cl Use of cyclodextrins for manipulating cellular cholesterol content By feedproxy.google.com Published On :: 1997-11-01 AE ChristianNov 1, 1997; 38:2264-2272Articles Full Article
cl Direct transesterification of all classes of lipids in a one-step reaction By feedproxy.google.com Published On :: 1986-01-01 G LepageJan 1, 1986; 27:114-120Articles Full Article
cl Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By feedproxy.google.com Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
cl Exploring the Obstacles and Opportunities for Expanded UK-Latin American Trade and Investment By feedproxy.google.com Published On :: Thu, 27 Feb 2020 12:40:01 +0000 Invitation Only Research Event 14 January 2020 - 8:30am to 11:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Trade and investment between the UK and Latin America is woefully underdeveloped. Latin America’s agricultural powerhouses Brazil and Argentina only accounted for a total of 1.6% of the UK’s agricultural market across eight sectors in 2018, all of those areas in which Argentina and Brazil have substantial comparative advantages. Conversely, UK exports to the large Latin American economies remain far below their potential. To cite a few examples, in 2018 in the electrical equipment sector, the UK only exported $95.7 million of those products to Brazil, making the ninth largest economy in the world only the 42nd export market for those goods from the UK; Mexico only imported $91.4 million of UK-made electrical goods, placing it directly behind Brazil as UK’s market for those goods.As we look to the future, any improvement to the relationship will depend on two factors: 1) how the UK leaves the EU and 2) whether Latin American agricultural producers can improve their environmental practices and can meet the production standards established by the EU and likely maintained by a potential post-Brexit Britain.In the first meeting of the working group, Chatham House convened a range of policymakers, practitioners and academics to explore this topic in depth, identify the key issues driving this trend, and begin to consider how improvements might best be made. Subsequent meetings will focus on specific sectors in commerce and investment.We would like to thank BTG Pactual, Cairn Energy plc, Diageo, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative. Event attributes Chatham House Rule Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
cl Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
cl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
cl {alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies. Full Article
cl Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Mon, 27 Apr 2020 15:50:01 +0000 28 April 2020 This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities. Read online Download PDF Haid Haid Senior Consulting Fellow, Middle East and North Africa Programme @HaidHaid22 2020-04-28-Syria-prison.jpg A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images. SummaryFollowing the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large. Department/project Middle East and North Africa Programme Full Article
cl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
cl Webinar: Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Wed, 06 May 2020 09:05:01 +0000 Research Event 12 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Haid Haid, Senior Consulting Fellow, Middle East and North Africa Programme, Chatham HouseSara Kayyali, Syria Researcher, Middle East and North Africa Division, Human Rights WatchModerator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House You can register your interest here. Alternatively, you can watch the webinar live on the MENA Programme Facebook page.Following the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.In a recent research paper, author Haid Haid argues that this approach to justice is deeply flawed as it raises concerns about due process and lacks the precise instruments to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. The paper proposes that a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members.In this webinar, part of the MENA Programme’s Online Event Series, speakers will examine the benefits of such an approach to justice for overcoming the limitations of the current, counterterrorism-focused framework. Panelists will discuss the alternative mechanisms local authorities and their key foreign backers can use to hold local ISIS members to account while contributing to the healing of communities. The event will be held on the record. Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Department/project Middle East and North Africa Programme, Syria from Within Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
cl Growth in a Multilateral World: The Role of Inclusive Trade and Quality Investment By feedproxy.google.com Published On :: Wed, 04 Apr 2018 00:00:00 +0100 Full Article
cl Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20 By feedproxy.google.com Published On :: Wed, 04 Jul 2018 00:00:00 +0100 Full Article
cl Cyber Security Series: Securing Elections and Reclaiming Democratic Processes By feedproxy.google.com Published On :: Mon, 03 Sep 2018 00:00:00 +0100 Full Article
cl The UK-Saudi Arabia Relationship: A Closer Look By feedproxy.google.com Published On :: Tue, 04 Sep 2018 00:00:00 +0100 Full Article
cl Talking to North Korea: Ending the Nuclear Standoff? By feedproxy.google.com Published On :: Tue, 09 Oct 2018 00:00:00 +0100 Full Article
cl International Security Institutions: A Closer Look By feedproxy.google.com Published On :: Tue, 13 Nov 2018 00:00:00 +0000 Full Article
cl The Challenge of Ambition? Unlocking Climate Action and the Outcomes of COP24 By feedproxy.google.com Published On :: Fri, 01 Mar 2019 00:00:00 +0000 Full Article
cl Power Shift: The Rise of Asia and the Decline of the West? By feedproxy.google.com Published On :: Tue, 28 May 2019 00:00:00 +0100 Full Article
cl Screening Room: Brexit - Behind Closed Doors By feedproxy.google.com Published On :: Thu, 27 Jun 2019 00:00:00 +0100 Full Article
cl Securing Our Climate Future: Risk, Resilience and Diplomacy By feedproxy.google.com Published On :: Thu, 04 Jul 2019 00:00:00 +0100 Full Article
cl Climate Action: A Role for Civil Disobedience? By feedproxy.google.com Published On :: Thu, 04 Jul 2019 00:00:00 +0100 Full Article
cl Climate, Food and Land By feedproxy.google.com Published On :: Wed, 13 Nov 2019 00:00:00 +0000 Full Article
cl Undercurrents: Episode 41 - Personalized Political Advertising, and Climate Justice in Chile By feedproxy.google.com Published On :: Fri, 29 Nov 2019 00:00:00 +0000 Full Article
cl Screening Room: Parts of a Circle - History of the Karabakh Conflict By feedproxy.google.com Published On :: Tue, 18 Feb 2020 00:00:00 +0000 Full Article
cl The Climate Briefing: Episode 1 - What Does Success Look Like At COP26? By feedproxy.google.com Published On :: Thu, 27 Feb 2020 00:00:00 +0000 Full Article
cl Undercurrents: Episode 48 - UK Intelligence Agencies, and Paying for Climate Action By feedproxy.google.com Published On :: Fri, 20 Mar 2020 00:00:00 +0000 Full Article
cl The Climate Briefing: Episode 2 - European Climate Ambitions By feedproxy.google.com Published On :: Fri, 03 Apr 2020 00:00:00 +0100 Full Article
cl The Climate Briefing: Episode 3 - Climate Change and National Security By feedproxy.google.com Published On :: Wed, 29 Apr 2020 00:00:00 +0100 Full Article
cl Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions. Full Article
cl The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Full Article
cl Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms. Full Article
cl Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2 [Enzymology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes. Full Article
cl Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency. Full Article
cl Climate, Food and Land By feedproxy.google.com Published On :: Wed, 30 Oct 2019 11:05:01 +0000 Members Event 13 November 2019 - 1:00pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Tim Benton, Director, Energy Environment and Resources Department, Chatham HouseChair: Laura Wellesley, Research Fellow, Energy, Environment and Resources Department, Chatham House In the summer of 2019, a major report on climate change and land use was released by the Intergovernmental Panel on Climate Change (IPCC).Prepared by 107 climate scientists, the report outlined the ways in which human activities have led to the degradation of land, increasingly turning the resource into a source of carbon, and not just a carbon sink, and thus mitigating the land’s ability to help curb climate change. Against this backdrop, one of the report’s authors, Professor Tim Benton, reflects on the relationship between land, food and climate change.He considers the challenges created by competing demands for the services land produces - such as food, energy, biodiversity and carbon storage - and the ways in which these demands are driving climate change and the degradation of land around the world.How can governments, corporations and civil society best manage competing demands over land use? Faced with growing populations and a need to maintain food security, what are the limits to the contribution of land in addressing climate change? And what is the role of changing societal demand, especially for meat produce, in mitigating the pressure on land? Event attributes Livestream Members Events Team Email Full Article
cl Negative Emissions and Managing Climate Risks Scenarios By feedproxy.google.com Published On :: Thu, 31 Oct 2019 18:15:01 +0000 Research Event 4 July 2019 - 1:30pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE This half-day strategic workshop, organized by Chatham House and E3G, brought together key climate experts, policymakers and influential actors, especially in Europe, for a focused and facilitated discussion on the roles, risks and potentials of negative emissions technologies (NETs). An interactive scenario exercise will be conducted, drawing on a climate simulation tool developed by Climate Interactive, to consider the potential roles and risks of different NETs deployments to meet the Paris Agreement targets and to consider the international co-operation required to manage the pathway to net-zero emissions. Participants will explore the political opportunities, discuss different scenarios and risks and identify areas of interventions and collective action.The meeting is part of a series of events being held at Chatham House as part of London Climate Action Week (LCAW). Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Full Article
cl Climate Change, Energy Transition, and the Extractive Industries Transparency Initiative (EITI) By feedproxy.google.com Published On :: Thu, 05 Dec 2019 15:45:01 +0000 Invitation Only Research Event 17 January 2020 - 9:30am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Climate change and energy transition are re-shaping the extractive sectors, and the opportunities and risks they present for governments, companies and civil society. As the central governance standard in the extractives sector, the EITI has a critical role in supporting transparency in producer countries.This workshop will bring together experts from the energy and extractives sectors, governance and transparency, and climate risk and financial disclosure initiatives to discuss the role of governance and transparency through the transition. It will consider the appropriate role for the EITI and potential entry points for policy and practice, and the potential for coordination with related transparency and disclosure initiatives. Please note attendance is by invitation only. Department/project Energy, Environment and Resources Programme Full Article
cl Climate Action in 2020: Time to Focus on Forests By feedproxy.google.com Published On :: Tue, 14 Jan 2020 09:26:46 +0000 14 January 2020 Alison Hoare Senior Research Fellow, Energy, Environment and Resources Programme LinkedIn More ambitious policies to reduce deforestation are key to effective climate policy, but to succeed, they require three big changes in approach. 2020-01-14-ReforestBrazil.jpg Mahogany tree seedlings being taken to be planted out in the Amazon. Photo: Getty Images. December’s UN climate talks held in Madrid were aptly titled ‘Time for Action’. While little progress was made at the conference in establishing an international framework that would help to instigate this, there is still much scope for action in 2020. The need for this has become all too apparent as the impacts of climate change are increasingly seen around the world.One of the key areas where progress can be made in 2020 is in increasing the ambition of nationally determined contributions (NDCs), these being governments’ plans to take action in response to climate change. To date, 184 countries have submitted NDCs, yet the commitments that have been made fall far short of what is needed to avert catastrophic climate change.In 2020, however, many countries will be revising their NDCs, presenting an important opportunity to shift momentum; to date 79 countries have announced that they will be enhancing the ambition of their NDCs.The forest sector is one area where more ambitious targets are likely to be set, and indeed, at the Climate Action Summit in September 2019, more than 20 countries made new commitments for the conservation, reforestation and restoration of their forests.This will be essential. As is well documented, reducing deforestation is critical to reducing carbon emissions, while healthy and diverse forests are vital for adapting and increasing resilience to climate change.However, while it is important that ambitious targets are set, this is relatively easy; the bigger challenge lies in ensuring that these are achievable.This is all too apparent from experience thus far. In 2014, the New York Declaration on Forests set the goal to halve forest loss by 2020, and to end it by 2030. In addition, it included the goal to restore 150 million hectares of degraded landscapes and forestlands by 2020, and a further 200 million hectares by 2030.The declaration has been endorsed by over 50 countries, as well as business and civil society organizations, yet the 2020 goals are far from being reached – in the six years since the declaration was launched, it has been found that forest loss increased rather than declined, and only about 27 million hectares of land have been restored.What then is needed to ensure that the commitments being made by governments in their NDCs will actually be met? Three big changes are required.Firstly, a shift in perspective is needed in many countries to a more forest-sensitive approach to development, one that gives adequate recognition to the full range of values provided by forests, rather than primarily focusing on their role as a global carbon sink. These include their importance for local and national economies, for livelihoods and the well-being of forest-dependent peoples, and for biodiversity and the regulation of local climate and water systems.The focus on nature-based solutions at the international level offers potential to support this shift. However, it is critical that these are not seen as ‘niche’ approaches, and that countries identify what nature-based solutions mean for them, and how forests and tree-rich landscapes can best be integrated into their development strategies.Fundamental to achieving this will be further improvements in governance, and this is the second change that is required. Legal and institutional reforms are needed in many countries as well as significant investments in human and technical resources. This will enable processes to be strengthened, or put in place, so that equitable strategies can be developed and implemented – strategies that reflect a balance of the needs and priorities of the full range of stakeholders, including local and global, rural and urban, women and men, young and old.Financing will of course be critical for this, and the least developed countries in particular will be hindered in the actions they can take without additional finance. This is the third area of change that is needed, and it is to be hoped that the international community will make better progress on this in 2020. Forest and land-use options are often described as a cost-effective means of tackling climate change, as is noted in the Santiago Call for Action on Forests for example.This is not to say that these will be easy or cheap – as Chatham House has documented, experience of forest governance reform has shown that it takes significant funding and time to bring about deep-rooted change. However, the huge potential benefits that can result, for the citizens of forest-rich countries as well as for the planet, mean that forests and sustainable land-use are a good investment. Full Article
cl Will a Devastating Bushfire Season Change Australia’s Climate Stance? By feedproxy.google.com Published On :: Thu, 23 Jan 2020 09:20:27 +0000 23 January 2020 Madeleine Forster Richard and Susan Hayden Academy Fellow, International Law Programme @maddiefors LinkedIn Professor Tim Benton Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme @timgbenton Google Scholar With Australians experiencing first-hand the risks of climate change, Madeleine Forster and Tim Benton examine the influencers, at home or abroad, that could push the government towards more action. 2020-01-23-FireNSW.jpg Residents look on as flames burn through bush on 4 January 2020 in Lake Tabourie, NSW. Photo: Getty Images. The 2019–20 fire season in Australia has been unprecedented. To date, an estimated 18 million hectares of fire has cut swathes through the bush – an area greater than that of the average European country and over five times the size of blazes in the Amazon.This reflects previous predictions of Australian science. Since 2008 and as recently as 2018, scientific bodies have warned that climate change will exacerbate existing conditions for fires and other climatic disasters in Australia. What used to be once-in-a-generation fires now re-appear within 10–15 years with increased ferocity, over longer seasons.In a country known for climate denial and division, debate has erupted around bushfire management and climate change. One of these is whether controlled burns are the answer to Australia’s climate-affected fire conditions.There is no single risk reduction strategy. Controlled burning remains key, if adapted to the environment and climate. But when three out of four seasons in a year can support destructive bushfires, there are clear limits to what controlled burning and other fire management techniques can achieve. Other ‘adaptation’ measures are also likely to provoke intense debate – including bush clearance. As one Australian expert offered to highlight where Australia has got to, families should probably not go on holiday to bush and beach during the height of summer when temperatures and fire risk peaks. So, unless Australia is prepared to debate radical changes to where people live and how land is used, the limits to adaptation imply the need for mitigation. This means supporting ambitious global greenhouse emissions reductions targets. As research from Victoria, one fire-prone state in Australia, highlights, ‘the emissions pathway we follow is the largest determinant of change to many variables [such as temperature] beyond the next few decades.’Can Australia become a more active global partner on emissions?Australia accounts for just over one per cent of global emissions, so reducing domestic emissions – even though on a per capita basis they are the highest in the world – will not reduce Australia’s climate risk. Showing international leadership and supporting a powerful coalition of the willing to tackle climate change is the only way ahead. By showing a willingness to adopt climate ambition, Australia can help more constructive worldwide action, and thereby reduce its own risk exposure. Leading by example is a politically difficult issue for Australia. Prime Minister Scott Morrison was re-elected in May 2019 on an economic stability platform, and a promise not to imperil employment growth through climate action. Australia has contested UN estimates that it will not meet its existing modest goals for domestic emissions, by seeking to rely on carryover credits from action under the Kyoto Protocol as proof of progress.It has also distanced itself from concerns over global supply and demand in fossil fuels. Australia remains a global supplier for fossil fuels, including coal – the nation’s coal exports accounted for $67 billion in revenues in 2019 in an expanding but changing Asian market, supplying ‘some of the cheapest electricity in the world’.Possible influencers of changeWith Australians experiencing first-hand the risks of climate change, there is already pressure to do more. Many are sceptical this will translate into domestic targets or export policies that give Australia the moral authority to ask for more action on the global stage.Here, diverse groups who share a common interest in seeing Australia recover from the bushfires and address future climate risks could be key.Importantly this includes rural and urban-fringe communities affected by the bushfires. They were part of Morrison’s traditional supporter-base but are angry at the government’s handling of the crisis and increasingly see how tiptoeing around emissions (including exports) has also ‘buried’ open discussion at home on climate-readiness.Australian states could also find themselves taking a lead role. Virtually all jurisdictions have now committed to their own goals, most based on zero-carbon goals by 2050 (as has New Zealand). These can support modelling for Australia’s energy transition from coal, through gas, to market competitive renewables, while also help to ensure this reflects community expectations on jobs, electricity prices and other costs. Other emerging voices include the insurance and banking sectors (the Reserve Bank of Australia warned of the long-term financial stability risks of climate change before the fires) and indigenous Australians (one group of Torres Strait Islanders have filed a complaint to the UN Human Rights Committee which, if heard, will place Australia’s emissions record under the spotlight again). Their challenge now is finding a common language on what a cohesive approach to addressing climate change risk looks like. The international picture is mixed. The United States’ poor federal climate policy is a buffer for Australia. French President Emmanuel Macron has tried to raise the cost of inaction for Australia in current EU–Australia trade negotiations, but many large emitters in the Indo-Pacific region remain key Australian trading partners, investors and buyers of Australian coal. In the meantime, the United Kingdom is preparing for the meeting of parties to the Paris Agreement in Glasgow in November. A key global event following Brexit, the UK will no doubt be hoping to encourage a leadership circle with national commitments that meet global need to make the Glasgow meeting a success.The UK public has expressed enormous sympathy for Australia in the bushfires and outrage over ‘climate denialism.’ Australia’s experience will be a cautionary tale of the effects of climate change at the meeting. Could the UK also support Australia to become a less reluctant partner in global climate action? Full Article
cl Maintaining Connections: How Might the UK Remain Engaged in the EU's Climate and Energy Strategies? By feedproxy.google.com Published On :: Thu, 23 Jan 2020 10:35:01 +0000 Invitation Only Research Event 3 March 2020 - 10:30am to 12:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE As the UK leaves the EU and the formal negotiations on the future relationship begins, this workshop will discuss any immediate changes and review the short and medium term impacts of Brexit on the energy sector. The workshop will look to cover:The implications for UK business and system operations of the UK leaving the Internal Energy Market.Current and future investment trends in the UK energy system.The trade of electricity and gas over inter-connectors.The need for the development of a new EU-UK operational framework mechanism.The UK's EU withdrawal agreement and the operation of the Single Electricity Market (SEM) across Ireland. Options for the UK outside of the EU Emissions Trading System (ETS) and the impact on carbon prices.This workshop is part of a programme funded by the UK Energy Research Centre on Brexit and the UK’s Net Zero Energy Policy being run by the University of Warwick and Chatham House.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme Chloé Prendleloup Email Full Article
cl The prospects of carbon dioxide removal in climate policymaking within the United States By feedproxy.google.com Published On :: Fri, 14 Feb 2020 10:40:01 +0000 Research Event 19 November 2019 - 9:00am to 5:00pm School of Law, University of California, Davis Agendapdf | 158.8 KB Meeting Summarypdf | 207.92 KB This meeting formed part of a programme of work which investigates the role of negative emissions technologies (NETs) in achieving the Paris Agreement climate targets. Previous meetings held in London and Brussels have looked at integrating negative emissions into EU policy-making, the implications and degree to which NETs, and in particular bioenergy with carbon capture storage (BECCS), can be an effective climate mitigation tool. This meeting focused on the possible deployment pathways of NETs and alternatives to BECCS for the US in particular, in the context of geographical constraints and socioenvironmental implications, the role of the private sector, and appropriate governance and finance mechanisms. Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Melissa MacEwen Project Manager, Energy, Environment and Resources Programme Email Full Article
cl To Advance Trade and Climate Goals, ‘Global Britain’ Must Link Them By feedproxy.google.com Published On :: Thu, 19 Mar 2020 17:12:54 +0000 19 March 2020 Carolyn Deere Birkbeck Associate Fellow, Global Economy and Finance Programme, and Hoffmann Centre for Sustainable Resource Economy @carolyndeere LinkedIn Google Scholar Dr Emily Jones Associate Professor, Blavatnik School of Government Dr Thomas Hale Associate Professor, Blavatnik School of Government COVID-19 is a sharp reminder of why trade policy matters. As the UK works to forge new trade deals, it must align its trade policy agenda with its climate ambition. 2020-03-19-Boris-Johnson-COP26.jpg Boris Johnson at the launch of the UK-hosted COP26 UN Climate Summit at the Science Museum, London on February 4, 2020. Photo by Jeremy Selwyn - WPA Pool/Getty Images. COVID-19 is a sharp reminder of why trade and climate policy matters. How can governments maintain access to critical goods and services, and ensure global supply chains function in times of crisis?The timing of many trade negotiations is now increasingly uncertain, as are the UK’s plans to host COP26 in November. Policy work continues, however, and the EU has released its draft negotiating text for the new UK-EU trade deal, which includes a sub-chapter specifically devoted to climate. This is a timely reminder both of the pressing need for the UK to integrate its trade and climate policymaking and to use the current crisis-induced breathing space in international negotiations - however limited - to catch up on both strategy and priorities on this critical policy intersection.The UK government has moved fast to reset its external trade relations post-Brexit. In the past month it formally launched bilateral negotiations with the EU and took up a seat at the World Trade Organization (WTO) as an independent member. Until the COVID-19 crisis hit, negotiations were also poised to start with the US.The UK is also in the climate spotlight as host of COP26, the most important international climate negotiation since Paris in 2015, which presents a vital opportunity for the government to show leadership by aligning its trade agenda with its climate and sustainability commitments in bold new ways.Not just an empty aspirationThis would send a signal that ‘Global Britain’ is not just an empty aspiration, but a concrete commitment to lead.Not only is concerted action on the climate crisis a central priority for UK citizens, a growing and increasingly vocal group of UK businesses committed to decarbonization are calling on the government to secure a more transparent and predictable international market place that supports climate action by business.With COP26, the UK has a unique responsibility to push governments to ratchet up ambition in the national contributions to climate action – and to promote coherence between climate ambition and wider economic policymaking, including on trade. If Britain really wants to lead, here are some concrete actions it should take.At the national level, the UK can pioneer new ways to put environmental sustainability – and climate action in particular - at the heart of its trade agenda. Achieving the government’s ambitious Clean Growth Strategy - which seeks to make the UK the global leader in a range of industries including electric cars and offshore wind – should be a central objective of UK trade policy.The UK should re-orient trade policy frameworks to incentivize the shift toward a more circular and net zero global economy. And all elements of UK trade policy could be assessed against environmental objectives - for example, their contribution to phasing out fossil fuels, helping to reverse overexploitation of natural resources, and support for sustainable agriculture and biodiversity.In its bilateral and regional trade negotiations, the UK can and should advance its environment, climate and trade goals in tandem, and implementation of the Paris Agreement must be a core objective of the UK trade strategy.A core issue for the UK is how to ensure that efforts to decarbonise the economy are not undercut by imports from high-carbon producers. Here, a ‘border carbon adjustment (BCA)’ - effectively a tax on the climate pollution of imports - would support UK climate goals. The EU draft negotiating text released yesterday put the issue of BCAs front and centre, making crystal clear that the intersection of climate, environment and trade policy goals will be a central issue for UK-EU trade negotiations.Even with the United States, a trade deal can and should still be seized as a way to incentivize the shift toward a net zero and more circular economy. At the multilateral level, as a new independent WTO member, the UK has an opportunity to help build a forward-looking climate and trade agenda.The UK could help foster dialogue, research and action on a cluster of ‘climate and trade’ issues that warrant more focused attention at the WTO. These include the design of carbon pricing policies at the border that are transparent, fair and support a just transition; proposals for a climate waiver for WTO rules; and identification of ways multilateral trade cooperation could promote a zero carbon and more circular global economy. To help nudge multilateral discussion along, the UK could also ask to join a critical ‘path finder’ effort by six governments, led by New Zealand, to pursue an agreement on climate change, trade and sustainability (ACCTS). This group aims to find ways forward on three central trade and climate issues: removing fossil fuel subsidies, climate-related labelling, and promoting trade in climate-friendly goods and services.At present, the complex challenges at the intersection of climate, trade and development policy are too often used to defer or side-step issues deemed ‘too hard’ or ‘too sensitive’ to tackle. The UK could help here by working to ensure multilateral climate and trade initiatives share adjustment burdens, recognise the historical responsibility of developed countries, and do not unfairly disadvantage developing countries - especially the least developed.Many developing countries are keen to promote climate-friendly exports as part of wider export diversification strategies and want to reap greater returns from greener global value chains. Further, small island states and least-developed countries – many of which are Commonwealth members – that are especially vulnerable to the impacts of climate change and natural disasters, need support to adapt in the face of trade shocks and to build climate-resilient, trade-related infrastructure and export sectors.As an immediate next step, the UK should actively support the growing number of WTO members in favour of a WTO Ministerial Statement on environmental sustainability and trade. It should work with its key trading partners in the Commonwealth and beyond to ensure the agenda is inclusive, supports achievement of the UN Sustainable Development Goals (SDGs) and helps developing countries benefit from a more environmentally sustainable global economy.As the UK prepares to host COP26, negotiates deals with the EU and US, and prepares for its first WTO Ministerial meeting as an independent member, it must show it can lead the way nationally, bilaterally, and multilaterally. And to ensure the government acts, greater engagement from the UK’s business, civil society and research sectors is critical – we need all hands on deck to forge and promote concrete proposals for aligning UK trade policy with the climate ambition our world needs. Full Article
cl Promoting a Just Transition to an Inclusive Circular Economy By feedproxy.google.com Published On :: Wed, 01 Apr 2020 11:19:03 +0000 1 April 2020 Considerations of justice and social equity are as important for the circular economy transition as they are in the contexts of low-carbon transitions and digitalization of the economy. This paper sets out the just transition approach, and its relevance in climate change and energy transition debates. Read online Download PDF Patrick Schröder Senior Research Fellow, Energy, Environment and Resources Programme @patricks_CH Google Scholar 2020-04-01-circular-economy.jpg Residents of Mount Ijen take sulphur at Ijen Crater, Banyuwangi, East Java, on 2 July 2018. Photo: Getty Images. Summary Many social and political issues have so far been neglected in planning for the circular economy transition. This paper aims to redress this by considering how ‘just transition’ and social equity may be achieved through policy and practice.The prevailing economic model is linear, in that resources are extracted, transformed into products, used, and finally discarded. In contrast, the circular economy recognizes that natural resources are finite, and aims to keep the materials in products in circulation for as long as possible: reusing, repairing, remanufacturing, sharing and recycling. While the concept of the circular economy is largely focused on developing new technologies and businesses to enable keeping materials in circulation, it also includes the notions of ‘designing out’ waste, substituting renewable materials for non-renewable ones, and restoring natural systems.The UN 2030 Agenda demonstrates that environmental, social and economic sustainability objectives cannot be separated. As the links between the environmental issues of climate change, overconsumption of resources and waste generation, and social issues of inequality and the future of work become increasingly obvious, the urgency to connect environmental with social justice is gaining in significance. The language of ‘just transition’ – a transition that ensures environmental sustainability, decent work, social inclusion and poverty eradication – has started to penetrate debates and research on sustainability policy, particularly in the contexts of climate change and low-carbon energy transition.A just transition framework for the circular economy can identify opportunities that reduce waste and stimulate product innovation, while at the same time contributing positively to sustainable human development. And a just transition is needed to reduce inequalities within and between countries, and to ensure that the commitment of the UN Sustainable Development Goals to leave no one behind is fulfilled.It is important to identify the likely impacts on employment as a result of digitalization and industrial restructuring. Combining circular economy policies with social protection measures will be important in order to ensure that the burden of efforts to promote circularity will not fall on the poor through worsening working conditions and health impacts, reduced livelihoods, or job losses. Identifying potential winners and losers through participatory ‘roadmapping’ can help shape effective cooperation mechanisms and partnerships nationally and internationally.Many low- and middle-income countries that rely heavily on ‘linear’ sectors such as mining, manufacturing of non-repairable fast-moving consumer goods, textiles and agriculture, and the export of these commodities to higher-income countries, are likely to be negatively affected by the shift to circularity. These countries will need support from the international community through targeted assistance programmes if international trade in established commodities and manufactures declines in the medium to long term. International cooperation to create effective and fair governance mechanisms, and policy coordination at regional, national and local levels will play an important role in shaping a just transition. Multilateral technical assistance programmes will need to be designed and implemented, in particular to support low- and middle-income countries.Governments, international development finance institutions and banks are among the bodies beginning to establish circular economy investment funds and programmes. Just transition principles are yet to be applied to many of these new finance mechanisms, and will need to be integrated into development finance to support the circular economy transition.New international cooperation programmes, and a global mechanism to mobilize dedicated support funds for countries in need, will be critical to successful implementation across global value chains. Transparent and accountable institutions will also be important in ensuring that just transition funds reach those affected as intended. Department/project Energy, Environment and Resources Programme Full Article
cl COP26 Diplomatic Briefing: Climate Ambition in Europe and its Potential Global Impact By feedproxy.google.com Published On :: Fri, 03 Apr 2020 14:05:01 +0000 17 February 2020 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Jacob Werksman, Principal Adviser to Directorate General for Climate Action, European CommissionImke Lübbeke, Head of EU Climate and Energy Policy, WWF European Policy Office Simon Petrie, Head of International Climate Strategy - Europe, UK Department for Business, Energy and Industrial StrategyJen Austin, Policy Director, We Mean Business CoalitionChair: Jill Duggan, Associate Fellow, Chatham House The President of the European Commission, Ursula von der Leyen, has declared that she wants Europe to become ‘the first climate-neutral continent by 2050’, and in December 2019, the Commission presented the European Green Deal in order to achieve this objective. However, even though greenhouse gas emissions from the EU have fallen by more than 20 per cent since 1990, the Union remains the third largest emitter in the world, after the United States and China.What are the opportunities and challenges for raising climate ambition in Europe? Will the EU increase its Nationally Determined Contribution and what impact might this have globally? How might Brexit affect climate action in the EU and the UK? The second event in the Chatham House COP26 Diplomatic Briefing Series will address these critical questions. Read meeting summarypdf | 118.6 KB Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Full Article
cl Why an Inclusive Circular Economy is Needed to Prepare for Future Global Crises By feedproxy.google.com Published On :: Wed, 15 Apr 2020 13:23:01 +0000 15 April 2020 Patrick Schröder Senior Research Fellow, Energy, Environment and Resources Programme @patricks_CH Google Scholar The risks associated with existing production and consumption systems have been harshly exposed amid the current global health crisis but an inclusive circular economy could ensure both short-term and long-term resilience for future challenges. 2020-04-15-Waste-Collection-Peru.jpg Lima city employees picking up garbage during lockdown measures in Peru amid the COVID-19 crisis. Photo: Getty Images. The world is currently witnessing how vulnerable existing production and consumption systems are, with the current global health crisis harshly exposing the magnitude of the risks associated with the global economy in its current form, grounded, as it is, in a linear system that uses a ‘take–make–throw away’ approach.These ‘linear risks’ associated with the existing global supply chain system are extremely high for national economies overly dependent on natural resource extraction and exports of commodities like minerals and metals. Equally vulnerable are countries with large manufacturing sectors of ready-made garments and non-repairable consumer goods for western markets. Furthermore, workers and communities working in these sectors are vulnerable to these changes as a result of disruptive technologies and reduced demand.In a recently published Chatham House research paper, ‘Promoting a Just Transition to an Inclusive Circular Economy’, we highlight why a circular economy approach presents the world with a solution to old and new global risks – from marine plastic pollution to climate change and resource scarcity.Taking the long viewSo far, action to transition to a circular economy has been slow compared to the current crisis which has mobilized rapid global action. For proponents of transitioning to a circular economy, this requires taking the long view. The pandemic has shown us that global emergencies can fast-forward processes that otherwise might take years, even decades, to play out or reverse achievements which have taken years to accomplish.In this vein, there are three striking points of convergence between the COVID-19 pandemic and the need to transition to an inclusive circular economy.Firstly, the current crisis is a stark reminder that the circular economy is not only necessary to ensure long-term resource security but also short-term supplies of important materials. In many cities across the US, the UK and Europe, councils have suspended recycling to focus on essential waste collection services. The UK Recycling Association, for example, has warned about carboard shortages due to disrupted recycling operations with possible shortages for food and medicine packaging on the horizon.Similarly, in China, most recycling sites were shut during the country’s lockdown presenting implications for global recycling markets with additional concerns that there will be a fibre shortage across Europe and possibly around the world.Furthermore, worldwide COVID-19 lockdowns are resulting in a resurgence in the use of single-use packaging creating a new wave of plastic waste especially from food deliveries – already seen in China – with illegal waste fly-tipping dramatically increasing in the UK since the lockdown.In this vein, concerns over the current global health crisis is reversing previous positive trends where many cities had established recycling schemes and companies and consumers had switched to reusable alternatives.Secondly, the need to improve the working conditions of the people working in the informal circular economy, such as waste pickers and recyclers, is imperative. Many waste materials and recyclables that are being handled and collected may be contaminated as a result of being mixed with medical waste.Now, more than ever, key workers in waste management, collection and recycling require personal protective equipment and social protection to ensure their safety as well as the continuation of essential waste collection so as not to increase the potential for new risks associated with additional infectious diseases.In India, almost 450 million workers including construction workers, street vendors and landless agricultural labourers, work in the informal sector. In the current climate, the poorest who are unable to work pose a great risk to the Indian economy which could find itself having to shut down.Moreover, many informal workers live in make-shift settlements areas such as Asia’s largest slum, Dharavi in Mumbai, where health authorities are now facing serious challenges to contain the spread of the disease. Lack of access to handwashing and sanitation facilities, however, further increase these risks but circular, decentralized solutions could make important contributions to sustainable sanitation, health and improved community resilience.Thirdly, it is anticipated that in the long term several global supply chains will be radically changed as a result of transformed demand patterns and the increase in circular practices such as urban mining for the recovery and recycling of metals or the reuse and recycling of textile fibres and localized additive manufacturing (e.g. 3D printing).Many of these supply chains and trade flows have now been already severely disrupted due to the COVID-19 pandemic. For example, the global garment industry has been particularly hard-hit due to the closure of outlets amid falling demand for apparel.It is important to note, workers at the bottom of these garment supply chains are among the most vulnerable and most affected by the crisis as global fashion brands, for example, have been cancelling orders – in the order of $6 billion in the case of Bangladesh alone. Only after intense negotiations are some brands assuming financial responsibility in the form of compensation wage funds to help suppliers in Myanmar, Cambodia and Bangladesh to pay workers during the ongoing crisis.In addition, the current pandemic is damaging demand for raw materials thereby affecting mining countries. Demand for Africa’s commodities in China, for example, has declined significantly, with the impact on African economies expected to be serious, with 15 per cent of the world’s copper and 20 per cent of the world’s zinc mines currently going offline. A further threat is expected to come from falling commodity prices as a result of the curtailment of manufacturing activity in China particularly for crude oil, copper, iron ore and other industrial commodities which, in these cases, will have direct impacts on the Australian and Canadian mining sectors.This is all being compounded by an associated decline in consumer demand worldwide. For example, many South African mining companies – leading producers of metals and minerals – have started closing their mining operations following the government’s announcement of a lockdown in order to prevent the transmission of the virus among miners who often work in confined spaces and in close proximity with one another. As workers are laid off due to COVID-19, there are indications that the mining industry will see fast-tracking towards automated mining operations. All of these linear risks that have been exposed through the COVID-19 pandemic reinforce the need for a just transition to a circular economy. But while the reduction in the consumption of resources is necessary to achieve sustainability, the social impacts on low- and middle- income countries and their workers requires international support mechanisms.In addition, the current situation also highlights the need to find a new approach to globalized retail chains and a balance between local and global trade based on international cooperation across global value chains rather than implementation of trade protectionist measures.In this vein, all of the recovery plans from the global COVID-19 pandemic need to be aligned with the principles of an inclusive circular economy in order to ensure both short-term and long-term resilience and preparedness for future challenges and disruptions. Full Article
cl COP26 Diplomatic Briefing Series: Climate Change and National Security By feedproxy.google.com Published On :: Tue, 21 Apr 2020 13:25:01 +0000 Research Event 25 March 2020 - 9:00am to 10:30am Event participants Lieutenant General Richard Nugee, Departmental Lead for Climate Change and Sustainability in the UK Ministry of DefenceRear Admiral Neil Morisetti, Vice Dean (Public Policy) Engineering Sciences at the University College London and Associate Fellow at Chatham HouseDr. Patricia Lewis, Research Director for Conflict, Science and Technology, and Director of the International Security Programme at Chatham HouseProfessor Yacob Mulugetta, Professor of Energy and Development Policy at the University College LondonChair: Glada Lahn, Senior Research Fellow, Chatham House Extreme weather, rising sea levels and a melting Arctic - the effects of climate change are posing an increasingly large threat to national security worldwide. Although the issue has gained traction within the international community in recent years, including within the UN Security Council, it is urgent that governments act more decisively to mitigate and respond to the threat, not least given that climate change is happening faster and in a more powerful way than originally anticipated. The third event in the Chatham House COP26 Diplomatic Briefing Series – 'Climate Change and National Security' - will analyze how climate change acts as a threat multiplier, fuelling instability and endangering economic, social and political systems across the globe. The briefing will also provide recommendations of what governments and other stakeholders should do to develop effective responses. Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
cl Closing the Global Access Gap in Palliative Care and Pain Relief: A Top Priority in Achieving Universal Health Coverage By feedproxy.google.com Published On :: Wed, 26 Jun 2019 13:50:01 +0000 Invitation Only Research Event 17 July 2019 - 12:30pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Tedros Adhanom Ghebreyesus, Director-General, World Health Organization The Lancet Commission on Palliative Care and Pain Relief estimated that in 2015, 61 million people experienced serious health-related suffering (SHS) that could have been ameliorated by palliative care. A large proportion of this burden – more than 80 per cent – fell on low- and middle-income countries (LMICs) despite an essential package of palliative care and pain relief services being cost-effective and affordable. As the director general of the World Health Organization (WHO) argues, there cannot be UHC without palliative care and thus, closing this coverage gap should be a top priority for the global UHC movement.The Centre on Global Health Security at Chatham House, building on the momentum of the Lancet Commission, is hosting a roundtable focused on the global unmet need for palliative care and effective pain relief. The primary purpose of this roundtable is to convene leading experts, palliative care service users and advocates with key figures from the UHC movement and global health to highlight the importance of prioritizing this vital part of the continuum of care in UHC reform processes. The roundtable will serve as a scholarly discourse in translating the recommendations of the Lancet Commission into concrete actions, focusing on the political and economic dimensions. Department/project Global Health Programme, Universal Health Coverage Policy Forum Alexandra Squires McCarthy Programme Coordinator, Global Health Programme +44 (0)207 314 2789 Email Full Article
cl SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement. Full Article
cl Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation. Full Article
cl A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women. Full Article
cl Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains. Full Article