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Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources]

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.




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M8R tropomyosin mutation disrupts actin binding and filament regulation: The beginning affects the middle and end [Molecular Bases of Disease]

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.




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High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity [Molecular Bases of Disease]

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.




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Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...




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Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).




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Naturally occurring hotspot cancer mutations in G{alpha}13 promote oncogenic signaling [Molecular Bases of Disease]

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.




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Allosteric activation of proto-oncogene kinase Src by GPCR-beta-arrestin complexes [Enzymology]

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.




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Hdac3 regulates bone modeling by suppressing osteoclast responsiveness to RANKL [Signal Transduction]

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.




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FUS contributes to mTOR-dependent inhibition of translation [Signal Transduction]

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes.




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Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of Disease]

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases.




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The Critical Transition: China’s Priorities for 2021

The Critical Transition: China’s Priorities for 2021 Research paper sysadmin 31 January 2017

This paper sets out the core issues for the Xi leadership, and focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president.

The Great Hall of the People during the closing ceremony of China’s National People’s Congress on 15 March 2015 in Beijing, China. Photo via Getty Images.

In 2017 Xi Jinping will complete his first full five-year term as China’s leader. Towards the end of the year, in autumn, the country is due to hold its 19th Party Congress. This major meeting usually marks the moment when the Communist Party of China (CPC) assesses its performance over the previous five years, sets out political goals for the coming five-year period and makes new appointments.

Xi Jinping’s leadership has been characterized by a number of significant domestic and international policy strategies. China’s economic growth rate is slowing, and the country’s economy is undergoing major restructuring. Export-led manufacturing growth and capital investment in fixed assets are now being replaced by consumer-led and service-dominated expansion. Meanwhile, the role of the CPC has been rearticulated with a major anti-corruption struggle since 2013 that has sought to clear away a raft of different networks and senior officials and connected business people. Xi has proved a more communicative, more populist and more nationalistic leader than his predecessors. He is also crafting an image of himself as a more visionary leader.

Internationally, China is striving for a relevance and role that it has never had before. Its reach is felt in international organizations, regionally, and through its economic and resource needs. It has a role in global affairs that embraces places once considered on its periphery, such as Latin America, the Arctic and Antarctic Circles, and the Middle East. Its impact in Asia is particularly striking, marked by activity in the South China Sea, and a new kind of relationship with Russia, India and the US. The major Belt and Road Initiative, in particular, has started to outline a new expansiveness in China’s relations with the outside world, despite the largely abstract nature of its overall shape and form at the moment.

The themes and viewpoints in this collection of essays are particularly geared towards those with an interest in policy engagement with China. While setting out the core issues for the Xi leadership, it also focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president. As the UK seeks a new kind of relationship with a rapidly changing China, this group of expert opinions maps out the key markers in the run up to 2021, when China is due to celebrate achieving the first of its centennial goals: the delivery of middle-income status and a moderately prosperous society.




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India Budget 2018: Who are the Biggest Winners and Losers?

India Budget 2018: Who are the Biggest Winners and Losers? Expert comment sysadmin 2 February 2018

Any claims to boost farmers’ prospects will inevitably be seen as political, coming ahead of a series of key elections. But this budget recognises India’s most pressing concerns - and seeks to address them.

Hundreds of farmers sit in pits as a protest against government plans for land acquisition in October 2017. Photo By Vishal Bhatnagar/NurPhoto via Getty Images.

In 2016 India’s prime minister, Narendra Modi, pledged to double farmers’ incomes by 2022. While the pledge may have been aspirational, reliant on good weather as much as government policy, the 2018/19 budget demonstrates the depth of the government’s commitment to the agriculture sector.

There’s clearly a political edge to any moves to bolster agriculture: any solace to rural India will be described as political opportunism until most people in India are not engaged directly or indirectly in the agricultural sector.

And with a number of state elections coming up this year and a general election next – suggestions that it will be brought forward have increased in volume since the budget – a politically-astute budget is unsurprising. At the same time, there is a real sense of crisis in Indian agriculture which the budget is attempting to ameliorate.

Significant hike in infrastructure spending

The budget – which has Keynesian undertones – announces both direct and indirect support for rural India; it increases significantly the price at which the government purchases agricultural produce, and offers a range of further support through initiatives in areas such as irrigation. Furthermore, there is a significant hike in spending on infrastructure – roads, railways, ports and waterways – with a major allocation for rural infrastructure.

While government spending on infrastructure had been growing, the 2018/19 budget appears to accept that innovative funding models to fund rural projects are unlikely to work – instead, rural highways will have to be funded from overall taxation, as is generally the norm.

The other bold initiative focuses on healthcare. One hundred million poor families (so around half a billion Indians in total) will receive up to Rs500,000 for medical care under a health insurance programme. Given the correlation between ill health and poverty, this should have implications for the economy as well as healthcare itself. At the moment poverty effectively excludes many Indians from private healthcare.

Education too received a boost, with several proposals including teacher training. There have long been concerns over the quality of Indian education. In particular, even where schools exist physically, teachers themselves are absent.

As is often the case with India, the question will be in the implementation. While there are bound to be hiccups, the current Indian government does appear to realise the need for on-the-ground, visible change.

The recent state election in Gujarat demonstrated that while the ruling Bharatiya Janata Party (BJP) is clearly favourite to win another term, it is not invulnerable. If the changes do not reach the “last mile”, then they will accrue neither the economic nor the political benefits.

The downsides? Increased taxes will raise inflation, potentially exacerbated by sustained government borrowing; a 20% rise in customs duty will affect imports of mobile phones (though benefit domestic producers and encourage other foreign firms to set up manufacturing plants in India) and some of the revenue projections appear optimistic.

On balance though, this is a budget that recognises the most pressing challenges which India faces, and attempts to provide solutions to them.

This article was originally published in The Independent.




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How Women are Transforming Indonesia

How Women are Transforming Indonesia Interview sysadmin 20 May 2019

In a series exploring women in international affairs, Isabel Dunstan speaks to Gitika Bhardwaj about the rise of the women’s movement in Indonesia.

Southeast Asia has one of the highest records of gender-based violence in the world and Indonesia was recently ranked as the second most dangerous place for women in the Asia-Pacific. What is the state of women’s rights and gender equality in Indonesia?

It is true that Indonesia has high rates of violence against women, however, it’s difficult to know the realities of women’s experiences because in the past the data has been somewhat unreliable. This has been due to reasons such as a lack of reporting mechanisms available to survivors of violence and the fact that discussing sexual violence is a taboo and, if reported, can result in stigmatization which limits the number of survivors who have come forward.

However, the first reliable nationwide survey on gendered violence in Indonesia was conducted in 2017 by the Indonesian Ministry of Women and Child Protection and the United Nations Population Fund. Interestingly, it showed that Indonesia’s rates of violence against women are on par with the global rate which is that 1 in 3 women are affected by sexual violence in their lifetime.

It’s therefore difficult to generalize that Indonesia is an unsafe place for women because it’s an extremely diverse country. There is a growing middle class while there is pervasive poverty. There is religious diversity where the eastern-most province of Aceh is the only province in the country where Sharia law is enforced, whereas in the western-most province of West Papua, the dominant religion is Christianity and the ways of life are completely different.

Nevertheless, violence against women is high in Indonesia and can happen in all places – rich or poor, east or west – and has different manifestations from street harassment and trafficking to domestic violence and workplace harassment.

In some parts of the country there are high rates of child marriage too and, according to UNICEF, 14 per cent of girls in Indonesia are married by the time they turn 18 which is shocking when we think about how child marriage limits girls’ access to education and makes them more vulnerable to sexual violence and therefore restricts their futures.

Child marriage is high in Indonesia in part due to rooted gender norms, low levels of education and discriminating legislation, such as the marriage law, which states that, although it is legal to marry at 21, girls can marry at 16 and boys can marry at 19 with parental consent. But this can be even lower meaning parents could get their daughters married at as young as 13. So the law is fundamentally unfair between girls and boys and the women’s movement in Indonesia has been fighting extremely hard to reform legislation that discriminates against women and girls.

From the country’s first female president, Megawati Sukarnoputri​, to incumbent finance minister Sri Mulyani Indrawati – who was voted ‘Best Minister in the World’ in 2018 – and maritime​ and fisheries minister Susi Pudjiastuti – who has become notorious for her tough stance against illegal fishing activities – how are women progressing in Indonesian politics?

Indonesia has come a long way since becoming a democracy in 1998. Before that, the second president and dictator, Suharto, ruled the country for almost 32 years and increased the inequality gap between men and women during his reign.

Since the fall of Suharto, however, gender equality is explicitly enshrined in Indonesia’s constitution and the country has ratified the Convention on the Elimination of Violence Against Women.

The country has also been undergoing a process of democratization which has involved slowly decentralizing its power. This means that greater authority has been distributed to the 34 provincial governments outside of the capital of Jakarta.

Furthermore, to aid gender equality, a quota system requiring political parties to be made up of 30 per cent women has been put in place, although remnants of Suharto’s old system of cronyism remain, limiting the impact of the quotas translating to more women in provincial parliaments.

But the defining approach to furthering gender equality in Indonesia has been through gender mainstreaming and gender-responsive budgeting which can be seen throughout provincial administrations in the country.

This means there is the intention to ensure infrastructure, health and education outcomes include results that address specific gender equality gaps. The challenge for effective gender mainstreaming, however, is the political will to translate the approach into well-resourced programmes from one province to another.

Indonesia has come a long way since becoming a democracy in 1998. Before that, Suharto, ruled the country for almost 32 years and increased the inequality gap between men and women.

Nevertheless, we have just seen Indonesia go through the most incredible presidential and legislative elections last month – won by the current president, Joko Widodo, who has often been called the ‘Barack Obama of Southeast Asia’ and whose existing cabinet has the highest number of women in the country’s history. This is not simply a matter of filling seats in the cabinet with women – such as the wives and sisters of male politicians – because it’s required by law. But, rather, there are some incredible female political figures who are there because they are strong, smart and capable.

You’ve rightly mentioned Minister of Maritime Affairs and Fisheries, Susi Pudjiastuti, who is a fabulous role model for a lot of women particularly women who have not had tertiary education because she entered politics through an unorthodox route.

Then there’s Minister of Finance, Sri Mulyani Indrawati, who is also the former leader of the World Bank and is such an inspiration to a lot of women who are looking to work in public life because of her experience as well as her work to include gender mainstreaming in state budgets.

There is also Minister of Women’s Empowerment and Child Protection, Yohana Susana Yembise, who is a Papuan woman, as well as many more female public figures.




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The Indo-Pacific: Geostrategic Perspectives 2019-24 – Workshop 2

The Indo-Pacific: Geostrategic Perspectives 2019-24 – Workshop 2 24 September 2019 — 9:00AM TO 2:00PM Anonymous (not verified) 4 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The roundtable brought together stakeholders within the UK strategic and policymaking communities to explore British perceptions of evolving strategic shifts in the Indo-Pacific until 2024.

The roundtable took place at Chatham House in London. The report below contains a summary of the discussions.

Read a summary




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The Indo-Pacific: Geostrategic Perspectives 2019-20 – Workshop 1

The Indo-Pacific: Geostrategic Perspectives 2019-20 – Workshop 1 11 September 2019 — 10:00AM TO 2:30PM Anonymous (not verified) 4 September 2019 East-West Center, 1819 L St., NW, Suite 600, Washington, DC 20036, USA

The roundtable brought together stakeholders within the US strategic and policymaking communities to explore American perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable was organized in cooperation with, and was held at, the East-West Center in Washington D.C.

The report below contains a summary of the discussions and an essay by Satu Limaye, Vice President and Director of the East-West Center in Washington, DC.

Read a summary report and essay




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The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3

The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3 17 October 2019 — 9:30AM TO 2:00PM Anonymous (not verified) 14 October 2019 Institut Francais des Relations Internationales, 27 rue de la Procession, 75740 Paris Cedex 15, France

The roundtable brought together stakeholders within the French strategic and policymaking community to explore French perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable was organized in cooperation with, and was held at, the Institut français des relations internationals in Paris.

The report below contains a summary of the discussions and an essay by Céline Pajon, Research Fellow, Center for Asian Studies, Institut français des relations internationals.

Read a summary and essay




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Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.




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Policy for Recovery in Africa: Rethinking Energy Solutions for Universal Electricity Access

Policy for Recovery in Africa: Rethinking Energy Solutions for Universal Electricity Access 10 December 2020 — 5:00PM TO 6:00PM Anonymous (not verified) 20 November 2020 Online

Approximately three quarters of Africa’s population do not have access to clean cooking fuel and face costs to their health. Speakers explore policy opportunities to bridge this gap, the key barriers that remain and the transformative potential of energy transition in delivering sustainable access for all.

Speakers explore policy opportunities to bridge the energy access gap, the key barriers that remain and the transformative potential of energy transition in delivering sustainable access for all.

African countries face an uphill battle as they confront the shocks of the coronavirus pandemic, seeking recovery in the context of global socio-economic difficulty and fragmented geopolitics.

With deficits in terms of governance, public health systems, social protection, and basic service delivery presenting challenges even before the outbreak, careful analysis and creative evidence-based policy solutions, as well as emphasis on implementation, will be crucial if Africa is to progress towards the SDGs and Agenda 2063.

The Policy for Recovery in Africa series brings together expert speakers and decision makers to examine and exchange on key challenges, potential solutions, and approaches for implementation.

The energy access gap in Africa presents one of the most serious obstacles to the long-term pandemic recovery effort, with almost half of the continent’s population estimated to still lack access to electricity, creating a negative annual GDP impact estimated to be over 25 billion USD.




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The Indo-Pacific: Geostrategic Perspectives until 2024 – Japanese perceptions

The Indo-Pacific: Geostrategic Perspectives until 2024 – Japanese perceptions 24 February 2020 — 9:00AM TO 1:00PM Anonymous (not verified) 22 March 2021 Chatham House

The roundtable brought together stakeholders within Japan’s strategic and policymaking communities to explore Japanese perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable took place in Tokyo and was organized in partnership with the Indo-Pacific Studies Group.

The report below contains a summary of the discussions and an essay by Hiroki Sekine, Visiting Fellow, Asia-Pacific Programme, Chatham House.

Read a summary and essay




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Nancy Pelosi in Taiwan: What lies ahead for China and the US?

Nancy Pelosi in Taiwan: What lies ahead for China and the US? Expert comment GBhardwaj 3 August 2022

Chatham House experts examine the implications for Taiwan, China and the United States of Nancy Pelosi’s visit to the island.

China’s fading ties with Washington?

Dr Yu Jie

US House Speaker, Nancy Pelosi’s, visit to Taiwan has plunged China-US relations into a new low as the reservoir of trust forged between the two sides over the last 40 years appears to be almost exhausted.

However, her move will likely not result in the full-scale crisis across the Taiwan strait that some hawkish voices in both Beijing and Washington believe. Instead, Beijing will most likely offer a combination of military posturing toward the US navy and economic sanctions on Taiwanese agricultural and manufacturing products in order to send a clear bellwether to any future potential visits by high-level Western political figures.

China will be careful not to stumble into an accidental conflict. 

Neither Beijing nor Washington has declared a willingness to change the current status quo as the present impasse benefits both governments – but for different reasons. For China, the best approach is to reach a military and economic capability that prevents US engagement with Taiwan without the use of force. For the US, the strategic ambiguity under the Taiwan Relations Act remains an effective card to counter China’s growing military influence in the Indo-Pacific and keep itself relevant within the region as a security guarantor. Yet, both sides have decided to kick the issue of Taiwan’s status down the road, believing that time is ultimately on their side.

Despite a chorus of nationalistic rhetoric, China will be careful not to stumble into an accidental conflict which risks colossal damage on all fronts. Chinese President, Xi Jinping, must weigh all of the options before him as Beijing cannot afford to be perceived as unilaterally seeking to change what it agreed with the US back in 1979 when ties were re-established. If that happens, it will provoke the US political establishment to reach a unanimous agreement to change its ‘One China Policy’ and, ahead of the 20th Communist Party Congress where Xi is expected to be crowned for a historic third term, the last thing he wants is an unnecessary conflict with Taiwan.

The road to escalation?

Dr Bill Hayton

Beijing has chosen to take issue over Nancy Pelosi’s visit to Taiwan in a way that it did not do for other recent US Congressional visits to the island. Several high-ranking US senators visited in April and May this year yet none of these visits triggered the prospect of a cross-strait crisis. So why has Beijing chosen to turn Pelosi’s visit into a stand-off?

Pelosi’s visit is part of a performance in which both actors – the US and China – are playing primarily for their domestic audiences. This comes at a time when ruling circles in Beijing are preparing for the five-yearly Communist Party Congress. Amid a slowing economy and successive COVID-19 variants, Xi Jinping cannot afford to look weak as he prepares the ground for his third term of office. Meanwhile, the US, represented either by President Joe Biden or House Speaker Pelosi, cannot back down at this point without looking weak itself.

The impact on a world economy already suffering major disruption because of the Russian invasion of Ukraine and the lingering effects of COVID-19 would be stark.

Both sides have moved military assets into strategic positions near Taiwan to demonstrate their resolve. Neither side wants confrontation yet neither wishes to be humiliated. Currently, Pelosi’s visit, amid posturing by China, will make the US appear strong, but the consequences are likely to play out over a longer period. Xi Jinping will need to appear to have recaptured the initiative between now and the congress in the autumn when the risk of an incident will be at its greatest.

Taiwan controls several isolated islands that could be pressured by Chinese forces in the event of a future crisis. The Kinmen and Matsu archipelagos lie just a few miles off the coast of the mainland and have been at the centre of previous confrontations. There are also two other points of concern. Pratas Island – known as Dongsha – sits halfway between Taiwan and Hong Kong. Itu Aba – known as Taiping – is the largest of the Spratly Islands in the centre of the South China Sea. All would be vulnerable to an attack by the People’s Liberation Army, the principal military force of China, and the armed wing of the Chinese Communist Party.

A military confrontation between China and the US over Taiwan, or further south in the South China Sea, would have major impacts on regional and global trade. An estimated $300 billion worth of trade passes through the area every month. Japan and South Korea depend heavily on flows of oil and gas through the sea. Exports from Vietnam, Malaysia, Indonesia and the Philippines would also be heavily affected by disruptions to shipping, increased insurance costs and interruptions in inflows of raw materials. The impact on a world economy already suffering major disruption because of the Russian invasion of Ukraine and the lingering effects of COVID-19 would indeed be stark.

Is a shift in US policy on the cards?

Dr Leslie Vinjamuri

Nancy Pelosi’s visit to Taiwan will undoubtedly be seen as a provocation by Beijing – even if it should not be. Pelosi’s trip to the Indo-Pacific, which also includes visits to Singapore, Malaysia, South Korea and Japan, comes at a time of growing tension between the US and China in the region.

It also comes at a time when the divide among Washington’s foreign policy elite is growing, with some arguing that it is time to abandon the country’s policy of ‘strategic ambiguity’, where it refrains from stating how it would react were China to openly and deliberately attack Taiwan. Indeed, recent statements by President Joe Biden have raised questions about whether the US is set to make a policy change. But, since both its ‘One China Policy’ and policy of strategic ambiguity have been largely successful, it would be wise for the US to maintain them.

It would be a mistake for the US to signal a major policy change away from strategic ambiguity and towards strategic clarity on Taiwan’s status.

During her visit, Pelosi is likely to reaffirm the US’ high regard for Taiwan’s democracy and embrace the language of shared values. She has embraced Biden’s framing of international relations as a contest between democracies and autocracies. This alone will continue to exacerbate tensions. It would be a mistake, though, to signal a major policy change away from strategic ambiguity and towards strategic clarity on Taiwan’s status. Even if the US decides later to embrace a policy shift of this size, such a message should be carefully considered and communicated clearly, and not by chance.

Congress has an important role to play but President Joe Biden and his national security team should make the final decision on US policy towards Taiwan. Getting the signals right in international politics is a key part of deterrence and, especially in East Asia, deterring both China and Taiwan’s ambitions is essential. 

Increasing insecurity in the region?

Dr John Nilsson-Wright and Ben Bland

Nancy Pelosi’s visit to Taiwan has provoked mixed responses from US allies across Asia.

For Japanese policymakers, the Taiwan issue is connected to the wider issue of regional security. Fears that a military conflict over the island will inevitably draw Japanese self-defense forces into a shooting war with China – a development that is neither formally mandated under the terms of the US-Japan Mutual Security Treaty nor necessarily constitutionally sanctioned – explains the concerns in Tokyo.

While the Japanese government of Prime Minister Fumio Kishida is increasingly worried about China’s growing military presence in the East and South China Seas, Japan’s heavy trade dependence on China and the country’s economic and security vulnerabilities make it imperative to avoid any further escalation of tensions.

Given Tokyo’s non-recognition policy towards Taiwan, Japanese ties with Taipei are handled informally by politicians of the governing Liberal Democratic Party (LDP), rather than at cabinet or foreign ministry level, and in recent weeks and months there has been an increase in visits by cross party delegations from Japan.

Though most Asian governments are keen to see the US constructively engaged in the region they also want to see stable China-US relations.

The death of former Prime Minister Shinzo Abe as removed from public life a vocal advocate in support of enhanced ties between Tokyo and Taipei, but with public opinion in Japan increasingly tilting in an anti-Chinese direction, and with younger politicians favouring a more combative approach towards Beijing, there is a risk that the government will face pressure at home to toughen its language on Taiwan. Bolstering deterrence through increased military cooperation among allies, along with a graduated increase in defence spending, is the best way of limiting risk over Taiwan.

Nevertheless, privately, many officials in Tokyo are likely to have viewed the Pelosi visit as an unhelpful intervention and will be puzzled and perhaps frustrated by the apparent inability of the Biden administration to persuade the US Speaker of the House of Representatives to cancel her visit.

In South Korea, the government of President Yoon Suk-yeol, faces similar pressures to Japan, given the heavy dependence of the South Korean economy on China for trade and investment opportunities.

Pelosi’s visit to the region will strikingly not include meetings with either the president or Foreign Minister Park Jin. With Yoon on vacation and Park attending the ASEAN Regional Forum meeting in Cambodia, the absence of high profile engagements for Pelosi might seem to be a purely practical matter, but Seoul may also be seeking to avoid antagonizing Beijing at a time when the Chinese government is seeking to pressure South Korea not to enhance alliance coordination with the United States and Japan or to expand its commitment to the controversial Terminal High Altitude Area Defence (THAAD) missile defence system.

As in Japan, public opinion in South Korea is increasingly anti-Chinese, but the logic of regional economic and security uncertainty, requires the Yoon government to avoid getting trapped in a worsening stand-off with Beijing.




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America’s vote shows a desire for stability and calm

America’s vote shows a desire for stability and calm Expert comment NCapeling 11 November 2022

Joe Biden has presided over the best midterm election results by a party in power in two decades, but the future for the Republican Party leadership is now uncertain.

For a president continually struggling with low approval ratings, the midterms provided a stunning result as the widely anticipated Republican red wave failed to materialize.

Although Democrats look set to lose their majority in the House, it is by a much smaller margin than either history or today’s pollsters anticipated. Democrats have maintained their majority in the Senate, a result that was confirmed four days after election day when Senator Catherine Cortez Masto won reelection. The final Senate seat will be decided by a 6 December run-off in the state of Georgia. 

The midterm elections were not good for the Republican party but were especially bad for Donald Trump who has until now managed to defy expectations and maintain his grip on the party even after his 2020 defeat at the polls.

After six years of chaos, this upset has been delivered with remarkably little chaos and, so far, no violence in a win for democracy and stability in the US

Trump managed to win the presidency once but he lost the popular vote twice and at no stage during his time in office did his approval ratings go above 40 per cent. Now, after six years of the most divisive and disruptive leadership the US has ever seen, he has presided over the worst midterm results a party out of power has suffered in two decades.

Trump’s influence is on the wane

Many of the candidates endorsed by the former president – including in battleground states such as Pennsylvania and Arizona – lost. In Georgia, the Republican governor and Trump GOP rival won, despite Trump’s opposition, and the candidate he endorsed for the US Senate has come up short of the 50 per cent needed to get over the line in the first round.

Trump’s nemesis, Ron DeSantis, the Republican governor of Florida, won a second four-year term in a landslide. Trump is suffering attacks from his own party and many loyal media supporters, such as Fox News, the New York Post, and the Wall Street Journal. None of this bodes well for the prospect of Trump leading the party through the 2024 presidential election.

After six years of chaos, this upset has been delivered with remarkably little chaos and, so far, no violence in a win for democracy and stability in the US which will reverberate beyond the US shores.

The system has worked, with multiple elections held across all 50 states. Hotly contested seats were decided peacefully even when the margins were thin. The midterm elections were also a win for democracy. In every battleground state, election deniers that were nominated to run for offices that would control state election systems, including in the 2024 presidential elections, have been defeated.

For a country with a polarized electorate and a radical Republican leader who has continued to spread disinformation and sought to rile his base, this election has been surprisingly normal.

Biden is still in the saddle and, instead of a battle for control inside the Democratic party, it is the Republicans who look set to descend into internal conflict and recrimination

This means the debate about the future of America’s international leadership is postponed. Biden is still in the saddle and, instead of a battle for control inside the Democratic party, it is the Republicans who look set to descend into internal conflict and recrimination.

The unofficial contest to win the Republican nomination for president has already begun. Donald Trump has signalled loudly that he plans to run. If he does, it could impact Republican prospects in the 6 December runoff for the final seat in the Senate. DeSantis may also run and could be followed by several aspiring Republican candidates. A disrupted party facing a period of significant change seems likely. 

Inflation and the economy proved key factors

As always, foreign policy barely featured in the elections but the result promises a period of continuity. Instead of facing dangerous sniping on Ukraine from an emboldened Republican House leadership, the Biden administration looks set to hold to its Ukraine policy.

Biden’s increasingly hard-line policy on China will continue to be qualified by a clear-headed determination – however hard – to cooperate on climate. Trade policy will remain stuck, as will US policy in the developing world.

Exit polls show Democrats were motivated to vote by the reversal of Roe vs Wade and the restrictions on abortion rights that followed, while Republicans voted against inflation.

But Democrats at the national level continually failed to effectively communicate the positive impacts of Biden’s legislative agenda for ordinary Americans, or to deliver a clear economic message.

The national leadership veered from abortion rights to the Inflation Reduction Act, to the future of democracy in the US – all of which proved too complicated to cut through.

The state level shows a more complex picture because inflation and the economy – which could have swept Republicans to victory – were blunted by dogged local campaigning from Democrats who knew their voters and spoke to the cost-of-living concerns which were top of their minds.




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Why technology does not make easy wars

Why technology does not make easy wars Interview LJefferson 28 November 2022

Stephanie Carvin explains why technology does not overcome the challenges of war.

The invasion of Ukraine has demonstrated that many of the assumptions held about the role of technology in contemporary warfare are flawed. The lesson that technology cannot overcome the challenges of warfare is one that the West has also yet to learn, despite a series of failed interventions since the end of the Cold War.

In a wide-ranging conversation, Isabel Muttreja sat down with Stephanie Carvin to talk about her contribution to the September 2022 issue of International Affairs on ‘how not to war’. They discuss the US’ over-reliance on technology and why ‘easy wars’ become ‘forever wars.’

You argue in your article that the US overly relies on technology in war. When did this start?

I don’t necessarily think the US is exceptional. I think all states have tried in some ways to use technologies. One of the key arguments in the article is that the US is an enlightenment country, and part of the enlightenment is a belief in rationality and science and that you can better things through the application of science.

The idea is that if you have perfect information, you are going to be able to dominate the battlefield, and that’s proven itself to be false.

I think that there is this particular scientific approach or embracing of technology, in the American and in fact larger Western tradition on technology as a way to save lives. There is a strange humanitarian impulse that often underlies this use of technology.

We are seeing a quest to try and get perfect information. The idea is that if you have perfect information, you are going to be able to dominate the battlefield, and that’s proven itself to be false. I’m not even sure you can ever get perfect information.

But it underlines this modern approach, that if you can have all the information that’s out there, crunch it into some kind of algorithm, that you can then target discriminately, proportionately, reduce the level of casualties, and reduce the level of unnecessary damage. And that’s a kind of liberal tradition. You are trying to have your cake and eat it too.

You talk about the US being an ultimately liberal state, but they have been involved in a lot of wars over the last 10–20 years. Is that a contradiction?

I hope it is. But I think it goes back to the enlightenment nature of the United States, which is that the US sees itself as a shining city on a hill that has to protect itself at all costs. Liberals abhor tyranny, and they abhor unnecessary deaths. But I think that the idea is that if you threaten us, we see ourselves as embodying these values, therefore, we have to protect ourselves.

There’s a tendency to not really recognize the kind of insurgencies that we’ve seen in Iraq and Afghanistan, or even Vietnam, as war. We don’t really see that as a kind of armed conflict, even though, arguably, that has been the dominant mode of conflict for some time. They even used to call it ‘military operations other than warfare’. We tend to still think of war as great power competition or as the Second World War.

The West has struggled to culturally understand the way other people fight. And that’s when the laws of war conventions have broken down.

My first book was on prisoners of war in the American tradition. What often determined the treatment of people as prisoners of war was if the United States recognized their form of warfare. There’s a racial element here too that I don’t want to dismiss.

So, for example, the US war in the Philippines at the start of the 20th century: They went in, won a very quick victory over the Spanish and effectively took over the Philippines. And then they had a long insurgency for two years with the native Filipinos who didn’t want US domination. While they gave the Spanish all the prisoner of war rights, they didn’t give them to the Filipinos.

This is because they recognized the form of conflict that the Spanish engaged in, but the Indigenous way of warfare was not recognized. The West has struggled to culturally understand the way other people fight. And that’s when the laws of war conventions have broken down between, say, the United States, the West, and other states.

You talk in your article about the US entering ‘easy wars’ and ending up with ‘forever wars’ – what does this mean?

There’s an allure to this high-tech version of warfare, that it can solve a lot of problems, but it’s an illusion. It is ultimately a bit of a false promise.

The idea that machines are going to replace humans is fundamentally untrue. We are seeing this to a certain extent right now, even in the Russia/Ukraine war. This is very much a battle of machines and soldiers. One of the themes of this issue of International Affairs is hubris. The idea that things that appear to be quick wins often tend to be long-term losses. And that’s exactly what this article is talking about.

‘Forever wars’ is not my favourite term, but it’s this concept that what was promised to be an easy war, a high technology-driven conflict, where you can go in, use some surgically precise weapons, take care of the problem, eliminate your opponent and then extract yourself from a situation, has actually turned into a quagmire.

There’s an allure to this high-tech version of warfare, that it can solve a lot of problems, but it’s an illusion.

The limits of technology become apparent within a few months as well as the fact of the messy business of state-building, or the fact that insurgencies and political movements don’t just disintegrate at the show of some high-tech, sophisticated weaponry. It just tends to mean that these wars do go on for a long time, and you have to eventually extricate yourself, but there’s no clean way to do this. We saw this of course with Afghanistan, and to a large extent Iraq.

We get distracted by the shiny object. We see this promise, we see this vision of a kind of warfare that for some may have great appeal.  There are new super weapons, whether it be cyber information warfare or artificial intelligence. Everyone wants to be ahead of the curve, right?

Are these lessons on technology and ‘easy wars’ applicable to other countries?

I think what we’ve learned about the Russian military is that there’s a lot more at the heart of it. Part of the problem Russia is experiencing is that its capabilities were not what it thought they were. It’s clear that Vladimir Putin was enamoured with a lot of the ideas, like that the Russian military was increasingly high-tech and that they had these hypersonic missiles.

They also had very powerful cyber weapons amongst other things. Putin, too, seems to have been caught up in this idea that he could have had a 72-hour special military operation, which would have taken Kyiv. Clearly, that hasn’t happened. Once again, we see the underestimation of the human factor.




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State of the Union has lessons for transatlantic unity

State of the Union has lessons for transatlantic unity Expert comment NCapeling 8 February 2023

Analysing key foreign policy aspects of President Joe Biden’s annual address, and what it means for the upcoming Munich Security Conference and the year ahead.

Trade and economics are key areas to watch

Daniel W. Drezner

Russia’s absence from the Munich Security Conference will allow US and European policymakers to brag about their flourishing partnership. The past year has seen repeated predictions of a fracturing transatlantic relationship – only to see repeated agreement on how to sanction Russia and which arms to ship to Ukraine.

Putin invaded because he thought the West was divided. Events have proven him wrong. When one takes a step back, however, and examines the Biden administration’s embrace of geoeconomics, Putin’s assumption becomes easier to comprehend.

The strongest throughline between the Trump and Biden administrations has been their shared mindset on weaponized interdependence. Both administrations have been wary of US interdependence with an increasingly autocratic China.

The primary difference has been that, while the Trump administration talked a good game, the Biden administration has passed laws and issued executive orders making the pivot away from trade liberalization a reality.

The passage of the CHIPS and Science Act, Bipartisan Infrastructure Law, and the Inflation Reduction Act (IRA) amount to the most ambitious US attempt at industrial policy in decades, accompanied by multiple executive orders examining US supply chain resilience and imposing unprecedented export controls targeting China.

The Biden administration’s restrictions on exchange with China’s semiconductors includes the use of the ‘foreign direct product rule’, essentially a means of applying US export controls in an extraterritorial manner.

The Biden administration’s angry response to the WTO panel ruling against US steel and aluminum tariffs makes it clear the US will apply an expanded definition of national security to restrict trade. In many ways, the sanctions on Russia are a continuation of a US foreign economic policy grounded in geoeconomics.

Several of these measures have rankled European officials. The IRA massively subsidizes the North American production of environmentally-friendly cars, discriminating against European producers. And continued US hostility to the WTO leaves European officials wondering if they are the last bastion of multilateralism left in the world. In Washington and Davos last month, European policymakers made their displeasure clear.

The strongest throughline between the Trump and Biden administrations has been their shared mindset on weaponized interdependence

Daniel W. Drezner

The sanctions against Russia and export controls against China threaten to be additional sore subjects. During the strategic embargo of the Soviet Union, US officials wanted to maximize restrictions while European allies wanted more trade opportunities. Since then, Europeans have suspected that the US uses multilateral export controls regimes to advance its commercial interests, while Americans worry Europe underestimates the risks of business-as-usual with China.

The Biden administration has tried to finesse these trade tensions, and was successful at persuading the Netherlands to join the US in the export controls on China. More generally, Biden officials talk about ‘friendshoring’ and propose mechanisms for greater policy coordination, such as the US-EU Trade and Technology Council. But even in these gestures, US officials have taken greater market access off the table.

In the State of the Union address, Biden bragged about how the US ‘came together to defend a stronger and safer Europe’ as well as defending his ‘buy American’ plans and pledging to make sure the ‘supply chain for America begins in America’. At the upcoming Munich Security Conference, attention should be on how much officials talk about trade and economic issues. The more that topic comes up, the clearer it will be that both sides are subtweeting each other about the future of the transatlantic economic relationship.

Division on China now would bring a high price

Dr Leslie Vinjamuri

President Biden has made unity his guiding principle and chief objective, but it is a tall order. His State of the Union address touted past bipartisan backing for investments in infrastructure, climate-friendly technologies, and semiconductor chips, along with a focus on creating jobs for working-class Americans, especially in manufacturing.

While Ukraine will continue to demand and deserve attention, the US will be looking beyond the urgent to focus on other less urgent but crucially important challenges. That means China

Dr Leslie Vinjamuri

Little was said that was explicitly about China, but the Biden administration has said that China is its pacing challenge, and competing with China has shaped the ambition behind these legislative successes.

In fact, the hallmark of the address was its foreign policy minimalism. Biden hailed unity in the US defence of democracy in Ukraine in the face of Russia’s aggression. And in defending US sovereignty in the face of China’s violations, this time with a balloon.

But the presidents temporary minimalism on foreign policy will be short-lived. And unity with America’s partners and allies will continue to be at the centre of Biden’s strategy. In the past 12 months, it is the yardstick by which he has measured America’s success with respect to Ukraine.

Russia’s invasion of Ukraine has so far served as a lubricant for the NATO alliance, and for the US relationship with its non-NATO allies.

This has not automatically sprung from the well of Russia’s aggression. NATO’s success, and transatlantic unity, has been achieved through the sheer force of diplomatic effort, not least by the US.

Now Biden is looking for unity on China. His administration has identified China as its pacing threat. While Ukraine will continue to demand and deserve attention, the US will be looking beyond the urgent to focus on other less urgent but crucially important challenges. That means China.

China’s balloon helps ensure unity will be an easy victory at home. For several days, the balloon floated across the US, captivating the American public, seizing the headlines, and hardening US attitudes towards its only peer competitor.

Republican leaders in Congress are determined to scrutinize US policy to ensure it is tough on China, especially on technology and deterrence. This intense domestic focus on China could put Biden in a bind as he seeks to resume diplomacy. It also explains why he was careful not to inflate the China threat in his address. Secretary Blinken’s visit to Beijing has already been postponed.

As the Munich Security Conference approaches, the president’s unity agenda will turn to Europe, but the timing is difficult. China is opening and a charm offensive across Europe is likely. Europe is vulnerable as it seeks to recover its economies, continue to hold Russia back, and inhibit greater alignment between Russia and China.

The risk for the US is that domestic pressure to take a harder line on China escalates and Europe refuses to keep up. But dividing on China would come at a high price, both for Europe and the US, so to avoid this, they should take a pragmatic and sequenced approach to cooperation.

The goal for now should be policy coordination, as success is vital to momentum and managing expectations in the current environment is critical. Alignment may be possible with discrete partners on specific topics. But the perfect should not be the enemy of the good.

The US has postponed, not cancelled, Blinken’s trip while Europe is preparing to ramp up its diplomacy with China. A collective but temporary and shared transatlantic pause on diplomacy would offer low hanging fruit to give momentum to transatlantic cooperation.

It would also signal to China a unity that has a power of its own. A clear and coordinated signal, soon, that Europe and the US are moving forward with diplomacy is essential.

Munich can move the talk into action on Ukraine

James Nixey

Russia’s excommunication from this year’s Munich Security Conference is an opportunity. The principle of inclusivity may have pros and cons, but the cons have been evident since at least 2007 – its use as a platform for Russia’s leadership to launch broadsides about ‘western injustice’ and a reflexive default to increasingly inappropriate and harmful diplomatic courtesies and allowances.

Without the distraction of listening to Russian lies, there is at least now the remote possibility of a more unified West agreeing to specific action beyond the talk. As at the recent Ramstein talks, it is unlikely Munich will result in an agreement to send F-16 fighter jets to Ukraine. That may prove a step too far for the West or it will need further Russian atrocities inflicted upon Ukrainians on a scale horrendous enough to prick consciences once again.

Most Ukrainian officials would privately argue that the danger to their country comes more from the West and forums such as the Munich Security Conference than it does from Russia

James Nixey

However, although President Biden’s State of the Union address has promised nothing new or innovative regarding Ukraine or Russia, it did re-establish the fundamentals of US support and so can serve as a ‘pre-read’ for a newfound resolve.

Although some European countries are a lost cause, others – Germany for example – have proved able to be guilted into action. The key lesson for everyone to understand is that Ukraine is sovereign. Or at least ‘nothing about Ukraine, without Ukraine’. The difference is moot but, from these simple precepts, all else flows.

Ukrainians will be their impassioned selves at Munich. But although publicly gracious and thankful, privately they are distraught at the West’s collective failure to affirm these principles and back them with the necessary support, not just to force a stalemate or a ‘frozen conflict’ but to engineer victory.

Most Ukrainian officials would privately argue that the danger to their country comes more from the West and forums such as the Munich Security Conference than it does from Russia, which can be defeated with the requisite tangible assistance. In Munich, beyond fine words of support – watertight from some, ambiguous from others – there lurks the ever-present danger of the politician who simply wants it all to go away by offering Putin an off-ramp.

The irony of the host city of this forum is that many times over the past year compromise ‘solutions’ have been described as having ‘a whiff of Munich’ about them – a reference of course to appeasement in 1938, which still haunts.

As it should, because the failure to ensure Ukraine’s victory with an outcome the Ukrainian government and people are content with and which convinces Russia it was a disastrous mistake to escalate, will lead to a global security collapse too catastrophic to contemplate.

Middle East security challenges must be dealt with

Dr Sanam Vakil

A trifecta of security concerns – Iran’s advancing nuclear programme, the export of unmanned aerial vehicles (UAVs) to support Russia in the war in Ukraine, and a heavy-handed response towards protests in Iran – has raised alarm bells in Washington, Europe and the UK. These intersecting challenges lay bare the lack of a broader Iran strategy and the deprioritization of Middle East security among transatlantic partners.

This downgrading of the Middle East was evident in President Biden’s State of the Union speech as, for the first time in decades, the region was not even mentioned. The upcoming Munich Security conference provides a much needed opportunity for the transatlantic community to align on next steps and multilateral policy responses.

Tehran has little confidence in the political and economic benefits that could emerge from the JCPOA and is choosing to double down with Moscow

Dr Sanam Vakil

Transatlantic partners have long relied on the prism of the JCPOA negotiations as the pathway to both separate and manage nuclear tensions from broader regional challenges associated with Iran’s export of lethal aid and sponsorship of proxy groups.

Despite repeated negotiation efforts led by the Biden administration since April 2021, the JCPOA has languished due to Tehran’s fears over another US retreat. The promise of sanctions relief has also failed to incentivise Iran’s return to the deal. Tehran’s nuclear programme has accelerated without the consistent IAEA oversight which was part of the initial deal and is now at a level where it can produce enough uranium enrichment for four nuclear weapons.

Tehran’s decision to send drones to support Moscow’s war effort has further elevated transatlantic concerns, and reports have circulated that Tehran may also export its missile capabilities and build a drone factory in Russia. In tandem, the two sanctioned states have begun to strengthen their economic arrangements.




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Europe's response to the US Inflation Reduction Act

Europe's response to the US Inflation Reduction Act 27 March 2023 — 2:00PM TO 3:15PM Anonymous (not verified) 9 March 2023 Chatham House and Online

This event explores the implications of the US Inflation Reduction Act, how Europe can respond and what options the UK has.

While the US Inflation Reduction Act (IRA) has led to an outcry in the EU, member states have different concerns and preferences for how to respond. The European Commission’s proposed ‘Green Deal Industrial Plan’ includes the relaxation of state aid rules to drive funding. But will this lead to a ‘subsidies race’ between the US and EU and is a ‘green trade war’ brewing?  
 
The UK’s response to the IRA has been much more muted than the EU’s. But caught between US subsidies and EU subsidies, can the UK compete and create an independent response to the IRA? And what steps can be taken to facilitate global cooperation and to make trade work for the green transition?

Dr Martin Porter, Executive Chair at the Cambridge Institute for Sustainability Leadership, will kick off the discussion with short remarks followed by an interactive discussion among all participants

This discussion is part of the Chatham House Global Trade Policy Forum. We would like to take this opportunity to thank our founding partner and supporting partners for their generous support of the forum.  




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SVB collapse shows interest rate financial stability threat

SVB collapse shows interest rate financial stability threat Expert comment LJefferson 15 March 2023

Governments must resist pressure to relax post-financial crisis regulation, while central banks should moderate their attack on inflation if financial stability is at risk.

The collapse of California’s Silicon Valley Bank (SVB) on 10 March has triggered a wave of volatility in global bank equity prices, raised questions about whether US bank regulation and its tech industry funding model are fit for purpose, and forced a rethink on the extent and pace of monetary policy tightening appropriate for the US and other advanced economies.

SVB was the US’s 16th largest bank with total assets of $212bn at the end of 2022 and a presence in eight countries around the world, including the UK. Since it was founded 40 years ago, it has maintained a strong focus on the technology sector, claiming recently that nearly half of all US venture-backed technology and life science companies banked with it. Partly as a consequence, some 95 per cent of its deposits came from corporates and hedge funds, far higher than the one-third typical of similarly sized banks.

What led to SVB’s collapse?

Ironically, SVB’s failure did not result from its core business model of serving a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. During the pandemic, SVB saw a very large inflow of corporate deposits. But rather than disincentivizing depositors or investing the funds attracted in assets of matching maturity, it chose to invest them in low credit risk, but long maturity bonds attracted by a small pick-up in return over shorter-term assets. 

When US interest rates began to rise rapidly in 2022 following Russia’s invasion of Ukraine, the value of SVB’s long-term bond portfolio declined sharply. It was left facing a large capital loss of some $15bn, roughly equivalent to its total shareholder funds. The management attempted to repair SVB’s balance sheet last week by crystalizing some of the loss and raising new capital.

But when this failed, the US supervisory authorities had no choice but to step in and close the institution.  This action was quickly followed by emergency action from other regulators vis-a-vis SVB subsidiaries and offices around the world.

Ironically, SVB’s failure did not result from its core business model of doing business with a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management.

The US entity has formally been taken over by the FDIC and a bridge bank established. All depositors have had their funds guaranteed, going beyond the normal federal deposit insurance limit of $250,000 per customer. However, bond holders and equity holders have been wiped out. The authorities have said that any loss will be covered by the industry as a whole via the FDIC.

In the UK, the Bank of England was able to sell the ring-fenced UK subsidiary of SVB to HSBC for £1 over the weekend, so that all its depositors and other liability holders have effectively had their funds guaranteed. In contrast to previous Bank of England rescues (such as Johnson Matthey Bank in 1984, the ‘small banks’ crisis in 1991 and the global financial crisis in 2008-9) no public money has been put at risk.

Four key questions

SVB’s rapid collapse raises four central questions:

First, how was it that the bank was able to take on such a risky interest rate maturity mismatch in its US operations? Maturity transformation is standard banking industry practice, but it is usually closely monitored by regulators who place limits on the extent of interest rate maturity mismatch and require liquidity buffers to offset the risk of deposit flight and forced asset sales.

SVB’s very high concentration of corporate deposits as compared to ‘sticky’ retail deposits, means that the risk of deposit flight was unusually high and so the bank should have been more, not less, cautious in its liquidity policy. SVB was classed as a regional bank in the US which means that it did not have to meet international regulatory standards under Basle III. And in 2018, the Trump administration approved legislation removing the post-financial crisis requirement that banks with assets under $250bn submit to stress testing and relaxing liquidity buffer requirements.

But it is still hard to understand why regulators allowed SVB to commit such a classic banking error. On Monday, the Federal Reserve ordered an inquiry into what it has correctly described as a regulatory failure. This should look at the role played by all the elements of the oversight system including the auditors, KPMG.

In 2018, the Trump administration approved legislation removing a post-financial crisis (regulatory) requirement…but it is still hard to understand why regulators allowed SVB to commit such a classic banking error.

Second, does SVB’s failure reflect a much bigger underlying risk in the US banking sector, and potentially other banking systems around the world, built up over the prolonged period of ultra-low interest rates? SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices – by close of play on 14 March, the S&P Regional Bank Index was down 22 per cent on a week before, with some individual bank stocks seeing much sharper falls.  

To the extent that banks have been covered by international bank regulatory requirements, the risk of a much broader problem should be limited because stress testing and other regulatory tests would have looked at precisely the scenario that has happened. Even where large market losses have been incurred, capital buffers should be sufficient to cover them. But as SVB has shown, there are some large banks that are seemingly not required to follow international rules, while the latest developments at Credit Suisse indicate that market concerns may still arise when other factors are in play.

SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices.

Third, how far, in the light of the potential vulnerability in banking systems, should central banks in advanced countries moderate their efforts to squeeze out inflationary pressures? While inflation already appears to have peaked in many economies and the pace of interest rate rises was expected to slow, inflation is far from vanquished, as recent data in the US has demonstrated.

Fourth, does the failure of SVB tell us something new about the financial risks facing the high technology sector?  It was remarkable that a single (and not particularly large, by international standards) financial institution could have played such a central role in the tech sector in both the US and UK. 

Why was this the case and does it reflect special features of the tech/start-up sector (e.g. the need for substantial cash deposits to cover relatively large negative cash flows in the early years of operation, or the need for highly specialized lending expertise). If so, should governments take steps to mitigate such risks, given the outsized importance of this sector in many national economic strategies? 




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