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Kruppel-like factor 3 (KLF3) suppresses NF-{kappa}B-driven inflammation in mice [Immunology]

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.




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Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.




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Distinct and Overlapping Sets of SUMO-1 and SUMO-2 Target Proteins Revealed by Quantitative Proteomics

Alfred C. O. Vertegaal
Dec 1, 2006; 5:2298-2310
Research




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Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues

Roland Bruderer
May 1, 2015; 14:1400-1410
Research




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Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources




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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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Comparative Proteomic Analysis of Eleven Common Cell Lines Reveals Ubiquitous but Varying Expression of Most Proteins

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time




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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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A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research




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Quantitative Phosphoproteomics of Early Elicitor Signaling in Arabidopsis

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research




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Trypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology




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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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Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research




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Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology




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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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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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Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.




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Five Foreign Policy Questions for the UK’s Next Prime Minister

18 June 2019

Thomas Raines

Director, Europe Programme
Even if most don’t get to vote in the Conservative leadership election, the public deserves serious answers on the foreign policy plans of those who want to lead the country.

2019-06-18-10D.jpg

10 Downing Street. Photo: Getty Images.

In a month’s time, the UK will have a new prime minister. The campaign has been dominated by candidates’ views on how to deliver Britain’s withdrawal from the EU by October, alongside some discussion of domestic issues.

But relatively little has been said about international affairs, despite the fact that foreign policy questions are becoming a more partisan issue and Britain is facing crucial questions around Brexit and the wider international context. These will be waiting for whoever finds themselves in Number 10 on 22 July. 

1. How can Britain influence Europe from outside the EU?

Theresa May was fond of saying that Britain is leaving the EU but not leaving Europe. Britain cannot change its geography. It will continue to share many strategic and security interests with the rest of the continent, but it will be outside of Europe’s central political and economic project. A new PM will not only have to negotiate Britain’s new relationship with the EU, but also think about how to influence it as a third country.

An aspect of this will be finding a new way to work with the EU on foreign, security and defence policy that meets the need for autonomy on both sides. How deep this relationship is or how institutionalized it will be is yet to be negotiated and can be shaped by the next PM.

The UK needs to decide how ambitiously it wants to engage with the new defence agenda in the EU (particularly its industrial components), and how to balance these with key bilateral relationships like France and Germany. Amid uncertainty about American security guarantees and Russian aggression, the next PM must also consider what Britain’s security role in Europe should be and NATO’s place within that.

Beyond conventional foreign policy issues, Britain is also going to be heavily shaped and influenced by the rule-making power of the EU, and how the world’s largest market regulates itself, from energy to financial services, consumer products and the environment.

The UK will need a strategy to influence the EU from the outside – something Swiss, Norwegians and Americans will acknowledge is no easy feat. This could include significantly increasing its diplomatic footprint across Europe, working closely with the UK’s private and non-profit sectors, utilizing Britain’s technical expertise in areas like sanctions, and creating new ad hoc groupings to share perspectives and ideas, building on examples like the Northern Future Forum

2. Should Britain do business with President Trump?

President Trump represents a fundamental challenge to Britain: an American president whose belligerent unilateralism runs counter to many of Britain’s foreign policy objectives. His frequent and often shameless diplomatic faux pas – from proposing Nigel Farage be the British ambassador to his dog-whistle attacks on the mayor of London – are compounded by real differences of substance on issues like trade, climate change and nuclear non-proliferation.

A new prime minister must decide how to manage relations with the US administration, whether to challenge or condemn a US president when he acts against Britain’s interests, or use flattery or quieter diplomacy to seek to influence him. Theresa May’s strategy of staying politically close to the president and playing to his ego has yielded little in policy terms, though other world leaders have fared little better.

A new PM will face some uncomfortable choices. Will they continue to defend the Iran nuclear deal alongside European allies while the US continues to undermine it? Do they believe a trade deal with America is desirable or achievable with the current administration, and what are they willing to sacrifice to achieve it? Is the American security guarantee for Europe secure with Donald Trump as president? Judgements on these questions should inform Britain's wider strategy, and its objectives for a future relationship with the European Union.

3. Should Britain prioritize economics or security in its relations with China?

Britain faces its own version of the challenge that many countries face – how to balance the economic and investment benefits of a positive relationship with China with concerns about repressive domestic politics and a more assertive Chinese role regionally and globally. This tension has become more acute for two reasons.

First, the economic dislocation of leaving the EU may create a greater reliance on Chinese trade and investment. China is already a major investor in the UK. If Brexit proves to be disorderly, Britain’s need may be all the greater (though China faces economic headwinds as well). Some in Brussels even fear that the economic difficulties of Brexit may make the UK a soft touch for emerging powers from which it seeks inward investment and market access.

Second, the deterioration in US–China relations means the UK may come under increasing pressure from the United States to take a tough line with China. The controversy over Huawei’s role in delivering 5G networks may become a more regular feature of transatlantic debates, with Britain facing Chinese economic pressure on one side and a squeeze from America over security issues on the other, without the weight of the EU behind it.  

A new prime minister should consider whether the UK’s interests are served by a security role in east Asia, and whether it has the capability to play one.

The UK remains a party to the Five Power Defence Arrangements. The Royal Navy has conducted freedom of navigation exercises in the South China Sea, prompting a rebuke from Beijing. It has also taken steps to deepen security ties with Japan.

But the UK government has struggled to present a coherent position. Some cabinet ministers have sought to open doors to the Chinese market at the same time as others announced their intentions to send aircraft carriers to the Pacific. The next PM will need to find a balance between China and the US, or accept the consequences of more directly taking sides on disputes about trade, technology, and security.

4. How can the contradictions between UK foreign and domestic policy be reconciled?

One of the many problems with the vague and unhelpful slogan ‘Global Britain’ is how it jars with many aspects of domestic policy. This incoherence reduces Britain’s foreign policy credibility and effectiveness.

Britain has actively supported the UN-led Yemen peace process while continuing to support Saudi Arabia’s military campaign through arms sales. Britain wants to build a new ambitious independent trade policy while restricting the migration that is crucial for services trade. British foreign secretaries trumpet the UK’s soft power while the Home Office deports members of the Windrush generation, bungles EU citizenship applications and sets unreasonable burdens for many people seeking visas simply to visit the country.

Global universities are celebrated while international students had their post-study visas cut (a policy that sensibly is likely to be reversed). Britain advocates international tax compliance and transparency while not taking robust steps to regulate the tax haven role played by crown dependencies and overseas territories.

A new prime minister has the chance to get to grips with these inconsistencies and develop foreign and domestic policies which are more coherent and self-re-enforcing.

5. At what level should Britain’s international ambitions be funded?

Successive governments have celebrated the fact the UK is the only Western country to spend 2% of GDP on defence and 0.7% on development. However, this masks some real pressures in the system.

There are significant problems in the defence budget and a growing gap between commitments and committed funds. Meanwhile, the funding of Britain’s diplomacy has been cut by successive governments – Labour, Conservative and coalition – for much of the last 20 years. Numerous bodies have highlighted the problems facing the overstretched and underfunded Foreign Office. Where would defence and diplomacy sit in the new prime minister’s hierarchy of priorities?

The problem is not purely one of funding, but the gap between ambitions, rhetoric and resources. It is not sustainable for British ministers to trumpet Britain’s global ambitions while not properly funding the tools of its influence abroad.

It would be reasonable and understandable for a new prime minister to adjust that ambition and tone down the rhetoric, or alternatively to address resource pressures by investing in diplomacy and defence. But that choice should be informed by a sober reflection on Britain’s international position and interests as it leaves the EU. Brexit offers a chance to revisit assumptions that have guided British policy for a generation. A new prime minister should seize this opportunity.

A realistic vision for the future

All these issues will be more pronounced if the UK leaves the EU with no deal at the end of October. ‘No deal’ would be not simply an economic shock but a diplomatic rupture that will colour the UK’s capacity to negotiate a new relationship with the EU, which will be the first order of business after a ‘no deal’ exit. Trust will be in short supply.

Even if they don’t get to vote on the new prime minister, the public deserves serious answers to these and other questions from the men who want to lead the country. Not the platitudes of ‘Global Britain’ or a reflexive and unexamined British exceptionalism, but a serious, realistic assessment of how Britain will cope with the disruptions of leaving the EU and how it might thrive outside the regional bloc it has been a part of for more than 45 years.




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Virtual Breakfast: Engaging with the EU From the Outside: A Perspective From Norway

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 Affairs
Chair: 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?

Alina Lyadova

Europe Programme Coordinator




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.




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Roles of active-site residues in catalysis, substrate binding, cooperativity, and the reaction mechanism of the quinoprotein glycine oxidase [Enzymology]

The quinoprotein glycine oxidase from the marine bacterium Pseudoalteromonas luteoviolacea (PlGoxA) uses a protein-derived cysteine tryptophylquinone (CTQ) cofactor to catalyze conversion of glycine to glyoxylate and ammonia. This homotetrameric enzyme exhibits strong cooperativity toward glycine binding. It is a good model for studying enzyme kinetics and cooperativity, specifically for being able to separate those aspects of protein function through directed mutagenesis. Variant proteins were generated with mutations in four active-site residues, Phe-316, His-583, Tyr-766, and His-767. Structures for glycine-soaked crystals were obtained for each. Different mutations had differential effects on kcat and K0.5 for catalysis, K0.5 for substrate binding, and the Hill coefficients describing the steady-state kinetics or substrate binding. Phe-316 and Tyr-766 variants retained catalytic activity, albeit with altered kinetics and cooperativity. Substitutions of His-583 revealed that it is essential for glycine binding, and the structure of H583C PlGoxA had no active-site glycine present in glycine-soaked crystals. The structure of H767A PlGoxA revealed a previously undetected reaction intermediate, a carbinolamine product-reduced CTQ adduct, and exhibited only negligible activity. The results of these experiments, as well as those with the native enzyme and previous variants, enabled construction of a detailed mechanism for the reductive half-reaction of glycine oxidation. This proposed mechanism includes three discrete reaction intermediates that are covalently bound to CTQ during the reaction, two of which have now been structurally characterized by X-ray crystallography.




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The recalibration of Chinese assertiveness: China's responses to the Indo-Pacific challenge

8 January 2020 , Volume 96, Number 1

Feng Liu

In response to the changing geopolitical landscape in Asia, both China and the United States attempt to alter the regional order in their own favour, both in the economic and security realms. This article shows how diverging views on future arrangements are leading to strategic shifts and increasing tension between these two Great Powers. As part of its quest for Great-Power status, China has been actively pushing its regional initiatives such as the Belt and Road Initiative (BRI) and the Asian Infrastructure Investment Bank (AIIB), as well as adopting assertive security policies towards its neighbours. In contrast, in order to counter China's growing influence America's regional strategy is undergoing a subtle shift from ‘rebalancing to Asia’ to focusing on the ‘Indo-Pacific’ region. However, amid an intensifying trade war and other challenges facing the region, China has chosen to moderate its proactive foreign policy-orientation in the past few years. In particular, China has made attempts to downplay its domestic rhetoric, rebuild strategic relationship with India and Japan, and to reassure ASEAN states in the South China Sea. In response to the Indo-Pacific strategy, it would be more effective for China to articulate a more inclusive regional vision and promote an institutional framework that also accommodates a US presence in the region.




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Evasive balancing: India's unviable Indo-Pacific strategy

8 January 2020 , Volume 96, Number 1

Rajesh Rajagopalan

India has adopted the Indo-Pacific concept with uncharacteristic speed. This article examines India's Indo-Pacific strategy, which evolved out of its earlier ‘Look East’ and ‘Act East’ policies but is much more focused on strategic concerns than on trade or connectivity. As such, the strategy is subset of its China policy, and includes contradictory elements of balancing China by building partnerships with the United States as well as with regional powers, while simultaneously pursuing a reassurance strategy to convince Beijing that India is not really balancing China. The combination of these contradictory elements is characterized as evasive balancing, which is a more useful concept than either pure balancing or hedging for understanding the policies of India and of many other countries in the region that are trying to manage China's rise. However, reassurance strategies rarely work and the combination of balancing and reassurance is even less likely to be viable.




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The Belt and Road Initiative: geo-economics and Indo-Pacific security competition

8 January 2020 , Volume 96, Number 1

Mingjiang Li

The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition.




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The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace

Invitation Only Research Event

12 May 2020 - 10:00am to 11:30am
Add to Calendar

Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria.
 
This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication.
 
Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation.

Nilza Amaral

Project Manager, International Security Programme




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Inclusive Peacebuilding

Members Event

9 March 2020 - 6:00pm to 7:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Awino Okech, Chair, Centre for Gender Studies, SOAS
Wajd Saleh Barahim, Post-war Recovery Specialist, Peace Track Initiative

Chair: Dr Patricia Lewis, Research Director, Conflict, Science & Transformation; Director, International Security Programme, Chatham House

In October 2000, the United Nations Security Council unanimously adopted Resolution 1325 which recognizes women’s rights in the context of international peace and security.

It stresses the importance of women’s meaningful participation in post-conflict peacebuilding and calls on member states to incorporate a gender perspective in peacekeeping and peacebuilding operations.

The 1325 framework has paved the way for the development of numerous institutions, initiatives and resolutions. Despite these developments – and considering the disproportionate impact of conflict on women – women remain underrepresented in peace processes.

This panel brings together women peacebuilders from around the world to share their experiences of being involved in peace processes and to discuss the critical importance of women’s involvement in achieving lasting stability.

What roles do women currently play in peacebuilding processes and how can we maximize cross-learning from their experiences? Why have multilateral and international commitments failed to normalize women’s participation in peace processes?

And how do we deconstruct narratives that might suggest women’s participation in peace processes is more legitimate if it is institutional?

Members Events Team




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Civil society perspectives on sexual violence in conflict: patriarchy and war strategy in Colombia

4 March 2020 , Volume 96, Number 2

Anne-Kathrin Kreft

In international policy circles, conflict-related sexual violence (CRSV) is commonly viewed as a weapon of war, a framing that researchers have criticized as overly simplistic. Feminist scholars in particular caution that the ‘weapon of war’ framing decontextualizes sexual violence in conflict from the structural factors of gender inequality that underpin its perpetration. In light of these tensions, how do politically relevant local actors perceive the nature and the origins of conflict-related sexual violence? Civil society organizations often actively confront conflict-related sexual violence on the ground. A better understanding of how their perceptions of this violence align or clash with the globally dominant ‘weapon of war’ narratives therefore has important policy implications. Interviews with representatives of Colombian women's organizations and victims' associations reveal that these civil society activists predominantly view conflict-related sexual violence as the result of patriarchal structures. The mobilized women perceive sexual violence as a very gendered violence that exists on a continuum extending through peace, the everyday and war, and which the presence of arms exacerbates. Strategic sexual violence, too, is understood to ultimately have its basis in patriarchal structures. The findings expose a disconnect between the globally dominant ‘weapon of war’ understanding that is decontextualized from structural factors and a local approach to CRSV that establishes clear linkages to societal gender inequality.




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Perspectives on Nuclear Deterrence in the 21st Century

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

Dr Beyza Unal

Senior Research Fellow, International Security Programme

Yasmin Afina

Research Assistant, International Security Programme

Dr Patricia Lewis

Research Director, Conflict, Science & Transformation; Director, International Security Programme

Dr John Borrie

Associate Fellow, International Security Programme

Dr Jamie Shea

Associate Fellow, International Security Programme

Peter Watkins

Associate Fellow, International Security Programme

Dr Maria Rost Rublee

Associate Professor of International Relations, Monash University

Cristina Varriale

Research Fellow in Proliferation and Nuclear Policy, RUSI

Dr Tanya Ogilvie-White

Adjunct Senior Fellow, Griffith Asia Institute, Griffith University

Dr Andrew Futter

Associate Professor of International Politics, University of Leicester

Christine Parthemore

Chief Executive Officer, Council on Strategic Risks (CSR)

2020-04-20-NuclearDeterrence.jpeg

Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence.

Summary

  • This collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.
  • Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.
  • Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.
  • Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.
  • Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. 
  • While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice.




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Victory and Memory: WW2 Narratives in Modern Day Russia and Ukraine

Invitation Only Research Event

11 May 2020 - 4:00pm to 5:30pm
Add to Calendar
Nina Tumarkin, Kathryn Wasserman Davis Professor of Slavic Studies; Professor of History; Director, Russian Area Studies Program, Wellesley College
Georgiy Kasianov, Head, Department of Contemporary History and Politics, Institute of History of Ukraine, National Academy of Sciences of Ukraine
Chair: Robert Brinkley, Chairman, Steering Committee, Ukraine Forum, Chatham House
In 2020 the world commemorates the 75th anniversary of the end of World War II. The Russian government has organized a wide range of activities to mark the USSR’s victory, aiming to raise the already prominent role of the USSR to a new level. Moscow also uses its narrative about the war as a propaganda tool. Ukraine, which suffered disproportionally huge human losses and material destruction during WWII, is departing from its Soviet legacy by focusing commemorative efforts on honouring the victims of WWII rather than on glorifying victory. 
 
This event will analyze the evolution of the WWII narratives in Russia and Ukraine in recent years. The panellists will discuss the role of those narratives in shaping national discourses and their implications for the countries' respective futures.
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274

Department/project




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India in Transition: The 2014 Election in Perspective

Research Event

16 October 2013 - 12:00pm to 1:00pm

Chatham House, London

Event participants

Sumantra Bose, Professor of International and Comparative Politics, LSE; Author, Transforming India: Challenges to the World's Largest Democracy

India's 16th general election in 2014 is shaping up to be a critical juncture in the evolution of the nation's politics. The speaker will discuss its significance, focusing particularly on the decisive emergence of regional leaders and parties as the dominant actors of India's democracy.

Department/project




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Alain de Botton on how the news should aim to improve our lives

6 February 2014 , Volume 70, Number 1

The author of books on love, religion and Proust, explains why the news agenda should be more positive

Agnes Frimston

deBotton.jpg

Photo: Getty Images

Is the news our society’s religion today?

In the developed economies, the news now occupies a position of power at least equal to that formerly enjoyed by the faiths. Matins has been transubstantiated into the breakfast bulletin, vespers into the evening report. It also demands that we approach it with some of the same deferential expectations we would once have harboured for the faiths. Here, too, we hope to receive revelations, learn who is good and bad, fathom suffering and understand the unfolding logic of existence. And here too, if we refuse to take part in the rituals, there could be imputations of heresy.

What would you like the news to be?

It feels like there is always an infinite amount of news, so much is happening in the world every day. Yet after a while it becomes clear that the same kinds of event are recurring again and again. The details change, but all circle round the same archetypal story. Men in highly responsible positions are coming unstuck because their desires lead them to do things that, when made public, are shameful.

Identifying the underlying theme is more important in the long run than going through the details of every case. The news that matters is not so much that this MP or banker did what they did. What we need to address is why such things happen.

How do you keep the public interested in the news that does matter?

We cannot be collectively dragged into being more responsible through guilt. The Arctic ice is melting and this is going to have major, lasting implications for sea levels and weather around the world. A few people care a lot but, strangely, Taylor Swift’s legs are far more captivating. The starting point has to be indulgence towards the way our minds work. We are interested in Swift’s legs not because we are evil – but because we are wired in unhelpful ways. If we are going to be interested en masse in the defrosting poles, we need to take our fragilities on board and therefore get serious about trying to make important news not just ‘important’, but also beguiling. Then things stand a chance of changing.

You argue that we should set aside ‘neutral reporting’. Are you asking for more bias?

Many people imagine that what makes news organizations serious is their ability to provide us with information that is ‘unbiased’. But facts can only become meaningful and relevant to us when they slot into some picture of important or trivial, right or wrong. News organizations that vaunt their neutrality forget that neutrality is simply impossible. There is no risk-free, all-knowing sober set of answers to cling to. At heart, the word ‘bias’ simply alludes to the business of having a ‘take’ on existence. One may have a better or worse take, but one can’t make any sense of the flotsam of daily events in the news without having one. All of the figures we revere in history have been highly biased: each of them had a strong sense of what mattered and why, and their judgments were anything but perfectly balanced. They were just flavoured in the right way. We don’t need news stripped of bias, we need news presented to us with the best kinds of bias.

What is the purpose of foreign reporting?

Foreign reporting implicitly defers to the priorities of the state and of business, occupying itself almost exclusively with whom and where we should fight, trade or sympathize. But it should instead offer us a means by which to humanize the Other who instinctively repels, bores or frightens us and with whom we can’t, without help, imagine having anything in common.

Foreign countries also furnish a scale against which our own nation and ways of living can be assessed; they may help us to see our national oddities, blind spots and strengths. Stories from them may lead us to a fresh appreciation of the imperfect freedoms and comparative abundance of our homelands, which otherwise would be treated only as matters for grumbling or blame. Alternatively, problems with which we are all too familiar may be revealed to have been solved better elsewhere.

You mention the importance of historical perspective in reporting, so that we can respond to issues with context.

Contrary to what the news usually suggests, hardly anything is ever totally new, few things are truly amazing and very little is absolutely terrible. The economic indices are grim, but we have weathered comparable drops many times over the past century and even the worst scenarios only predict that we will return to a standard of living we had a few decades ago. A bad avian flu may disrupt international travel and defeat known drugs for a while, but research will eventually understand and contain it. The floods look dramatic, but in the end, they will affect merely a fraction of the population and recede soon.

How can photography change the way we report news?

There are now more images than ever before in the coverage we consume, but the problem lies in the lack of ambition behind their production and display. We might usefully divide news photographs into two genres. The first are images of corroboration, which do little other than confirm something we have learnt about a person or an event through an accompanying article. The second is a rarer kind of image, the photograph of revelation, whose ambition is not simply to back up what the text tells us but to advance our level of knowledge to a new point. It sets out to challenge cliché. We have lost any sense of photography’s potential as an information-bearing medium, as a force to properly introduce us to a planet that we keep conceitedly assuming that we know rather well already.

Do you feel oppressed by the news?

The pressure of not missing out makes one feel one has to care about a given topic, even when one doesn’t want to. Take Mandela’s funeral. One was supposed to care a lot, and yet, you don’t. You know the reasons why it is important, but they don’t grip you because you are focused elsewhere on subjects that, while tiny in the grand scheme of things, matter a lot within your context. It would be dangerous if hardly anyone paid attention to what the Government was doing, or what was happening to the environment. But it is not right to go from this to the demand that everyone should be interested in every item whenever the news machine calls. We badly need people whose attention is not caught up in the trends of the moment and who are not looking in the same direction as everyone else. We need people scanning the less familiar parts of the horizon.

Do you think we get the news we deserve?

Much of what we now take for granted as news has its origins in the information needed by those people taking major decisions or who are at the centre of national affairs. Ease of communication and a generous democratic impulse means that selections from the knowledge base, originally designed for decision-makers, now gets routinely sent via the media to very large numbers of people. It is as if a dossier which might properly arrive upon the desk of a Minister has accidentally been delivered to the wrong address and ends up on the breakfast table of an electrician in Pitlochry. Every day the news gives us stuff that is both interesting for some people and irrelevant to you. No wonder we’re sometimes a bit bored. It’s not our fault.




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Human Development as Positive Freedom: A World View Since 1870

Invitation Only

26 February 2014 - 8:15am to 9:30am

Chatham House, London

Event participants

Leandro Prados de la Escosura, Professor, Economic History, Universidad Carlos III de Madrid 

This meeting will see the launch of the Chatham House-CAGE briefing paper ‘Human Development as Positive Freedom: A World View since 1870’. The author of the paper will argue that while substantial gains in world human development have been achieved since 1870, the main period of improvement actually occurred between World War I and 1970. He will further argue that, despite initial successes in lifting human development, the socialist experiments of the 20th century failed to sustain momentum and then (with the exception of Cuba) stagnated and fell behind prior to the socialist model's ultimate demise. Finally, he will contend that since 1970, while most OECD countries have experienced a second (later life) health transition, all developing regions have fallen behind in this dimension.

The briefing paper is the 12th publication in the Chatham House-CAGE series, published in partnership with the Centre for Competitive Advantage in the Global Economy (CAGE) at the University of Warwick.

Attendance at this event is by invitation only.




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Human Development as Positive Freedom: A World View Since 1870

1 February 2014

Substantial gains in world human development have been achieved since 1870, but research shows that the main improvement actually occurred between the First World War and 1970.

Leandro Prados de la Escosura

20140200CAGEhumandevelopmentW.jpg

Photo by 1xpert /iStock.

Summary points:

  • Substantial gains in world human development have been achieved since 1870, but research shows that the main improvement actually occurred between the First World War and 1970.
     
  • Across-the-board advances took place in life expectancy and education between 1920 and 1950, a phase during which there was a major backlash against economic globalization. This is evidence of a development puzzle: economic growth and human development do not always go hand in hand.
     
  • Between 1913 and 1970 the absolute gap between most countries in the OECD and the rest of the world widened, with different regions experiencing mixed success in catching up. Since the 1970s the performance of developing regions has varied greatly.
     
  • Despite initial successes in lifting human development, the socialist experiments of the 20th century failed to sustain momentum and then (with the exception of Cuba) stagnated and fell behind prior to the socialist model’s ultimate demise.
     
  • Education has been the driving force behind the limited catching-up of developing regions in terms of long-term human development. In terms of life expectancy,these regions achieved significant gains only during the first (early-life) health transition. Since 1970, while most OECD countries have experienced a second (later-life) health transition, all developing regions have fallen behind.
Project: Shifting Competitive Advantage in the Global Economy 


Launch event

Human Development as Positive Freedom: A World View Since 1870
26 February 2014

 

 




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The Crisis in Syria from the Perspective of Syrian Kurds

Research Event

20 May 2014 - 10:00am to 2:00pm

Chatham House, London

Event participants

Salih Muslim, Chairman, Democratic Union Party (PYD), Syria

This expert-level meeting will bring together policy-makers, analysts and Chatham House experts to discuss the crisis in Syria from the perspective of Syrian Kurds. 

Salih Muslim is a prominent member of the Kurdish opposition in Syria and chairman of the Democratic Union Party (PYD), which controls Rojava, an autonomous administration area in northern Syria. He is also the deputy coordinator of the National Coordination Committee for Democratic Change. At this roundtable he will discuss the movement for a political settlement and prospects for a Kurdish democratic model in Syria.

To enable as open a debate as possible, the question and answer session will be held under the Chatham House Rule.

Event attributes

Chatham House Rule




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Islamism and Its Alternatives in the GCC

Research Event

14 December 2014 - 9:00am to 15 December 2014 - 2:00pm

Doha, Qatar

This expert-level workshop will bring together around 30 Gulf scholars, experts and practitioners from a variety of professional and academic backgrounds to share their analysis and research on the role of Islam in social and political movements in the GCC countries, as well as alternatives to Islamism. It will place political Islam in historical context, explore the differences between different strands of political Islam and the ways in which different country contexts have shaped the behaviour of movements that claim to have religious legitimacy, such as the institutions and legal regulations governing political movements.

This event is part of Chatham House’s Future Trends in the GCC research project, and is held in partnership with Qatar University’s Gulf Studies Center in Doha, Qatar.

Event attributes

External event




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Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake

S Xu
Jul 1, 1997; 38:1289-1298
Articles




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Lipidomics reveals a remarkable diversity of lipids in human plasma

Oswald Quehenberger
Nov 1, 2010; 51:3299-3305
Research Articles




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Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells

JL Dixon
Feb 1, 1993; 34:167-179
Reviews




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Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

JM Dietschy
Oct 1, 1993; 34:1637-1659
Reviews




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The Morass of Central American Migration: Dynamics, Dilemmas and Policy Alternatives

Invitation Only Research Event

22 November 2019 - 8:15am to 9:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Anita Isaacs, Professor of Political Science, Haverford College; Co-Director, Migration Encounters Project
Juan Ricardo Ortega, Principal Advisor for Central America, Inter-American Development Bank
Chair: Amy Pope, Associate Fellow, Chatham House; US Deputy Homeland Security Adviser for the Obama Administration (2015-17)

2019 has seen a record number of people migrating from Central America’s Northern Triangle – an area that covers El Salvador, Guatemala and Honduras. Estimates from June 2019 have placed the number of migrants at nearly double of what they were in 2018 with the increase in numbers stemming from a lack of economic opportunity combined with a rise in crime and insecurity in the region. The impacts of migration can already be felt within the affected states as the exodus has played a significant role in weakening labour markets and contributing to a ‘brain drain’ in the region. It has also played an increasingly active role in the upcoming US presidential election with some calling for more security on the border to curb immigration while others argue that a more effective strategy is needed to address the sources of migration. 

What are the core causes of Central American migration and how have the US, Central American and now also Mexican governments facilitated and deterred migration from the region? Can institutions be strengthened to alleviate the causes of migration? And what possible policy alternatives and solutions are there that could alleviate the pressures individuals and communities feel to migrate?   

Anita Isaacs, professor of Political Science at Haverford College and co-director of the Migration Encounters Project, and Juan Ricard Ortega, principal advisor for Central America at the Inter-American Development Bank, will join us for a discussion on the core drivers of migration within and across Central America.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




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Civil society perspectives on sexual violence in conflict: patriarchy and war strategy in Colombia

4 March 2020 , Volume 96, Number 2

Anne-Kathrin Kreft

In international policy circles, conflict-related sexual violence (CRSV) is commonly viewed as a weapon of war, a framing that researchers have criticized as overly simplistic. Feminist scholars in particular caution that the ‘weapon of war’ framing decontextualizes sexual violence in conflict from the structural factors of gender inequality that underpin its perpetration. In light of these tensions, how do politically relevant local actors perceive the nature and the origins of conflict-related sexual violence? Civil society organizations often actively confront conflict-related sexual violence on the ground. A better understanding of how their perceptions of this violence align or clash with the globally dominant ‘weapon of war’ narratives therefore has important policy implications. Interviews with representatives of Colombian women's organizations and victims' associations reveal that these civil society activists predominantly view conflict-related sexual violence as the result of patriarchal structures. The mobilized women perceive sexual violence as a very gendered violence that exists on a continuum extending through peace, the everyday and war, and which the presence of arms exacerbates. Strategic sexual violence, too, is understood to ultimately have its basis in patriarchal structures. The findings expose a disconnect between the globally dominant ‘weapon of war’ understanding that is decontextualized from structural factors and a local approach to CRSV that establishes clear linkages to societal gender inequality.




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Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease]

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.




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A kainate receptor-selective RNA aptamer [Neurobiology]

Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2'-OH group with 2'-fluorine. These 2'-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits.




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Victory and Memory: WW2 Narratives in Modern Day Russia and Ukraine

Invitation Only Research Event

11 May 2020 - 4:00pm to 5:30pm
Add to Calendar
Nina Tumarkin, Kathryn Wasserman Davis Professor of Slavic Studies; Professor of History; Director, Russian Area Studies Program, Wellesley College
Georgiy Kasianov, Head, Department of Contemporary History and Politics, Institute of History of Ukraine, National Academy of Sciences of Ukraine
Chair: Robert Brinkley, Chairman, Steering Committee, Ukraine Forum, Chatham House
In 2020 the world commemorates the 75th anniversary of the end of World War II. The Russian government has organized a wide range of activities to mark the USSR’s victory, aiming to raise the already prominent role of the USSR to a new level. Moscow also uses its narrative about the war as a propaganda tool. Ukraine, which suffered disproportionally huge human losses and material destruction during WWII, is departing from its Soviet legacy by focusing commemorative efforts on honouring the victims of WWII rather than on glorifying victory. 
 
This event will analyze the evolution of the WWII narratives in Russia and Ukraine in recent years. The panellists will discuss the role of those narratives in shaping national discourses and their implications for the countries' respective futures.
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274

Department/project




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Growth in a Multilateral World: The Role of Inclusive Trade and Quality Investment




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




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Planning for Africa's Future: Youth Perspectives from Kenya and South Africa




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




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Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20