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High Resolution Clear Native Electrophoresis for In-gel Functional Assays and Fluorescence Studies of Membrane Protein Complexes

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research




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Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




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Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research




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Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae

Sean R. Collins
Mar 1, 2007; 6:439-450
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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A Versatile Nanotrap for Biochemical and Functional Studies with Fluorescent Fusion Proteins

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research




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Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research




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SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation]

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.




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12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction]

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.




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NF-{kappa}B mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages [Signal Transduction]

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.




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Biophysical characterization of SARAH domain-mediated multimerization of Hippo pathway complexes in Drosophila [Signal Transduction]

Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity.




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The Rise of China and the Future of the Transatlantic Relationship

29 July 2019

The growth of China's wealth and military power represents an epochal change in international politics. This briefing argues that China’s rise has worrying implications for the liberal international order and explores how this will affect the transatlantic relationship.

Jennifer Lind

Associate Fellow, US and the Americas Programme and Asia-Pacific Programme (based in the US)

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Teams from France, Great Britain, the US, China, Australia and Japan race against each other during the SailGP on 4 May 2019 in San Francisco, California. Photo: Getty Images

Summary

  • The stakeholders in the transatlantic relationship – the US, Canada and Europe – have long sought to stabilize international politics and economies by spreading support for the liberal goals of free markets, democracy and human rights. As their own commitment to this agenda appears to waver, China is becoming wealthier and more assertive. This briefing explores the extent to which these goals – along with the unity of the transatlantic relationship – are now in jeopardy.
  • Great uncertainty surrounds this question, including over the direction of US foreign policy, risks to European cohesion and slowing growth in China. However, two decades of revisionist behaviour by the authorities in Beijing show that China’s values and interests already conflict with transatlantic goals in trade, cyberspace, international development, security and human rights.
  • On trade, China pursues protectionist policies while engaging actively in intellectual property theft. China’s military modernization and its view of maritime law challenge the territorial status quo in East Asia and raise the risk of military crisis there. China lends unconditionally to countries that abuse human rights and are corrupt, undermining efforts by Western governments to promote good governance and human rights.
  • Defending liberal goals is complicated by asymmetric interests among the transatlantic partners, especially over security. China also uses ‘wedge’ strategies to pick off potential allies, thus diluting the power and will of any counterbalancing effort.
  • This briefing argues that China’s rise has worrying implications for the liberal international order. In response, the US should recognize its own strong interest in European unity, while Europeans must be ready to align more with the US (and East Asian allies) in order to temper Chinese behaviour.




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Vassilis Ntousas

Stavros Niarchos Foundation Academy Fellow, Europe Programme

Biography

Vassilis Ntousas is hosted by the Europe Programme. His research focuses on the links between EU foreign policy in an era of global institutional turbulence and the defence and transformation of the multilateral system.

From 2015-2019, he was the senior international relations policy advisor at the Foundation for European Progressive Studies (FEPS) in Brussels. In this role, he was responsible for leading the design and implementation of the foundation’s global research and activity programmes, covering the world’s major regions.

Prior to FEPS, he worked as a communications and political advisor at the Municipality of Thessaloniki, Greece, providing advice in the areas of international affairs and intercity diplomatic relations.

He regularly comments on international developments for international and Greek media outlets.

Vassilis holds an MSc in International Relations from the London School of Economics and a BA in International Relations and Politics from the University of Sheffield.

Areas of expertise

  • European foreign policy
  • Transatlantic relations
  • The politics and policies of the EU towards the Middle East
  • Iran nuclear agreement

Past experience

2015-19Senior international relations policy advisor, Foundation for European Progressive Studies

2013-14

Political and communications advisor, Municipality of Thessaloniki, Greece

2012

Project assistant, APCO Worldwide, Brussels office




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Transatlantic Dialogue on China

A joint Chatham House-RUSI project that focuses on strengthening common understanding across the Atlantic and develop new ideas for how the US and Europe can better engage with and respond to China’s rise.

This will be done through examining transatlantic approaches and responses to China through the lens for four key themes (digital technology; trade and investment; governance of global commons; and climate change and the environment) that have been identified as crucial to developing effective policy responses and fostering collaboration.

The project will strengthen national, regional and international responses to the risks and opportunities posed by China’s changing role within the global economy and international rules-based order.

Department contact

Pepijn Bergsen

Research Fellow, Europe Programme
020 795 75748

More on Transatlantic Dialogue on China




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An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1 [Enzymology]

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.




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Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics]

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.




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Review essay: Where is the Anthropocene? IR in a new geological epoch

8 January 2020 , Volume 96, Number 1

Dahlia Simangan

Several disciplines outside the natural sciences, including International Relations (IR), have engaged with the Anthropocene discourse in order to theorize their relevance and translate their practical value in this new phase of the Earth's history. Some IR scholars have called for a post-humanist IR, planet politics, a cosmopolitan view, and ecological security, among other approaches, to recalibrate the theoretical foundations of the discipline, making it more attuned to the realities of the Anthropocene. Existing discussions, however, tend to universalize human experience and gravitate towards western ontologies and epistemologies of living in the Anthropocene. Within this burgeoning scholarship, how is the IR discipline engaging with the Anthropocene discourse? Although the Anthropocene has become a new theoretical landscape for the conceptual broadening of conventional IR subjects, this review reveals the need for sustained discussion that highlights the differentiated human experiences in the Anthropocene. The existing IR publications on the Anthropocene locates the non-spatial narratives of vulnerability and historical injustice, the non-modernist understanding of nature, the agency of the vulnerable, and the amplification of security issues in the Anthropocene. It is in amplifying these narratives that the IR discipline can broaden and diversify the discourse on the Anthropocene and, therefore, affirm its relevance in this new geological age.




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Ana Alecsandru

Research Assistant, International Security Programme

Biography

Ana Alecsandru is a research assistant for the International Security programme, covering projects related to nuclear weapons policy and emerging technologies. She is also a PhD candidate at the University of Birmingham (awaiting Viva examination).

Her doctoral research examined the relationship between trust and verification in nuclear arms control negotiations between the United States and Russia.

Prior to joining Chatham House, she worked at the University of Birmingham on various projects concerning nuclear weapons policy while doing her PhD.

Ana completed an internship in the Arms Control, Disarmament, and WMD Non-Proliferation Centre at NATO HQ in Brussels in 2014. She was also a research intern at the United Nations Office for Disarmament Affairs (UNODA) in New York in 2016.

During her doctoral studies, she received full grants to participate in the 2017 IGCC’s Public Policy and Nuclear Threats Boot Camp hosted at UC San Diego and the 2017 Nuclear Safeguards and Non-Proliferation Training Course hosted by the European Commission’s Research Centre in Ispra.

Ana holds an MA in Security Studies and an MA in Research Methods from the University of Birmingham. She completed her BSc (hons) in International Relations at the University of Bath. For her doctoral research, she was awarded a studentship by the UK Economic and Social Research Council. 

Areas of expertise

  • Nuclear weapons policy
  • Nuclear arms control and strategic stability
  • Emerging military technologies
  • Emotions in strategic decision-making




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A Transatlantic Partnership for WTO Reform in the Age of Coronavirus

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 University
Jennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11
Chair: 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.




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Webinar: Will COVID-19 Mark the Endgame for Iraq's Muhasasa Ta'ifia?

Research Event

30 April 2020 - 2:00pm to 3:00pm

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Control of oil rents underpins Iraq’s post-2003 political order. This political order, known as Muhasasa Ta’ifia (ethno-sectarian apportionment), features an elite bargain inclusive of all major ethnic and sect-based political groups. It has enabled the state's continuity and apparent stability through multiple crises, including the 2008 financial crisis, the 2014 oil crisis, and the war with ISIS.

In a recent article, Ahmed Tabaqchali examines how the crash in oil rents, brought about by COVID-19’s disruption of the world economy, exposes the structural inconsistencies and inherent contradictions of the Muhasasa Tai’fia system. The article argues that the current Iraqi political elite is ill-equipped to resolve the multi-faceted challenge facing the country because of its increasing fragmentation and the erosion of its legitimacy, advanced institutional decay and fundamentally different oil dynamics.

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, the article’s author will discuss the deficiencies of the Muhasasa Ta’ifia system and will offer his insight into the future of this governance model in the context of a worsening economic crisis resulting from the COVID-19 pandemic and existing demographic pressures.
 
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.
 

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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The certainties that underpin the Kingdom need reappraisal

6 February 2014 , Volume 70, Number 1

From the point of view of a Saudi policy-maker, the country, the region and the world look to be increasingly complex places

Sir Tom Phillips, British Ambassador to Saudi Arabia 2010-12

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Saudi Arabia's King Abdullah in discussions with John Kerry, the US Secretary of State. Photo: Brendan Smialowski/AFP/Getty




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The Power of Sacred Geography in Iraq

18 June 2014

Sasan Aghlani
Former Consultant, International Security
Too much of a focus on body counts, resource scarcity and national borders as the main indicators of why people fight can obscure the significant impact that religious space can have on a conflict.

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Lady Zaynab mosque, Sayyidah Zaynab, in the southern suburbs of Damascus, Syria, 2007. Photo: Wikimedia.

Loss of territory to the Islamic State of Iraq and al-Sham (ISIS) and the mass executions of Shia have undoubtedly had an impact on the mobilization of fighters inside Iraq opposing the group. But after the capture of Mosul and Tikrit by ISIS, a message from the group’s spokesman, Abu Muhammad al-Adnani, highlighted the power of religion as a mobilizing force in armed conflict. In the audio message Adnani addressed Prime Minister Nouri al Maliki as ‘Rafidi’, a derogatory term for Shia meaning rejectionist. He pledged that ‘the settling of debts will not be in Samarra and Baghdad, rather in Karbala al-munajjasah [Karbala the defiled] and Najaf al-ashrak [Najaf the most polytheistic]’.

His use of the words ‘munajjasah’ and ‘ashrak’ was a sectarian play on words referring to the two cities viewed by the Shia as being the most important cities in Islam after Mecca and Medina. Karbala is also known as Karbala al-Muqaddasa (Karbala the Holy), and contains the mausoleum of the third Shia Imam, Hussein ibn Ali. Najaf is commonly referred to as Najaf al-Ashraf (Najaf the Most Honourable), and contains the mausoleum of the first Shia Imam and fourth ‘rightly guided’ caliph, Ali ibn Abi Talib.

Threats against Karbala and Najaf have prompted an immediate reaction from Shia both inside Iraq and beyond its borders. When a representative of Grand Ayatollah Ali Sistani, the most influential living Shia religious authority, called on all able-bodied Iraqis to ’confront and fight the terrorists’, Sistani was compelled to reiterate that the subject of his call were Iraqis, and not just Shia. Ayatollah Fadhil al-Milani, Sistani’s representative in London, also released a video message clarifying that there was no need for Shia outside of Iraq to confront ISIS.

Fighters are already mobilized in Syria on the basis that Shia shrines in Damascus such as the Sayyidah Zainab Mosque are under threat from extremist ‘Takfiri’ militant groups intent on destroying these holy sites. The narrative of protecting Zainab’s shrine is a potent one: militias in the country bear names such as the Brigade of Zainab’s Protector and the Abu al-Fadhl Abbas Brigades. In 2013, Hezbollah Secretary General Hassan Nasrallah warned that the destruction of Zainab’s shrine would ‘carry with it grave consequences’, and that ‘countries supporting these groups [would] be held responsible for this crime if it takes place.’ Iran’s President Hassan Rouhani has also stated unequivocally on live television that ‘regarding the holy Shia shines in Karbala, Najaf, Khadhimiya and Samarra, we announce to the killers and terrorists that the big Iranian nation will not hesitate to protect holy shrines’.

Understanding sacred geography in conflict

The explicit threat against the sacred geography of Najaf and Karbala has the potential to escalate the crisis in Iraq from a domestic to transnational conflict, drawing in fighters from around the world. For this reason, there should be a greater attempt to understand how sacred geography can transform the stakes of armed conflict.

In 2001, UN General Assembly Resolution 55/254 called upon states to ‘exert their utmost efforts to ensure that religious sites are fully respected and protected’ and ‘adopt adequate measures aimed at preventing […] acts or threats of violence’. Just what these ‘adequate measures’ should be remains unclear. Armed forces across the world often need to operate in religious sites but at the risk of undermining long-term relations with the local population; and those making the calculations are often unaware of the repercussions.

This is not to assert that sacred geography is the only factor to look at when assessing militant mobilization in Iraq and elsewhere. Nevertheless, incorporating a less secular lens for analysing international security would be useful and working through the practical implications of the UN resolution – and setting firmer guidelines − should therefore become a priority.

To comment on this article, please contact Chatham House Feedback




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Why Turkey’s Disapproval of the West’s Response to the Coup Has Limited Merit

10 August 2016

Fadi Hakura

Consulting Fellow, Europe Programme
Although Turks across the political and ideological spectrum are seething at the West’s apparently lukewarm condemnation of the abortive coup on 15 July, there are valid reasons behind the response.

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A Turkish flag attached to helium balloons as people gather to protest at Konak Square, Izmir during the July 15 failed military coup attempt. Photo by Getty Images

Signs of growing anger at the restrained denunciation of Pennsylvania-based Muslim cleric Fethullah Gulen - whose followers are thought to have played a key role in the attempted coup - are being vocalised more and more, but this criticism only shows part of the true picture.

It is true that prominent liberal Turkish intellectual Soli Ozel spoke for many when he criticised EU politicians and Western media for failing to recognise the “invaluable democratic resistance shown by all political parties in a parliament bombed by war planes”, as well as demonstrating “a lack of sensitivity, empathy and solidarity that cannot be easily digested” by not sending anyone from an EU institution to offer solidarity with the Turkish parliament.

The criticism is reasonable - officials from Western governments and regional institutions such as the Council of Europe exhibited unconditional solidarity with Ukraine during its bitter feud with Russia, which leads some to believe that Muslim-majority Turkey does not apparently deserve the same treatment as its neighbours also experiencing an unlawful attempt to seize control of the state.

Moral authority at risk

It is also right that the West should have censured the coup plotters more forcefully and built upon Turkey’s fragile unity to encourage the country to pursue further democratic reform. To quote former Swedish Prime Minister and Foreign Minister Carl Bildt: “Europe risks losing its moral authority if it does not appear particularly engaged in dealing with the coup itself.”

In addition, the EU’s strong criticism of Turkey but not France, for imposing a state of emergency and for temporarily suspending the European Convention on Human Rights, undeniably, smacks of double-standards.

However, some of the criticism falls short. To begin with, the West’s tepidity can be explained (though not wholly justified) by Erdogan’s abrasive behaviour at home and towards Western and international media.

Just three days after the coup, Erdogan threatened in his characteristically defiant tone to revive the controversial construction plans that sparked the 2013 Gezi Park protests, saying: “If we want to preserve our history, we must rebuild this historic [Ottoman-era barracks] structure, [and] we will rebuild it.”

It is also fair for Turkey to be reproached for the widespread crackdown against tens of thousands of suspected Gulenists in the aftermath of the coup. Even if it is conceivable that all 1,577 university deans who were forced to resign were Gulenists, this action will also have a lasting negative impact on the reputations and career prospects of academics unconnected to Gulen.

Fervour against Gulenism

The vigilance by the West is understandable given the Turkish government’s fervour against Gulenism in the immediate post-coup period. It would make no sense for the West to attack the coup and yet, at the same time, equivocate on flagrant violations of due process and human rights. Both efforts are mutually inclusive and identifying such violations has the greatest potential to encourage policy reversals or corrective measures.

Similarly understandable is the attention on Erdogan himself. He is the most formidable and powerful figure in a hierarchical and top-down political system, able to make fateful decisions with few effective checks and balances. He single-handedly replaced Ahmet Davutoglu as prime minister with Binali Yildirim in a clear breach of the Turkish constitution.

Despite Erdogan’s tactical attempts at embracing all the opposition parties apart from the pro-Kurdish Peoples’ Democratic Party (HDP), his refusal to renounce his ambition to transform Turkey into a powerful executive presidency indicates that this fragile political unity will not last.

Only the West has the wherewithal to moderate his policies by continuing to express its friendship with Turkey, whilst not shying away from closely monitoring, scrutinising and commenting on the post-coup developments.

Contact Chatham House Feedback

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Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol

James M. Ntambi
Sep 1, 1999; 40:1549-1558
Reviews




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A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




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Bile salt biotransformations by human intestinal bacteria

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews




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Partisanship Meets Trump’s Impeachment

19 December 2019

Dr Lindsay Newman

Senior Research Fellow, US and the Americas Programme
History shows that if those pushing for impeachment and removal want to succeed, they need to drive up popular support for a senate conviction.

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Opposing protests during the House of Representatives debate on whether to charge President Donald Trump with two articles of impeachment. Photo by Sarah Silbiger/Getty Images.

The vote to impeach Donald Trump holds almost no surprises - on both the abuse of power and obstruction of congress articles, the votes were split entirely on party lines with nearly all the majority-led House Democrats but not a single Republican voting to impeach Trump.

However, this ‘pre-ordained’ outcome of the House impeachment inquiry does serve to highlight that the US is in the midst of a hyper-partisan political moment. Policy gridlock has led to two government shutdowns during Donald Trump’s presidency, with one further budgetary fight narrowly avoided.

With a few notable exceptions (such as USMCA), policy areas that lend themselves to bipartisanship - including infrastructure and drug pricing - have seen very little progress under divided congressional chambers. Party identification can now be overlaid with the cable news channel one watches or the newspaper one reads.

Impeachment now moves to the Senate for a trial, requiring a two-thirds majority of the Republican-led senate (or 67 senators) for a conviction. Given the congressional partisanship we are seeing, the baseline scenario continues to be that the senate will not vote to convict Trump and remove him from office - despite much being made of how many senators are likely to vote for a Senate conviction.

Why public opinion could be crucial

There is another story to keep a close eye on. The number to track is 47.2 – the current polling average of public support for Trump’s impeachment. Polling averages from the end of September 2019 (before the hearings began, but after House Speaker Nancy Pelosi announced a formal inquiry) had 49.4% supporting impeachment versus 47.2% this week.

Here’s why this number matters. If those pushing for impeachment and removal are unable to drive popular support across a critical threshold level, then those against impeachment and removal are not going to abandon the president and vote for a senate conviction. With Trump consistently polling in the low 40s on job approval, but in the high 80s/low 90s within the Republican party, this means Republican congress members concerned about re-election are extremely hesitant to distance themselves from him without a clear mandate from the domestic public. 

A tale of the two most recent presidents to face impeachment underscores this point. Gallup polling claimed 58% of adults supported impeaching and removing President Richard Nixon from office in August 1974, whereas only 35% of the public supported impeaching President Bill Clinton in December 1998, the month he was impeached.

Given the respective outcomes of those two impeachments, it suggests public support for impeachment and removal needs to increase well beyond the current 47.2%, to avoid the foregone conclusion of acquittal in the Senate (even if there are signs of the tide moving in the opposite direction with those against impeachment overtaking support for the first time in December).   

What does this mean for Democrats?

In the short term, if the Democrats want to make inroads into the hearts and minds of those across the partisan gulf, it will be critical to secure senate testimony from those in Trump’s inner circle at the time of the Ukrainian affair.

After Trump ordered individuals with first-hand knowledge of the administration’s efforts vis-à-vis Ukraine not to testify, House investigators were unable to call many witnesses with direct evidence (which in fact left the House testimony exposed to Republican claims of hearsay). With Trump impeached, more of the public is likely to tune in to the senate proceedings, and direct evidence by inner circle administration officials required to testify presents an opportunity to move public opinion.

House speaker Nancy Pelosi recognizes how crucial the procedures and participants for the senate trial will be, and has said she could delay sending the articles of impeachment to the senate as leverage for a 'fair trial'.

Democrats also have to consider how an impeachment inquiry that - at least from this vantage point - does not end in a conviction of the president plays out for the 2020 election campaign, especially if this also likely means that public opinion - and certainly Republican-party views - of Trump have not shifted.




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Arturo Sarukhan

Associate Fellow, US and the Americas Programme (based in the US)

Biography

Ambassador Arturo Sarukhan is the founder and president of Sarukhan + Associates. Now a consultant and public speaker, he was a career diplomat in the Mexican foreign service for 22 years, receiving the rank of career ambassador in 2006.

From 2007 to 2013, he served as Mexico's ambassador to the US. Previously, he served, among other positions, as consul general in New York, chief of policy planning and deputy director general for inter-American affairs.

In 2006 he requested a leave of absence from the foreign service to become foreign policy advisor and international spokesperson for the Calderon presidential campaign. He subsequently led the foreign policy transition team.

A digital diplomacy pioneer, he became the first ambassador accredited in Washington to use Twitter as a public diplomacy tool. He publishes regularly and appears frequently on US and international media.

He sits on several non-profit and corporate boards, and has several academic and think-tank affiliations in the US.

He holds a BA in international relations from El Colegio de Mexico and an MA in American Foreign Policy from SAIS-Johns Hopkins.

Areas of expertise

  • US foreign and domestic policy
  • Mexican foreign and domestic policy; US-Mexico and North American relations
  • Digital Diplomacy/Public Diplomacy
  • Inter-American affairs
  • New global challenges: migration; transnational organized crime; disinformation and weaponization of social media

Past experience

2014 - presentPresident and founder, Sarukhan + Associates, LLC 
2007-13Mexican Ambassador to the US 
2006Coordinator, Presidential Foreign Policy Transition Team
2006Foreign Policy Advisor and international spokesperson, Calderon presidential campaign
2003-06Consul General, New York City
2000-03Chief for Policy Planning, Mexican Foreign Ministry
1989-2000Senior Advisor to the Foreign Minister
1995-98Head of the Counternarcotics section, Mexican Embassy USA
1993-95Chief of Staff to the Ambassador, Mexican Embassy USA
1992-93Deputy Director General for Inter-American Affairs
1992Admission to the Foreign Service, Instituto Matias Romero
1989-91MA, School of Advanced International Studies, Johns Hopkins University
1987-89Executive Assistant, Ford Foundation Bilateral Commission on the Future of US-Mexico Relations
1984-88BA, International Relations, El Colegio de México
1982-84BA studies, History, Universidad Nacional Autónoma de México




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A Transatlantic Partnership for WTO Reform in the Age of Coronavirus

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 University
Jennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11
Chair: 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.




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Coronavirus Risks Worsening a Food Crisis in the Sahel and West Africa

1 May 2020

Dr Leena Koni Hoffmann

Associate Fellow, Africa Programme

Paul Melly

Consulting Fellow, Africa Programme
In responding to the spread of the coronavirus, the governments of the Sahel and West Africa will need to draw on their collective experience of strategic coordination in emergency planning, and work together to prioritize the flow of food across borders.

2020-05-01-Africa-Market-Virus

An informal market in the Anyama district of Abidjan, Côte d’Ivoire, is sanitized against the coronavirus. Photo by SIA KAMBOU/AFP via Getty Images.

The COVID-19 pandemic has struck the Sahel and West Africa at a time when the region is already under severe pressure from violent insecurity and the effects of climate change on its land, food and water resources.

By the end of April, there had been 9,513 confirmed coronavirus cases across the 17 countries of the region, and some 231 deaths, with the highest overall numbers recorded in Nigeria, Ghana, Guinea, Côte d’Ivoire, Senegal, Niger and Burkina Faso. Low testing rates mean than these numbers give only a partial picture.

The Food Crisis Prevention Network (RPCA) forecast in early April that almost 17 million people in the Sahel and West Africa (7.1 million in Nigeria alone) will need food and nutritional assistance during the coming lean season in June–August, more than double the number in an average year. The combined impact of violent insecurity and COVID-19 could put more than 50 million other people across the region at risk of food and nutrition crisis.

Rippling across the region

The effects of the collapse in global commodity prices, currency depreciations, rising costs of consumer goods and disruptions to supply chains are rippling across the region. And for major oil-exporting countries such as Nigeria, Ghana, Chad and Cameroon, the wipe-out of foreign currency earnings will hammer government revenues just as the cost of food and other critical imports goes up. It is likely that the number of people who suffer the direct health impact of the coronavirus will be far outstripped by the number for whom there will be harsh social and economic costs.

In recent years, valuable protocols and capacities have been put in place by governments in West and Central Africa in response to Ebola and other infectious disease outbreaks.

But inadequate healthcare funding and infrastructure across this region compound the challenge of responding to the spread of the COVID-19 infection – which is testing the resources of even the world’s best-funded public health systems.

Over many years, however, the region has steadily built up structures to tackle humanitarian and development challenges, particularly as regards food security. It has an established system for assessing the risk of food crisis annually and coordinating emergency support to vulnerable communities. Each country monitors climate and weather patterns, transhumance, market systems and agricultural statistics, and terrorist disruption of agricultural productivity, from local community to national and regional level.

The system is coordinated and quality-controlled, using common technical data standards, by the Permanent Interstate Committee for Drought Control in the Sahel (CILSS), a regional intergovernmental body established in 1973 in response to a devastating drought. Collective risk assessments allow emergency support to be mobilized through the RPCA.

For almost three months already, countries in Sahelian West Africa have been working with the World Health Organization to prepare national COVID-19 response strategies and strengthen health controls at their borders. Almost all governments have also opted for domestic curfews, and variations of lockdown and market restrictions.

Senegal has been a leader in rapidly developing Africa’s diagnostic capacity, and plans are under way to speed up production of test kits. Niger was swift to develop a national response strategy, to which donors have pledged €194.5 million. While the IMF has agreed emergency financial assistance to help countries address the urgent balance-of-payments, health and social programme needs linked to the COVID-19 pandemic, signing off $3.4 billion for Nigeria, $442 million for Senegal and $130 million for Mauritania.

Steps are also now being taken towards the formulation of a more joined-up regional approach. Notably, Nigeria’s President Muhammadu Buhari has been chosen by an extraordinary session of the Economic Community of West African States to coordinate the regional response to COVID-19. As Africa’s biggest economy and home to its largest population, Nigeria is a critical hub for transnational flows of goods and people. Its controversial August 2019 land border closure, in a bid to address smuggling, has already painfully disrupted regional agri-food trade and value chains. The active engagement of the Buhari administration will thus be crucial to the success of a multifaceted regional response.

One of the first tough questions the region’s governments must collectively address is how long to maintain the border shutdowns that were imposed as an initial measure to curb the spread of the virus. Closed borders are detrimental to food security, and disruptive to supply chains and the livelihoods of micro, small and medium-sized entrepreneurs that rely on cross-border trade. The impact of prolonged closures will be all the more profound in a region where welfare systems are largely non-existent or, at best, highly precarious.

Nigeria, in particular, with more than 95 million people already living in extreme poverty, might do well to explore measures to avoid putting food further beyond the reach of people who are seeing their purchasing power evaporate.

In taking further actions to control the spread of the coronavirus, the region’s governments will need to show faith in the system that they have painstakingly developed to monitor and respond to the annual risk of food crisis across the Sahel. This system, and the critical data it offers, will be vital to informing interventions to strengthen the four components of food security – availability, access, stability and utilization – in the context of COVID-19, and for charting a post-pandemic path of recovery.

Above all, careful steps will need to be put in place to ensure that preventing the spread of the coronavirus does not come at the cost of even greater food insecurity for the people of the Sahel and West Africa. The region’s governments must prioritize the flow of food across borders and renew their commitment to strategic coordination and alignment.




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Undercurrents: Episode 2 – The Calabrian Mafia and Transatlantic Relations




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How is Saudi Arabian Society Changing?




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Should the Super-Rich Pay for a Universal Basic Income?




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Undercurrents: Episode 10 - Artificial Intelligence in International Affairs, and Women Drivers in Saudi Arabia




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The UK-Saudi Arabia Relationship: A Closer Look




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Evan Davis In Conversation With Christian Ulbrich, CEO, JLL




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A Vision for the Future of the Transatlantic Relationship




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Evan Davis In Conversation With Sir Howard Davies, Chairman of RBS




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Can Europe Save the Liberal International Order?




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Migration and Health: Barriers and Means to Achieving Universal Health Coverage




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The Transatlantic Relationship: Challenges and Opportunities




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Undercurrents: Episode 26 - China's Economy, and UK Relations with Saudi Arabia




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What Brexit Satisfies the Democratic Will of the People?




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In Conversation With Bob Dudley, Group Chief Executive, BP




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Screening Room: For Sama




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Saudi Arabia's Foreign Policy Priorities




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Young and Male: Identity and Politics in Saudi Arabia




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A Conversation With: Steven T Mnuchin, Secretary, US Treasury




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Britain’s Soft Power Potential: In Conversation with Penny Mordaunt




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The Use of Sanctions to Protect Journalists