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

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




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A "Proteomic Ruler" for Protein Copy Number and Concentration Estimation without Spike-in Standards

Jacek R. Wiśniewski
Dec 1, 2014; 13:3497-3506
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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A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

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




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A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
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Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents

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




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Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics

Shao-En Ong
May 1, 2002; 1:376-386
Research




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Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes [Molecular Bases of Disease]

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.




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Europe should become the top priority for Liz Truss

Europe should become the top priority for Liz Truss Expert comment NCapeling 3 September 2022

Liz Truss has the chance to be a better prime minister than Boris Johnson was, not least in the UK’s foreign policy.

For all the smoke-and-mirrors talk now commonplace about Brexit opportunities, there is real potential that Liz Truss could extract from the aftermath of that upheaval as well as from the turmoil in the world.

But the approach and priorities she revealed during her one year as a better UK foreign secretary than Boris Johnson was – although he did set a low bar – as well as the past three months campaigning for the leadership of her party contain a warning.

She has shown a willingness to aggravate relationships with allies in pursuit of the support of her party faithful, and of a vision of British independence as well as a tendency to dismiss economic analysis when it inconveniently questions her assertions about favoured policies.

At the heart of her political identity is a notion which is both a strength and a potentially calamitous weakness – a love of the notion of being a disrupter which injects a deliberate unpredictability into her approach towards a world in extreme flux.

If she indulges this without good judgment, she could do real damage to Britain’s prospects and standing in the world.

Ukraine and the energy crisis

In foreign policy, Europe should be her starting point and the opportunity here for the UK is clear. The war in Ukraine and crisis in the cost of energy gives it a role – despite having left the European Union (EU) – in talking to EU governments about the future of the continent on many fronts.

Johnson’s emphatic support of President Zelensky gave the UK a position of moral and strategic clarity which Truss can build on through what will be an exceptionally difficult winter for Europe’s governments.

At the heart of her political identity is a notion which is both a strength and a potentially calamitous weakness – a love of the notion of being a disrupter

She is in a position to persuade European leaders to remain united in Ukraine’s support while planning better how they are going to source energy. She could expand on that to help the EU find a way through its many other problems, such as upholding democratic values throughout the bloc or finding a response to migration.

There is also a chance for the UK to shape Europe’s thinking on the development and regulation of digital technology and medicine, energy, and the environment.

Truss’s declaration that the UK should now spend three per cent of its GDP on defence could help her in taking that kind of role. However this campaign declaration is not yet credible, given the pressures on the national finances and her silence so far on support for households on energy costs.

But that is the opportunity in theory and the signs are this is not her approach to Europe. Her provocative and opportunistic comment that the ‘jury’s out’ on whether President Macron (and France) was a friend or foe shocked both Britain’s allies and opponents.

For those keen to see divisions among democracies, it gave unexpected, heady encouragement, and to those within those countries, it injected a doubt about shared values which was deeply damaging. The chilly poise of Macron’s response – that the UK and France would always be allies – showed how far she had departed from normal protocol.

The episode encapsulated one of the sources of unease about the Truss style – improvisation under the banner of ‘disruption’ without thought of consequences.

Her instinctive liking for the US will help Truss in relations with Washington at a difficult time, and her apparent intention to designate China as ‘a threat’ will support that relationship too

However, she has shown consistency over the Northern Ireland Protocol with little sign of compromise, and that alone could cause much unnecessary damage to UK interests. It also puts her on a collision course with the EU and the UK House of Lords, due to consider controversial legislation again in early October after the Conservative party conference.

There is huge opposition in the Lords to two aspects of the legislation. The first target is the intention of the Johnson government – likely to be repeated by a Truss government – to use the bill to jettison aspects of the protocol, which many argue breaks international law. The second is the delegated power the bill would give ministers.

The cost of a new, serious clash – or worse, a full trade war – with the EU is high. There is the loss of trade, the increase in friction for business, which is consistently underestimated by the UK government, and the loss of scientific and research partnerships.

More than that, though, there is the weakening of ties to a set of allies with common values sharing an increasingly troubled neighbourhood.

US, China, and others remain important

And to say Europe should come first is not to dismiss other claims on the UK’s foreign policy. Her instinctive liking for the US will help Truss in relations with Washington at a difficult time, and her apparent intention to designate China as ‘a threat’ will support that relationship too.




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Independent Thinking: Lula wins in Brazil, US midterms

Independent Thinking: Lula wins in Brazil, US midterms Audio NCapeling 4 November 2022

The third episode of our new podcast analyses the results from the Brazil presidential election, and looks ahead to the crucial midterm elections in the US next week.

Bronwen Maddox and her guests examine the tight election result from Brazil and its impact on both the country and the region, and preview the US midterm elections being held on 8 November and the start of COP27.

In Brazil, former president Luiz Inácio Lula da Silva beat incumbent Jair Bolsonaro by the narrowest of margins. Meanwhile in the US, the Democrats are fighting to retain the House and Senate from a resurgent Republican Party still enamoured with Donald Trump.

Joining Bronwen Maddox this week are Leslie Vinjamuri, director of Chatham House’s US and Americas programme, Christopher Sabatini, senior fellow on Latin America in the same programme, and Ana Yang, executive director of Chatham House’s Sustainability Accelerator.




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Microtubule affinity-regulating kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and exacerbates neurodegeneration [Neurobiology]

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.




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Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia [Molecular Bases of Disease]

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.




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How modular renewables can reduce the costs of relying on carbon capture

How modular renewables can reduce the costs of relying on carbon capture Expert comment LToremark

COP29 must raise countries’ ambitions to deploy vastly more low-cost modular renewable technologies to help meet the tripling of renewables target set at COP28 and reduce our reliance on expensive carbon capture systems.

The most important international climate conference is around the corner. COP29 in Baku, Azerbaijan will be especially important because next year countries will submit their five-yearly national climate plans – or Nationally Determined Contributions (NDCs) – as set out under the Paris Agreement.

At COP28 in Dubai last year, the final text was heralded as a last-minute success as – somewhat surprisingly – it was the first ever COP to commit to ‘transition away from fossil fuels in energy systems in a just, orderly and equitable manner’. To support this, over 200 countries also committed to triple renewable capacity by 2030.

Under current NDCs, even if all countries achieve their most ambitious decarbonization plans, the world would still fall 30 per cent short of tripling renewable capacity by 2030. 

At COP29 in November, hosted by a petrostate, additional agreement is needed to operationalize the removal of fossil fuels from the global energy system and set the ambition for those crucial NDCs in 2025. Failing to do so means the opportunity to triple renewables by 2030 will slip away. But the actions of oil producing nations, international oil companies, their associated supply chains and networks of lobbyists have in recent years done their best to disrupt and slow down the energy transition and water down key negotiations during COPs and elsewhere

During the final days of COP28, the Organization of the Petroleum Exporting Countries (OPEC) sent private letters to its 13 members – including COP28 host the United Arab Emirates (UAE) – urging them to ‘proactively reject any text or formula that targets energy, i.e. fossil fuels, rather than emissions’. OPEC members own 80 per cent of global oil reserves.

Due to the startling decline in the cost of renewables and electric vehicles, fossil fuel producers are increasingly concerned. To fight back they are turning to carbon capture and storage (CCS) technologies and carbon removal options, which would enable the continued burning of fossil fuels – and protect their assets and business models.

A key battle ground for oil and gas producers is the difference between abated and unabated fossil fuels.

Abatement is the process of capturing CO2 as fossil fuels are burnt to prevent a proportion of those CO2 emissions from entering the atmosphere, either by using that CO2 in products or storing it in geological formations deep underground in near perpetuity, commonly referred to as CCS.

After COP28 there was optimism that the final agreement was significant and covered all fossil fuels without ambiguity around whether they are unabated or abated. 

But the definition of unabated has not actually been agreed within the COP process. During the 2021 COP26 summit, the Glasgow Climate Pact mentioned unabated in reference to coal. Could a gas power station capturing 51 per cent of the emitted CO2 be considered abated?

And what about the so-called downstream emissions? Downstream emissions from cars, planes, tanker ships and diesel generators etc make up 50–80 per cent of the total emissions from oil – and there are no plans to attach mini-CCS systems to cars.

CCS and engineered carbon removals are also likely to be expensive. Analysis by the Oxford Smith School of Enterprise and the Environment has shown that high CCS pathways to net zero emissions in 2050 would cost at least $30 trillion more than a low CCS pathway with more renewables – roughly $1 trillion more per year.

The rapid cost reductions of solar, wind and batteries are due to their modular nature.

The costs of CCS have also remained the same for the past 40 years, while the costs of renewables like solar, wind and lithium-ion batteries have dropped radically. Solar costs have declined by 90 per cent in the last decade

The rapid cost reductions of solar, wind and batteries are due to their modular nature. Around 70 billion solar cells will be manufactured this year, the majority in China. It is the repetitive modular manufacturing process that has led to rapid efficiency improvements and cost reductions. Each Tesla has around 7,000 lithium-ion battery cells, and the price of these modular batteries fell 14 per cent between 2022 and 2023 alone. 

The modular criteria can help define the technology winners of the future, technologies we should selectively support and accelerate over the coming years. 

While huge industrial power stations, oil rigs and refineries have their benefits, they are not modular in the same way. Their economy of scale is in the large size of each asset. CCS is bolted on to fossil fuel infrastructure but there are less than 50,000 fossil fuel producing assets globally. By contrast, there were 1.5 billion solar panels produced in 2022. The cost of deploying CCS is therefore unlikely to benefit from the rapid cost reductions of modular renewables. Nuclear even less so. There are 440 nuclear power stations in operation today, they take many years to build and remain hugely expensive. 




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China’s economic policy pendulum has swung towards stimulus – but keep expectations low

China’s economic policy pendulum has swung towards stimulus – but keep expectations low Expert comment jon.wallace

Beijing historically swings between stimulus and frugality. But Xi Jinping’s ambition for self-reliance will constrain any new efforts to boost the economy.

Policymakers in Beijing have spent the past three weeks trying to convince the world that they are determined to deliver meaningful support to China’s sagging economy. 

Since late September statements have come from the central bank, which promised to cut interest rates, release liquidity, and provide funding to securities firms; from the politburo, which said it wanted to stabilize the real estate market, boost the capital market and shift towards looser fiscal and monetary policy; from the government’s main planning body, which promised a package of policies to support domestic demand; and from the finance minister himself, who at the weekend committed to issue more debt to recapitalize banks, support local governments and aid unhappy consumers.

Chinese authorities have been wrestling with two conflicting objectives: to grow the economy, and to minimize the risk of financial instability.

Though details have been scant, the Chinese stock market has responded enthusiastically to this flurry of rhetoric. But the bigger question for the global economy is whether a boost in Chinese demand can return the country to its former status as a reliable destination for global exports and capital.

With that measure of success in mind, it is worth keeping expectations low. For the past 15 years, Chinese authorities have been wrestling with two conflicting objectives: to grow the economy, and to minimize the risk of financial instability. Those goals sit uneasily with each other because the effort to boost growth has relied on borrowing; and yet a rise in debt can increase the risk of a debt crisis.  

Chinese policymaking has responded to this dilemma by taking on a pendulum-like quality. Sometimes the authorities boost the economy by funding more investment spending. At other times that stimulus gets reined back as policymakers worry about the economy’s indebtedness.

In the aftermath of the great financial crisis of 2008, for example, Beijing’s over-riding priority was to protect the Chinese economy from the risk of recession by implementing a huge credit-financed stimulus to spur investment in infrastructure and real estate. 

By 2012, though, concerns about over-indebtedness began to dominate, and a withdrawal of stimulus saw the Chinese economy sag. In late 2015,a new round of stimulus measures emerged, only to be withdrawn again around 2018.

With that pendulum in mind, the optimistic take on what policymakers have said in recent weeks is that we are now back in stimulus mode. That’s true in part, but three factors suggest that this time is a little different.

Different times

First, China’s rising debt burden increases authorities’ worries about financial stability. Data from the BIS show that China’s private sector debt almost doubled in the past 15 years to 200 per cent of GDP at the end of 2023. The comparable debt stock for the US and the Eurozone was much lower, at 150 per cent each.

China’s entrepreneurs’ animal spirits remain in the doldrums. They are likely to stay there as long as President Xi Jinping’s preference is for ‘bigger, better, stronger’ state-owned enterprises.

Second, ideology is playing a growing role in shaping Chinese economic policy. The most visible effect has been to prioritize Chinese state-owned enterprises, at the expense of the private sector. This became especially visible in 2021 with a campaign against the ‘unrestrained expansion of capital’ – Beijing’s way of expressing its anxiety that China’s corporate sector was behaving in a manner inconsistent with Chinese Communist Party goals. 

Although that phrase is no longer current, entrepreneurs’ animal spirits remain in the doldrums. They are likely to stay there as long as President Xi Jinping’s preference is for ‘bigger, better, stronger’ state-owned enterprises, which use capital much less efficiently than private firms.

Third, today Chinese policy is shaped by Beijing’s perception of geopolitical risks that it faces. Those risks became starkly apparent in February 2022 after Russia’s invasion of Ukraine, when essentially every country that prints a reserve currency joined to freeze Russia’s access to its foreign exchange reserves. That enveloped the Russian economy in a network of sanctions that sharply constrained its access to a whole range of imports.

It is not difficult to consider a similar scenario confronting China. Beijing’s approach to economic policy is therefore heavily influenced by the need to insulate itself from that kind of risk (though Chinese policy had in any case been tilting in this direction for years).

‘Asymmetric decoupling’

This policy can be described as ‘asymmetric decoupling’: a simultaneous effort on the one hand to reduce China’s reliance on the rest of the world by substituting imports with domestic production; and, on the other hand, to increase the rest of the world’s reliance on China by establishing itself as a ‘zhizao qiangguo’, or manufacturing powerhouse.

The defensive pursuit of economic self-reliance constrains Beijing’s willingness to boost consumer spending.

This is the right context in which to understand a central economic goal of the authorities, which is to reduce the economy’s dependence on real estate investment. 

The intention is to allow capital and credit resources to migrate to new sectors of the economy that will help to build that manufacturing powerhouse: high-tech and green energy, in particular. What that means in practice is that any forthcoming support for the real estate sector will be rather limited.




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The US election could create the need for a G7 alternative – without American representation

The US election could create the need for a G7 alternative – without American representation Expert comment jon.wallace

Traditional allies of the US need to find a way to work together on some global policy issues even when the US itself is not engaged. A ‘G6 plus’ group could provide an answer.

When Jamaica pulled out of the nascent West Indies Federation in 1961, Trinidad and Tobago’s then prime minister, Dr Eric Williams, famously said ‘One from ten leaves nought’. In the run up to the US elections on 5 November, the US’s longstanding allies need to ask themselves if the same logic must apply to the G7. 

A Donald Trump victory will result in stark differences between the US and its closest partners on key global economic issues. US allies would no doubt try and persuade the new president to moderate his position, but experience suggests that this will have little, if any, effect.  

They may then want to work around the US, or on a parallel track. But doing so will be very hard unless they have a framework for discussing and developing ideas collectively. Could some form of ‘G6 plus’ forum help?

The role of the G7 today

The G7 no longer acts as a steering group for the global economy. However, it remains a critical forum for the US and its allies to coordinate their efforts to help solve global problems, to defend common Western interests, to resolve internal disputes and to underpin information exchange. 

In the past two years, the G7 has come to be seen by the US and other members as one of the most effective international mechanisms. It has played a critical role coordinating Western efforts to recover from the last pandemic and prepare for future ones.  

It has been pivotal in weakening Russia’s economy following the attack on Ukraine and has acted to strengthen Western economic security and resilience more broadly.  

The G7 has also responded to ‘Global South’ calls for help in dealing with the pandemic aftermath and the Ukraine war. 

Trump’s approach to the G7

The problem is that the G7’s effectiveness depends critically on full US engagement, sometimes as a leader of initiatives (such as the decision to impose an ‘oil price cap’ on Russia in autumn 2022) or as an essential partner. 

If elected, former President Trump is likely to abandon the G7 as an instrument of international economic policy. This is effectively what happened during his first presidency and there are reasons to expect this to be repeated. 

Many of Trump’s international economic policies are highly controversial with US allies, including his apparent determination to withdraw from the Paris Agreement, impose across the board 10-20 per cent tariffs and even punish countries for not using the dollar. His domestic policies, including mass deportation of undocumented immigrants and aggressive deregulation and fiscal easing could lead to further sharp disagreements.  

Furthermore, Trump demonstrates general antipathy towards multilateralism. Under his presidency, US representatives in the G7 and G20 sought to weaken core values and policies that have underpinned international economic cooperation for decades – including the importance of a rules based international system, the IMF’s global safety net role, and the responsibility of the advanced world to assist the poorest countries financially.  

In the event of a second Trump administration, the most likely scenario for the G7 is a repeat of the paralysis of 2017-20.

Other G7 and G20 countries tried to preserve as much as possible of the previous consensus. But in the case of climate change, the only solution was to have a separate text for the US. Critically, such efforts diverted time and attention from the enormous challenges facing the world at the time. 

Trump went through four different G7/G20 Sherpas during his presidency and disowned the final declaration of the 2018 Canadian G7 summit after hundreds of hours of negotiation, and despite previously signing off on the text. The US failed to host a final leaders’ summit, even virtually, during his administration’s G7 presidency.  

Of course, how far Trump carries through his most radical policies will depend, among other things, on the outcome of the Congressional elections and the stance taken by US courts. 

He may also have second thoughts if elected. His first administration sometimes supported significant multilateral economic initiatives, notably the G20’s Debt Service Suspension Initiative and ‘Common Framework’ for debt rescheduling. 

But, in the event of a second Trump administration, the most likely scenario for the G7 is a repeat of the paralysis of 2017-20, which would be even more costly today.

Should Vice President Kamala Harris win on 5 November, the situation should in theory be very different. She will likely continue with President Joe Biden’s collaborative approach to the G7.

Nonetheless, major issues may still arise where America’s allies want to take a fundamentally different approach and need a mechanism to do so. These could include policy on the WTO, de-risking the economic relationship with China, restricting carbon leakage, and regulating US-dominated big tech.  

How should US allies respond?

No US ally will want to be seen to be leading development of a new ‘G6’ that excludes the US. The top priority will be securing the best possible relationship with the incoming president. Political weakness and/or new governments in France, Germany, the UK and Japan will add to this hesitancy.

Any new forum should be described as…intended to coordinate activity among Western economic powers in those areas where the US chooses not to engage.

Any new forum will therefore need to be as low profile as possible. The concept should initially be discussed in private by sherpas from each participating country. Once established, officials should as far as possible meet online. Leaders should only meet online, at least initially.  

Participants should be fully transparent about the forum’s existence and avoid any grand ‘framing’ along the lines of the EU’s ‘strategic autonomy’. Instead, it should be described as a practical, largely technocratic forum intended to coordinate activity among Western economic powers in those areas where the US chooses not to engage. A suitably innocuous name – such as the ‘the sustainable growth club’ could help.

Topics should be limited to those requiring urgent collective global action, such as climate, health, tech governance, development finance and trade – and where the US federal government is not an ‘essential’ partner. Such a forum should not therefore address defence.  




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As the ruling party claims victory in Georgia’s disputed election, Western condemnation is no longer enough

As the ruling party claims victory in Georgia’s disputed election, Western condemnation is no longer enough Expert comment LToremark

As tens of thousands take to the streets to protest the election results, Georgia faces a familiar crisis – with a few key differences.

As the people of Georgia went to the polls on 26 October, many were hoping not only for a democratic change of government but also for an end to one-party dominance and a return to the path of European integration. The previously weak and divided opposition had grouped itself into four major electoral centres, promising a coalition government and framing these elections as a choice between Europe and Russia. 

Ahead of the election, President Salome Zourabishvili had put forward the Georgian Charter, a blueprint for a stable and democratic transition to a new style of governance and for initiating reforms to fulfil conditions for EU accession. It was signed by all pro-European and pro-Western opposition parties. 

A new electoral system had created a not unreasonable expectation that these elections, if held freely, would result in a coalition government.

The official election results gave the ruling Georgian Dream party a 54 per cent majority in contrast with exit polls that gave the opposition a 10 per cent lead. President Zourabishvili and the opposition parties refuse to recognize the results, beginning a long process of contestation with allegations of fraud and street protests. As the disappointment sets in and the streets once again replace the ballot box as a conduit for democratic change, there is a sense of déja vu.

Georgia has seen this before. A party sweeps to power on the tide of popular protest, initiates reforms to meet public expectations but, by the end of its second term, it takes an authoritarian turn. As it overstays its welcome, it starts manipulating elections to cling to power. People once again take to the streets and a new party wins by a landslide only to repeat the same cycle. But with each turn, the grip the ruling elites have on power gets stronger and the methods they use become more sophisticated. State security becomes equated with regime stability, leaving no space for normal democratic contestation or expressions of dissent. 

Although what is happening in Georgia fits this familiar pattern, there are some consequential differences. 

First, these were the first fully proportional elections. Previously, a mixed system of representation meant that the incumbency always had an advantage by dominating majoritarian districts. A new electoral system had created a not unreasonable expectation that these elections, if held freely, would result in a coalition government. The hope was this could help break the vicious cycle of Georgian politics, sustained by an extreme form of majoritarianism and a winner-takes-all political culture.

The Georgian Dream party was contesting its fourth consecutive term against a backdrop of falling popularity and growing societal mobilization in opposition to its authoritarian inclinations. Despite all this, it secured – some would insist manufactured – an absolute majority in elections that international observers say were marred by serious irregularities and fell short of democratic standards. 

The second important difference is that these elections were not only about saving Georgia’s democracy but also about rescuing its European perspective. Since Georgia was granted EU candidate status in December 2023, its parliament has adopted Russian-style laws on foreign agents and combating LGBTIQ+ ‘propaganda’. 

It has also adopted a strongly Eurosceptic political discourse, pushing back on international criticism and accusing EU and US officials of interference in domestic affairs and disregard for Georgia’s sovereignty. In response, the EU has suspended accession talks with Georgia indefinitely while the US has imposed targeted sanctions on high-ranking Georgian officials and judges. 

Georgia’s democratic backsliding at home and its pivot away from the West are both simultaneous and interrelated. It was widely hoped these elections would be a course correction and return Georgia to the path of European and Euro-Atlantic integration. The election results, if they stick, will prevent this from happening. A Georgian Dream government will not work to fulfil conditions for EU accession, viewed as a challenge to its hold on power. 

The third and final difference is that these elections took place in the context of heightened geopolitical confrontation. The Georgian Dream ‘victory’ is a win for anti-liberal, conservative forces around the world championed, among others, by Hungary’s Viktor Orbán. He was the first to congratulate Georgian Dream for its declared success and even visited Tbilisi in a show of solidarity and ideological alignment. 

The election result is also a win for Russia. It strengthens Moscow’s influence in the South Caucasus, which has waned as a result of the war in Ukraine and the fall of Nagorny-Karabakh. Russian officials and propagandist were quick to congratulate Georgian Dream, wishing them success in standing up to Western pressures and offering help in case things got tough. 

From Moscow’s perspective, Georgia’s elections are part of a global hybrid war. They represent a local battle in the ongoing geopolitical contest between Russia and the West, between the rules-based global order and competitive multipolarity. 

As Georgia repeats a familiar pattern, what do the election results mean for its future? While clear predictions are difficult at this stage, it is worth bearing in mind that as the democratic resilience of the Georgian society has strengthened over time, so too has the state capacity to supress and control. 




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In conversation with Julien Harneis, UN Assistant Secretary-General

In conversation with Julien Harneis, UN Assistant Secretary-General 18 November 2024 — 2:30PM TO 3:30PM Anonymous (not verified) Chatham House and Online

In this discussion, Julien Harneis will give critical insights into the UN’s humanitarian response in Yemen and the importance of maintaining independent humanitarian assistance.

According to the United Nations, Yemen has faced the world’s worst humanitarian crisis in the last decade, with over 20 million people in need of assistance. Years of ongoing conflict have devastated infrastructure, displaced millions, and caused widespread food insecurity and health emergencies. Access to essential services remains a daily struggle, and the escalating economic collapse has left vulnerable communities facing critical shortages in food, water, and medical supplies.

However, humanitarian actors are continually facing challenges in delivering aid to Yemen due to security threats and supply chain barriers, highlighting the urgent need for coordinated and sustainable international assistance.

UN Assistant Secretary-General and Humanitarian Coordinator for Yemen, Julien Harneis, will provide an account of the humanitarian mission and evolving strategies in Yemen, the impact of regional conflicts in the delivery of aid and discuss other key questions including:

  • What are the priorities and goals of the UN’s current aid plan for Yemen, and how is it designed to reach those most in need?
  • How are recent developments in the Red Sea affecting food security, trade routes, and humanitarian access in Yemen?
  • What strategies are in place to ensure the delivery of humanitarian aid remains independent and neutral?

This is a ‘register interest’ event. Confirmations to successful applicants for in-person attendance will be sent on Thursday at 16.00 GMT. Virtual attendees will be granted access to the event.

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.

 

 




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




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Should Debt in the Developing World be Cancelled?




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Unfulfilled Ambitions: the State of Democracy in Africa




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The Reconstruction of Iraq: Lessons from Mosul




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Unelected Power: Finding Legitimacy in Central Banking and the Regulatory State




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A Decade on from the Financial Crisis: the Legacy and Lessons of 2008 - The Rt Hon Lord Darling of Roulanish




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Can and Should Brexit Be Stopped?




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Evan Davis In Conversation With Christian Ulbrich, CEO, JLL




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Leadership in an Era of Geopolitical Turbulence




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Chatham House Primer: National Populism




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Can Multilateralism Survive?




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Undercurrents: Episode 22 - China's Belt and Road Initiative, and the Rise of National Populism




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China’s Dream: The Chinese Communist Party’s Culture, Resilience and Power




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Undercurrents: Episode 30 - The Crisis in Kashmir, and How to Regulate Big Tech




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A Gulf Divided: The Anatomy of a Crisis




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The Korean Peninsula: A Diplomatic Outlook




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Direct Democracy: Participation Without Populism?




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Who Should Regulate Free Speech Online?




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Undercurrents: Episode 37 - Women in Leadership, and Europe's Ageing Population




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Simulation: The Implications of Drone Warfare




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Schapiro Lecture: The Would-Be Federation Next Door – What Next for Britain?




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Secularism, Nationalism and India's Constitution




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

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




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Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth

MS Brown
Jul 1, 1980; 21:505-517
Reviews




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Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




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Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells

W Gamble
Nov 1, 1978; 19:1068-1070
Articles




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Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles




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Intracellular cholesterol transport

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews




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Gene expression regulation by retinoic acid

James E. Balmer
Nov 1, 2002; 43:1773-1808
Reviews




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

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




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Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles