks to life and other rights. This ‘trickle-up’ effect of human rights was prominent in the case of State of the Netherlands vs the Urgenda Foundation (2019) where the Dutch Supreme Court held that reducing emissions with the highest possible level of ambition amounts to a ‘due diligence standard’ for states to comply with their positive duties to adopt adequate measures to address climate change. Human rights law was also used by the court to fill in the content of the due diligence standards. There is also a growing trend for rights-based actions to be brought against corporations, such as a recent case which drew on the UN Guiding Principles on Business and Human Rights to define the parameters of Shell’s duty of care and due diligence obligations in relation to carbon emissions under Dutch law. The court ordered Shell to reduce emissions by a net rate of 45 per cent by the end of 2030 – relative to 2019 figures – through its group corporate policy. 3. Avoiding harm in climate action The global human rights regime is also increasingly invoked in litigation concerning states’ negative obligations to ensure that their climate mitigation and adaptation activities do not themselves contribute to human rights violations (including discrimination) and that states prioritize adaptation measures for those most at risk in a just and equitable way. As Chatham House’s paper makes clear, this kind of litigation ‘puts pressure on governments to expand their approach to tackling climate change beyond purely a regulatory one to a more holistic strategy’. Closing the climate justice gap Climate and environmental litigation grounded in human rights is set to continue given the overwhelming scientific evidence of risks associated with human-induced climate change and the limited confidence in pledges made by states and corporations alike – including those made recently at COP26. A growing collaboration between civil society organizations and vulnerable communities in relation to both the protection of nature and the enjoyment of their land and cultural rights was evident at COP26, and this alliance will add further momentum to the trend for rights-based climate litigation based on the rights of indigenous and other vulnerable communities, especially on issues such as deforestation. Building on scientific developments in climate attribution, rights-based litigation is now tackling other difficult questions such as apportioning responsibility and remedial action But more challenges are coming. International human rights law recognizes a duty of international cooperation but there remain significant hurdles for climate-vulnerable communities in developing countries to compel action by richer nations despite the vast debts of ‘carbon colonialism.’ One big issue is the problem of extraterritoriality, as the extent to which states owe obligations to individuals outside their territory is contested. Courts in both Germany and the Netherlands have rejected claimants from developing countries in domestic class actions on this basis. But a recent decision of the UN Committee on the Rights of the Child on a complaint brought by Greta Thunberg and other youth activists against five countries opens the door for further litigation. One of a number of cases being brought by youth claimants across the world, the committee concluded that a state’s human rights duties can – in some instances – extend to children in other countries. This includes any activities on the territory that host states have the power to prevent from causing ‘transboundary harm’ – such as emissions from the territory – where these activities ‘significantly’ impact the enjoyment of human rights of persons outside the territory. To date, high-profile rights-based cases have argued for policy change and stronger targets underpinned by binding legislation responsive to the science. Claims are set to become more complex and contested. Building on scientific developments in climate attribution, rights-based litigation is now tackling other difficult questions such as apportioning responsibility and remedial action. These cases examine both historically high emitters and the public and private actors who either continue specific activities or refrains from action in the face of the overwhelming science linking human activities such as extraction and burning of fossil fuels to deforestation and climatic consequences. Courts are also likely to explore the duties that states and corporations owe to deliver a ‘just transition’ away from carbon-intensive industries, given the benefits of growth and climate action are already unevenly distributed. A holistic human-rights based approach Several states together with civil society are leading the charge for global recognition of the right to a healthy, clean, and sustainable environment in the United Nations (UN) Human Rights Council, and multi-stakeholder processes are defining what effective corporate due diligence looks like. In addition, UN-appointed special rapporteurs are delivering practical guidance on how to devise solutions which are fair, non-discriminatory, participatory, and climate-resilient without exacerbating inequality – including difficult issues of planned relocation – and UN Human Rights Treaty Bodies are unpacking the duty of international cooperation to act in good faith to address loss and damage. Recently the Committee on the Elimination of Discrimination Against Women recommended the Marshall Islands, in order to meet its duty to its citizens, should actively seek international cooperation and assistance – including climate change financing – from other countries but in particular the US, whose ‘extraterritorial nuclear testing activities have exacerbated the adverse effects of climate change and natural disasters’ in the islands. Full Article
cli China's Climate Commitments and Energy Ambitions Beyond COVID-19 By www.chathamhouse.org Published On :: Thu, 17 Sep 2020 15:32:51 +0000 Source Oxford Energy Forum URL https://www.oxfordenergy.org/wpcms/wp-content/uploads/2020/07/OEF123.pdf Release date 01 July 2020 Expert Dr Sam Geall In the news type Op-ed Hide date on homepage Full Article
cli Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction. Full Article
cli Impact of the US Election on Global Climate Politics By www.chathamhouse.org Published On :: Mon, 16 Nov 2020 16:19:46 +0000 Impact of the US Election on Global Climate Politics 25 November 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 16 November 2020 Online Panellists discuss how Joe Biden’s victory will impact international efforts to tackle climate change. Will climate finally become a common area for global cooperation? Joe Biden’s victory over Donald Trump is already having a positive impact on international efforts to tackle climate change. Leaders from across the world, including the UK, Canada, Australia and Fiji, have used their first messages to the President-elect to draw attention to the climate crisis. Biden has promised to re-join the global community in its commitment to the Paris Agreement – but this could be the easy part. More difficult will be whether and how Biden is able to deliver his ambitious climate plan, and how effectively he is able to integrate climate change into foreign policy efforts and national security strategies. Global climate action has also moved forward in the last four years. The European Union recently pledged to become climate neutral by 2050, and China, Japan and South Korea have committed to achieving carbon neutral economies. How will the US re-enter this global landscape of distributed leadership and what difficulties does it face? Will the US be willing to work within a competitive partnership with the EU and China? How will Biden’s win change the dynamic of COP26 next year? Full Article
cli Climate action and gender equality: Can we close the gap on one without the other? By www.chathamhouse.org Published On :: Mon, 15 Feb 2021 16:04:18 +0000 Climate action and gender equality: Can we close the gap on one without the other? 8 March 2021 — 2:30PM TO 4:00PM Anonymous (not verified) 15 February 2021 Online In partnership with the COP26 presidency, policymakers and experts examine the interrelationship between gender equality and climate action, and highlight innovative examples of policy and practice from around the world. Marking International Women’s Day, this event organized by the COP26 presidency in partnership with Chatham House, will explore how gender equality and climate action go hand-in-hand. The agreement of the Gender Action Plan (GAP) at COP25 sent the message that the time for gender-responsive climate action is now. This will be a unique opportunity to hear from policymakers and civil society leaders discussing whether enough is being done, as well as highlighting cutting-edge work around the world and suggesting what the future could hold. The event will be livestreamed on this event page. Full Article
cli Youth voices on climate action By www.chathamhouse.org Published On :: Mon, 22 Mar 2021 14:40:49 +0000 Youth voices on climate action 22 April 2021 — 12:30PM TO 2:00PM Anonymous (not verified) 22 March 2021 Online To celebrate Earth Day, youth activists, local change-makers, innovators and entrepreneurs discuss opportunities and challenges for youth-led climate activism. Young people will bear the brunt of the intensifying impacts of climate change over time. Facing this challenge, youth around the world have emerged at the forefront of climate activism at an unprecedented scale. School strikes, marches, and declarations complement youth engagement in diplomacy, technology, science, and law. Providing a platform for young people involved in climate action at the local, national and global levels is essential to promote collaboration, generate new policy ideas, and demand accountability from political and business leaders. Panellists engage in critical conversation about COP26; global leadership in climate mitigation, adaptation, and finance; and how to develop the full potential of youth-led global initiatives going forward. Full Article
cli From local to global: A roadmap for US climate action By www.chathamhouse.org Published On :: Sun, 28 Mar 2021 15:50:49 +0000 From local to global: A roadmap for US climate action 14 April 2021 — 6:30PM TO 8:00PM Anonymous (not verified) 28 March 2021 Online Ahead of Biden’s Earth Day Summit, panellists discuss a range of climate issues, from city-level climate management to the international security implications of climate deals. On their first day in office, the Biden-Harris administration sent a strong message to Americans and allies by rejoining the Paris Agreement. Experienced climate and environmental leaders were appointed to senior leadership roles as part of a ‘whole of government approach’ to climate action. Although decisive action is welcomed by many Americans and international partners, the divided domestic perspectives on climate and a changed international landscape pose significant challenges. Ahead of the Earth Day Summit on April 22, an event hosted by Joe Biden to mark America’s formal return to global climate talks, panellists discuss a range of climate issues, from city-level climate management to the international security implications of climate deals. How will post-COVID domestic priorities and policy influence the international approach of the US to climate action? How will US policy, both foreign and domestic, need to respond to the security and geopolitical elements posed by climate change? What actions are needed during the upcoming Earth Day Summit for the US to establish credibility as a climate leader? What shape are key debates taking on US-China climate relations ahead of COP 26, and how might climate issues be approached in relation to wider geopolitical tensions? Full Article
cli Prioritizing equity and justice in climate action By www.chathamhouse.org Published On :: Thu, 10 Jun 2021 13:45:31 +0000 Prioritizing equity and justice in climate action 30 June 2021 — 11:00AM TO 12:00PM Anonymous (not verified) 10 June 2021 Online London Climate Action Week event: Why understanding equity and justice is essential to the ability to meaningfully inform climate politics. Citizen-led climate activism is demonstrating the need to think about climate change ‘not just as a problem for science to solve’ but also as a problem of equity, human rights and justice. The disproportionate impacts of climate change on the poor and the marginalized across the world means that understanding equity and justice is essential for the ability to meaningfully inform climate politics. Excluding these issues risks ignoring, or intentionally omitting, the consequences of policies, tools and frameworks on those who are most likely to face the severe costs of any climate action or inaction. In a pivotal year for climate decision-making, this event explores the necessity of equity and justice in climate action and how the world can move the political conversation to one that is more inclusive. The speakers explore how communities themselves articulate the justice dimensions of climate change and how fairness can create a greener future for current and future generations. This event is being hosted as a part of Strengthening Climate Diplomacy, a series of events from Chatham House during London Climate Action Week 2021. Full Article
cli Cities as climate leaders: Progress and ambition By www.chathamhouse.org Published On :: Tue, 16 Nov 2021 13:44:24 +0000 Cities as climate leaders: Progress and ambition 1 December 2021 — 12:00PM TO 1:00PM Anonymous (not verified) 16 November 2021 Online This panel discusses the progress cities have already made, whether progress at COP26 was enough, and what more needs to be done to scale action and ambition internationally. Cities are critical to tackling the pressing environmental challenges of our time. While they now account for an estimated 75 per cent of global CO2 emissions, cities also offer a unique opportunity for devolved leadership on climate action. At the recent COP26, some significant progress was made in elevating cities’ position on climate action with a flurry of announcements and commitments. For example, more than 1,000 cities are now committed to the Cities Race to Zero and C40’s Clean Construction Declaration saw multiple cities committing to at least halving emissions from initial construction of buildings by 2030. A raft of financing commitments were also made to improve urban resilience in the face of climate change. This builds on existing momentum before COP26. Over 50 world cities are now on track to meet Paris Agreement and the Marrakech Partnership is further enabling collaboration between governments and cities within the UNFCCC processes. Therefore, how we design, build, govern and use our urban places will be a key factor for decarbonization and climate change adaptation. On the back of COP26, this panel brings together leaders from across urban development sectors to discuss the progress cities have already made, whether progress at COP26 was enough, and what more needs to be done to scale action and ambition internationally. Full Article
cli Feminist solutions to the climate crisis By www.chathamhouse.org Published On :: Tue, 01 Mar 2022 12:07:14 +0000 Feminist solutions to the climate crisis 8 March 2022 — 11:00AM TO 12:00PM Anonymous (not verified) 1 March 2022 Online This International Women’s Day panel explores intersectional feminist approaches to solving the climate crisis. Gender inequality and climate change are closely intertwined. Due to their different and unequal social roles and status, women, girls and people of marginalised genders are disproportionately affected by climate change impacts, also differentiated by factors such as age, race, ability and location. They are also leading innovative solutions to climate change at all levels, especially in frontline communities. Yet as the Glasgow Women’s Leadership statement highlighted at COP26, there is still a lack of momentum for prioritising their knowledge, tools and leadership in climate policy and action. This panel considers what feminist approaches can bring to climate change communication and movement building, spotlighting a range of local and regional gender-responsive climate initiatives. It also discusses concrete examples of feminist and gender-responsive policies to address climate change, such as the Feminist Green New Deal. The panel highlights the critically important work being carried out by diverse feminist activists and researchers, and how the audience can centre gender and social equality in their work on climate change. Full Article
cli Climate finance and conflict dynamics on the road to COP27 By www.chathamhouse.org Published On :: Fri, 09 Sep 2022 07:37:13 +0000 Climate finance and conflict dynamics on the road to COP27 21 September 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 9 September 2022 Online Stakeholders discuss the role of conflict and conflict sensitivity in climate finance and action. With climate change, fragility and conflict challenges worsening, the role of international climate finance is more urgent than ever. From the implementation of climate finance and who it reaches to the rush for renewable energy, the inclusion of conflict analysis and conflict sensitivity principles often remain absent from climate finance discussions and planning. With COP27 around the corner and for the occasion of International Peace Day, stakeholders ranging from government representatives to climate activists discuss their perspectives on the role of conflict and conflict sensitivity as part of climate finance and action. This event was organized in partnership with International Alert. Full Article
cli Food system transformation: A blind spot for climate and biodiversity action? By www.chathamhouse.org Published On :: Wed, 05 Oct 2022 10:57:14 +0000 Food system transformation: A blind spot for climate and biodiversity action? 20 October 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 5 October 2022 Chatham House and Online How can COP27 and COP15 accelerate the agenda for sustainable food systems and land use? Tackling the dual crises of climate change and biodiversity loss requires extraordinary levels of action at an unprecedented speed. Agriculture is the biggest user of land, the biggest source of methane emissions, a major contributor to total greenhouse gas emissions and the leading driver of biodiversity loss. Anything short of a food system transformation puts climate and biodiversity objectives in peril. However, governments have not yet produced credible pathways and strong policies for tackling our growing ‘foodprint’ – the negative impacts of what we grow and eat. In advance of COP27 in Sharm El-Sheikh for climate and COP15 in Montreal for biodiversity, Chatham House has published a new briefing paper which examines aligning food systems with climate and biodiversity targets. The paper reviews the climate and biodiversity policy landscape to 2030, with a focus on land-based aspects and the inclusion of food and agriculture. The paper highlights serious conflicts between the impacts of the food system and goals to protect and restore biodiversity and mitigate climate change. In light of this, opportunities for joined-up action on food, climate and biodiversity are identified, including three key steps for countries to take this decade to produce suitably ambitious and effective policies across the climate–biodiversity–food nexus. This event brings together leading voices from the international policy arenas for climate and biodiversity to react to the briefing paper and discuss how COP27 and COP15 can accelerate the agenda for sustainable food systems and land use. Full Article
cli Climate Change and the Pacific: Impacts and Adaptation By www.chathamhouse.org Published On :: Wed, 14 Nov 2018 14:20:01 +0000 Climate Change and the Pacific: Impacts and Adaptation 27 November 2018 — 8:30AM TO 10:00AM Anonymous (not verified) 14 November 2018 Royal Academy of Arts Pacific Island leaders have identified climate change as the single greatest challenge facing the region. Warming oceans and the increasing incidence of extreme weather events threaten Pacific peoples and their way of life. This event will explore the existing impacts of climate change on the South Pacific and what solutions are feasible for the region. This discussion will follow a brief screening of the documentary film, Subject to Change, which looks at the impact of climate change in New Zealand and Fiji and documents the personal stories of a tiny Pacific community faced with rising and acidifying seas, extreme weather conditions, tidal events and social changes. It also looks at New Zealand’s efforts to amplify the voices of its Pacific neighbours and to drive domestic and global action on climate change. This event is being held in partnership with the New Zealand government. THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Full Article
cli Trichotomy for the orbits of a hypercyclic operator on a Banach space By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST Jian Li Proc. Amer. Math. Soc. 152 (), 5207-5217. Abstract, references and article information Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Mon, 21 Oct 2024 03:29:19 -0700 outrageous toes posted a reply: Hi everyone I am Emily Naomi wanna give a big thanks to this wonderful psychic for bringing my husband back to me.. I never really believed in magic spells or anything spiritual but a trusted friend opened my eyes to the truth about life. My marriage was heading to divorce a few months ago. I was so confused and devastated with no clue or help on how to prevent it, till I was introduced to this psychic Priest Ray that did a love spell and broke every spiritual distraction from my marriage. A day later my husband started showing me love and care even better than it used to be, he’s ready to talk things through and find ways for us to stay happy. It’s such a miracle that my marriage can be saved so quickly without stress. You can also contact him for help by email psychicspellshrine@gmail.com or you can also visit his website: psychicspellshrine.wixsite.com/my-site Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Mon, 21 Oct 2024 04:06:19 -0700 Drummerdelight posted a reply: emilynaomi126: Does your husband have a camera? Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Mon, 21 Oct 2024 04:33:04 -0700 Ian Razey. posted a reply: Drummerdelight: emilynaomi126 is a SPAM account. Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Wed, 23 Oct 2024 11:42:03 -0700 rageforst posted a reply: Hi I'm Rage and I'm a Designer from Mexico, I love colors and I hope all of you doing well Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Wed, 06 Nov 2024 14:01:51 -0800 rslbturner posted a reply: Hello, I have very recently joined Flickr, as everybody else looking to share my photographs. I live in the UK and consider myself mostly a pleasure photographer, I do love it! I hope you like my pictures. Thank you Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Thu, 07 Nov 2024 07:28:14 -0800 Maskimov1935 posted a reply: Hello everyone. I'm Igor. I've joined Flickr today. I live in Russia and taking pictures mostly in "dark fantasy" style, as one of my friend calls it. Hope you'll check my photos. Have a good day! Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Fri, 08 Nov 2024 07:59:51 -0800 clarasouzin posted a reply: En besoin d'aide financière veuillez nous contacter par E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Fri, 08 Nov 2024 08:01:49 -0800 clarasouzin posted a reply: En besoin d'aide financière veuillez nous contacter par E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com. Full Article
cli Reply to Introduce Yourself: Click Here! By www.flickr.com Published On :: Fri, 08 Nov 2024 08:02:33 -0800 clarasouzin posted a reply: In need of financial assistance please contact us by E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com E-mail: clarasouzin@gmail.com... Full Article
cli The heptameric structure of the flagellar regulatory protein FlrC is indispensable for ATPase activity and disassembled by cyclic-di-GMP [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 The bacterial enhancer-binding protein (bEBP) FlrC, controls motility and colonization of Vibrio cholerae by regulating the transcription of class-III flagellar genes in σ54-dependent manner. However, the mechanism by which FlrC regulates transcription is not fully elucidated. Although, most bEBPs require nucleotides to stimulate the oligomerization necessary for function, our previous study showed that the central domain of FlrC (FlrCC) forms heptamer in a nucleotide-independent manner. Furthermore, heptameric FlrCC binds ATP in “cis-mediated” style without any contribution from sensor I motif 285REDXXYR291 of the trans protomer. This atypical ATP binding raises the question of whether heptamerization of FlrC is solely required for transcription regulation, or if it is also critical for ATPase activity. ATPase assays and size exclusion chromatography of the trans-variants FlrCC-Y290A and FlrCC-R291A showed destabilization of heptameric assembly with concomitant abrogation of ATPase activity. Crystal structures showed that in the cis-variant FlrCC-R349A drastic shift of Walker A encroached ATP-binding site, whereas the site remained occupied by ADP in FlrCC-Y290A. We postulated that FlrCC heptamerizes through concentration-dependent cooperativity for maximal ATPase activity and upon heptamerization, packing of trans-acting Tyr290 against cis-acting Arg349 compels Arg349 to maintain proper conformation of Walker A. Finally, a Trp quenching study revealed binding of cyclic-di-GMP with FlrCC. Excess cyclic-di-GMP repressed ATPase activity of FlrCC through destabilization of heptameric assembly, especially at low concentration of protein. Systematic phylogenetic analysis allowed us to propose similar regulatory mechanisms for FlrCs of several Vibrio species and a set of monotrichous Gram-negative bacteria. Full Article
cli Has the Dollar Started Its Long Decline? By www.chathamhouse.org Published On :: Fri, 28 Aug 2020 11:54:24 +0000 28 August 2020 Jim O'Neill Chair, Chatham House Ultimately, the dollar’s dominance cannot persistently outweigh the relative decline of the US economy in the world. At some point, it will start to be replaced by something else. But don’t confuse that with where the dollar’s price is heading against other currencies. 2020-08-28-us-dollar-oneill.jpg A statue of George Washington is pictured in front of the New York Stock Exchange (NYSE) on 16 March 2020, at Wall Street in New York City. Photo by JOHANNES EISELE/AFP via Getty Images. One of the features of financial markets since early summer has been a decline in the value of the dollar against many currencies, and with it, an especially interesting acceleration in the price of gold. In addition to the usual professional market analysis about the dollar’s movement, this has led to speculation that it might be the beginning of the end of the dollar’s pre-eminence.Having spent far too much of my professional life as a supposed currency expert, I reiterate something I learnt early on: the foreign exchange business sometimes grants an analyst their 15 minutes of fame, but no expert is a match for the millions who participate in this huge global market all day long. But I spent over 30 years in the financial markets, the vast majority in the hubbub of the forex market. And along the journey, I think I learnt a few tricks of the trade.At the core of trying to answer questions about the dollar, I learnt a long time ago that there are two entirely separate questions, one of which has two subsections, about the dollar. Firstly, there is the question about the use of the dollar. Will it continue to dominate the world’s financial system as the most widely accepted medium of exchange?This is not at all the same issue as the dollar’s day-to-day performance against other currencies. This is the second question, which is almost definitely the most pertinent one to what has happened during the summer. How the dollar’s value moves against other currencies is driven by a structural, or a valuation component, and a cyclical component. Each can be analysed separately, and if you were daft enough to devote the years I did to the process, you can combine the two, to have a dynamically adjusted fair value, persuading yourself at least that such an approach combines all available information at any point in time.In terms of valuation, the most common approach is so-called purchasing power parity, which holds that a currency, in equilibrium, will ultimately reflect the difference in prices between two countries. If inflation is persistently higher in the US than in the eurozone, then the equilibrium value of the dollar will decline over time. I developed my own version of equilibrium currency rates, as it seemed to me in the real world, that the real inflation adjusted value of a currency was not stable, and that it moved over time. This was a reflection of productivity differentials between two countries. I christened it GSDEER: 'the Goldman Sachs Dynamic Equilibrium Real Exchange Rate' when I joined the firm in 1995.What I learned is that when a currency is more than two standard deviations away from its fair value, it makes a huge amount of sense to watch closely, and when the momentum changes, it is worth going with this trend reversal. The momentum can change based on a change in the forces that have driven the currency away from its fair value, although it can be often easier to detect simply by watching the change in price.One of the things that has frustrated currency participants over the past decade, with the exception of the Swiss franc and the pound, is that other major currencies have not been that far away from their fair value against the dollar or each other. Even during the dollar’s rise in recent years, including the period up to the summer, while it had clearly become overvalued, with the possible exception of the pound, it hadn’t become more than two standard deviations above its own fair value. In this regard, I have believed that one might be on the lookout for a chance to buy the pound against the dollar, and perhaps against the yen.The cyclical component of a currency’s movement around its conceptual equilibrium can perhaps best be captured in the nominal interest rate adjusted for inflation expectations. I persuaded myself that the actual spot exchange rate of the dollar on any one day should be close to the adjusted GSDEER, and if it was not, then it would be useful for traders.The dollar had become more interesting pre-COVID, as it appeared to have risen notably against many currencies, including the euro. And in this regard, the dollar was highly susceptible, and has turned out to be actually vulnerable, to a change in the state of the US and euro area economies. Now that the Federal Reserve has returned to extremely expansive monetary policy, and with it, lower real interest rates, a dollar decline seemed pretty inevitable.At current prices, on 26 August, the dollar still seems modestly expensive compared to dynamically adjusted fair value. The dollar decline could persist. In the late 1980s and mid 1990s, the dollar fell to very low levels and became very undervalued — this tended to coincide with widespread talk about the dollar’s preeminence, which turned out to be, at least for that era, wrong. And I do share the views of some people who believe, as a result of US policies, conditions are more conducive to a sustained period of dollar weakness. This requires strong ongoing evidence that Europe, China and much of the rest of Asia continue to manage COVID-19 better than the US, and that their cyclical recoveries from the pandemic continue to surprise relative to the US.Now as for the first question, about the demise of the dollar’s dominance, let me repeat that this is largely a separate issue, but I encourage any reader to be careful about getting sucked into this belief in making an investment or hedging decision.It is quite possible that the use of the dollar can decline, and start off a systematic decline even when its value is strong. Indeed, in the past couple of years when its value was largely rising, decisions made by US policymakers to use the dollar’s dominance as a way of penalising other countries has resulted in those countries reducing their share of dollar currency reserves. Russia is a particular example, and there is some modest evidence that China is doing likewise.And the opposite can also be true.Ultimately, the dollar’s dominance cannot persistently outweigh the relative decline of the US economy in the world, which has been occurring now for 20 years. At some point, it will start to be replaced by something else. Whether that is, the renminbi, the euro, Bitcoin, the return of gold — all are conceivable, and may happen. It might be starting now. But don’t confuse that with where the dollar’s price is heading against other currencies in coming days, weeks, or in 2021.This article was originally published in The Article. Full Article
cli Climate migration: Ways ahead from the next generation By www.chathamhouse.org Published On :: Wed, 25 May 2022 10:05:22 +0000 Climate migration: Ways ahead from the next generation The World Today rsoppelsa.drupal 25 May 2022 Ella Dennis and Mike Higgins talk to young activists seeking solutions as global warming wreaks havoc in sub-Saharan Africa Africa has the lowest carbon emissions per capita yet the highest rate of temperature increase in the world. Rising levels of desertification, drought and flooding are already forcing millions of Africans to relocate to find more stable livelihoods. The continent’s youth will bear the brunt of this climate migration problem. It is estimated that by 2050, Africa will be home to 86 million internal climate migrants. How is climate migration already affecting sub-Saharan Africa and what frameworks could tackle it? To begin to answer those questions, five young activists from across the region, who are members of Chatham House’s Common Futures Conversations, took part in a panel discussion at the world’s first youth-led Conference on Climate Migration, convened in April by the Alliance for Citizen Engagement, a nonpartisan think tank based in the US. [Farmer-herder] conflicts will pose even larger security concerns as climate migration intensifies Laura Mukhwana, Kenyan PhD candidate The conversation and follow-up discussions focused on a common problem – climate migration brings people into conflict and puts pressure on infrastructure. In Kenya, droughts have left 3.5 million people hungry and the chronic flooding of several lakes in the Rift Valley has displaced hundreds of thousands, said Gerald Muchiri, 29, a social scientist from Kenya. One result has been outbreaks of violence between pastoralists such as the Orma people and the farmers of the Pokomo community, said Laura Mukhwana, 33, a PhD student in Kenya. She believes this violence is likely to worsen. ‘Inter-group conflicts will pose even larger security concerns for surrounding communities as climate migration intensifies,’ she said. Suleman Nuhu, 24, a farmer and veterinary student from Nigeria, said farmer-herder conflicts were his country’s most significant climate-migration issue. The movement of nomadic tribes from the north had affected him personally: ‘Nomads have trespassed on [my family’s] farms many times while moving with their livestock, destroying our crops.’ Changes in climate also force people to move from rural to urban areas. Nigeria, for instance, struggles with the so-called ‘Lagos problem’, said Temiloluwa Lawal, 25, a lawyer and researcher from Nigeria. An estimated 22 million people, a number that is rising fast, are crammed into a city smaller than Greater London. While not on the same scale, Zimbabwe experiences comparable challenges, said Tinotenda Dube, 29, a Zimbabwean finance director. Thanks to drought, unemployed rural migrants arriving in cities ‘put excessive pressure on service delivery against a low tax base,’ he said. ‘People, including close family members of mine, are crowded in dilapidated homes because they cannot afford to pay rent for decent housing.’ But there is hope, say the activists. Dube believes that affordable housing is an ‘integral component of [tackling] the climate migration crisis’. In Zimbabwe, he has developed a low-cost home finance model that, he said, has helped more than 250 low-income households find good-quality accommodation. Alongside this initiative, Dube has co-founded a property and construction company, Solinfra Zimbabwe Private Ltd, to provide low-cost housing. Muchiri is taking action in Kenya, founding an NGO called Social Assistance Welfare to tackle public health issues, he said: ‘As climate migration becomes more intense, I expect preventable health issues to increase throughout the region, and thus see Social Assistance Welfare as an important mitigation.’ To mitigate food security problems, we must reduce reliance on rain-fed agriculture through irrigation schemes Suleman Nuhu, farmer and veterinary student from Nigeria In Nigeria, Nuhu noted that to help reduce conflict between farmers and herders social-media campaigns are encouraging pastoralists to move from nomadic livestock farming to more efficient intensive systems, using ranching and grazing reserves. ‘As for food security problems, the best mitigation is to reduce reliance on rain-fed agriculture through irrigation schemes,’ he said. All five agreed that, in their experience, the youth of sub-Saharan Africa could be better informed about climate migration. But they took encouragement from the fact the young are passionate about tackling issues arising from the broader climate crisis. In Kenya, Mukhwana pointed to successful youth projects around agro-forestry and tree-planting. She added that there is ‘a growing movement of urban youth who are advocating for climate justice, such as the Kenyan Youth Environmental Network and Fridays for the Future Kenya’. It was pleasing too, she said, that when the Kenyan government revised its contributions to the Paris Climate Accords it staged a week-long youth conference to include their opinions. ‘Overall, I am quite hopeful about how the youth are mobilizing themselves in Kenya,’ she added. Find out more about Chatham House’s Common Futures Conversations Full Article
cli Climbing out of the Chinese debt trap By www.chathamhouse.org Published On :: Mon, 01 Aug 2022 07:21:45 +0000 Climbing out of the Chinese debt trap The World Today mhiggins.drupal 1 August 2022 Beijing must play a pivotal role in soothing African economic distress, says Alex Vines. Poorer countries across the world – including many in Africa – are facing $35 billion in debt-service payments in 2022. According to the World Bank, around 40 per cent of this total is owed to China. Across the African continent, the economic impacts of the coronavirus pandemic have increased rates of extreme poverty and inequality. Since early 2022 the situation has worsened even further, due to the knock-on effects of spiking inflation and interest rates following the Russian invasion of Ukraine. Shortages of fuel and foodstuffs have caused prices to leap upwards. Urban unrest is on the rise, and African governments are having to make tough economic choices as their budgets are squeezed ever more tightly. Across the continent, progress on the UN’s Sustainable Development Goals is being jeopardized, and non-energy-producing lower and lower-middle income African governments are struggling to repay their loans. During the Covid pandemic, the G20 assisted 31 out of 36 eligible African countries with its Debt Service Suspension Initiative (DSSI). Established in May 2020, the DSSI helped countries concentrate their resources on fighting the pandemic and safeguarding the lives and livelihoods of millions of the most vulnerable people before it expired at the end of 2021. From 2022, it has been replaced by the G20’s Common Framework for Debt Treatments. As the second-largest economy in the world after the United States, and the dominant lender for many African states, China has an important role to play in such initiatives. Beijing still tries to keep a low profile and renegotiate its terms on a bilateral basis – although it did support Angola’s early call for G20 action on an initiative that would fulfil what the DSSI delivered. The challenge is to encourage more consistency and trust in such initiatives, as Chinese officials consider them to be too western-oriented. China’s lending to Africa peaked in 2016 Contemporary views of Chinese lending in Africa remain coloured by the rapid expansion of Chinese finance from the early 2000s to resource-rich African states, and oil producers in particular. The reality is that much of China’s lending has evolved, and is neither intrinsically predatory nor problematic for African partners – and China increasingly prefers to do business with states it considers to be better run. In fact, as commodity prices and growth rates declined from 2015, Chinese lending to Africa fell significantly, from a peak of $29.5 billion in 2016 to $7.6 billion in 2019. The socio-economic impact of the pandemic has made this situation worse. Over the past two decades, Chinese finance has contributed to an infrastructure boom in many African countries That China has attracted criticism is often due to a lack of transparency in its investments, especially those in Kenya and Zambia. This reputation has not been helped by opaque lending arrangements imposed by Chinese state-owned banks, requiring borrowers to prioritize them for repayment. This could lead to cutbacks in key areas of social spending, with direct impacts on African communities. Over the past two decades, Chinese finance has contributed to an infrastructure boom in many African countries. Angola, for example, was able to undertake a rapid post-conflict reconstruction of its infrastructure, with new roads and bridges being built across the country. New models of financing are being developed: in Kenya, the new Nairobi expressway was constructed under a $600 million Build-Operate-Transfer model that provides for ownership to revert to the national government after a 30-year concession period. Chinese companies have helped African countries build and upgrade over 10,000km of railway, around 100,000km of highway, 1,000 bridges and 100 ports, as well as power plants, hospitals and schools. China’s involvement in African debt has varied considerably between countries and over time. Although in recent years this involvement has been framed in the context of the Belt and Road Initiative, it has for the most part been uncoordinated and unplanned, with credit being offered by competing lenders with links to different elements of the Chinese state. In recent years, as reports have emerged around the poor quality of some of China’s past lending, the authorities in Beijing have sought greater control over new development lending and have imposed new sustainability requirements. At the same time, African countries have sought to diversify sources of supply for infrastructure contracts beyond China. Loans are generally now on a smaller, more manageable scale. With the introduction of its Global Development Initiative in September 2021, there are indications that China is moving to a ‘new development paradigm’, with the emphasis on providing flows of foreign direct investment rather than loans and a focus on supporting small and medium-sized enterprises, human capital investments and green development. African debt distress A paper drawing on expertise from Chatham House’s Africa, Asia and Global Economy and Finance experts will be published before the G20 summit in Bali in November 2022. It examines seven African countries that the World Bank deemed in 2020 to be in most debt distress or at risk of debt distress because of their Chinese stock – Angola, Cameroon, Republic of Congo, Djibouti, Ethiopia, Kenya and Zambia. Two countries – Côte d’Ivoire and South Africa – have received new loans from China and are not in any distress. The paper observes that a lack of transparency over the nature of the terms agreed by these African governments has led to intense domestic criticism and international accusations that China is seeking control over strategic assets. China may have fallen into its own debt trap through profligate and uncoordinated lending to Angola and Zambia In fact, in Angola and Zambia, China may have accidently fallen into its own debt trap through profligate and uncoordinated lending. Zambia became the first pandemic-era default in 2020 and is seeking relief on $17 billion of external debt. After holding general elections in August 2022, Angola and Kenya will also seek additional debt relief, but both may also seek more funds from the private commercial market because of the slow progress of the G20’s Common Framework – something flagged as a concern by China. All seven of the countries that are most indebted to China are actively seeking to reduce this financial reliance on Beijing in the future. China has a pivotal role to play in finding effective solutions to these and other African countries’ debt distress. Improved coordination and cooperation between creditors in China and in other parts the world could enhance the positive impact of multilateral initiatives, such as the Common Framework, which has aimed to bring China and India to the negotiating table along with the IMF, the Paris Club group of creditor nations and private creditors. So far, Chad, Ethiopia and Zambia are the only African countries to have signed up to the framework since its launch in 2020. Although China is suspicious of the IMF, if African states collectively encouraged Beijing to engage with the Common Framework, it could be improved so as to provide debt relief to those African countries finding it difficult to repay their loans. Full Article
cli The Climate Briefing: The nexus of water security and climate policy By www.chathamhouse.org Published On :: Mon, 22 Aug 2022 10:20:04 +0000 The Climate Briefing: The nexus of water security and climate policy Audio NCapeling 22 August 2022 Examining the crossover between water security and climate change with the next two COPs taking place in regions with a history of being water stressed. What should policymakers and negotiators from the Middle East and Africa working on water security focus on at COP27? What does it mean to achieve water security? What are the main barriers or challenges? How is water security relevant to climate change? This podcast was produced in collaboration with the UK Aid-funded Knowledge, Evidence and Learning for Development (K4D) programme which facilitates the use of evidence and learning in international development policy and programming. Full Article
cli A natural climate change priority for Africa By www.chathamhouse.org Published On :: Wed, 28 Sep 2022 15:39:21 +0000 A natural climate change priority for Africa Expert comment LJefferson 28 September 2022 Nature-based solutions can protect African nations’ shared natural endowment and meet the needs of their people. Africa’s principal climate change negotiators have long understood the important contribution of ‘nature-based solutions’ (NBS) in delivering land (and sea) based options as part of the goals of the Paris Agreement. Limiting temperature rises to only 1.5°C by 2050 will demand finding innovative ways to protect Africa’s vast natural endowment that also meets the equally acute needs of its people. Nature-based solutions may do both. Decision-makers on the continent and across the world need to understand that ‘business as usual’ cannot be an option given the potential for loss of life, conflict and chaos. The urgency for Africa cannot be overstated. At a Chatham House conference in Libreville, the Gabonese minister for the environment highlighted that if global warming surges by 2.5° or 3°C the impact would be at least 6°C for Africa. Decision-makers on the continent and across the world need to understand that ‘business as usual’ cannot be an option given the potential for loss of life, conflict and chaos. Adaption, mitigation, or both? Although adaptation to climate change has hitherto tended to be the continent’s main concern, there has also been growing recognition of the ways that Africa’s natural environments, from forests and grasslands, to peatlands and coastal and marine ecosystems, all also mitigate its impacts by sequestering carbon. The Congo Basin alone is said to store upwards of 4 per cent of global emissions annually. Arguing that African states should slow the development of their economies in response to a crisis born of the already-industrialized world does not find a responsive audience in a continent hungry for jobs and opportunity. These environments are under increasing pressure. Deforestation is a sad reality, caused mostly by unsustainable and extensive agricultural practices focused on cash crops for export more than food production to feed local populations. And arguing that African states and peoples should slow the development of their economies and infrastructure in response to a crisis born of the already-industrialized world does not find a responsive audience in a continent hungry for jobs and opportunity. Nature-based solutions offer an answer to this conundrum. There is growing evidence that natural habitats both help avoid losses from climate change-related disasters and can drive economic growth. There is thus potential for NBS to tackle both adaptation and mitigation challenges at relatively low cost. NBS – the rocky road from commitment to policy It was logical therefore for Africa and like-minded countries to work to integrate NBS more strongly into the climate change agenda at COP26. The final Glasgow Climate Pact duly emphasized the importance of protecting ecosystems. The Global Forest Finance Pledge signed in the margins was also significant. African focus, with COP 27 in Egypt soon to take place, is now on domestic implementation and delivery of these pledges. The new African Union Climate Change and Resilient Development strategy (2022-2032) sets out many of the challenges and opportunities. Choosing the right development pathway is tough, requiring political will and inclusive governance. Besides the challenge of securing alternative national revenue if a country moves away from fossil-intensive fuels – particularly acute for Africa’s resource-producing states – there is a dizzying array of policy decisions to be taken. African governments need to choose the most appropriate renewable energy sources, secure alternative livelihoods and continue to meet basic needs of the most vulnerable in the context of radical restructuring. Towards African solutions There can be no one-size-fits-all answer to these questions – it is sadly still necessary to underline the enormous geographic, cultural and political diversity of the continent – but African experts have begun to draw together some emerging common themes from work already underway. Maintaining the ‘status quo’ in agricultural practices is no longer an option. Emphasis on sustainable agriculture is urgently needed andthat includes the elaboration of a ‘new deal’ between nature and people. Conservation also needs to be reframed as an economic opportunity, particularly in the elaboration and development of ecosystem services that deliver the true value of Africa’s forests, and that involve, value and reward local communities, respecting their rights and livelihoods. Maintaining the ‘status quo’ in agricultural practices is no longer an option. Emphasis on sustainable agriculture is urgently needed. Regional cooperation is likewise key, including on the management of forest, wildlife and water resources – Africa’s ecosystems do not respect arbitrary political boundaries, and accomplishing the dual feat of protecting cross-border systems at the same time as realizing their economic potential will demand effective collaboration, as well as training, education and communication at all levels. The imperative of finance A further imperative will be securing sufficient developed country financing – whether that be to secure value for net sequestration and effective forest management or for models of context-appropriate ‘smarter’ sustainable rural conservation and ecosystem resilience. Full Article
cli The Translation of Dosimetry into Clinical Practice: What It Takes to Make Dosimetry a Mandatory Part of Clinical Practice By jnm.snmjournals.org Published On :: 2024-09-05T07:37:49-07:00 Full Article
cli Challenges with 177Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice By jnm.snmjournals.org Published On :: 2024-09-19T06:38:07-07:00 Full Article
cli Intraarterial Administration of Peptide Receptor Radionuclide Therapy in Patients with Advanced Meningioma: Initial Safety and Efficacy By jnm.snmjournals.org Published On :: 2024-10-24T11:58:49-07:00 Visual Abstract Full Article
cli Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI By jnm.snmjournals.org Published On :: 2024-10-30T08:04:14-07:00 Visual Abstract Full Article
cli Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with 213Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Visual Abstract Full Article
cli Addressing Climate Catastrophe Concerns in Asthma Medication Delivery: Rethinking Inhaler Use for Environmental and Clinical Efficacy By www.bmj.com Published On :: Tuesday, November 12, 2024 - 13:24 Full Article
cli A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia By www.mcponline.org Published On :: 2020-11-30 Ka-Won KangNov 30, 2020; 0:RA120.002169v1-mcp.RA120.002169Research Full Article
cli Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling [Signal Transduction] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein–coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterization for the GCGR is lacking. Using endocytic colocalization and ubiquitination assays, we have identified a correlation between the ubiquitination profile and recycling of the GCGR. Our experiments revealed that GCGRs are constitutively ubiquitinated at the cell surface. Glucagon stimulation not only promoted GCGR endocytic trafficking through Rab5a early endosomes and Rab4a recycling endosomes, but also induced rapid deubiquitination of GCGRs. Inhibiting GCGR internalization or disrupting endocytic trafficking prevented agonist-induced deubiquitination of the GCGR. Furthermore, a Rab4a dominant negative (DN) that blocks trafficking at recycling endosomes enabled GCGR deubiquitination, whereas a Rab5a DN that blocks trafficking at early endosomes eliminated agonist-induced GCGR deubiquitination. By down-regulating candidate deubiquitinases that are either linked with GPCR trafficking or localized on endosomes, we identified signal-transducing adaptor molecule–binding protein (STAMBP) and ubiquitin-specific protease 33 (USP33) as cognate deubiquitinases for the GCGR. Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist-activated GCGRs at early endosomes. A mutant GCGR with all five intracellular lysines altered to arginines remains deubiquitinated and shows augmented trafficking to Rab4a recycling endosomes compared with the WT, thus affirming the role of deubiquitination in GCGR recycling. We conclude that the GCGRs are rapidly deubiquitinated after agonist-activation to facilitate Rab4a-dependent recycling and that USP33 and STAMBP activities are critical for the endocytic recycling of the GCGR. Full Article
cli Problem Notes for SAS®9 - 66504: Clicking a link to pass a group break value to a SAS Web Report Studio report returns an HTTP 400 error By Published On :: Thu, 20 Aug 2020 14:07:26 EST SAS Web Report Studio enables you to link reports based on a group break value. However, when you click the link, it might fail with an HTTP 400 error. The exact message you see depends on which browser you are u Full Article CITATIONWEB+SAS+Web+Report+Studio
cli UK clinics may be able to offer mitochrondrial donation next spring By www.bmj.com Published On :: Thursday, December 1, 2016 - 15:46 Full Article
cli Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice [Research Articles] By www.jlr.org Published On :: 2020-10-01T00:05:17-07:00 Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related increases in IL-6 levels reduce progesterone substrate availability, resulting in a decline in AlloP levels and an increase in CORT. Furthermore, our results indicate that AlloP is a critical link between inflammatory cytokines and the age-related decline in cognitive function. Full Article
cli pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates [Metabolism] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 SLC19A2 and SLC19A3, also known as thiamine transporters (THTR) 1 and 2, respectively, transport the positively charged thiamine (vitamin B1) into cells to enable its efficient utilization. SLC19A2 and SLC19A3 are also known to transport structurally unrelated cationic drugs, such as metformin, but whether this charge selectivity extends to other molecules, such as pyridoxine (vitamin B6), is unknown. We tested this possibility using Madin-Darby canine kidney II (MDCKII) cells and human embryonic kidney 293 (HEK293) cells for transfection experiments, and also using Caco-2 cells as human intestinal epithelial model cells. The stable expression of SLC19A2 and SLC19A3 in MDCKII cells (as well as their transient expression in HEK293 cells) led to a significant induction in pyridoxine uptake at pH 5.5 compared with control cells. The induced uptake was pH-dependent, favoring acidic conditions over neutral to basic conditions, and protonophore-sensitive. It was saturable as a function of pyridoxine concentration, with an apparent Km of 37.8 and 18.5 μm, for SLC19A2 and SLC19A3, respectively, and inhibited by the pyridoxine analogs pyridoxal and pyridoxamine as well as thiamine. We also found that silencing the endogenous SLC19A3, but not SLC19A2, of Caco-2 cells with gene-specific siRNAs lead to a significant reduction in carrier-mediated pyridoxine uptake. These results show that SLC19A2 and SLC19A3 are capable of recognizing/transporting pyridoxine, favoring acidic conditions for operation, and suggest a possible role for these transporters in pyridoxine transport mainly in tissues with an acidic environment like the small intestine, which has an acidic surface microclimate. Full Article
cli High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy [Research] By www.mcponline.org Published On :: 2020-11-01T00:05:37-07:00 Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45+) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC. Full Article
cli CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens [Research] By www.mcponline.org Published On :: 2020-09-22T12:35:16-07:00 CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17 and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared to interferon gamma (IFN) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor-antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire. Full Article
cli A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia [Research] By www.mcponline.org Published On :: 2020-11-30T16:35:18-08:00 Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology. Full Article
cli Ethical principles, opportunities and constraints in clinical proteomics [Research] By www.mcponline.org Published On :: 2021-01-04T06:35:18-08:00 Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further. Full Article
cli The Role of Sub-state and Non-state Actors in International Climate Processes: Civil Society By www.chathamhouse.org Published On :: Tue, 27 Nov 2018 09:59:58 +0000 The Role of Sub-state and Non-state Actors in International Climate Processes: Civil Society Research paper sysadmin 27 November 2018 Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance. — Photo by The Climate Reality Project, ‘People’s Climate March Protest’, via Unsplash, 2017. This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes. Summary Following the failure of the 15th Conference of the Parties (COP 15) in Copenhagen in 2009, there was a step change in the sophistication and unity of civil society engagement on climate policy. This ensured that, subsequently, civil society was more effective in exercising multiple channels of influence around the negotiations for the Paris Agreement in 2015. Civil society proved to be particularly effective at harnessing the twin narratives of climate science and economics, and at leveraging an emerging multi-level governance architecture, to create political space for climate leadership. Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance. In particular, the shift to a more ‘nationally grounded’ implementation regime focusing on individual states’ climate commitments will require civil society to become more effective at influencing domestic politics. At the same time, civil society will need to continue to seek strategic synergies at the international level. Civil society has a central role to play in ensuring that the first key test of the Paris ‘ratchet’ mechanism – revising countries’ pledged climate actions, or Nationally Determined Contributions (NDCs), by 2020 – is robust, science-informed and strongly rooted in domestic politics. 2018-11-28-non-state-actors-climate-civil-society-guy (PDF) Full Article
cli The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector By www.chathamhouse.org Published On :: Tue, 27 Nov 2018 10:09:06 +0000 The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector Research paper sysadmin 27 November 2018 Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. — Photo by Priscilla Du Preez, ‘Climate Reality’ via Unsplash, 2017. This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes. Summary The corporate sector has traditionally engaged governments at national rather than international level in lobbying for action related to climate change. Where it has engaged at an international level, this has often been to restrain regulation and ambition, such as in air transport. Over time, many businesses have increasingly understood that there is more commercial opportunity in a strong, consistent approach to tackling climate mitigation and adaptation, and an increasing number are willing to speak up on the issue. The Paris Climate Conference in 2015 demonstrated this positive engagement. Businesses are more powerful when engaging directly with national governments on detailed policies – by demonstrating what is possible and indirectly influencing national governments’ international pledges. Traditional trade/industry sector associations and groups have tended to suffer from the ‘lowest common denominator’ effect of their least progressive members. Progressive business groups coalescing around climate ambition can help to counter this. Unlike at the Copenhagen climate talks in 2009, the business community provided a positive, supportive backdrop to the 2015 Paris talks, mindful of the public relations opportunities in taking a progressive stance and of the benefits of targets that reflected the science. The carbon market was a particular focus for corporates, which succeeded in getting emissions trading options and market mechanisms included in Article 6 of the Paris Agreement. Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. With increasing awareness of resource scarcity, businesses are pursuing ever more creative solutions. Wide recognition that the avoidance of future emissions is increasingly dependent on developing and emerging economies means that business voices from these countries will potentially be more influential in the next few years. 2018-11-28-non-state-actors-climate-corporate-duggan (PDF) Full Article
cli The Role of Sub-state and Non-state Actors in International Climate Processes By www.chathamhouse.org Published On :: Tue, 27 Nov 2018 10:18:41 +0000 The Role of Sub-state and Non-state Actors in International Climate Processes Research paper sysadmin 27 November 2018 In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever. — Photo by UNclimatechange, ‘Bonn Climate Change Conference - October 2014’ via Flickr, 2014. Summary Climate action from sub-state and non-state actors such as subnational governments, cities, corporations and NGOs has very significant potential to enhance national efforts to curb CO2 emissions, close the so-called ‘emissions gap’ – between current commitments and the action necessary to meet climate targets – and help move the world on to a ‘1.5°C pathway’ that would limit global warming to 1.5°C above pre-industrial levels by 2100. In addition to their own climate action, sub-state/non-state actors can contribute to climate governance by developing new policies and business models to support emissions cuts and build resilience. Knowledge exchange and capacity-building have a role to play in helping these innovations to spread internationally. Politically, measures implemented by sub-state/non-state actors can help national governments to implement existing targets faster and more effectively, while helping to build political support for more ambitious climate action. The post-Paris climate regime of the United Nations Framework Convention on Climate Change (UNFCCC) reflects the growing importance of sub- and non-state actors, and has featured the creation of institutional structures to engage and coordinate them. In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever. However, more questions about the robustness of sub- and non-state action are also likely to be raised. With the 2020 deadline approaching for countries to submit details of enhanced Nationally Determined Contributions (NDCs), long-term climate strategies and other means of raising policy ambition, the next two years are set to provide significant opportunity for sub- and non-state action. Many governments are already developing ways to engage with sub- and non-state actors to identify opportunities to strengthen action by 2020. Key questions in this respect include (a) whether sub- and non-state actors can mobilize across sectors; and (b) whether action can be extended beyond the ‘usual suspects’ to include contributions from less familiar sources, such as business sectors with limited opportunities for climate action or corporations in the Global South. 2018-11-28-non-state-sctors-climate-synthesis-hale-final (PDF) Full Article
cli The Role of Sub-state and Non-state Actors in International Climate Processes: Financial Institutions By www.chathamhouse.org Published On :: Thu, 20 Dec 2018 10:15:53 +0000 The Role of Sub-state and Non-state Actors in International Climate Processes: Financial Institutions Research paper sysadmin 20 December 2018 The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment. — Photo by João Barbosa, ‘The need to keep growing’, 2018. This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes. Summary The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment, and on the role of the financial sector as a potentially powerful non-state actor in the international climate debate. Leading individual financial institutions reacted to the Paris Agreement by framing it in terms of what it would mean for markets – i.e. risks and opportunities – and by underlining the importance of national implementation of climate change commitments. Key recent developments signal that the financial sector actively supports Paris-compatible government action on climate change, as well as company-level action to understand the physical and ‘transition’ risks and opportunities associated with climate change and policy responses. Financial sector engagement is taking place through well-organized and well-supported international initiatives and platforms. A critical part of this process entails robust activity by financial institutions to embed climate change and broader sustainability factors into strategies and operations. At country level, attention to implementation of Nationally Determined Contributions (NDCs) and associated sector-level policy development has been largely separate from the broader ‘sustainable finance’ dynamic. National-level action has not benefited from the same level of organized financial sector involvement evident in international action. One of the reasons for this is that, with some notable exceptions, international financial initiatives lack the capacity and resources to participate in the granular detail of national policy processes. Policymakers in turn often lack the internal capacity to consult or engage with the financial sector domestically. This paper includes some thoughts on further international and national climate actions. Ensuring that messages from successful international financial sector initiatives are heard in regional and non-climate forums offers one avenue for building a stronger foundation for greater climate ambition. Building the resource base for stronger national climate policy engagement, as a counter-voice to incumbent interests and to ensure that the quality of policy is ‘investment grade’, is another. This will be critical to the delivery of policy outcomes. Other key elements include the need to pool knowledge across relevant parts of the finance sector, build alliances, and shift action towards joint problem-solving with policymakers. A ‘Talanoa 2.020’-type initiative offers one potentially promising approach to advancing dialogue in this respect. 2018-12-21-non-state-actors-climate-financial-institutions-hamilton (PDF) Full Article