ag The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications. Full Article
ag Rigid continuation paths I. Quasilinear average complexity for solving polynomial systems By www.ams.org Published On :: Tue, 10 Mar 2020 10:59 EDT Pierre Lairez J. Amer. Math. Soc. 33 (2019), 487-526. Abstract, references and article information Full Article
ag PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life By feedproxy.google.com Published On :: 2012-08-01 M. WangAug 1, 2012; 11:492-500Technological Innovation and Resources Full Article
ag A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking By feedproxy.google.com Published On :: 2006-04-01 Christian TagwerkerApr 1, 2006; 5:737-748Research Full Article
ag The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra By feedproxy.google.com Published On :: 2007-09-01 Ignat V. ShilovSep 1, 2007; 6:1638-1655Technology Full Article
ag The Human Plasma Proteome: History, Character, and Diagnostic Prospects By feedproxy.google.com Published On :: 2002-11-01 N. Leigh AndersonNov 1, 2002; 1:845-867Reviews/Perspectives Full Article
ag Phosphate-binding Tag, a New Tool to Visualize Phosphorylated Proteins By feedproxy.google.com Published On :: 2006-04-01 Eiji KinoshitaApr 1, 2006; 5:749-757Technology Full Article
ag Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents By feedproxy.google.com Published On :: 2004-12-01 Philip L. RossDec 1, 2004; 3:1154-1169Research Full Article
ag {gamma}-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion. Full Article
ag NF-{kappa}B mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled. Full Article
ag Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article
ag EU Security Ambitions Are Hostage to the Brexit Process By feedproxy.google.com Published On :: Fri, 21 Jun 2019 11:46:55 +0000 25 June 2019 Professor Richard G Whitman Associate Fellow, Europe Programme @RGWhitman Google Scholar The EU faces a fundamental contradiction in its goals to become more strategically autonomous in defence matters. 2019-06-20-Eurocorps.jpg Soldiers of a Eurocorps detachment raise the EU flag at the European Parliament in Strasbourg. Photo: Getty Images. Three years ago, as the UK was holding its referendum on Brexit, the EU was rolling out its Global Strategy for a more cohesive and effective security and defence policy. Since then, EU member states have set impressive goals and, as significantly, taken important practical steps to make an EU defence capability a tangible proposition, despite differing collective defence commitments, traditions of neutrality among some member states and very different strategic cultures.All of these developments have taken place with the UK as reluctant observer. The UK has been traditionally hostile to a deepening of defence collaboration within the EU (and consistent of the view that Europe’s military security was best provided through NATO). But the Brexit referendum vote has placed the UK as a bystander as EU security and defence initiatives have been pursued which have overridden the past red lines of British governments.There is, however, a Brexit-related paradox in all these developments.A central goal of the security and defence-related aspects of the EU Global Strategy is for the EU to have the capacity to act independently of the United States and, through indigenous defence industries, the ability to produce the means to make that possible.With the UK outside the EU, and its opposition absent, it is easier to create a political consensus to push for more defence integration. But without the UK there are diminished collective defence capabilities which would make European strategic autonomy much harder to achieve. The May government has been an enthusiast for preserving close security and defence cooperation with the EU. The Withdrawal Agreement and the Political Declaration both seek to provide for a close EU–UK relationship post-Brexit.However, the Article 50 negotiations have made clear that the EU’s institutions are hostile to special treatment for the UK beyond that normally accorded to a third country. Disagreements over the terms of the UK’s continuing participation in the Gailleo dual-use satellite system, which has a significant security and defence utility, have signalled that there is a strong lobby in Brussels and some national capitals seeking to significantly circumscribe collaboration with Britain.The scale and capabilities of the UK’s military, its defence expenditure (notably on defence research and development) and its defence industrial base make any British decoupling from the EU’s security and defence a major issue. Disconnecting the UK from EU developments entirely would be a costly political choice for both sides.And excluding the UK from new initiatives in defence R&D and new defence procurement arrangements would be suboptimal in delivering a stronger European defence, technological and industrial base. Duplicating existing UK capabilities, especially strategic enablers such as strategic airlift, target acquisition and intelligence, surveillance and reconnaissance capabilities, would be an unnecessary squandering of already hard-pressed European defence budgets.At present the common procurement and defence industry plans driven by the EU Global Strategy are embryonic. And significant defence capability decisions are taking place detached from the EU’s plans, which could reinforce a divide between the UK and other member states.As illustrative, the formal agreement this week between France, Germany and Spain on the Future Combat Air System (FCAS) to develop a next-generation stealth fighter is competing with the UK-supported Tempest project that shares the same objective. The 20-year timescales for the delivery of the FCAS and Tempest projects are a reminder that defence procurement decisions are of multi-decade significance.As the EU’s ambitions are nascent, it is too early to fully assess what might be the impact of any decision by the EU and the UK to keep each other at an arms-length in security and defence cooperation. With a more detached relationship, the UK will have significant concerns if it sees the EU’s common procurement arrangements develop in a manner that actively discriminates against the UK defence industry.Outside of procurement and defence issues there may be other areas of future concern for the UK – for example, the extent to which the EU might deepen and broaden cooperation with NATO in a manner that makes the collective influence of EU member states within NATO more apparent, or to which the footprint of future EU conflict and security activities in third countries starts to overshadow the activities of the UK.As the UK has been grappling with Brexit domestically, the EU has been evolving its security and defence policy ambitions. These are developments that will impact on the UK and in which, therefore, it has a stake but as a departing member state it has a weakening ability to shape.Any aspect of future EU–UK cooperation is hostage to the vagaries of how the Brexit endgame concludes. Full Article
ag How Can the EU Learn the Language of Power? By feedproxy.google.com Published On :: Tue, 03 Dec 2019 09:51:04 +0000 3 December 2019 Vassilis Ntousas Stavros Niarchos Foundation Academy Fellow, Europe Programme @vntousas LinkedIn The new EU foreign policy chief, Josep Borrell, has an eye-catching declaration of intent. But what does it mean in practice? 2019-12-03-Borrell.jpg High Representative of the Union for Foreign Policy and Security Policy Josep Borrell answers the questions of members of the European Parliament in Brussels in October. Photo: Getty Images. The new European Commission has finally started its work this week. In a world increasingly defined by great power competition and deprived of the certainties of a strong transatlantic partnership, this might well be the first commission where foreign and security policy issues will be equally important to internal EU ones.Amid an escalating Sino-American rivalry, there is a growing realization in Brussels that something has to change in the way the EU thinks and acts internationally.Charting a more successful path forward will not be easy. Josep Borrell, the EU’s new high representative for foreign affairs and security policy, during his confirmation hearing, offered a hint as to what might be needed to get there: ‘The EU has to learn to use the language of power.”’What might this mean in practice?Four issues illustrate some of the key dilemmas ahead for the EU and its new executive.Hard powerThe most revealing of these concerns hard power.For a union so addicted to the US security guarantee, and so used to the softer approaches of exercising its influence, this was always going to be a difficult discussion. The recent disagreement between Germany and France over the future of NATO gave a taste of how fraught and complex this discussion can be.Underpinning it are three fundamental questions. If the EU has to enhance its capacity to defend its interests with military power, how (and how quickly) is it to move ahead, how much additional responsibility will that mean and to what degree will this responsibility need to be shouldered autonomously, potentially distancing itself from NATO or Washington? Moving forward with this agenda while balancing the competing interests of member states and preserving the fragile progress already achieved with initiatives such as PESCO will not be easy.Discussion and debate among member states should not be discouraged, but the new commission has a role to play in ensuring that such discussion is constructive. Distracting talks about an EU army or a nuclear ‘Eurodeterrent’ should be shelved, with the focus as much as possible on acquiring tangible capabilities, getting the defence architecture right, ensuring operational readiness and spending defence budgets smartly.How to use powerGreat powers have traditionally been able to cooperate in certain areas while competing in others. Given their wide reach, powers like the US have generally not allowed disagreement on one issue to interfere with the ability to work together on others.If the EU aspires to be a more assertive global player, it will need to grow comfortable with this compartmentalization. For example, if Brussels wants to stand up to Beijing regarding human rights, the South China Sea or issues of acquisition of European infrastructure, this should not mean that cooperation on areas such as peacekeeping, arms control or climate change needs to be blocked.Footing the billUrsula von der Leyen, the new commission president, has announced that she wants an increase of 30% for external action in the 2021–27 Multi-annual Financial Framework (the EU budget). But with the Brexit budget gap looming, and little appetite to increase contributions or reduce the funds allocated to costly schemes, like the Common Agricultural Policy, compromises will have to be made for this to happen.This will be one of the first key tests for the new commission. Power costs money, not just gestures, and therefore specific commitments already made under the Juncker mandate regarding the European Defence Fund or the new Neighbourhood, Development and International Cooperation Instrument need to be guaranteed, if not expanded.Internal politicsNone of these steps are possible if the internal workings of the EU become too dysfunctional. A stronger stance internationally would make the sometime incoherence of internal EU management more of a liability to the bloc’s credibility. For example, how can the EU advocate for the rule of law beyond its borders while some of its own member states violate the same principles? And there remains the perpetual question of how much more power member states are willing to cede – if any – to deliver faster and more efficient decision-making. If the bloc’s reflexes – often slow, consensual and risk averse – are out of place with the role of a modern great power, how does the commission envision introducing decision-making mechanisms, like qualified majority voting, in foreign and security policy matters?Borrell’s résumé shows his extensive experience in handling critical policy dossiers. He is also expected to travel less than his predecessor, being mindful of the even heavier institutional work ahead, not least in working with a more politically fragmented European Council and a more politicized European Parliament.Ultimately, learning the language of power might mean that the EU finally deals with the basics of international affairs as a coherent and cohesive actor, rather than as an occasional ensemble. This endeavour clearly lacks a fixed path or destination. But the new commission seems to be mindful that the EU will have to find new ways to use power as the world changes around it. In doing so, it should keep in mind that the language of power is best articulated not with words, but with actions. Full Article
ag Don’t Be Afraid of Political Fragmentation By feedproxy.google.com Published On :: Mon, 16 Dec 2019 11:00:17 +0000 16 December 2019 Pepijn Bergsen Research Fellow, Europe Programme @pbergsen LinkedIn If managed correctly, splintering and more volatile political systems – so-called ‘Dutchification’ – need not be a ticket to political and policy paralysis. 2019-12-16-Dutch-Election.jpg Voters cast their vote as part of the Dutch general elections on March 15, 2017 at a polling station in a mill in Oisterwijk. Photo by ROB ENGELAAR/AFP via Getty Images. In recent decades, political party systems across Europe have fragmented and electoral volatility has increased. The number of parties represented in parliaments across the continent has grown and the formerly dominant mainstream parties have seen their support base collapse, forcing parties into often uncomfortable and unstable coalitions.From the United Kingdom to Germany, politicians and commentators talk of such scenarios in often apocalyptic terms and associate it with political instability and policy paralysis.They shouldn’t. Instead they should focus their energy on making these increasingly competitive political markets work.The Netherlands is frequently held up as a prime example of this process, which is therefore sometimes referred to as ‘Dutchification’. Its highly proportional political system has created the opportunity for new parties and specific interest groups to win parliamentary representation, ranging from an animal rights party and a party catering specifically to the interests of the elderly.This has been accompanied by increased electoral volatility. In the 1970s, less than 15% of seats in the Dutch parliament would change party at any election, but in the last election in 2017, this was just over a quarter. The system also created space for the relatively early rise of populist far-right parties, though it was not the cause of their rise.Nevertheless, despite the regularly difficult coalition politics, it remains one of the most well-governed countries in the world.A short history of fragmentationLooking at the effective number of parties represented in parliaments, the number of parties, corrected for their size, provides a good measure of the extent of fragmentation. In the Netherlands this steadily increased from around four in the 1980s to over eight following the election in 2017. Even the populist far-right vote has fragmented, with two parties partly competing for the same electorate. In other countries it has been a more recent phenomenon. Spain remained a de facto two-party system until the financial crisis. Dissatisfaction with both mainstream parties has seen challenger parties on both the left and the right attract significant support, making it harder to form stable coalitions. Political fragmentation decreased slightly in Italy in recent years, but that was from a high base as it shot up in the early 1990s when the post-war political settlement crumbled.German politics, long a hallmark of stability, is struggling with the decrease in support for the parties that dominated its political scene in the post-war period. The Christian Democrats and Social Democrats only barely managed to win a majority together in the election in 2017, at 53.4% of the vote compared with the 81.3% achieved 30 years earlier. The latest polls suggest they would only get to 40% together if an election were held today.A similar trend is visible within the European Parliament. Whereas the two largest groups in the European Parliament, the Christian Democrats and the Social Democrats, together won 66% of the vote in the election in 1999, they did not even manage to win a majority together in 2019, taking just 39.5% of the vote.No crisis of democracyIf electoral volatility and political fragmentation does indeed constitute some sort of crisis of democracy, we should expect to see voters become unhappy about how their national democracy functions. Largely, the opposite seems to be the case.In the Netherlands, satisfaction with its democracy went up at the same time as Dutchification did its work. Similar trends are visible in other highly fragmented European political systems, often those with very proportional systems. Despite regular minority governments, satisfaction with democracy is above 90% in Denmark and at 80% in Sweden, according to the latest Eurobarometer data.In comparison, it stood at 52% in the United Kingdom and 53% in France, where the electoral system has, at least on the surface, prevented the kind of fragmentation supposedly plaguing proportional systems.Satisfaction with democracy seems to be affected by a number of factors. This includes the state of the economy, particularly in countries that were hit the hardest by the global financial and euro zone crises. Nevertheless, the data suggests that, even if we can’t say that Dutchification by definition leads to more satisfaction with democracy, it is clearly not associated with falling faith in the system.A competitive political marketDutchification should be seen as accompanying a more competitive political marketplace. A more emancipated, demanding and politically engaged electorate than in the post-war decades is willing to shop around instead of merely vote according to socioeconomic class or other dividing lines, such as religious ones. The fragmented parliaments that emerge as a result provide better representation of different groups within European societies.This makes life harder for Europe’s political parties and politicians, as they juggle large coalitions, or changing coalitions under minority governments, but provides voters with more choice and democratic renewal. If handled correctly this would also allow more responsiveness to shifts in public opinion.Such democratic creative destruction in competitive political markets is to be celebrated in a well-functioning democracy. Just as companies prefer to operate in an oligopoly, political parties prefer the stability of limited political competition. But wishing for this kind of stability comes perilously close to preferring stability over proper representation.Worrying about Dutchification risks confusing a crisis of the traditional mainstream parties with a crisis of democracy. For some countries, particularly those like the Netherlands and Denmark which have longer histories of consensus-based politics and coalition building, this is an easier adjustment. But this should not be an excuse to not attempt to make politics work better as they were forced to go through, arguably still ongoing, adjustment processes too.Instead of investing in futile attempts to get back to how things were in the old days, or hoping this will somehow magically happen, political leaders and parties across Europe need to reassess how they deal with the new reality of Dutchification. Full Article
ag Virtual Breakfast: Engaging with the EU From the Outside: A Perspective From Norway By feedproxy.google.com Published On :: Tue, 07 Apr 2020 14:45:01 +0000 Invitation Only Research Event 24 April 2020 - 8:30am to 9:30am Event participants Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign AffairsChair: Dr Robin Niblett, Director; Chief Executive, Chatham House Please note this an online-only event.Norway is one of the few European countries that remains outside of the European Union. After the country’s population rejected the prospect of joining the EU twice, Norway’s relationship with the Union has been based on its membership of the European Economic Area (EEA), alongside Iceland and Liechtenstein.The ‘Norway Model’ was often mentioned in the run up to the Brexit vote as a possible basis for Britain’s future relationship with the bloc, not least because it offers the least disruption to the current arrangement. Equally, Norway is not subject to the EU fisheries policy - an anticipated major issue in the next phase of Brexit talks. Nor is it part of the EU Customs Union.Even though Prime Minister Johnson has now ruled out the type of deep economic and regulatory integration with the EU that Norway enjoys through its EEA membership, the country’s experience can still offer valuable lessons for the UK as it prepares to exit the transition period at the end of 2020.In this session, the speaker will share Norway’s experience as a long-standing EEA member and discuss the challenges of engaging with the EU from the outside. What lessons can Norway offer the UK ahead of the negotiations on the future of UK-EU relations? What are the limits of its current arrangement with the EU? And is there any appetite among the Norwegian population to revisit it? Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
ag Virtual Breakfast: Europe in the Age of COVID-19: Priorities and Debates By feedproxy.google.com Published On :: Tue, 21 Apr 2020 12:15:01 +0000 Invitation Only Research Event 6 May 2020 - 9:00am to 10:00am Event participants Duncan Robinson, Charlemagne Columnist; Brussels Bureau Chief, the EconomistChair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House The new European Commission had a bold new agenda when it began its work in December 2019, with climate change, digital transformation and strengthening European democracy among its priorities. Less than six months later, the European continent is in the midst of the worst crisis since the second World War and business as usual has been taken over by crisis management.Has COVID-19 monopolized the agenda in Brussels? What priorities are still on the table and what debates have fallen victim to the coronavirus? Is the current crisis reigniting and exacerbating existing faultlines in the EU or creating new ones?Reflecting on his first four months as the Economist’s Charlemagne columnist, the speaker will share what decision-making in Brussels looks like during a pandemic and what debates are dominating conversations in the EU capital today. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
ag Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
ag Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin [Computational Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency. Full Article
ag Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
ag Trump’s Threat to Target Iran’s Cultural Heritage Is Illegal and Wrong By feedproxy.google.com Published On :: Tue, 07 Jan 2020 13:57:57 +0000 7 January 2020 Héloïse Goodley Army Chief of General Staff Research Fellow (2018–19), International Security Targeting cultural property is rightly prohibited under the 1954 Hague Convention. 2020-01-07-Trump.jpg Donald Trump at Mar-a-Lago in December. Photo: Getty Images As tensions escalate in the Middle East, US President Donald Trump has threatened to strike targets in Iran should they seek to retaliate over the killing of Qassem Soleimani. According to the president’s tweet, these sites includes those that are ‘important to Iran and Iranian culture’.Defense Secretary Mark Esper was quick on Monday to rule out any such action and acknowledged that the US would ‘follow the laws of armed conflict’. But Trump has not since commented further on the matter.Any move to target Iranian cultural heritage could constitute a breach of the international laws protecting cultural property. Attacks on cultural sites are deemed unlawful under two United Nations conventions; the 1954 Hague Convention for the Protection of Cultural Property during Armed Conflict, and the 1972 UNESCO World Heritage Convention for the Protection of the World Cultural and Natural Heritage.These have established deliberate attacks on cultural heritage (when not militarily necessary) as a war crime under the Rome Statute of the International Criminal Court in recognition of the irreparable damage that the loss of cultural heritage can have locally, regionally and globally.These conventions were established in the aftermath of the Second World War, in reaction to the legacy of the massive destruction of cultural property that took place, including the intense bombing of cities, and systematic plunder of artworks across Europe. The conventions recognize that damage to the cultural property of any people means ‘damage to the cultural heritage of all mankind’. The intention of these is to establish a new norm whereby protecting culture and history – that includes cultural and historical property – is as important as safeguarding people.Such historical sites are important not simply as a matter of buildings and statues, but rather for their symbolic significance in a people’s history and identity. Destroying cultural artefacts is a direct attack on the identity of the population that values them, erasing their memories and historical legacy. Following the heavy bombing of Dresden during the Second World War, one resident summed up the psychological impact of such destruction in observing that ‘you expect people to die, but you don’t expect the buildings to die’.Targeting sites of cultural significance isn’t just an act of intimidation during conflict. It can also have a lasting effect far beyond the cessation of violence, hampering post-conflict reconciliation and reconstruction, where ruins or the absence of previously significant cultural monuments act as a lasting physical reminder of hostilities.For example, during the Bosnian War in the 1990s, the Old Bridge in Mostar represented a symbol of centuries of shared cultural heritage and peaceful co-existence between the Serbian and Croat communities. The bridge’s destruction in 1993 at the height of the civil war and the temporary cable bridge which took its place acted as a lasting reminder of the bitter hostilities, prompting its reconstruction a decade later as a mark of the reunification of the ethnically divided town.More recently, the destruction of cultural property has been a feature of terrorist organizations, such as the Taliban’s demolition of the 1,700-year-old Buddhas of Bamiyan in 2001, eliciting international condemnation. Similarly, in Iraq in 2014 following ISIS’s seizure of the city of Mosul, the terrorist group set about systematically destroying a number of cultural sites, including the Great Mosque of al-Nuri with its leaning minaret, which had stood since 1172. And in Syria, the ancient city of Palmyra was destroyed by ISIS in 2015, who attacked its archaeological sites with bulldozers and explosives.Such violations go beyond destruction: they include the looting of archaeological sites and trafficking of cultural objects, which are used to finance terrorist activities, which are also prohibited under the 1954 Hague Convention.As a war crime, the destruction of cultural property has been successfully prosecuted in the International Criminal Court, which sentenced Ahmad Al-Faqi Al-Mahdi to nine years in jail in 2016 for his part in the destruction of the Timbuktu mausoleums in Mali. Mahdi led members of Al-Qaeda in the Islamic Maghreb to destroy mausoleums and monuments of cultural and religious importance in Timbuktu, irreversibly erasing what the chief prosecutor described as ‘the embodiment of Malian history captured in tangible form from an era long gone’.Targeting cultural property is prohibited under customary international humanitarian law, not only by the Hague Convention. But the Convention sets out detailed regulations for protection of such property, and it has taken some states a lot of time to provide for these.Although the UK was an original signatory to the 1954 Hague Convention, it did not ratify it until 2017, introducing into law the Cultural Property (Armed Conflicts) Act 2017, and setting up the Cultural Protection Fund to safeguard heritage of international importance threatened by conflict in countries across the Middle East and North Africa.Ostensibly, the UK’s delay in ratifying the convention lay in concerns over the definition of key terms and adequate criminal sanctions, which were addressed in the Second Protocol in 1999. However, changing social attitudes towards the plunder of antiquities, and an alarming increase in the use of cultural destruction as a weapon of war by extremist groups to eliminate cultures that do not align with their own ideology, eventually compelled the UK to act.In the US, it is notoriously difficult to get the necessary majority for the approval of any treaty in the Senate; for the Hague Convention, approval was achieved in 2008, following which the US ratified the Convention in 2009.Destroying the buildings and monuments which form the common heritage of humanity is to wipe out the physical record of who we are. People are people within a place, and they draw meaning about who they are from their surroundings. Religious buildings, historical sites, works of art, monuments and historic artefacts all tell the story of who we are and how we got here. We have a responsibility to protect them. Full Article
ag Politics, policy-making and the presence of images of suffering children By feedproxy.google.com Published On :: Thu, 07 May 2020 08:45:52 +0000 7 May 2020 , Volume 96, Number 3 Helen Berents Read Online In 2017 Trump expressed pity for the ‘beautiful babies’ killed in a gas attack on Khan Shaykhun in Syria before launching airstrikes against President Assad's regime. Images of suffering children in world politics are often used as a synecdoche for a broader conflict or disaster. Injured, suffering, or dead; the ways in which images of children circulate in global public discourse must be critically examined to uncover the assumptions that operate in these environments. This article explores reactions to images of children by representatives and leaders of states to trace the interconnected affective and political dimensions of these images. In contrast to attending to the expected empathetic responses prompted by images of children, this article particularly focuses on when such images prompt bellicose foreign policy decision-making. In doing this, the article forwards a way of thinking about images as contentious affective objects in international relations. The ways in which images of children's bodies and suffering are strategically deployed by politicians deserves closer scrutiny to uncover the visual politics of childhood inherent in these moments of international politics and policy-making. Full Article
ag Webinar: Reimagining the Role of State and Non-State Actors in (Re)building National Health Systems in the Arab World By feedproxy.google.com Published On :: Wed, 15 Apr 2020 14:15:01 +0000 Research Event 22 April 2020 - 1:00pm to 2:00pm Event participants Fadi El-Jardali, Professor of Health Policy and Systems, American University of BeirutModerator: Nadim Houry, Executive Director, Arab Reform Initiative As new cases of COVID-19 continue to surge, countries around the world struggle to mitigate the public health and economic effects of the virus. It is becoming increasingly clear that an effective pandemic response requires a whole-of-government, whole-of-society approach. In the Arab world, where health systems are already strained by armed conflicts and displaced populations, a whole-of-society response to the pandemic is particularly critical as countries have become increasingly dependent on non-state actors, notably the private sector, for healthcare provision and any response that includes the state alone may not be sufficient to address the pandemic.In a recent article, Fadi El-Jardali, argued that while the pandemic will have grave health and economic consequences for years to come, it brings with it a valuable opportunity to re-envision the role of state and non-state actors in strengthening health systems. The article addressed the need for increased collaboration between state and non-state actors, and the rethinking of existing cooperation models to provide quality healthcare services for all. In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, Dr El-Jardali will discuss how state and non-state actors can collaborate more effectively to address the shortcomings of national health care systems amidst the pandemic and beyond. The article’s author will share insights on the different capacities available in Arab societies that governments can draw upon to ensure that Universal Health Coverage, equity considerations and social justice are at the core of health systems.You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page. Department/project Middle East and North Africa Programme, The Future of the State in the Middle East Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
ag Webinar: Coordinating the Fight Against Financial Crime By feedproxy.google.com Published On :: Fri, 17 Apr 2020 16:10:01 +0000 Corporate Members Event Webinar 1 July 2020 - 5:00pm to 6:00pmAdd to CalendariCalendar Outlook Google Yahoo Che Sidanius, Global Head of Regulation & Industry Affairs, RefinitivPatricia Sullivan, Global Co-Head, Financial Crime Compliance, Standard CharteredDame Sara Thornton, Independent Anti-Slavery Commissioner, UKChair: Tom Keatinge, Director, Centre for Financial Crime and Security Studies, RUSI Illicit finance not only threatens financial stability and inclusion but also provides support for terrorism and is a primary incentive for human trafficking, the illegal wildlife trade and narcotics smuggling. Frequently, actors capitalize on loopholes and inefficiencies resulting from the lack of a coordinated response to financial crime and an underpowered global system for tracking illicit financial flows. Enhanced public-private partnerships, in addition to investment in tackling financial crime from governments, international bodies and private industries, are necessary to develop regulatory frameworks, effective responses and valuable coordination between law enforcement, policymakers, regulators and financial institutions. But how should businesses structure their efforts so that their business interests are protected and the work they do is of use to others fighting financial crime?This webinar will explore solutions to enable public-private partnerships to work together to combat financial crime. What do successful partnerships need from each side to ensure that the work being done is efficient and effective? How can the industry’s internal effectiveness impact the ‘real-world’ victims? And what barriers impede public-private partnerships operating as a force for good? 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
ag Virtual Breakfast: Europe in the Age of COVID-19: Priorities and Debates By feedproxy.google.com Published On :: Tue, 21 Apr 2020 12:15:01 +0000 Invitation Only Research Event 6 May 2020 - 9:00am to 10:00am Event participants Duncan Robinson, Charlemagne Columnist; Brussels Bureau Chief, the EconomistChair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House The new European Commission had a bold new agenda when it began its work in December 2019, with climate change, digital transformation and strengthening European democracy among its priorities. Less than six months later, the European continent is in the midst of the worst crisis since the second World War and business as usual has been taken over by crisis management.Has COVID-19 monopolized the agenda in Brussels? What priorities are still on the table and what debates have fallen victim to the coronavirus? Is the current crisis reigniting and exacerbating existing faultlines in the EU or creating new ones?Reflecting on his first four months as the Economist’s Charlemagne columnist, the speaker will share what decision-making in Brussels looks like during a pandemic and what debates are dominating conversations in the EU capital today. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
ag A Transatlantic Partnership for WTO Reform in the Age of Coronavirus By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:45:01 +0000 Webinar Research Event 28 April 2020 - 2:00pm to 3:00pm Event participants Ignacio Garcia Bercero, Director, Directorate General for Trade of the European Commission; European Union Visiting Fellow, Oxford UniversityJennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House Global trade and the WTO – which has been at the heart of the rules-based international trade system since its creation in 1995 – faced a critical moment even before COVID-19. The Appellate Body’s demise in December 2019 led to a renewed focus on the future of the WTO. But the challenges facing the WTO run deeper than that – the organization has lost relevance as a negotiation forum, resulting in the global trade rules not having kept pace with changes in technology and the rise of China. While the WTO provides a forum for international cooperation to address the trade fallout from COVID-19, what implications will the pandemic have for the long-term reform of the global trade system?Both the US and EU have proposed various WTO reform strategies and taken steps towards collaboration, but is a transatlantic partnership for WTO reform feasible? Do the US and EU believe that a rules-based international trade system is in their interest – especially in light of COVID-19? What are the biggest issues dividing the US and EU on reforming the WTO, and is there a common assessment of the key problems? What steps can the US and EU take to address the dispute settlement function of the WTO and to modernize the trade rules? Are there broader issues, such as environmental and social sustainability, that should be included in a transatlantic agenda for WTO reform?This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ag Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ag Virtual Roundtable: Evaluating Outcomes in Fragile Contexts: Adapting Research Methods in the Time of COVID-19 By feedproxy.google.com Published On :: Mon, 04 May 2020 08:55:01 +0000 Invitation Only Research Event 5 May 2020 - 12:00pm to 1:00pm Agendapdf | 107.59 KB Event participants Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of ChicagoTom Gillhespy, Principal Consultant, ItadShodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House This virtual roundtable has been co-convened by Chatham House and the Aga Khan Foundation. While conducting research in fragile and conflict-affected contexts has always presented challenges, the outbreak of COVID-19 creates additional challenges including travel restrictions, ethical challenges, and disruptions to usual modes of working. This virtual roundtable will explore how organizations can adapt their research and monitoring and evaluation models in response to the coronavirus pandemic. This event aims to discuss the research methods being used to mitigate the impact of the COVID-19 crisis; the important role of technology; and ways to engage policy and decision-makers during this time. Event attributes Chatham House Rule Department/project Asia-Pacific Programme, Conflict, Peace and Stability, Geopolitics and Governance Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
ag Iraq on the International Stage: Foreign Policy and National Identity in Transition By feedproxy.google.com Published On :: Thu, 13 Jun 2013 16:22:44 +0000 Research Event 4 July 2013 - 5:00pm to 7:00pm Chatham House, London Programme Report: Iraq on the International Stage: Foreign Policy and National Identity in Transition pdf | 532.64 KB Event participants Dr Ghanim Al-Jumaily, Ambassador of Iraq to Saudi ArabiaJane Kinninmont, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseDr Phebe Marr, Historian of Modern Iraq, Middle East InstituteProfessor Gareth Stansfield, Director, Institute of Arab and Islamic Studies, University of ExeterChair: Omar Sirri, Research Assistant, Middle East and North Africa Programme, Chatham House As Iraq emerges from the shadow of war and occupation, it has sought to regain influence as a major actor in an ever-more volatile region. Though the 'new Iraq' attempts to project an independent foreign policy, renewed instability and violence inside the country has challenged the state's ability to develop a coherent and unified foreign policy stance.Jane Kinninmont and Gareth Stansfield will present the findings of their new report which explores how foreign policy in Iraq today is developed and implemented, and analyses the extent to which Iraq's foreign policy aims are identifiable, independent and national in nature. They will also engage in a wider discussion with an expert panel on Iraqi foreign policy, particularly towards the conflict in Syria and how issues in neighbouring states are intertwined with domestic Iraqi politics. Event attributes Livestream Department/project Middle East and North Africa Programme, Future Dynamics in the Gulf Full Article
ag Iraq on the International Stage: Foreign Policy and National Identity in Transition By feedproxy.google.com Published On :: Wed, 03 Jul 2013 17:45:31 +0000 1 July 2013 Jane Kinninmont @janekinninmont Former Deputy Head and Senior Research Fellow, Middle East and North Africa Programme Gareth Stansfield and Omar Sirri This report aims to shed light on the key actors, processes and narratives that are shaping Iraq's foreign policy behaviour and options, at a time when the country is seeking to emerge from international sanctions and resume a more normal role in international affairs.Iraq's foreign relations are increasingly intertwined with the country's own divisions, and the increasing polarization of key Middle Eastern countries over Syria threatens to escalate Iraq's internal crisis. Syria has become the most divisive foreign policy issue facing Iraq, with little consensus on how to respond to the conflict. To protect against the risk of spillover from Syria, Iraq's political groupings must develop at least a basic agreement on their strategic response to the conflict. Western governments should caution their allies in the Gulf that the exploitation of sectarian discourses will have toxic effects that could last for at least a generation.More on Iraq Related documents Programme Report: Iraq on the International Stage: Foreign Policy and National Identity in Transition pdf | 532.64 KB Department/project Middle East and North Africa Programme, Future Dynamics in the Gulf Full Article
ag The Great War: The Soldier, the League, the Imagination By feedproxy.google.com Published On :: Tue, 18 Feb 2014 17:48:30 +0000 Conference Members Event 20 March 2014 - 6:00pm to 7:00pm Chatham House, London Transcript: The Great War: The Soldier, the League, the Imaginationpdf | 93.51 KB Q&A: The Great War: The Soldier, the League, the Imaginationpdf | 69.38 KB Full Article
ag Syria Showcases the Failure to Engage Locals in Development By feedproxy.google.com Published On :: Thu, 20 Aug 2015 10:03:40 +0000 20 August 2015 Kholoud Mansour Former Academy Associate The problems of the international humanitarian response in the war-torn country are part of a broader difficulty in connecting development with local sustainability. 20150820UNSyriaEnvoys.jpg UN Deputy Special Envoy to Syria Ramzy Ezzeldin Ramzy, UNDP Representative in Syria Yacoub al-Helo and the commissioner general of UNRWA, Pierre Krahenbuhl, answer questions during an interview on 14 April 2015 in Damascus. Photo by Getty Images. The international community’s response to the Syria crisis has been unsatisfactory on many fronts, and humanitarian aid and development is no exception. While there has been renewed emphasis by development organizations on the importance of engaging local actors − notably highlighted in the new Sustainable Development Goals − the reality is this has been woefully lacking in practice. And Syria is simply one example of many where the failure of UN agencies and other humanitarian actors to partner with local actors has hampered the response to humanitarian crises.Double standardsThe problem is that international agencies usually have high and unfair expectations from Syrian individuals and organizations, requiring them to speak the ‘language’ of development, meet international standards, and demonstrate a wide range of expertise. However, these demands are not reciprocated by international organizations and experts being expected to have the same depth of knowledge of the local context in which they are operating. In addition, while Syrian actors are expected to be neutral, impartial and politically unaffiliated, foreign aid appears to be driven − explicitly and unashamedly − by the political objectives of the donor countries.There is a double standard at work. In many cases, international ‘experts’ on Syria have little local knowledge, but there are no channels to measure or question their level of expertise. At the same time, including local Syrians in decision-making is seen as a threat to predetermined objectives, rather than as an asset.Syrians could add an indispensable source of knowledge and context to international agencies, as well as add local credibility. But too often they are brought on board to be part of the humanitarian and development picture or to get their simple feedback for evaluation and needs assessment reports to satisfy donors’ requirements, rather than employed as an integral component of designing and implementing projects. Though some of this is down to a pretext of lack of capacity, it raises the question of whether there is an international political willingness and genuine organizational courage to involve Syrians at programming, decision and policy making-levels.The importance of localThe Syrian example is not isolated. While there is now a debate to encourage engaging local actors, this does not happen in practice. The Local to Global Protection Initiative study reported that local and national humanitarian actors received only 0.2% of the overall direct global humanitarian response in 2013.Moreover, the international humanitarian and development systems are designed, together with foreign aid policy, to be self-contained and to exclude local actors. This allows donor governments to use the systems as political tools for leveraging control. It is equally difficult for both outsiders as well as insiders to understand how the system really functions. The UN-led coordination structure is one example of the heavy international architecture that remains unable to reform itself, learn from its previous mistakes, or to engage with local actors.And that engagement matters. The Independent Research Forum emphasized in its brief in February 2014 how engaging local researchers and implementing bottom-up participatory learning can make countries better prepared to achieve the post-2015 Sustainable Development Goals. Those goals, as well as the upcoming World Humanitarian Summit, highlight the importance of including local actors in the humanitarian and development responses.Moving forwardFortunately, such initiatives are creating a momentum within the development community to make radical changes through bottom-up approaches that put sustainability into practice. But if the Sustainable Development Goals want to affect real change, there will have to be a significant drive to move from rhetoric and ‘intentions’ to reality and actions. Currently it seems that the international community prefers to simply maintain the current status quo. It only takes a brief reflection on how many Syrians are included in every project or programme and how many Syrians are in positions to contribute at the policy and decision-making levels to realise the scale of the impetus required to change this system. To make that change might provide an opportunity for Syrians to restore some of the ownership to the outcomes and decisions of their conflict.To comment on this article, please contact Chatham House Feedback Full Article
ag A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent By feedproxy.google.com Published On :: 1989-04-01 M el-SaadaniApr 1, 1989; 30:627-630Articles Full Article
ag Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein By feedproxy.google.com Published On :: 1997-11-01 DL BrasaemleNov 1, 1997; 38:2249-2263Articles Full Article
ag Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans By feedproxy.google.com Published On :: 2005-11-01 Saverio CintiNov 1, 2005; 46:2347-2355Research Articles Full Article
ag Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By feedproxy.google.com Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
ag The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ By feedproxy.google.com Published On :: Wed, 22 Jan 2020 13:35:01 +0000 Invitation Only Research Event 30 January 2020 - 8:15am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Philippe Sands QC, Professor of Law, UCL Richard Burt, Managing Partner, McLarty AssociatesChair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project US and the Americas Programme US and Americas Programme Email Full Article
ag A Transatlantic Partnership for WTO Reform in the Age of Coronavirus By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:45:01 +0000 Webinar Research Event 28 April 2020 - 2:00pm to 3:00pm Event participants Ignacio Garcia Bercero, Director, Directorate General for Trade of the European Commission; European Union Visiting Fellow, Oxford UniversityJennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House Global trade and the WTO – which has been at the heart of the rules-based international trade system since its creation in 1995 – faced a critical moment even before COVID-19. The Appellate Body’s demise in December 2019 led to a renewed focus on the future of the WTO. But the challenges facing the WTO run deeper than that – the organization has lost relevance as a negotiation forum, resulting in the global trade rules not having kept pace with changes in technology and the rise of China. While the WTO provides a forum for international cooperation to address the trade fallout from COVID-19, what implications will the pandemic have for the long-term reform of the global trade system?Both the US and EU have proposed various WTO reform strategies and taken steps towards collaboration, but is a transatlantic partnership for WTO reform feasible? Do the US and EU believe that a rules-based international trade system is in their interest – especially in light of COVID-19? What are the biggest issues dividing the US and EU on reforming the WTO, and is there a common assessment of the key problems? What steps can the US and EU take to address the dispute settlement function of the WTO and to modernize the trade rules? Are there broader issues, such as environmental and social sustainability, that should be included in a transatlantic agenda for WTO reform?This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ag Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ag Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article
ag Virtual Roundtable: Evaluating Outcomes in Fragile Contexts: Adapting Research Methods in the Time of COVID-19 By feedproxy.google.com Published On :: Mon, 04 May 2020 08:55:01 +0000 Invitation Only Research Event 5 May 2020 - 12:00pm to 1:00pm Agendapdf | 107.59 KB Event participants Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of ChicagoTom Gillhespy, Principal Consultant, ItadShodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House This virtual roundtable has been co-convened by Chatham House and the Aga Khan Foundation. While conducting research in fragile and conflict-affected contexts has always presented challenges, the outbreak of COVID-19 creates additional challenges including travel restrictions, ethical challenges, and disruptions to usual modes of working. This virtual roundtable will explore how organizations can adapt their research and monitoring and evaluation models in response to the coronavirus pandemic. This event aims to discuss the research methods being used to mitigate the impact of the COVID-19 crisis; the important role of technology; and ways to engage policy and decision-makers during this time. Event attributes Chatham House Rule Department/project Asia-Pacific Programme, Conflict, Peace and Stability, Geopolitics and Governance Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
ag Politics, policy-making and the presence of images of suffering children By feedproxy.google.com Published On :: Thu, 07 May 2020 08:45:52 +0000 7 May 2020 , Volume 96, Number 3 Helen Berents Read Online In 2017 Trump expressed pity for the ‘beautiful babies’ killed in a gas attack on Khan Shaykhun in Syria before launching airstrikes against President Assad's regime. Images of suffering children in world politics are often used as a synecdoche for a broader conflict or disaster. Injured, suffering, or dead; the ways in which images of children circulate in global public discourse must be critically examined to uncover the assumptions that operate in these environments. This article explores reactions to images of children by representatives and leaders of states to trace the interconnected affective and political dimensions of these images. In contrast to attending to the expected empathetic responses prompted by images of children, this article particularly focuses on when such images prompt bellicose foreign policy decision-making. In doing this, the article forwards a way of thinking about images as contentious affective objects in international relations. The ways in which images of children's bodies and suffering are strategically deployed by politicians deserves closer scrutiny to uncover the visual politics of childhood inherent in these moments of international politics and policy-making. Full Article
ag How images frame China's role in African development By feedproxy.google.com Published On :: Thu, 07 May 2020 09:21:23 +0000 7 May 2020 , Volume 96, Number 3 George Karavas Read online Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’. Full Article
ag Undercurrents: Episode 5 - Chokepoints in Global Food Trade, and How the Internet is Changing Language By feedproxy.google.com Published On :: Thu, 05 Apr 2018 00:00:00 +0100 Full Article
ag Chatham House Forum: Is the West Losing its Power on the Global Stage? By feedproxy.google.com Published On :: Wed, 11 Apr 2018 00:00:00 +0100 Full Article
ag Undercurrents: Episode 6 - Tribes of Europe, and the International Women's Rights Agenda at the UN By feedproxy.google.com Published On :: Thu, 19 Apr 2018 00:00:00 +0100 Full Article
ag Reconstruction in Syria: Between Political Pragmatism and Human Rights Idealism By feedproxy.google.com Published On :: Fri, 25 May 2018 00:00:00 +0100 Full Article
ag Global Trade Landscape Series: US Trade in an Age of Protectionism By feedproxy.google.com Published On :: Fri, 15 Jun 2018 00:00:00 +0100 Full Article
ag Red Flags: The Outlook for Xi Jinping's China By feedproxy.google.com Published On :: Wed, 12 Sep 2018 00:00:00 +0100 Full Article
ag Managing the Real and Perceived Challenges Facing the World By feedproxy.google.com Published On :: Mon, 24 Sep 2018 00:00:00 +0100 Full Article
ag Migration and Health: Barriers and Means to Achieving Universal Health Coverage By feedproxy.google.com Published On :: Fri, 18 Jan 2019 00:00:00 +0000 Full Article