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JL Dixon
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John M. Dietschy
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Chatham House Prize: Malawi Judges Win for Election Work News Release NCapeling 23 October 2020

Malawi’s constitutional court judges have won the 2020 Chatham House Prize in recognition of their 'courage and independence in the defence of democracy'.

Lord Hammond Joins Panel of Senior Advisers News Release NCapeling 10 December 2020

Chatham House is pleased to announce that Lord Hammond of Runnymede is joining our Panel of Senior Advisers.

Facebook's power under scrutiny as Trump ban upheld Expert comment NCapeling 6 May 2021

Keeping Donald Trump’s Facebook ban in place shows the vast power social media platforms hold, raising questions of whether that power is appropriately used.

Kate Jones

From a human rights perspective, the Oversight Board’s decision is a strong one, and not at all surprising. The board decided Facebook was right to suspend the former president’s access to post content on Facebook and Instagram, but not indefinitely.

It found Donald Trump’s posts violated Facebook’s community standards because they amounted to praise or support of people engaged in violence and that, applying a human rights assessment, Facebook’s suspension of Trump was a necessary and proportionate restriction of his right to freedom of expression.

However the board also found Trump’s indefinite suspension was neither in conformity with a clear Facebook procedure nor consistent with its commitment to respect human rights. Its decision requires Facebook to make a new decision on the future of Donald Trump’s account, grounded in its rules.

While opinions on this result will differ, the increased call for clear and accessible rules and respect for human rights in their implementation that the Oversight Board brings to Facebook’s operations is welcome.

But the Oversight Board’s powers are limited to content moderation – Facebook declined to answer the board’s questions about amplification of Trump’s posts through the platform’s design decisions and algorithms. This limitation on the board’s role should be lifted. It is in content amplification, not just content moderation, that Facebook should face scrutiny and accountability for the sake of the human rights of its users.

Fundamentally, human rights is not a veneer which can mask or legitimize underlying power dynamics or public policy – those still fall to be assessed for themselves.

The Trump/Facebook saga does highlight the vast power Facebook and other major social media platforms have over political discussion and persuasion. Through granting or denying, or through amplifying or quietening the voices of political figures, Facebook has the power to shape politics, electorates, and democratic processes. Improving content moderation through the Oversight Board, although important, does little to constrain that power.

Facebook itself, unlike a government, has no accountability to the general public, and the Oversight Board must not distract us from the need for a full conversation about the extent to which Facebook’s power is appropriately held and properly wielded.

Emily Taylor

This decision marks a coming of age for Facebook’s content moderation process. For years, decisions to take down content or ban users have been opaque, conducted by a human workforce that Facebook and other platforms have been hesitant to acknowledge. The platforms have also been worried that being seen to exercise an editorial function might put at risk the legal protections which prevent the platforms being held responsible for user-generated content.

When the Oversight Board was first posited, observers questioned whether a body funded by Facebook could properly exercise a legitimate appeals function. Now there is a reasoned decision which partly supports the decision to de-platform a serving president, but also takes issue with the indefinite nature of the ban.

Facebook specifically asked the Oversight Board to consider specific challenges involved when the person involved is a political leader. The board concluded that Trump’s ‘status as head of state with a high position of trust not only imbued his words with greater force and credibility but also created risks that his followers would understand they could act with impunity’. The storming of the US Capitol and role President Trump played in stirring up the violence underlined that political leaders’ words can motivate others to take harmful actions.

Just as the events of January 6 remain shocking, it remains shocking that private platforms have exercised the power to curb the speech of a US president. It also remains shocking that the platforms sat back and took no action over the previous four years, but waited until the final days of the transition.

The board’s decision is an evolution in private-sector content moderation, with a diverse board giving a reasoned opinion on a Facebook decision. But to fully comply with the principles of open justice, board decisions should include more detail on the individuals who have made the decision – at present, it appears all members of the board review the decision but it is not clear which individuals were involved in its drafting, or that they were clear from conflicts. If the process is to gain respect as a truly independent oversight on the platform’s decisions, greater transparency over the identity of decision-makers will be needed.

Mark Zuckerberg expressed concern about Facebook becoming an arbiter of truth or free speech and, overall, the difficulty of having private companies managing the application of fundamental rights on their platforms has not been solved. Just because companies have the financial resources to do it, does not mean they necessarily should.

Yet no other international governance or arbitration system has emerged to handle the complexities of platform power over speech. In the context of that vacuum, the Oversight Board’s decision is a welcome step.

Undercurrents: The Oversight Board's Trump decision, and Merkel's legacy Audio bhorton.drupal 25 June 2021

Was Facebook right to suspend Trump? And how will Merkel be remembered?

In the wake of the storming of Capitol Hill on 6 January 2021, social media platforms took steps to remove former President Donald Trump from their websites for infringing community standards. This step was welcomed by many, but also raised serious questions about the power of social media companies to limit free speech and censor elected officials. The suspension of President Trump from Facebook was referred to the Oversight Board, an independent body of experts set up to scrutinise the platform’s content moderation decisions.  

In this episode, Ben speaks to Thomas Hughes and Kate Jones about the outcome of the Oversight Board’s inquiry into the Trump suspension, and the wider implications for content moderation on social media.  

Then Lara is joined by Hans Kundnani to assess the political outlook in Germany and reflect on the legacy of outgoing Chancellor Angela Merkel.  

Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel News release jon.wallace 14 January 2022

Founder of the International Law Programme at Chatham House recognized for her major contribution to the law of England and Wales.

Elizabeth Wilmshurst CMG, distinguished fellow of Chatham House’s International Law Programme, has been awarded the title of Honorary Queen’s Counsel (QC Honoris Causa), recognizing her major contribution to the law of England and Wales, outside practice in the courts. The Lord Chancellor will preside over an appointment ceremony at Westminster Hall on 21 March 2022.

Elizabeth founded the International Law Programme at Chatham House and is an academic expert member of Doughty Street Chambers. She was a legal adviser in the United Kingdom diplomatic service between 1974 and 2003. Between 1994 and 1997 she was the Legal Adviser to the United Kingdom mission to the United Nations in New York. She also took part in the negotiations for the establishment of the International Criminal Court.

Throughout her career, Elizabeth has worked to strengthen the role of international law in reducing global tensions, addressing cross-border challenges and promoting individual liberty, including through influential publications at the Institute such as The Chatham House Principles of International Law on the Use of Force in Self-Defence. 

Robin Niblett CMG, Director and Chief Executive of Chatham House said:

‘We are delighted by this award which recognizes Elizabeth’s outstanding contribution to the field of international law, both in government and – on a continuing basis – through the International Law Programme at Chatham House.’

Chatham House welcomes 2022 interns News release jon.wallace 11 May 2022

Internships provide learning opportunities about shaping policy, influencing debate and creating real change.

Chatham House is excited to welcome the second cohort to the Molchanov Sustainability Internship Programme.

Introduced in January 2021, the programme has been made possible following the gift of Pavel Molchanov, to support the next generation of leaders in sustainability.

The internships grant invaluable, practical learning opportunities about shaping policy, influencing debate and creating real change towards a sustainable future.

Alis Martin, Internships and Outreach Manager at Chatham House, said:

‘We are delighted to welcome the second cohort to the Molchanov Sustainability Internship Programme. This cohort brings a diversity of new and invaluable perspectives and ideas to the work of our programmes.

‘Over the course of 12 weeks, interns will be working alongside internationally respected experts in Chatham House programmes, exploring issues of sustainability through the lenses of climate change, the circular economy, conflict prevention, emerging technology, global health, governance, human rights, security policy, sustainable cities and sustainable finance.

‘Fostering sustainable and equitable growth and engaging the next generation of policy leaders is central to Chatham House’s vision. We are committed to providing the best experience and opportunities to our interns who share an interest in pursuing a career in the field of sustainability.

‘It is crucial that we incorporate the views and knowledge of those who will be affected most in the future and I very much look forward to seeing the innovative and impactful ideas that will undoubtedly result from their work.’

Mr Molchanov said:

‘Recent headlines around the world underscore the importance of taking the broadest possible perspective on sustainability. Energy supply concerns, rising food prices, and continued pandemic pressure are all interconnected with climate issues. I look forward to hearing about the work in which this year’s internship participants engage.’

Jerome Puri, intern, Middle East and North Africa Programme, said:

‘I applied for this internship to gain a holistic insight into the coordination of a policy institute and to understand how Chatham House promotes international cooperation and accountable governance around the world.  Chatham House offers an unparalleled opportunity to contribute to projects on frontier issues facing the MENA region and develop a diverse range of skills ranging from project management and communications to policy-oriented research skills.’

Obioma Egemonye, intern, Africa Programme, said:

‘I was particularly interested in joining the Africa Programme at Chatham House after learning an immeasurable amount from their work on the Social Norms and Accountable Governance (SNAG) research for my undergraduate dissertation. I am most looking forward to attending the variety of events held by Chatham House and the Africa programme specifically.’

Valdone Sniukaite, intern, Europe Programme, said:

‘I am excited to be joining the Europe Programme team and getting exposure to the inner workings of a policy and research think tank. I’m mostly looking forward to building my organizational skill set by working on the Belvedere Forum and using the opportunity of being around experts in the field of international affairs to broaden my knowledge.’

Lucile de Laforcade, intern, Queen Elizabeth II Academy for Leadership in International Affairs, said:

‘As part of the Academy, I am able to work at the crossroads of research, leadership, international affairs and personal development. This makes the Academy a place of constant challenge to find innovative, sustainable solutions, and emulate new ideas. As an aspiring academic, this is particularly empowering! I am hoping to gain new skills, further develop independent thinking, and cultivate my own research interests in the vibrant environment of a leading policy institute.’

Katie McCann, intern, Communications and Publishing, said:

‘I’m really interested in youth engagement in international politics so I’m very excited to be working on the Common Futures Conversations platform which brings young people across Europe and Africa into the debate on the pressing global issues of our time. I hope my time at Chatham House will expose me to people of different backgrounds and beliefs which will encourage me to engage even more critically with international affairs.’

Rachael Mullally, intern, International Law Programme, said:

‘What I admire most about the International Law Programme here is its position as a dependable yet experimental source on global governance debates. I am especially excited to get working on the Human Rights Pathways Project, focusing on tangible ideas as to how the human rights framework can evolve to meet power shifts between states and non-state actors.’

Elia Duran-Smith, intern, International Security Programme, said:

‘I was particularly drawn to this internship because of the thematic focuses of the programme around nuclear security and emerging technologies in the sector, which are fundamental to understanding the future of the global security environment. I am looking forward to learning more about these topics while developing and expanding my research and writing skills, as well as gaining an understanding of project management and how Chatham House engages with stakeholders on policy.’

Rory Selvey, intern, Sustainability Accelerator, said:

‘For me, speeding up the transition towards a fairer, low-carbon society is one of most important global challenges. I’m really excited to be an intern at the Sustainability Accelerator, collaborating with different teams and exploring innovation solutions to this challenge. Chatham House will help me develop vital knowledge and skills, acting as a fantastic springboard for a potential career in sustainable finance, macroeconomics, or international development.’

Bruna Miguel, intern, Environment and Society Programme, said:

‘Being an intern in the Environment and Society Programme will give me the opportunity to further investigate how these issues relate and how we can achieve true sustainability. I look forward to learning from the experts in the area that I will meet (and hopefully find a dissertation topic!).’

Ritvij Singh, intern, Global Health Programme, said:

‘My view of healthcare delivery is from the frontlines as a medical doctor. I applied to this internship to widen my perspective and get an insight into the institutions that will help facilitate universal health. I will use this experience to pursue a career in global health.’

For more information about the internships, please contact Alis Martin.

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

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In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.