and France, the UK and Europe: New Partnerships and Common Challenges By feedproxy.google.com Published On :: Fri, 28 Feb 2020 00:00:00 +0000 Full Article
and 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
and Undercurrents: Episode 49 - EU Responses to COVID-19, and the Politics of Celebrity By feedproxy.google.com Published On :: Thu, 16 Apr 2020 00:00:00 +0100 Full Article
and Undercurrents: Episode 50 - The Coronavirus Communications Crisis, and Justice in Myanmar By feedproxy.google.com Published On :: Thu, 23 Apr 2020 00:00:00 +0100 Full Article
and 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
and Undercurrents: Episode 51 - Preparing for Pandemics, and Gandhi's Chatham House Speech By feedproxy.google.com Published On :: Thu, 30 Apr 2020 00:00:00 +0100 Full Article
and Undercurrents: Episode 52 - Defining Pandemics, and Mikheil Saakashvili's Ukrainian Comeback By feedproxy.google.com Published On :: Thu, 07 May 2020 00:00:00 +0100 Full Article
and Correction: Diversity in the Protein N-Glycosylation Pathways Within the Campylobacter Genus. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Full Article
and Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal. In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested. Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation. Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient. Full Article
and 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
and Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation. Full Article
and A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
and 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
and X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
and Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB. Full Article
and Tracking isotopically labeled oxidants using boronate-based redox probes [Methods and Resources] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products. Full Article
and Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases. Full Article
and A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning. Full Article
and 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
and 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
and 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
and COP26 Diplomatic Briefing Series: Outcomes of COP25 and What It Means for 2020 By feedproxy.google.com Published On :: Thu, 05 Dec 2019 16:15:01 +0000 Invitation Only Research Event 22 January 2020 - 4:30pm to 6:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Meeting summary pdf | 98.03 KB Event participants HE Raffaele Trombetta, Italian Ambassador to the UK, Co-Host, COP 26Archie Young, UK Lead Climate Negotiator, Cabinet Office Peter Betts, Associate Fellow, Energy, Environment and Resources Department, Chatham HouseChair: Professor Tim Benton, Research Director, Energy, Environment and Resources, Chatham House The UK will host the 26th Conference of the Parties (COP26) in November 2020 in Glasgow. In the run up, Chatham House is organizing a monthly briefing series targeted to:The diplomatic service based in London, in particular, staff of the London embassies who are reporting on climate change issues.Senior UK government civil servants, officials and politicians engaged in climate change.Academics, experts, business representatives and NGOs.The first briefing in the series focuses on the results from COP25 held in Madrid in December 2019 and what this means for 2020.This briefings series offer an opportunity to discuss, in an informal setting, the most pressing and complex climate issues of the day with UK and international government officials and experts. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Johanna Tilkanen Project Manager, Energy, Environment and Resources Department Email Full Article
and Subsidies and Sustainable Agriculture: Mapping the Policy Landscape By feedproxy.google.com Published On :: Tue, 10 Dec 2019 18:36:21 +0000 11 December 2019 Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies. Download PDF Christophe Bellmann Associate Fellow, Hoffmann Centre for Sustainable Resource Economy, Chatham House 2019-12-06-Wheat-Field-China.jpg Aerial view of a wheat field on 24 May 2019 in Linyi, Shandong Province of China. Photo: Getty Images. SummaryAgricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals. Full Article
and Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? By feedproxy.google.com Published On :: Mon, 06 Jan 2020 13:55:01 +0000 Invitation Only Research Event 23 January 2020 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Richard King, Senior Research Fellow, Energy, Environment and Resources Department, Chatham HouseChair: Duncan Brack, Associate Fellow, Energy, Environment and Resources Department, Chatham House In the context of the feasibility of reducing greenhouse gas emissions to net zero, policymakers are beginning to pay more attention to options for removing carbon dioxide from the atmosphere. A wide range of potential carbon dioxide removal (CDR) options are currently being discussed and modelled though the most prominent among them are bioenergy with carbon capture and storage (BECCS) and afforestation and reforestation.There are many reasons to question the reliance on BECCS assumed in the models including the carbon balances achievable, its substantial needs for land, water and other inputs and technically and economically viable carbon capture and storage technologies.This meeting will examine the potentials and challenges of BECCS in the context of other CDR and emissions abatement options. It will discuss the requisite policy and regulatory frameworks to minimize sustainability and socio-political risks of CDR approaches while also avoiding overshooting climate goals.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, Sustainable Transitions Series Chloé Prendleloup Email Full Article
and 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
and Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? By feedproxy.google.com Published On :: Wed, 29 Jan 2020 11:51:45 +0000 29 January 2020 Policymakers are in danger of sleepwalking into ineffective carbon dioxide removal solutions in the quest to tackle climate change. This paper warns against overreliance on bioenergy with carbon capture and storage (BECCS). Read online Download PDF Duncan Brack Associate Fellow, Energy, Environment and Resources Programme @DuncanBrack Google Scholar Richard King Senior Research Fellow, Energy, Environment and Resources Programme LinkedIn Reaching Net Zero: Does BECCS Work? Policymakers can be influenced by ineffective carbon dioxide removal solutions in the quest to tackle climate change. This animation explores the risks of using bioenergy with carbon capture and storage (BECCS). SummaryCurrent climate efforts are not progressing quickly enough to prevent the world from overshooting the global emissions targets set in the Paris Agreement; accordingly, attention is turning increasingly to options for removing carbon dioxide from the atmosphere – ‘carbon dioxide removal’ (CDR). Alongside afforestation and reforestation, the main option under discussion is bioenergy with carbon capture and storage (BECCS): processes through which the carbon emissions from burning biomass for energy are captured before release into the atmosphere and stored in underground reservoirs.This pre-eminent status is not, however, based on a comprehensive analysis of the feasibility and impacts of BECCS. In reality, BECCS has many drawbacks.Models generally assume that biomass for energy is inherently carbon-neutral (and thus that BECCS, by capturing and storing the emissions from combustion, is carbon-negative), but in reality this is not a valid assumption.On top of this, the deployment of BECCS at the scales assumed in most models would consume land on a scale comparable to half that currently taken up by global cropland, entailing massive land-use change, potentially endangering food security and biodiversity. There is also significant doubt about the likely energy output of BECCS solutions.BECCS may still have some role to play in strategies for CDR, depending mainly on the feedstock used; but it should be evaluated on the same basis as other CDR options, such as nature-based solutions or direct air carbon capture and storage (DACCS). Analysis should take full account of carbon balances over time, the requirements of each CDR option in terms of demand for land, water and other inputs, and the consequences of that demand.There is an urgent need for policymakers to engage with these debates. The danger at the moment is that policymakers are ‘sleepwalking towards BECCS’ simply because most models incorporate it – or, almost as bad, it may be that they are simply ignoring the need for any meaningful action on CDR as a whole. Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Full Article
and China's 2020: Economic Transition, Sustainability and the Coronavirus By feedproxy.google.com Published On :: Tue, 04 Feb 2020 21:15:01 +0000 Corporate Members Event 10 March 2020 - 12:15pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham HouseDavid Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, CitiJinny Yan, Managing Director and Chief China Economist, ICBC StandardChair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House Read all our analysis on the Coronavirus ResponseThe coronavirus outbreak comes at a difficult time for China’s ruling party. A tumultuous 2019 saw the country fighting an economic slowdown coupled with an increasingly hostile international environment. As authorities take assertive steps to contain the virus, the emergency has - at least temporarily - disrupted global trade and supply chains, depressed asset prices and forced multinational businesses to make consequential decisions with limited information. Against this backdrop, panellists reflect on the country’s nascent economic transition from 2020 onward. What has been China’s progress towards a sustainable innovation-led economy so far? To what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility? And how are foreign investors responding to these developments in China? Members Events Team Email Full Article
and Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’ By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:00:22 +0000 4 March 2020 , Volume 96, Number 2 Emma Tomalin Read Online In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this. Full Article
and 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
and Webinar: OPEC, Falling Oil Prices and COVID-19 By feedproxy.google.com Published On :: Tue, 31 Mar 2020 12:00:01 +0000 Corporate Members Event Webinar 7 April 2020 - 1:00pm to 2:00pm Online Event participants Julian Lee, Oil Strategist, Bloomberg LP LondonDr John Sfakianakis, Associate Fellow, Middle East and North Africa Programme, Chatham House; Chief Economist and Head of Research, Gulf Research CenterProfessor Paul Stevens, Distinguished Fellow, Energy, Environment and Resources Programme, Chatham HouseEmily Stromquist, Director, Castlereagh AssociatesChair: Dr Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House In early March, global oil prices fell sharply, hitting lows of under $30 a barrel. Two factors explain this collapse: firstly the decrease in global demand for oil as a result of the COVID-19 pandemic and, secondly, the breakdown in OPEC-Russian relations and the subsequent Saudi-Russian price war which has seen both countries move to flood the market with cheap oil. Against this backdrop, the panellists will reflect on the challenges currently facing OPEC as well as the oil industry as a whole. How are OPEC countries affected by the ever-evolving Covid-19 pandemic? What are the underlying causes behind the Saudi-Russian price war? Is the conflict likely to be resolved soon? And what are the implications of these challenges for the oil industry?This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members and giving circles.Not a corporate member? Find out more. Full Article
and 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
and 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
and Episode 25: Oz: The Great and Powerful By feedproxy.google.com Published On :: Fri, 22 Mar 2013 07:56:00 +0000 Review of Oz: The Great and PowerfulMovie Homework: Network/CloserWhat We Watched: Dredd, Undefeated, Sassy Pants, Game of Thrones, Gummo, This is 40Download the episode here. (right click to save)Next Week's Main Review: Springbreakers Full Article
and 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
and Acting Early, Saving Lives: Prevention and Promotion By feedproxy.google.com Published On :: Fri, 05 Jul 2019 09:25:01 +0000 Invitation Only Research Event 9 September 2019 - 9:00am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Universal Health Coverage (UHC) is driving the global health agenda and is embedded in the Sustainable Development Goals (SDGs). According to the World Health Organization, universal health coverage means that ‘all people and communities can use the promotive, preventive, curative, rehabilitative and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship’.Despite this comprehensive starting point, it has been observed that UHC efforts to date have focused more on provision of treatment services than promotion and prevention strategies. Not only is this a missed opportunity from a financing perspective (public health interventions often offer better value for money than curative services), without robust health promotion and prevention efforts, UHC may not fulfil its potential towards reducing health inequity.Primary health care (PHC) is a whole-of-society approach to health that aims to ensure the highest possible level of health and well-being and equitable distribution. PHC has been described as the cornerstone of UHC. As set out in the recent World Health Assembly report by the Director-General Primary health care towards universal health coverage: ‘..with its emphasis on promotion and prevention, addressing determinants and a people-centred approach, primary health care has proven to be a highly effective and efficient way to address the main causes of, and risk factors for, poor health...UHC and the health-related Sustainable Development Goals can only be sustainably achieved with a stronger emphasis on primary health care.’The 2018 Declaration of Astana has sparked a renewed commitment to PHC. For NCD and mental health advocates there is an opportunity to now build on the foundations of PHC, to deliver more equitable, people-centred and sustainable UHC.This event sets out why promotive and preventive health services for NCDs and mental health disorders are such an important part of UHC. It will focus on two key dimensions: the role of health promotion and preventative services within UHC in delivering health for all, and sustainable financing through innovative fiscal policy.As one of the first high level events looking exclusively at prevention in the context of UHC, it will serve as an important reference for those going forward into the High Level Meeting on UHC as well as a unique opportunity for participants from a range of perspectives to discuss the barriers to progress.The event is convened by Chatham House and the UK Working Group on NCDs – a coalition of over 20 UK-based NGOs with an interest in the inclusion of NCDs as an international development priority.ObjectivesTo understand how NCD prevention and mental health promotion are a key aspect of universal health coverage.To explore the case for investment in NCD prevention and mental health promotion, for both governments and donors/global health actors.To share experiences of financing and delivering prevention and promotion services, and to reflect on the potential of PHC to support NCD and mental health goals.Attendance at this event is by invitation only. Department/project Global Health Programme Alexandra Squires McCarthy Programme Coordinator, Global Health Programme +44 (0)207 314 2789 Email Full Article
and Towards an Outcome-Oriented Food and Agricultural Aid and Development System By feedproxy.google.com Published On :: Mon, 29 Jul 2019 12:35:02 +0000 Invitation Only Research Event 21 May 2019 - 9:00am to 24 May 2019 - 5:00pm The Rockefeller Foundation, Bellagio Center, Italy Chatham House, in partnership with the European Centre for Development Policy Management (ECDPM), convened leading experts and key stakeholders to consider how the system of global institutions that provide aid and finance, global public goods and technical assistance to low-income countries can be better aligned to support the realization of SDG 2 in the context of those countries’ own efforts with a focus on SDGs 2.3 and 2.4.This meeting aimed to contribute to an outcome-oriented food and agricultural aid development system; create greater understanding of the comparative advantages of key institutions, areas of duplication or inefficiency and gaps; identify topics for further research and analysis; and identify key near-term political moments to focus the community and catalyze steps towards change. Event attributes Chatham House Rule Department/project Global Health Programme Alexandra Squires McCarthy Programme Coordinator, Global Health Programme +44 (0)207 314 2789 Email Full Article
and Reviewing Antimicrobial Resistance: Where Are We Now and What Needs to Be Done? By feedproxy.google.com Published On :: Fri, 30 Aug 2019 14:55:01 +0000 Research Event 8 October 2019 - 10:30am to 12:00pm RSA House, 8 John Adam Street, London, WC2N 6EZ Event participants Tim Jinks, Head of Drug-Resistant Infections Programme, WellcomeJim O’Neill, Chair, Review on Antimicrobial Resistance; Chair, Chatham HouseHaileyesus Getahun, Director of Global Coordination and Partnership on Antimicrobial Resistance, World Health Organization Juan Lubroth, Chief Veterinary Officer, Food and Agriculture Organization (Videolink)Jyoti Joshi, Head, South Asia, Center for Disease Dynamics, Economics & PolicyEstelle Mbadiwe, Coordinator-Nigeria, Global Antibiotic Resistance PartnershipCharles Clift, Senior Consulting Fellow, Chatham House; Report Author The Review on Antimicrobial Resistance, chaired by Jim O’Neill, was commissioned by former UK prime minister, David Cameron, in July 2014. Supported by the UK government and the Wellcome Trust, the final report of the review was published in May 2016 and has had a global impact in terms of motivating political leaders and decision-makers to take more seriously the threat posed by antimicrobial resistance.Yet there is now a perception that the political momentum to address the issue is waning and needs to be reinvigorated.In a further report produced by Chatham House, the progress of the recommendations of the review is assessed and the key ways to move forward are identified.Panellists at this event, where highlights of the report are presented, provide their assessment of the progress so far and discuss priorities for future action.The report was funded by Wellcome. Department/project Global Health Programme, Antimicrobial Resistance Alexandra Squires McCarthy Programme Coordinator, Global Health Programme +44 (0)207 314 2789 Email Full Article
and England and Australia Are Failing in Their Commitments to Refugee Health By feedproxy.google.com Published On :: Mon, 09 Sep 2019 12:50:31 +0000 10 September 2019 Alexandra Squires McCarthy Former Programme Coordinator, Global Health Programme Robert Verrecchia Both boast of universal health care but are neglecting the most vulnerable. 2019-09-09-Manus.jpg A room where refugees were once housed on Manus Island, Papua New Guinea. Photo: Getty Images. England and Australia are considered standard-bearers of universal access to health services, with the former’s National Health Service (NHS) recognized as a global brand and the latter’s Medicare seen as a leader in the Asia-Pacific region. However, through the exclusion of migrant and refugee groups, each is failing to deliver true universality in their health services. These exclusions breach both their own national policies and of international commitments they have made.While the marginalization of mobile populations is not a new phenomenon, in recent years there has been a global increase in anti-migrant rhetoric, and such health care exclusions reflect a global trend in which undocumented migrants, refugees and asylum seekers are denied rights.They are also increasingly excluded in the interpretation of phrases such as ‘leave no one behind’ and ‘universal health coverage’, commonly used by UN bodies and member states, despite explicit language in UN declarations that commits countries to include mobile groups.Giving all people – including undocumented migrants and asylum seekers – access to health care is essential not just for the health of the migrant groups but also the public health of the populations that host them. In a world with almost one billion people on the move, failing to take account of such mobility leaves services ill-equipped and will result in missed early and preventative treatment, an increased burden on services and a susceptibility to the spread of infectious disease.EnglandWhile in the three other nations of the UK, the health services are accountable to the devolved government, the central UK government is responsible for the NHS in England, where there are considerably greater restrictions in access.Undocumented migrants and refused asylum seekers are entitled to access all health care services if doctors deem it clinically urgent or immediately necessary to provide it. However, the Home Office’s ‘hostile environment’ policies towards undocumented migrants, implemented aggressively and without training for clinical staff, are leading to the inappropriate denial of urgent and clearly necessary care.One example is the case of Elfreda Spencer, whose treatment for myeloma was delayed for one year, allowing the disease to progress, resulting in her death.In England, these policies, which closely link health care and immigration enforcement, are also deterring people from seeking health care they are entitled to. For example, medical bills received by migrants contain threats to inform immigration enforcement of their details if balances are not cleared in a certain timeframe. Of particular concern, the NGO Maternity Action has demonstrated that such a link to immigration officials results in the deterrence of pregnant women from seeking care during their pregnancy.Almost all leading medical organizations in the United Kingdom have raised concerns about these policies, highlighting the negative impact on public health and the lack of financial justification for their implementation. Many have highlighted that undocument migrants use just and estimated 0.3% of the NHS budget and have pointed to international evidence that suggests that restrictive health care policies may cost the system more.AustraliaIn Australia, all people who seek refuge by boat are held, and have their cases processed offshore in Papua New Guinea (PNG) and Nauru, at a cost of almost A$5 billion between 2013 and 2017. Through this international agreement, in place since 2013, Australia has committed to arrange and pay for the care for the refugees, including health services ‘to a standard of care broadly comparable to that available to the general Australian community under the public health system’.However, the standard of care made available to the refugees is far from comparable to that available to the general population in Australia. Findings against the current care provision contractor on PNG, Pacific International Hospital, which took over in the last year, are particularly damning.For instance, an Australian coroner investigating the 2014 death from a treatable leg infection of an asylum seeker held in PNG concluded that the contractor lacked ‘necessary clinical skills’, and provided ‘inadequate’ care. The coroner’s report, issued in 2018, found the company had also, in other cases, denied care, withheld pain relief, distributed expired medication and had generally poor standards of care, with broken or missing equipment and medication, and services often closed when they were supposed to be open.This has also been reiterated by the Royal Australasian College of Physicians, which has appealed to the Australian government to end its policies of offshore processing immediately, due to health implications for asylum seekers. This echoes concerns of the medical community around the government’s ongoing attempts to repeal the ‘Medivac’ legislation, which enables emergency medical evacuation from PNG and Nauru.Bad policyBoth governments have signed up to UN Sustainable Development Goals commitment to ‘safe and orderly migration’, an essential component of which is access to health care. The vision for this was laid out in a global action plan on promoting the health of refugees and migrants, agreed by member states at the 2019 World Health Assembly.However, rather than allow national policies to be informed by such international plans and the evidence put forward by leading health professionals and medical organizations, the unsubstantiated framing of migrants as a security risk and economic burden has curtailed migrant and refugee access to health care.The inclusion of migrants and refugees within universal access to health services is not merely a matter of human rights. Despite being framed as a financial burden, ensuring access for all people may reduce costs on health services through prevention of costly later-stage medical complications, increased transmission of infections and inefficient administrative costs of determining eligibility.Thailand provides an example of a middle-income country that recognized this, successfully including all migrants and refugees in its health reforms in 2002. Alongside entitling all residents to join the universal coverage scheme, the country also ensured that services were ‘migrant friendly’, including through the provision of translators. A key justification for the approach was the economic benefit of ensuring a healthy migrant population, including the undocumented population.The denial of quality health services to refugees and undocumented migrants is a poor policy choice. Governments may find it tempting to gain political capital through excluding these groups, but providing adequate access to health services is part of both governments’ commitments made at the national and international levels. Not only are inclusive health services feasible to implement and good for the health of migrants and refugees, in the long term, they are safer for public health and may save money. Full Article
and PANDORA By feedproxy.google.com Published On :: Thu, 19 Dec 2019 15:05:20 +0000 The PANDORA consortium aims to develop and strengthen effective outbreak response capacities across all geographical regions in sub-Saharan Africa, in partnership with national governments and other international stakeholders. The Pan-African Network For Rapid Research, Response, Relief and Preparedness for Infectious Disease Epidemics is a novel multidisciplinary ‘One Health’ initiative consisting of 13 African institutions and 9 European institutions, including Chatham House.The Centre leads on the consortium’s efforts to engage policy makers, global public health bodies and communities, focusing on the ethical, administrative, regulatory and operational obstacles during outbreaks. Full Article
and Strengthening National Accountability and Preparedness for Global Health Security (SNAP-GHS) By feedproxy.google.com Published On :: Thu, 19 Dec 2019 15:43:55 +0000 The project aims to identify the enablers and barriers to enhance data use by National Public Health Institutes (NPHIs), producing outputs that will facilitate strengthening of the role of NPHIs in monitoring potential public health threats, and in shaping and informing domestic policies on health security and preparedness. Global health security is underpinned by the actions taken at a national level to ensure capacities exist to sufficiently prepare for and respond to acute threats and crises. In many contexts, National Public Health Institutes (NPHIs) were first established because of, and in response to, specific public health challenges typically related to infectious diseases.The Strengthening National Accountability and Preparedness for Global Health Security (SNAP-GHS) project evolved from a series of roundtables and discussions hosted by the Centre on Global Health Security at Chatham House, in collaboration with the Graduate Institute of Geneva.The outcome of the project is a SNAP-GHS Toolkit to support NPHIs in better diagnosing and understanding the challenges to data use within their own institutes, as well as in relation to external stakeholders and agencies. The toolkit is intended to be used for further circulation and dissemination by the International Association of National Public Health Institutes (IANPHI).The project is led by the Centre on Global Health Security at Chatham House in collaboration with the Ethiopian Public Health Institute, the Nigeria Centre for Disease Control, and the National Institute for Health in Pakistan. Full Article
and Coronavirus: Public Health Emergency or Pandemic – Does Timing Matter? By feedproxy.google.com Published On :: Fri, 01 May 2020 14:48:43 +0000 1 May 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks The World Health Organization (WHO) has been criticized for delaying its announcements of a public health emergency and a pandemic for COVID-19. But could earlier action have influenced the course of events? 2020-05-01-Tedros-WHO-COVID WHO director-general Dr Tedros Adhanom Ghebreyesus at the COVID-19 press briefing on March 11, 2020, the day the coronavirus outbreak was classed as a pandemic. Photo by FABRICE COFFRINI/AFP via Getty Images. The World Health Organization (WHO) declared the spread of COVID-19 to be a Public Health Emergency of International Concern (PHEIC) on January 30 this year and then characterized it as a pandemic on March 11.Declaring a PHEIC is the highest level of alert that WHO is obliged to declare, and is meant to send a powerful signal to countries of the need for urgent action to combat the spread of the disease, mobilize resources to help low- and middle-income countries in this effort and fund research and development on needed treatments, vaccines and diagnostics. It also obligates countries to share information with WHO.Once the PHEIC was declared, the virus continued to spread globally, and WHO began to be asked why it had not yet declared the disease a pandemic. But there is no widely accepted definition of a pandemic, generally it is just considered an epidemic which affects many countries globally.Potentially more deadlyThe term has hitherto been applied almost exclusively to new forms of flu, such as H1N1 in 2009 or Spanish flu in 1918, where the lack of population immunity and absence of a vaccine or effective treatments makes the outbreak potentially much more deadly than seasonal flu (which, although global, is not considered a pandemic).For COVID-19, WHO seemed reluctant to declare a pandemic despite the evidence of global spread. Partly this was because of its influenza origins — WHO’s emergency programme executive director said on March 9 that ‘if this was influenza, we would have called a pandemic ages ago’.He also expressed concern that the word traditionally meant moving — once there was widespread transmission — from trying to contain the disease by testing, isolating the sick and tracing and quarantining their contacts, to a mitigation approach, implying ‘the disease will spread uncontrolled’.WHO’s worry was that the world’s reaction to the word pandemic might be there was now nothing to be done to stop its spread, and so countries would effectively give up trying. WHO wanted to send the message that, unlike flu, it could still be pushed back and the spread slowed down.In announcing the pandemic two days later, WHO’s director-general Dr Tedros Adhanom Ghebreyesus reemphasised this point: ‘We cannot say this loudly enough, or clearly enough, or often enough: all countries can still change the course of this pandemic’ and that WHO was deeply concerned ‘by the alarming levels of inaction’.The evidence suggests that the correct message did in fact get through. On March 13, US president Donald Trump declared a national emergency, referring in passing to WHO’s announcement. On March 12, the UK launched its own strategy to combat the disease. And in the week following WHO’s announcements, at least 16 other countries announced lockdowns of varying rigour including Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Netherlands, Norway, Poland, Portugal, Serbia, Spain and Switzerland. Italy and Greece had both already instituted lockdowns prior to the WHO pandemic announcement.It is not possible to say for sure that WHO’s announcement precipitated these measures because, by then, the evidence of the rapid spread was all around for governments to see. It may be that Italy’s dramatic nationwide lockdown on March 9 reverberated around European capitals and elsewhere.But it is difficult to believe the announcement did not have an effect in stimulating government actions, as was intended by Dr Tedros. Considering the speed with which the virus was spreading from late February, might an earlier pandemic announcement by WHO have stimulated earlier aggressive actions by governments?Declaring a global health emergency — when appropriate — is a key part of WHO’s role in administering the International Health Regulations (IHR). Significantly, negotiations on revisions to the IHR, which had been ongoing in a desultory fashion in WHO since 1995, were accelerated by the experience of the first serious coronavirus outbreak — SARS — in 2002-2003, leading to their final agreement in 2005.Under the IHR, WHO’s director-general decides whether to declare an emergency based on a set of criteria and on the advice of an emergency committee. IHR defines an emergency as an ‘extraordinary event that constitutes a public health risk through the international spread of disease and potentially requires a coordinated international response’.In the case of COVID-19, the committee first met on January 22-23 but were unable to reach consensus on a declaration. Following the director-general’s trip to meet President Xi Jinping in Beijing, the committee reconvened on January 30 and this time advised declaring a PHEIC.But admittedly, public recognition of what a PHEIC means is extremely low. Only six have ever been declared, with the first being the H1N1 flu outbreak which fizzled out quickly, despite possibly causing 280,000 deaths globally. During the H1N1 outbreak, WHO declared a PHEIC in April 2009 and then a pandemic in June, only to rescind both in August as the outbreak was judged to have transitioned to behave like a seasonal flu.WHO was criticized afterwards for prematurely declaring a PHEIC and overreacting. This then may have impacted the delay in declaring the Ebola outbreak in West Africa as a PHEIC in 2014, long after it became a major crisis. WHO’s former legal counsel has suggested the PHEIC — and other aspects of the IHR framework — may not be effective in stimulating appropriate actions by governments and needs to be reconsidered.When the time is right to evaluate lessons about the response, it might be appropriate to consider the relative effectiveness of the PHEIC and pandemic announcements and their optimal timing in stimulating appropriate action by governments. The effectiveness of lockdowns in reducing the overall death toll also needs investigation. Full Article
and 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
and 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
and Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD. Full Article
and Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction. Full Article
and The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning. Full Article
and Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: connections with cardiovascular diseases [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis. Full Article
and Lipid rafts in glial cells: role in neuroinflammation and pain processing [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions. Full Article
and Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases. Full Article
and Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy. Full Article