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The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation]

The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity.




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Chatham House appoints Adam Ward as deputy director

17 January 2017

Chatham House is pleased to announce that Adam Ward will join the institute in a new role as deputy director.

Adam Ward takes up the position of deputy director on 10 April 2017 and will join Chatham House from the International Institute of Strategic Studies (IISS) in London, where he has served as director of studies since 2009.

As deputy director, Adam will oversee and coordinate Chatham House's multiple areas of research, help manage the institute's relationships with key external constituencies, ensure the delivery of high-quality publications and deputize for the institute’s director, Dr Robin Niblett.

This is a new position, created after a period of sustained growth for Chatham House, especially in research and policy outputs. The appointment also coincides with the opening this spring of new working and meeting space for the institute in Ames House, the building adjacent to Chatham House on Duke of York Street in the St James's area of central London.

At IISS, publishers of the renowned annual Military Balance and other high-quality publications and organizers of influential annual security summits, including the Shangri-La Dialogue, Adam was responsible for the oversight of its worldwide research activities, which are also conducted from IISS offices in the Middle East, Asia and the US. Adam led the establishment of the office in Washington and was previously a senior fellow for East Asia.

Dr Robin Niblett, director of Chatham House, said:‘I am delighted that Adam Ward will shortly be joining Chatham House. At a time of great uncertainty and risk in international affairs, his experience in leading research at the prestigious IISS and knowledge of how research institutes can develop and communicate their ideas on public policy will be of enormous value. His wide-ranging expertise on geopolitics and the foreign policies of China and the United States will also help the institute develop integrated projects that reflect the changing balance of world power. I very much look forward to working with him.

Adam Ward said:‘I am excited to take up this opportunity to join Chatham House's executive leadership and to work with Robin Niblett and his senior management team. Chatham House has a well-deserved reputation for rigour and excellence in its research and for providing insights and solutions across a comprehensive range of international challenges. Chatham House's capacity for inter-disciplinary research is one of its distinctive strengths, and I look forward to ensuring its ideas are brought to bear on an ever more complex policy environment.’ 

Editor's notes

About Chatham House

Chatham House, the Royal Institute of International Affairs, is an independent policy institute based in London. Its mission is to help build a sustainably secure, prosperous and just world. Founded in 1920, Chatham House engages governments, the private sector, civil society and its members in open debate and confidential discussion on the most significant developments in international affairs. Each year, the institute runs more than 300 private and public events – conferences, workshops and roundtables – in London and internationally with partners. Its convening power attracts world leaders and the best analysts in their respective fields from across the globe.

About Adam Ward

As director of studies of the IISS, Adam Ward has since 2009 led the execution of the Institute’s worldwide research activities, including setting priorities, raising funds and the management of a research staff distributed across four international offices. Between 2009 and 2014 he organized the annual series of IISS Global Strategic Review conferences. He represents the institute internationally among its audiences in government, the expert community and business.

Adam was previously, from 2006, executive director of the IISS office in Washington DC, where he led the relocation of the office to larger premises, an expansion in its staff, the development of a busy events programme and research activities and acted as the institute’s principal liaison with US government agencies and the Washington-based diplomatic and academic community. Prior to this, he served from 2001 simultaneously as the IISS senior fellow for East Asian security and editor of Strategic Comments, a series of analytical briefing papers on global topics.

He began his career in 1997 as an analyst and editor at the consulting firm Oxford Analytica, focusing on the Asia-Pacific region. He holds a bachelor’s degree in German and Politics and an MA in International Relations, both from the University of Warwick, and also studied for one academic year at the University of Salzburg in Austria.




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Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources

30 May 2019

Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department.

He brings substantial expertise on food systems and environmental change to the role and will focus on establishing new initiatives at the intersection of research and policymaking.

Tim was appointed as a distinguished visiting fellow of Chatham House in the Energy, Environment and Resources Department in 2016. He has since contributed to the institute in a number of ways, not least through leading the GCRF-AFRICAP project which aims to enhance policy making in Sub-Saharan Africa, through building climate-smart food systems.

Tim’s research focuses on food security and building food systems that are resilient and sustainable, working within the broader areas of ecology, natural resources and climate change impacts. He has published over 150 academic papers, most tackling the core themes of agriculture’s environmental impact and more generally how systems respond to environmental change. He is a lead author of the upcoming Intergovernmental Panel on Climate Change (IPCC) special report on climate change and land. He is also coordinating lead author on international risks for the UK’s Climate Change Risk Assessment, which draws on his broader interests in sustainable finance, trade and energy. He has advised other governments as well as global companies on related issues.

Tim joins Chatham House in his new capacity from the University of Leeds where he is dean of strategic research initiatives. Prior to this, from 2011 to 2016, Tim was the champion of the UK’s Global Food Security programme, a large multi-agency partnership of the UK’s public bodies involved in addressing challenges around food. He has also been research dean in the Faculty of Biological Sciences, and head of department, at Leeds.

Dr Robin Niblett, director of Chatham House, said: 'Tim’s wealth of experience will be especially valuable as we build up our interdisciplinary Chatham House research theme of promoting sustainable growth. We look forward to welcoming Tim to his new role in early July.'

Tim Benton said: 'I am honoured to be joining Chatham House as Research Director for Energy, Environment and Resources. Chatham House has a global reputation in these areas, on which we can build. Informed analysis, combined with effective action to transition towards sustainable economies, is needed now, more than ever.'

About the Energy, Environment and Resources Department

The Energy, Environment and Resources department at Chatham House seeks to advance the international debate on energy, environment and development policy and to influence and enable decision-makers – governments, NGOs and business – to take well-informed decisions that contribute to achieving sustainable development. Independent of any actor or ideology, we do this by carrying out innovative research on major policy challenges, bringing together diverse perspectives and constituencies and injecting new ideas into the international arena.

Tim Benton takes over the role from Rob Bailey who has joined Marsh & McLennan Insights as Director, Climate Resilience.




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Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy

19 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.

The Chatham House Prize is awarded to the person, persons or organization who is deemed to have made the most significant contribution to the improvement of international relations in the previous year. The presentation ceremony and panel discussion with the winners will be livestreamed on Wednesday.

The Blue Planet II series highlighted the damage caused by discarded plastics to the world’s oceans and marine wildlife. It is estimated that there are more than 150 million tonnes of plastic in the world’s oceans; resulting in the deaths of 1 million birds and 100,000 sea mammals each year. 

Dr Robin Niblett, director of Chatham House said: ‘Plastic pollution is one of the gravest challenges facing the world’s oceans, and undoubtedly an international issue. Sir David and the BBC Studios Natural History Unit played an instrumental role in helping to put this issue at the forefront of the public agenda. Blue Planet II spurred a passionate global response and generated clear behavioural and policy change.’

This year the G20 agreed on an international framework to address marine plastic litter, acknowledging the increasing urgency of the issue and the need for an international solution. This follows action from the UK government, including a plan to ban common plastic items and investment in global research.

See full award citation

Read more about Chatham House's research work in this area

Other nominees

Dr Niblett thanked Chatham House members for voting and acknowledged the outstanding achievements of the 2019 nominees:

Abiy Ahmed, prime minister of Ethiopia, nominated for his efforts to transform civic leadership and promote plural politics, free speech and peace in Ethiopia 

Katrín Jakobsdóttir, prime minister of Iceland, nominated for her commitment to gender equality and women’s financial inclusion in Iceland 

Event

The Prize was presented to Sir David and Julian Hector by Her Majesty The Queen at Chatham House on Wednesday 20 November.

Watch video from the event

For more information please contact

Chatham House Press Office
pressoffice@chathamhouse.org
+44 (0)207 957 5739

BBC Studios Natural History Unit Communications Manager
Lynn.li@bbc.co.uk
+44 (0) 7513 137893

About the Chatham House Prize

The Chatham House Prize is voted for by Chatham House members, following nominations from the institute’s staff. The award is presented on behalf of the institute's patron, Her Majesty the Queen, representing the non-partisan and authoritative character of the Prize.

The Chatham House Prize was launched in 2005. Previous recipients of the Prize include the Committee to Protect Journalists, Colombian president Juan Manuel Santos, president of Ghana John Kufuor, Médecins Sans Frontières and Melinda Gates, co-founder of the Bill and Melinda Gates Foundation.

Chatham House is a world-leading policy institute based in London. Our mission is to help governments and societies build a sustainably secure, prosperous and just world. We engage governments, the private sector, civil society and our members in open debate and private discussions about the most significant developments in international affairs.  Our research and policy ideas involve rigorous analysis of critical global, regional and country-specific challenges and opportunities.

About BBC Studios Natural History Unit 

BBC Studios Natural History Unit produces the world’s most iconic natural history programmes, such as Blue Planet II and Planet Earth II, which have been watched by more than a billion people globally. Ranging from technically challenging live shows and super-landmarks to long-running series and children’s content, The Natural History Unit programmes include Dynasties, Blue Planet Live, Springwatch, Animal Babies: First Year On Earth, Andy’s Dinosaur Adventures as well as the currently on air Seven Worlds, One Planet presented by Sir David Attenborough and third-party commissions for Discovery, Apple, Quibi, National Geographic and BBC America. 

The Natural History Unit is part of BBC Studios, a subsidiary of the BBC, which develops, produces and distributes bold, British content, making over 2,500 hours of content each year, operating in 22 markets globally and generating revenue of around £1.4bn. In the year to March 2019, it returned £243m to the BBC Group, complementing the BBC’s licence fee and enhancing programmes for UK audiences.




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Regulatory Issues and TTIP

Invitation Only Research Event

24 November 2014 - 8:45am to 10:00am

Chatham House, London

Event participants

Ignacio Garcia Bercero, Director General, Trade, European Commission
Chair: Quentin Peel, Mercator Senior Fellow, Europe Programme, Chatham House

This event will focus on the challenges of regulatory issues in the negotiations with the United States, including how to promote convergence of regulations and standards and how to explore equivalency in a number of sectors such as automobiles, financial services, and pharmaceuticals. The event will also examine how closer regulatory cooperation between the US and EU can improve international cooperation on regulatory matters.

Attendance at this event is by invitation only.

US and Americas Programme




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The Shifting Economic and Political Landscape in the US and Europe - What Factors Matter?

Invitation Only Research Event

2 November 2017 - 8:15am to 9:15am

Chatham House, London

Event participants

Megan Greene, Managing Director and Chief Economist, Manulife Asset Management 

Megan Greene will join us for a discussion on the prospect of future economic and political uncertainty on both sides of the Atlantic.

The first year of Donald Trump’s presidency and the ongoing saga of Brexit negotiations underscore the amount of uncertainty about the economic future on both sides of the Atlantic.

Despite that, business and consumer confidence in the US and continental Europe have soared. Are we still stuck in secular stagnation, or are we breaking out of the low growth, low inflation, low rate environment we’ve been in for years?

What opportunities and risks are posed by this year’s elections in France and Germany, the upcoming elections in Italy, and the mid-term elections in the US?

This event is part of the US and Americas Programme ongoing series on Transatlantic Perspectives on Common Economic Challenges. This series examines some of the principal global challenges that we face today and potentially differing perspectives from across Europe and the US.

Attendance at this event is by invitation only.

Event attributes

Chatham House Rule

Courtney Rice

Senior Programme Manager, US and the Americas Programme
(0)20 7389 3298




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The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation]

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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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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The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism]

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.




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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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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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Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research




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The Proteome of the Mouse Photoreceptor Sensory Cilium Complex

Qin Liu
Aug 1, 2007; 6:1299-1317
Research




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Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules

Yi Zhang
Sep 1, 2005; 4:1240-1250
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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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

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




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The Human Plasma Proteome: History, Character, and Diagnostic Prospects

N. Leigh Anderson
Nov 1, 2002; 1:845-867
Reviews/Perspectives




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Reply to Cosgrove: Non-enzymatic action of expansins [Letters to the Editor]

In our computational study, we use molecular simulations to substantiate a hypothetical mechanism for glycosidic bond cleavage in the presence of a single catalytic acid at the active site of the mutant D10N HiCel45A. In addition to discussing this plausible mechanism from the context of structurally related MltA lytic transglycosylase and subfamily C GH45s, we also suggest the implications of the plausible mechanism for our current understanding of the action of expansins and lytic transglycosylases. As correctly pointed out by Professor Cosgrove (1), there is large body of evidence, a significant portion of which was regrettably not discussed in our paper, that suggests that expansins are incapable of lytic action on polysaccharide substrates. Whereas these insights do not change the results or the conclusions of our article, we would like to thank Professor Cosgrove for these additional insights. In particular, our main point with respect to expansins is that our results suggest the possibility that expansins are capable of nonhydrolytic lytic activity. Our intention was not to suggest this was the mechanism of expansins, but that it should be considered based on our results and the similarity of the active sites.The molecular mechanisms of how expansins enable cell wall expansion remains to be fully understood. Whereas our proposed mechanism resulting in the formation of the 1,6-anhdro product might be found in expansins and might contribute to the mode of action of expansins, we would like to emphasize that the intent of this study was only to suggest this as a...




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Non-enzymatic action of expansins [Letters to the Editor]

From their simulations of endoglucanase Cel45A, Bharadwaj et al. (1) propose that structurally related expansins and MltA may cut glycan backbones without generating reducing ends. This is tenable for MltA, a peptidoglycan lytic transglycosylase whose action produces nonreducing 1,6-anhydro products, but is untenable for expansins.Expansins loosen plant cell walls and induce wall expansion. Contrary to the assertion by Bharadwaj et al., the conclusion that expansins are not lytic is not merely based on lack of new reducing ends but is supported by multiple (negative) tests for polysaccharide cleavage that do not rely on detection of reducing ends. At least eight studies with three divergent groups of expansins document this point. For instance, α-expansin did not reduce the viscosity of various wall polysaccharide solutions, an endolytic assay that does not rely on measuring reducing ends (e.g. see Ref. 2 and other studies).Walls treated with α-expansin did not release saccharide fragments, measured by pulsed amperometric detection, which can detect nonreducing saccharides (3).In the case of β-expansins, protein treatments did not cleave the backbones of a wide range of dye-coupled cross-linked wall polysaccharides; nor did they cleave backbones of polysaccharides extracted from plant cell walls, measured by gel permeation chromatography (4).For five microbial expansins, tests with a range of dye-coupled cross-linked polysaccharides likewise did not detect lytic activity (e.g. see Ref. 5). Thus, extensive published evidence argues against lytic action by expansins, as proposed by Bharadwaj (1), and attempts to identify 1,6-anhydro products seem unlikely to succeed.




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The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation]

The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity.




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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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Polarization of protease-activated receptor 2 (PAR-2) signaling is altered during airway epithelial remodeling and deciliation [Immunology]

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.




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Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology]

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.




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Phosphoproteomic characterization of the signaling network resulting from activation of the chemokine receptor CCR2 [Genomics and Proteomics]

Leukocyte recruitment is a universal feature of tissue inflammation and regulated by the interactions of chemokines with their G protein–coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CC chemokine ligand 2 (CCL2), plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to conduct an unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition MS analysis, we quantified both the proteome and phosphoproteome in FlpIn-HEK293T cells stably expressing CCR2 at six time points after activation with CCL2. Differential expression analysis identified 699 significantly regulated phosphorylation sites on 441 proteins. As expected, many of these proteins are known to participate in canonical signal transduction pathways and in the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors and GTPase-activating proteins. Moreover, we identified regulated phosphorylation sites in numerous proteins that function in the nucleus, including several constituents of the nuclear pore complex. The results of this study provide an unprecedented level of detail of CCR2 signaling and identify potential targets for regulation of CCR2 function.




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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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What Europe Can Learn From the Law and Justice Party’s Victory in Poland

15 October 2019

Dr Angelos Chryssogelos

Associate Fellow, Europe Programme
The EU must remain vigilant about threats to liberal democracy in Poland, but European leaders must also accept that PiS’s electoral success is reflective of its ability to deliver on things that other political parties in Europe have long neglected.

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The button of a PiS supporter on election day. Photo: Getty Images.

The Polish election on 13 October resulted, as expected, in a victory for of the ruling Law and Justice party (PiS).

But despite again securing a slim majority in parliament, it has not been wholly a triumph for PiS. And though there continue to be concerns about the party’s authoritarian tendencies, the election has illuminated some important nuances to its support and appeal, which hold lessons for politics across Europe.

Even though some opinion polls had suggested PiS were close to winning a supermajority in parliament that would have allowed it to pursue constitutional changes, the party fell short of that target, while it lost its majority in the Senate. Thus, while PiS may well renew its efforts to consolidate its control over the state apparatus and the media or meddle with the justice system, it becomes much more difficult with the opposition controlling the Senate and being able to scrutinize laws or have a say in the appointment of public officials.

Most importantly, the election result has shown that while Polish citizens were willing to reward a party that delivered on promises of economic growth and redistribution, they were not ready to hand a blank cheque for full-blown institutional realignment to PiS. Tellingly, many moderate candidates in PiS lists performed quite well among the party’s voters. 

Even though they rewarded a party that at times employed harsh rhetoric against Brussels, Polish voters have long expressed some of the strongest rates of support for EU membership, according to Eurobarometer surveys. The government has also faced massive protests against its most radical initiatives, such as reform of the judicial system and a law to almost completely ban abortion that was ultimately scrapped. It is therefore more likely that the party’s radicalism kept it from increasing its share, rather than helping it to secure victory.

This is not to say that the threat of illiberalism does not remain alive in Poland. But it shows that the degree of PiS dominance in Poland has never been comparable to that of Fidesz in Hungary, with which it is often compared.

This was reflected in the party’s own rhetoric. In the election campaign the government mostly focused on its economic record, recognizing that much of its support is conditional on conventional measures of political success like voter welfare. PiS may not give up on its ambition to establish a ‘new Polish republic’, but the elections have made it clear that economic stability rather than political radicalism will ensure its longevity in power – with the latter perhaps even being a liability as the party experiences fatigue in office.

Similarly, despite the government’s antagonistic stance towards the EU on various issues, PiS never entertained ideas of withdrawing from the EU, as some of its critics feared earlier in its term. With the Polish economy deeply entwined with the European market and Poland expecting – probably for the last time – to receive substantial subsidies from the next EU budget, EU membership is a necessary precondition for the economic success for which PiS is claiming credit.

With the pro-European left returning to parliament but also an extreme party of the right winning representation, the next government will have a difficult balancing act as it tries to draw on the benefits of EU membership while maintaining its defiant image towards Brussels.

Ultimately, beneath the rhetoric and the posturing, PiS is a party that has shrewdly combined popular policies from the left and right, fulfilling promises of both cultural sovereignty and economic redistribution. Its reelection should not come as a surprise given that it fulfilled its electoral pledges by delivering some of the things that many voters in western Europe also crave but that mainstream parties there have largely failed to provide.




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Why Britain’s 2019 Election Is Its Most Unpredictable in Recent History

7 November 2019

Professor Matthew Goodwin

Visiting Senior Fellow, Europe Programme
Leadership concerns and a collapse of traditional party loyalties make the December vote uncommonly volatile.

On 12 December, Britain will hold the most consequential election in its postwar history. The outcome of the election will influence not only the fate of Brexit but also the likelihood of a second referendum on EU membership, a second independence referendum in Scotland, the most economically radical Labour Party for a generation, Britain’s foreign and security policy and, ultimately, its position in the wider international order.

If you look only at the latest polls, then the outcome looks fairly certain. Ever since a majority of MPs voted to hold the election, the incumbent Conservative Party has averaged 38%, the opposition Labour Party 27%, the Liberal Democrats 16%, Brexit Party 10%, Greens 4% and Scottish National Party 3%. Prime Minister Boris Johnson and his party continue to average an 11-point lead which, if this holds until the election, would likely deliver a comfortable majority.

Johnson can also point to other favourable metrics. When voters are asked who would make the ‘best prime minister’, a clear plurality (43%) say Johnson while only a small minority (20%) choose the Labour Party leader, Jeremy Corbyn. Polls also suggest that, on the whole, Johnson is more trusted by voters than Corbyn to deal with Brexit, the economy and crime, while Jeremy Corbyn only tends to enjoy leads on health. All of this lends credence to the claim that Britain could be set for a Conservative majority and, in turn, the passing of a withdrawal agreement bill in early 2020.

But these polls also hide a lot of other shifts that are taking place and which, combined, make the 2019 general election unpredictable. One concerns leadership. While Boris Johnson enjoys stronger leadership ratings than Jeremy Corbyn, it should be remembered that what unites Britain’s current generation of party leaders is that they are all unpopular. Data compiled by Ipsos-MORI reveals that while Johnson has the lowest ratings of any new prime minister, Labour’s Jeremy Corbyn has the lowest ratings of any opposition leader since records began.

Another deeper shift is fragmentation. One irony of Britain’s Brexit moment is that ever since the country voted to leave the European Union its politics have looked more ‘European’. Over the past year, one of the world’s most stable two-party systems has imploded into a four-party race, with the anti-Brexit Liberal Democrats and Nigel Farage’s strongly Eurosceptic Brexit Party both presenting a serious challenge to the two mainstream parties.

In the latest polls, for example, Labour and the Conservatives are attracting only 61 per cent of the overall vote, well down on the 80 per cent they polled in 2017. Labour is weakened by the fact that it is only currently attracting 53 per cent of people who voted Labour at the last election, in 2017. A large number of these 2017 Labour voters, nearly one in four, have left for the Liberal Democrats, who are promising to revoke Article 50 and ‘cancel Brexit’. This divide in the Remain vote will produce unpredictable outcomes at the constituency level.

At the other end of the spectrum, the Conservatives are grappling with a similar but less severe threat. Nigel Farage and the Brexit Party are attracting around one in ten people who voted Conservative in 2017, which will make Boris Johnson’s task of capturing the crucial ‘Labour Leave’ seats harder. There is clear evidence that Johnson has been curbing Farage’s appeal, but it remains unclear how this rivalry on the right will play out from one seat to the next.

One clue as to what happens next can be found in those leadership ratings. While 80 per cent of Brexit Party voters back Johnson over Corbyn, only 25 per cent of Liberal Democrat voters back Corbyn over Johnson. Johnson may find it easier to consolidate the Leave vote than Corbyn will find the task of consolidating the Remain vote.

All of this reflects another reason why the election is unpredictable: volatility. This election is already Britain’s fifth nationwide election in only four years. After the 2015 general election, 2016 EU referendum, 2017 general election and 2019 European parliament elections, Britain’s political system and electorate have been in a state of almost continual flux. Along the way, a large number of voters have reassessed their loyalties.

As the British Election Study makes clear, the current rate of ‘vote-switching’ in British politics, where people switch their vote from one election to the next, is largely unprecedented in the post-war era. Across the three elections held in 2010, 2015 and 2017, a striking 49 per cent of people switched their vote.

This is not all about Brexit. Attachment to the main parties has been weakening since the 1960s. But Brexit is now accelerating this process as tribal identities as ‘Remainers’ or ‘Leavers’ cut across traditional party loyalties. All this volatility not only gives good reason to expect further shifts in support during the campaign but to also meet any confident predictions about the election result with a healthy dose of scepticism.




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The EU Cannot Build a Foreign Policy on Regulatory Power Alone

11 February 2020

Alan Beattie

Associate Fellow, Global Economy and Finance Programme and Europe Programme
Brussels will find its much-vaunted heft in setting standards cannot help it advance its geopolitical interests.

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EU Commission President Ursula von der Leyen speaks at the European Parliament in Strasbourg in February. Photo: Getty Images.

There are two well-established ideas in trade. Individually, they are correct. Combined, they can lead to a conclusion that is unfortunately wrong.

The first idea is that, across a range of economic sectors, the EU and the US have been engaged in a battle to have their model of regulation accepted as the global one, and that the EU is generally winning.

The second is that governments can use their regulatory power to extend strategic and foreign policy influence.

The conclusion would seem to be that the EU, which has for decades tried to develop a foreign policy, should be able to use its superpower status in regulation and trade to project its interests and its values abroad.

That’s the theory. It’s a proposition much welcomed by EU policymakers, who know they are highly unlikely any time soon to acquire any of the tools usually required to run an effective foreign policy.

The EU doesn’t have an army it can send into a shooting war, enough military or political aid to prop up or dispense of governments abroad, or a centralized intelligence service. Commission President Ursula von der Leyen has declared her outfit to be a ‘geopolitical commission’, and is casting about for any means of making that real.

Through the ‘Brussels effect’ whereby European rules and standards are exported via both companies and governments, the EU has indeed won many regulatory battles with the US.

Its cars, chemicals and product safety regulations are more widely adopted round the world than their American counterparts. In the absence of any coherent US offering, bar some varied state-level systems, the General Data Protection Regulation (GDPR) is the closest thing the world has to a single model for data privacy, and variants of it are being adopted by dozens of countries.

The problem is this. Those parts of global economic governance where the US is dominant – particularly the dollar payments system – are highly conducive to projecting US power abroad. The extraterritorial reach of secondary sanctions, plus the widespread reliance of banks and companies worldwide on dollar funding – and hence the American financial system – means that the US can precisely target its influence.

The EU can enforce trade sanctions, but not in such a powerful and discriminatory way, and it will always be outgunned by the US. Donald Trump could in effect force European companies to join in his sanctions on Iran when he pulled out of the nuclear deal, despite EU legislation designed to prevent their businesses being bullied. He can go after the chief financial officer of Huawei for allegedly breaching those sanctions.

By contrast, the widespread adoption of GDPR or data protection regimes inspired by it may give the EU a warm glow of satisfaction, but it cannot be turned into a geopolitical tool in the same way.

Nor, necessarily, does it particularly benefit the EU economy. Europe’s undersized tech sector seems unlikely to unduly benefit from the fact that data protection rules were written in the EU. Indeed, one common criticism of the regulations is that they entrench the power of incumbent tech giants like Google.

There is a similar pattern at work in the adoption of new technologies such as artificial intelligence and the Internet of Things. In that field, the EU and its member states are also facing determined competition from China, which has been pushing its technologies and standards through forums such as the International Telecommunication Union.

The EU has been attempting to write international rules for the use of AI which it hopes to be widely adopted. But again, these are a constraint on the use of new technologies largely developed by others, not the control of innovation.

By contrast, China has created a vast domestic market in technologies like facial recognition and unleashed its own companies on it. The resulting surveillance kit can then be marketed to emerging market governments as part of China’s enduring foreign policy campaign to build up supporters in the developing world.

If it genuinely wants to turn its economic power into geopolitical influence – and it’s not entirely clear what it would do with it if it did – the EU needs to recognize that not all forms of regulatory and trading dominance are the same.

Providing public goods to the world economy is all very well. But unless they are so particular in nature that they project uniquely European values and interests, that makes the EU a supplier of useful plumbing but not a global architect of power.

On the other hand, it could content itself with its position for the moment. It could recognize that not until enough hard power – guns, intelligence, money – is transferred from the member states to the centre, or until the member states start acting collectively, will the EU genuinely become a geopolitical force. Speaking loudly and carrying a stick of foam rubber is rarely a way to gain credibility in international relations.

This article is part of a series of publications and roundtable discussions in the Chatham House Global Trade Policy Forum.




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A Credit-fuelled Economic Recovery Stores Up Trouble for Turkey

17 February 2020

Fadi Hakura

Consulting Fellow, Europe Programme
Turkey is repeating the mistakes that led to the 2018 lira crisis and another freefall for the currency may not be far off.

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Headquarters of the Central Bank of the Republic of Turkey. Photo: Getty Images.

Since the 2018 economic crisis, when the value of the lira plummeted and borrowing costs soared, Turkey’s economy has achieved a miraculous ‘V-shaped’ economic recovery from a recession lasting three quarters to a return back to quarterly growth above 1 per cent in the first three months of 2019.

But this quick turnaround has been built on vast amounts of cheap credit used to re-stimulate a consumption and construction boom. This so-called ‘triple C’ economy generated a rapid growth spurt akin to a modestly able professional sprinter injected with steroids.

This has made the currency vulnerable. The lira has steadily depreciated by 11 per cent against the US dollar since the beginning of 2019 and crossed the rate of 6 lira versus the US dollar on 7 February. And there are further warning signs on the horizon.

Credit bonanza

Statistics reveal that Turkish domestic credit grew by around 13 per cent on average throughout 2019.  The credit bonanza is still ongoing. Mortgage-backed home sales jumped by a record high of 600 per cent last December alone and the 2019 budget deficit catapulted by 70 per cent due to higher government spending.

Turkey’s central bank fuelled this credit expansion by cutting interest rates aggressively to below inflation and, since the start of this year, purchasing lira-denominated bonds equivalent to around one-third of total acquisitions last year to push yields lower.

Equally, it has linked bank lending to reserve requirements – the money that banks have to keep at the central bank – to boost borrowings via state and private banks. Banks with a ‘real’ loan growth (including inflation) of between 5 and 15 per cent enjoy a 2 per cent reserve ratio on most lira deposits, which authorities adjusted from an earlier band of 10-20 per cent that did not consider double-digit inflation.

Cumulatively, bond purchases (effectively quantitative easing) and reserve management policies have also contributed to eased credit conditions.

Commercial banks have also reduced deposit rates on lira accounts to less than inflation to encourage consumption over saving. Together with low lending rates, the boost to the economy has flowed via mortgages, credit card loans, vehicle leasing transactions and general business borrowings.

Accordingly, stimulus is at the forefront of the government’s economic approach, as it was in 2017 and 2018. It does not seem to be implementing structural change to re-orient growth away from consumption towards productivity. 

In addition, governance is, again, a central issue. President Recep Tayyip Erdogan’s near total monopolization of policymaking means he guides all domestic and external policies. He forced out the previous central bank governor, Murat Cetinkaya, in July 2019 because he did not share the president’s desire for an accelerated pace of interest rate reductions.

New challenges

Despite the similarities, the expected future financial turbulence will be materially different from its 2018 predecessor in four crucial respects. 

Firstly, foreign investors will only be marginally involved. Turkey has shut out foreign investors since 2018 from lira-denominated assets by restricting lira swap arrangements. Unsurprisingly, the non-resident holdings of lira bonds has plummeted from 20 per cent in 2018 to less than 10 per cent today.

Secondly, the Turkish government has recently introduced indirect domestic capital controls by constraining most commercial transactions to the lira rather than to the US dollar or euro to reduce foreign currency demand in light of short-term external debt obligations of $191 billion.

Thirdly, the Turkish state banks are intervening quite regularly to soften Lira volatility, thereby transitioning from a ‘free float’ to a ‘managed float’. So far, they have spent over $37 billion over the last two years in a futile effort to buttress the lira. This level of involvement in currency markets cannot be maintained.

Fourthly, the Turkish state is being far more interventionist in the Turkish stock exchange and bond markets to keep asset prices elevated. Government-controlled local funds have participated in the Borsa Istanbul and state banks in sovereign debt to sustain rallies or reverse a bear market.  

All these measures have one running idea: exclude foreign investors and no crisis will recur. Yet, when the credit boom heads to a downturn sooner or later, Turks will probably escalate lira conversions to US dollars; 51 per cent of all Turkish bank deposits are already dollar-denominated and the figure is still rising.

If Turkey’s limited foreign reserves cannot satisfy the domestic dollar demand, the government may have to impose comprehensive capital controls and allow for a double digit depreciation in the value of the lira to from its current level, with significant repercussions on Turkey’s political stability and economic climate.

To avoid this scenario, it needs to restore fiscal and monetary prudence, deal the with the foreign debt overhang in the private sector and focus on productivity-improving economic and institutional reforms to gain the confidence of global financial markets and Turks alike.




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The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding]

Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis.




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A Legionella effector kinase is activated by host inositol hexakisphosphate [Enzymology]

The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.




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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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Wish you were here: Meetings, no meetings, meeting reports [Editorial]

We've all been saying it: These are unprecedented times. The impacts of the COVID-19 pandemic are incredibly wide-ranging and affect all facets of life. One that is hitting the scientific community very hard is the cancellation of meetings, large and small. While we are well-versed in connecting with colleagues and collaborators across a variety of online platforms, these do not replace the immensely gratifying aspects of attending meetings in person: the pleasure of catching up with old friends and making new ones, the insights gained from having real-time conversations with others working on the same topic but with different expertise and perspectives, and the stimulating new scientific ideas we carry home. We have all been feeling the disappointment as we learn that one meeting after another is forced to cancel, from the vibrant ASBMB annual meeting to summer conferences of all types.Another loss from the appropriate but painful decision to cancel the ASBMB annual meeting was the chance to hear from our Herbert Tabor Early Career Investigator Awardees, who represent the best science published in JBC in the preceding year. This year, the competition was particularly fierce. We hope and anticipate that we will be able to hear from the winners at next year's ASBMB annual meeting. But in the meantime, we want to raise a toast to Wenchao Zhao, Yue Yang, Manisha Dagar, Febin Varghese, and Ayumi Nagashima-Kasahara as our 2020 winners. We've captured their award-winning 2019 papers (1–5) on the JBC website (6), and extended profiles of the...




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Understanding the dynamics of the Indo-Pacific: US–China strategic competition, regional actors, and beyond

6 November 2019 , Volume 96, Number 1

The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region.

Kai He and Mingjiang Li

As a geographical concept, ‘Indo-Pacific’ has existed for decades. As a political and strategic concept, it has since 2010 gradually become established in the foreign policy lexicon of some countries, especially Australia, India, Japan and the United States. However, China seems to be reluctant to identify itself as part of the Indo-Pacific; Chinese leaders believe that the US-led Indo-Pacific strategy aims to contain China's rise. While the battle between the two geographical concepts ‘Indo-Pacific’ and ‘Asia–Pacific’ may be fairly easily settled in the future, US–China strategic competition has just begun. Will the Indo-Pacific become a battlefield for US–China rivalry? How will China cope with the US ‘free and open Indo-Pacific’ (FOIP) strategy? How will other regional actors respond to the US–China strategic competition in the Indo-Pacific? What are the strategic implications of the ‘Indo-Pacific’ concept for regional order transformation? How will the Indo-Pacific be institutionalized, economically, politically and strategically? This article introduces the January 2020 special issue of International Affairs, which aims to address those questions, using both country-specific and regional perspectives. Seven articles focus on the policy responses of major players (Australia, China, India, Indonesia, Japan and ASEAN) to the US FOIP strategy and related US–China rivalry in the region. A further three articles examine the profound implications of Indo-Pacific dynamics for regional institution-building and for geopolitical and geo-economic architecture.




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Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’

4 March 2020 , Volume 96, Number 2

Emma Tomalin

In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this.




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It's a man's world: carnal spectatorship and dissonant masculinities in Islamic State videos

7 May 2020 , Volume 96, Number 3

Manni Crone

Islamic State videos have often been associated with savage violence and beheadings. An in-depth scrutiny however reveals another striking feature: that female bodies are absent, blurred or mute. Examining a few Islamic State videos in depth, the article suggests that the invisibility of women in tandem with the ostentatious visibility of male bodies enable gendered and embodied spectators to indulge in homoerotic as well as heterosexual imaginaries. In contrast to studies on visual security and online radicalization which assert that images affect an audience, this article focuses on the interaction between video and audience and argues that spectators are not only rational and emotional but embodied and gendered as well. Islamic State videos do not only attract western foreign fighters through religious–ideological rhetoric or emotional impact but also through gendered forms of pleasure and desire that enable carnal imagination and identification. The article probes the analytical purchase of carnal aesthetics and spectatorship.




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Accountability, denial and the future-proofing of British torture

7 May 2020 , Volume 96, Number 3

Ruth Blakeley and Sam Raphael

When powerful liberal democratic states are found to be complicit in extreme violations of human rights, how do they respond and why do they respond as they do? Drawing on the example of the United Kingdom's complicity in torture since 9/11, this article demonstrates how reluctant the UK has been to permit a full reckoning with its torturous past. We demonstrate that successive UK governments engaged in various forms of denial, obfuscation and attempts to obstruct investigation and avoid accountability. The net effect of their responses has been to deny the victims redress, through adequate judicial processes, and to deny the public adequate state accountability. These responses are not simply aimed at shielding from prosecution the perpetrators and those who have oversight of them, nor preventing political embarrassment. The various forms of denial and obstruction are also designed to ensure that collusion can continue uninterrupted. A core concern of intelligence officials and ministers has been to prevent any process that would lead to a comprehensive prohibition on involvement in operations where torture and cruel, inhuman and degrading treatment are a real possibility. The door remains wide open, and deliberately so, for British involvement in torture.




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Webinar: Director's Briefing – US Elections: The Road to November 2020

Corporate Members Event Webinar Partners and Major Corporates

16 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Edward Luce, US National Editor and Columnist, Financial Times
Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As the coronavirus crisis deepens globally, the effects have reverberated through the American economy, and in only a few short weeks, the US presidential election race has changed beyond recognition. Unemployment claims have hit unprecedented levels and look set to continue to rise with stark warnings that the worst is still to come. Polling, however, has suggested that over half the country approves of the way President Trump is handling the crisis. No issue is likely to be more important to voters come November than the recovery and rebuilding of America once the pandemic subsides.
 
In this discussion, Ed Luce and Dr Lindsay Newman will examine the new uncertain outlook for the November 2020 election and discuss how it might play out in these challenging circumstances. Where are we versus where we thought we would be at this point in the election cycle? What should we be watching for in the coming months as the US looks to hold elections in these uncharted waters? Will the elections effectively become a referendum on Trump’s handling of the coronavirus pandemic? And what will this mean for potential policy priorities of the president?

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to rsvp@chathamhouse.org.




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Webinar: Reimagining the Role of State and Non-State Actors in (Re)building National Health Systems in the Arab World

Research Event

22 April 2020 - 1:00pm to 2:00pm

Event participants

Fadi El-Jardali, Professor of Health Policy and Systems, American University of Beirut
Moderator: Nadim Houry, Executive Director, Arab Reform Initiative

As new cases of COVID-19 continue to surge, countries around the world struggle to mitigate the public health and economic effects of the virus. It is becoming increasingly clear that an effective pandemic response requires a whole-of-government, whole-of-society approach. In the Arab world, where health systems are already strained by armed conflicts and displaced populations, a whole-of-society response to the pandemic is particularly critical as countries have become increasingly dependent on non-state actors, notably the private sector, for healthcare provision and any response that includes the state alone may not be sufficient to address the pandemic.

In a recent article, Fadi El-Jardali, argued that while the pandemic will have grave health and economic consequences for years to come, it brings with it a valuable opportunity to re-envision the role of state and non-state actors in strengthening health systems. The article addressed the need for increased collaboration between state and non-state actors, and the rethinking of existing cooperation models to provide quality healthcare services for all.  

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, Dr El-Jardali will discuss how state and non-state actors can collaborate more effectively to address the shortcomings of national health care systems amidst the pandemic and beyond. The article’s author will share insights on the different capacities available in Arab societies that governments can draw upon to ensure that Universal Health Coverage, equity considerations and social justice are at the core of health systems.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

 

Reni Zhelyazkova

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




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Webinar: Idlib at Risk – Doctors and First Responders in Northwest Syria

Members Event Webinar

23 April 2020 - 5:00pm to 6:00pm

Online

Event participants

Dr Munzer al-Khalil, Head, Idlib Health Directorate
Raed Al Saleh, Director, Syria Civil Defence (The White Helmets)
Alaa Rajaa Mughrabieh, Child Protection Officer, Hurras Network
Chair: Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

 

In Syria, uncertainty about the safety of the ceasefire agreed between Russia and Turkey last month is inhibiting 1 million people who have been displaced since December 2019 from returning home.

The looming COVID-19 global health crisis threatens to further devastate those most vulnerable as the conditions in northwest Syria’s refugee camps make it hard to practice common social distancing guidelines. Added to this, the medical infrastructure in the region has been decimated after years of bombings which has disabled over 70 health facilities since April 2019.

This webinar highlights the potentially catastrophic risks of a coronavirus outbreak in Idlib and displacement camps in northwest Syria by speaking with medical and civil society actors working in the region. How are doctors and local humanitarian organizations scaling up their medical and prevention response to the COVID-19 outbreak?

What key supplies such as ventilators, testing kits and critical sanitary equipment are still lacking? And how can the international community step in to help mitigate the potentially devastating consequences of an outbreak in these refugee camps?

This event is run in collaboration with The Syria Campaign, a human rights organization working with Syrian civil society to raise the voices of those struggling for democracy, and support frontline activists and humanitarians.




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Webinar: Director's Briefing – Democracy in the Americas

Corporate Members Event Webinar Partners and Major Corporates

30 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Luis Almagro, Secretary General, Organization of American States (OAS); Foreign Minister, Uruguay (2010-15)
Respondent: Dr Elena Lazarou, Associate Fellow, US and the Americas Programme, Chatham House
Respondent: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As governments in the Americas grapple with the economic and health emergencies posed by COVID-19, the region continues to face socioeconomic and political challenges reflected in the protests that erupted in many countries in 2019. According to an annual survey by Latinóbarometro, of 18 countries across Latin America, trust in government dropped from 45 per cent in 2009 to 22 per cent in 2018, and those expressing dissatisfaction with democracy has increased from 51 per cent to 71 per cent. 

Recently re-elected to a new term, Luis Almagro, secretary general of the Organization of American States, will reflect on the state of democracy in the Americas. What are the greatest threats and opportunities to democratic governance and political participation in the region? How can multilateral organizations and states defend democratic institutions and human rights in a changing global environment? To what extent might the ongoing COVID-19 pandemic provide leaders with an opportunity to undemocratically consolidate power? Or, conversely, might the crisis spark a new understanding of the social contract between states and governed and greater consensus around national policies and leadership?  

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to lbedford@chathamhouse.org.




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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
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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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Webinar: Director's Briefing – National Leadership in Times of Crisis

Corporate Members Event Webinar Partners and Major Corporates

14 May 2020 - 6:00pm to 7:00pm
Add to Calendar

Online

Janet Napolitano, President, University of California; US Secretary of Homeland Security (2009-13)

Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

Across the globe, leaders on the local, national and international levels are grappling with the impacts of COVID-19 on their communities and the economy. But the coronavirus pandemic is just one of several existential crises the world is currently facing. Climate change, political instability and growing tensions with China and Russia, along with a lack of strong global leadership, has made it more difficult for individual nations to respond and coalesce in times of crisis.

This discussion will explore how leaders at all levels can best negotiate both the practical issues and the larger questions associated with these ‘grand challenges’. How is current US foreign policy affecting our collective ability to respond to issues such as pandemics or climate change? Has the COVID-19 crisis cemented the US retreat from global leadership and if so, who might step into the breach? How do we maintain momentum on other issues in the midst of a public health disaster of this magnitude? And what is the role of the business community, higher education institutions and other sectors in responding to these crises and shaping future public policy?

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to lbedford@chathamhouse.org.




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Joseph Nye, the inventor of the term 'soft power'

3 June 2013 , Volume 69, Number 3

He shares his thoughts on on America’s role in an increasingly affluent world, Russia’s decline and China’s own goals

Alan Philps

Interview.jpg

Photo: Alex Wong/Getty Images




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Settlers in Contested Lands: Territorial Disputes and Ethnic Conflict

Members Event

21 April 2016 - 1:00pm to 2:00pm

Chatham House London, UK

Event participants

Oded Haklai, Associate Professor, Department of Political Studies, Queen's University, Ontario
Neophytos Loizides, Reader, University of Kent; Leverhulme Trust Research Fellow
Madurika Rasaratnam, Lecturer, International Conflict Analysis, University of Kent
Chair: Evangelos Liaras, IE University, Madrid; Academy Associate, Chatham House

This panel will discuss the phenomenon of settlement and the role of settlers in modern conflicts, drawing from recently published work on Israel and the West Bank, Turkish settlers in Cyprus and government run farmer settlement schemes in Sri Lanka.

The panelists, experts in the respective cases, will analyse the role of settlers in mobilization and violence, the conceptual framing of settlement during negotiations and the clash of legal principles versus pragmatism for the resolution of these conflicts. Looking beyond these specific cases, the panel will also raise larger questions about settlers and settlement in international politics.

Members Events Team




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Syria: Destruction of Civil Society Means Dictatorship, Extremism and Displacement

7 October 2016

Rana Marcel Khalaf

Former Academy Associate
The void in governance in Syria caused by the conflict has enabled a previously oppressed civil society to rise. Now this new society is under threat. Sustained commitment from the international community is required.

2016-10-07-white-helmets-syria2.jpg

Syrian civil defence volunteers, known as the White Helmets, search amid the rubble of destroyed buildings following an air strike on the rebel-held neighbourhood of Aleppo, on October 4, 2016. Photo: Getty Images.

The void in governance created by the ongoing Syrian conflict has been capitalized upon by warlords, militias and extremist groups to expand and consolidate their power – but has also helped to generate activism, with new leaders born as a reaction to authoritarian governance and conflict limitations.

As public social services have been taken over as war tools, local coordination committees, local councils, humanitarian support groups, citizen journalist networks, women’s groups, and more, have mushroomed across all of Syria. But this new civil society continues to be threatened by many challenges.

It remains hindered by structural weakness and limited capacity - largely as a result of the legacy of Ba’athist policies, which did not allow civil society to exist in the so-called Damascus Spring, but only under the umbrella of the Government, First Lady Asma al-Assad and business NGOs (GoNGOs, FLNGOs and BoNGOs). Beyond this, civil society was limited to purely charitable and religious causes, known as “moujtamaa ahli”.

In addition, Syrian civil society is often a victim of counter-terrorism legislation, with laws and regulations across many countries and institutions prohibiting Syrians from registering an organization and opening bank accounts.  This makes it difficult to secure financial support in an environment where funding has already been dwindling due to a “Syria fatigue” among potential donors, and where any money available is mainly directed at large, often international, NGOs.

Trust, hope and legitimacy

To reach funds, many organizations have to submit to this “NGOization” process. But even this rarely allows for civil society to foster its own interests through core funding. Civil society in Syria is treated more as a “project” with strict indicators, deals and deadlines, when working under conflict necessitates building relationships of trust with a community over time and often has to cover the direct needs on the ground to gain local legitimacy and increase effectiveness. Trust, hope and legitimacy are not aspects you can report against or cover in a sophisticated proposal.

But despite such obstacles, activists and civil society groups continue to volunteer for various causes, ensuring many have not had to seek refuge elsewhere. And their work has included challenging authoritarian and extremist governance.

In Aleppo in 2014, it was civil society with the support of a military faction of Jaish Al Mujahideen that helped expel ISIS. Local councils have since been providing services ranging from humanitarian aid and garbage collection to re-establishing order and resolving local conflicts, thus challenging the legitimacy of jihadist institutions.

NGOs such as the Civil Defense Forces (known as the White Helmets) continually risk their lives to save others by rescuing people from bombed out buildings. On September 19, when a UN sanctioned aid convoy was attacked in Aleppo – reportedly by Russian aircraft – it was the White Helmets that responded, before then coming under attack themselves.

Human rights activists, meanwhile, persist in documenting human rights abuses in the hope that the perpetrators will eventually be held accountable.

However, a Syrian civil society tragedy is unfolding as their work is struggling to survive. To give but one example, Kesh Malek, one of the biggest groups running home-based schooling for children in Aleppo, has already had to close some of its schools.

Lacking international protection, the fate of these children in relation to arms and radicalization is all the more alarming.  Several local councils have also been much weakened, especially vis-à-vis warlords, authoritarian and/or extremists actors.

At its best, the current bombing campaign serves to kill any potential alternatives to an authoritarian regime, and only boosts human suffering, radicalization and displacement.

If this situation is to be reversed, international actors need to ensure security at the local Syrian level, showing that Syrian security is as important as that of Europe.

This means financial security through a deeper and more sustainable capacity building and funding to civil society, and it means protecting civilians and civil society groups though the creation of a safe haven.

To comment on this article, please contact Chatham House Feedback




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History for Fantasy Writers: Do You Have a Moment?

This is the second part of a two-part article on how time was perceived and measured in ancient and medieval Europe.

In the last installment of History for Fantasy Writers I addressed years, months, weeks, and days. Now I turn to shorter lengths: days, hours and still shorter periods. I’ll close with a more general consideration of time and the awareness of time.

Hours

We carve the day into twenty-four hours, but in the past the hour was a malleable thing. There were twelve hours of daylight and twelve hours of night, regardless of the season. The day began with zero at sunrise. Then came the first hour, the second, and so on. The twelfth hour fell at sunset. A winter daylight hour was therefore shorter than a summer hour.

This feels a little nuts at first, but it’s actually pretty sensible. At least the word midnight makes sense in that system—it’s the mid-point of the night, regardless of how long is the night. All we have to do is abandon the notion that an hour is a unit of time, to consider it as marking portions of a day.

Continue reading History for Fantasy Writers: Do You Have a Moment? at Mythic Scribes.



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  • how time was perceived and measured