mo Digital politics threatens democracy and must change By www.chathamhouse.org Published On :: Fri, 13 Jan 2023 16:08:06 +0000 Digital politics threatens democracy and must change Expert comment NCapeling 13 January 2023 Violence in Brazil has again brought into focus the need for technology platforms to prioritize social responsibility to help prevent anti-democratic action. Immediately following the violent storming of Brazil’s congressional building, supreme court, and presidential palace, comparisons to the infamous events of 6 January 2021 in the US came quickly and easily – and with good reason. Both Donald Trump and Jair Bolsonaro built a fervent – albeit inchoate – political base of grievance which included Christian evangelicals, gun enthusiasts, and the disenfranchised. Both cynically spread doubts about the election victories of their successors without evidence. And it has been claimed both incited their supporters to overturn these results. But this list of similarities extend beyond mere politics. The attack on democracy in Brazil was recorded, amplified, coordinated, and funded by exactly the same technologies used by the protesters in the US on 6 January. In Brazil, the main engines of misinformation and insurrection planning were Telegram, Facebook, and WhatsApp, although some election-denying diehards also shifted to Twitter. Tactical use of social media to mobilize and fundraise When Bolsonaro was originally elected in 2018, these platforms were already a medium for promoting disinformation, conspiracy, and fear. But in the lead-up to the violence of 8 January, they became a means by which ‘Bolsonaristas’ raised funding for an attack and mobilized supporters to come to Brasilia – advertising the availability of buses and even free food for marchers – using the Festa da Selma hashtag. Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices To avoid detection by authorities, organizers used a simple switch of the letter ‘v’ to ‘m’ so that Selva, meaning ‘jungle’, became Selma – which means ‘party in the jungle’ to those in the know. But the authorities in the Brasilia state of Distrito Federal appeared to care little about preventing the attack anyway. Civil society organizations have warned for decades that policies made in a Silicon Valley boardroom fit poorly to the realities of countries such as Brazil, Somalia, or Myanmar. Content moderation is a near-impossible task at the scale demanded by platforms as vast as those operated by big tech, and automated solutions are far from being a silver bullet as they create as many problems as they solve. Extremism has found an unfettered enabler on mainstream platforms, and an increasingly sprawling network of alternative tech has made such voices resilient to challenge. Platforms such as Gettr, Gab, and Telegram have become go-to platforms for extremist networks when fringe voices find themselves blocked by mainstream platforms. Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results. The sordid events in Brasilia are just the latest chapter in digital extremism and conspiracy- mongering which often erupts into anti-democratic violence, and should serve as a reminder of the urgent risks of disinformation and the role digital technology plays in inciting, coordinating, fundraising, and amplifying such events. But the checks on the power of private social media companies are still few and splintered. In Brazil, Supreme Court Justice Alexandre de Moraes, head of the elections tribunal, attempted to crack down on social media, banning users for spreading misinformation in a move which sparked complaints of censorship from Bolsonaro supporters. Following the elections, Moraes has advocated for greater judicial authority to regulate social media – but the justice is only one person and his impartiality is already being challenged given his aggressive pursuit of Bolsonaro supporters posting inflammatory messages. And one justice doing it alone only inflames an already volatile situation. Effective regulation of social media requires an independent body vested with multiparty support and operating under clearly-defined rules and authority. A global movement to find solutions Brazil is not alone in an increasingly frantic search for checks on digital power as dozens of regulatory regimes are springing up around the world. All are premised on platforms being responsible for their own fiefdoms, but few tackle the threat posed to democracy by unchecked corporate power over digital commons. Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices who see any rules as an attack on freedoms of expression or corporate decision-making. Democracies are traditionally cautious in managing speech, in separating good information from bad information, or in defining acceptable politics. The steady watering down of the UK’s Online Safety Bill, now so thin on disinformation as to be essentially homeopathic, shows that democratic regulation is willing to go only so far in tackling challenges posed by digital politics. Full Article
mo Distinct and Overlapping Sets of SUMO-1 and SUMO-2 Target Proteins Revealed by Quantitative Proteomics By www.mcponline.org Published On :: 2006-12-01 Alfred C. O. VertegaalDec 1, 2006; 5:2298-2310Research Full Article
mo Molecular Composition of IMP1 Ribonucleoprotein Granules By www.mcponline.org Published On :: 2007-05-01 Lars JønsonMay 1, 2007; 6:798-811Research Full Article
mo Lysine Propionylation and Butyrylation Are Novel Post-translational Modifications in Histones By www.mcponline.org Published On :: 2007-05-01 Yue ChenMay 1, 2007; 6:812-819Research Full Article
mo In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy By www.mcponline.org Published On :: 2008-01-01 Ivan MaticJan 1, 2008; 7:132-144Research Full Article
mo The Proteome of the Mouse Photoreceptor Sensory Cilium Complex By www.mcponline.org Published On :: 2007-08-01 Qin LiuAug 1, 2007; 6:1299-1317Research Full Article
mo Comparative Proteomic Analysis of Eleven Common Cell Lines Reveals Ubiquitous but Varying Expression of Most Proteins By www.mcponline.org Published On :: 2012-03-01 Tamar GeigerMar 1, 2012; 11:M111.014050-M111.014050Special Issue: Prospects in Space and Time Full Article
mo Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules By www.mcponline.org Published On :: 2005-09-01 Yi ZhangSep 1, 2005; 4:1240-1250Research Full Article
mo Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics By www.mcponline.org Published On :: 2012-11-01 Amelia C. PetersonNov 1, 2012; 11:1475-1488Technological Innovation and Resources Full Article
mo Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins By www.mcponline.org Published On :: 2006-04-01 Leigh AndersonApr 1, 2006; 5:573-588Research Full Article
mo Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway By www.mcponline.org Published On :: 2005-03-01 Albrecht GruhlerMar 1, 2005; 4:310-327Research Full Article
mo Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein By www.mcponline.org Published On :: 2005-09-01 Yasushi IshihamaSep 1, 2005; 4:1265-1272Research Full Article
mo Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 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. Full Article
mo ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis) [Microbiology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens. Full Article
mo SNF Dialogues: Social media, social movements and political change By www.chathamhouse.org Published On :: Wed, 15 Jun 2022 13:02:13 +0000 SNF Dialogues: Social media, social movements and political change 6 July 2022 — 2:30PM TO 3:45PM Anonymous (not verified) 15 June 2022 Online Experts and activists explore how the digital world has changed the nature of social movements and the impact this has on policymaking. From Extinction Rebellion to Black Lives Matter, social movements are increasingly harnessing social media to project their calls for action. This event, convened in partnership with the SNF Dialogues series, will reflect on the value of social media to social movements and the effects of such digital movements on policymakers. Experts and activists from around the world will explore whether social media is an effective tool for social movements or a distraction, the extent to which digital forms of protest incite social change, and finally if this change has an impact on policy decisions. The SNF Dialogues, an initiative of the Stavros Niarchos Foundation (SNF), are a series of monthly discussions whose goal is to foster the exchange of ideas, inspire a new way of thinking and acting, and encourage and elevate public discourse across geographic boundaries. The Dialogues discussions are free and open to the public, aiming to bring to light timely questions and developments, share informed reflections and concerns, highlight new data and angles, and present fascinating people, projects and ideas. The Dialogues are curated and moderated by Anna-Kynthia Bousdoukou and are facilitated by the non-profit journalism organization iMEdD (incubator for Media Education and Development). The discussion will be conducted in English with simultaneous interpretation into Greek. If you wish to watch the discussion in Greek, tune in here. Full Article
mo Redefine the Commonwealth now to safeguard its future By www.chathamhouse.org Published On :: Thu, 06 Oct 2022 10:49:47 +0000 Redefine the Commonwealth now to safeguard its future Expert comment NCapeling 6 October 2022 Although seen as one of the Queen’s greatest legacies, the Commonwealth must provide tangible benefits to its citizens in an era of geopolitical competition. The Commonwealth’s breadth allows a wide diversity of countries of different sizes, geographies, cultures, and values to be members – it is both rich and poor, north and south, and ethnically diverse. This makes it more interesting than many other multilateral institutions such as the G7, NATO, and the European Union (EU). But it suffers from an unclear purpose. Since its inception, successive UK governments have grappled with its role – whether it is a preferential trading bloc or merely a source of most of Britain’s post-war immigration. This lack of purpose – and structure – has left the Commonwealth impotent in dealing with a host of bilateral difficulties between the UK, its overseas territories, and Commonwealth partners in recent years. Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand – while development aid, one of the most tangible ways the UK worked with many Commonwealth countries, has been cut and the UK’s defence focus has pivoted towards the Indo-Pacific and Europe’s Eastern front. The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns The UK also suffered embarrassing and overwhelming defeats in both the UN General Assembly (UNGA) and the International Court of Justice (ICJ) on the legality of its continued occupation of the Chagos Islands and has avoided directly challenging India’s tacit support for Russia’s invasion of Ukraine in the hope of securing a trade deal. At the recent Commonwealth Heads of Government Meeting (CHOGM), Boris Johnson reportedly attempted to depose Baroness Scotland, the Commonwealth’s Secretary General, but suffered a humiliating defeat in a vote of Commonwealth members. These challenges are likely to continue, especially in the wake of the death of HM The Queen which could be seen by republican movements as an opportune time to rally support. Australia and New Zealand’s leaders, both republicans, downplayed the idea of a poll on the monarchy immediately after the Queen’s death, but it would be a mistake to assume this has gone quiet forever. Antigua and Barbuda’s prime minister has already said there will be a referendum on becoming a republic within three years. Defining a new vision for the future A concrete vision for the Commonwealth is long overdue and there is no better time to cast one than now. HM The Queen was more than just a figurehead for the Commonwealth and it remains unknown exactly what role King Charles III will see for himself. But, unlike his mother who was a young, modern Queen heralding a post-imperial future, Charles takes the throne at a later age and at a time when important questions need to be addressed in an increasingly fractured world. Most importantly the UK should avoid the temptation to define the Commonwealth in terms of shared principles and values. India, Pakistan, and Bangladesh all abstained on the United Nations (UN) motion condemning Russia’s invasion of Ukraine, and Commonwealth members are likely to be similarly divided over China’s territorial claims, the US-China conflict, the net-zero agenda, and nuclear non-proliferation. The Commonwealth’s breadth – its greatest strength – means consensus is often impossible, and so should not be the goal. Instead the Commonwealth should focus on tangible areas of cooperation where there is mutual interest such as trade, aid, and migration. Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns, from post-COVID vaccine provision to climate financing. Boosting the aid budget and opening borders may prove more important in engaging developing country partners than traditional diplomatic avenues. Liz Truss’s British International Investment project could be a valuable vehicle for financing, especially if it leverages private sector funding, but many Commonwealth countries are feeling the more immediate impact of the UK’s aid cuts. In these circumstances many have already turned to Chinese infrastructure financing. This is where the Commonwealth could be valuable. In the Pacific, it links certain island nations to the UK, Australia, and New Zealand at a time of renewed geopolitical competition with China in the Pacific. The fact the Commonwealth is not explicitly about promoting a particular ideology or countering China is helpful. Commonwealth should be less UK-centric There is also no reason why all the Commonwealth operations need to be based in London, which is not only expensive but also reinforces an approach to governance that assumes everything must be decided by civil servants in London. As the world’s largest democracy, India is an obvious alternative candidate although its reluctance to condemn Russia’s invasion and its domestic political tensions may count against it. It is also important the Commonwealth’s wealthier members – the UK, Canada, and Australia – provide financing for countries such as India to take on extra responsibilities. The Commonwealth Games is a good place to start – despite having 72 competing nations and territories, the games have only been held three times outside the UK, Canada, Australia, and New Zealand. The Commonwealth also needs to be forward-looking and one of its most exciting assets is its demographic youthfulness. Europe, China, and the US have ageing populations whereas Nigeria, India, and Bangladesh have some of the world’s largest young populations. Full Article
mo UK is too tight on the money and too vague on China By www.chathamhouse.org Published On :: Mon, 13 Mar 2023 19:38:00 +0000 UK is too tight on the money and too vague on China Expert comment NCapeling 13 March 2023 The new UK Integrated Review fills gaps left by the last one but is dominated by defence. It needs more clarity on Europe, trade, and development – and more money. Following a long two years, the UK’s Integrated Review from March 2021 now looks prescient in calling Russia the main threat to UK interests. And Russia’s invasion of Ukraine is the main – but not the only – reason forcing an update of the review only 24 months later. The UK’s commitment to Ukraine is now centre stage and so therefore is its cost, which immediately exposes a prime weakness of this review. An extra £5 billion on defence is more than nothing, as was originally rumoured, but far less than £11 billion which UK defence secretary Ben Wallace argues is needed. UK military support for Ukraine cost £2.3 billion in the past year and a continuation will use up £2 billion of the new money. The report also notes £3 billion will go on infrastructure for building nuclear submarines at Barrow and nuclear training. That does not leave much for anything else. There is a pledge to end the reduction of the armed forces which is essential if the UK contribution to Ukraine and European defence is to be credible. But an ambition to spend 2.5 per cent of GDP on defence by an unspecified date is all but meaningless – albeit prudent phrasing given fiscal uncertainties. China challenge is one of balance Ministers have been wrestling for months over their choice of language on China, and ‘epoch defining challenge’ is what has emerged, while also expressing concern over China’s links with Russia. But the review is careful to stop short of calling China a threat as Liz Truss intended. An ambition to spend 2.5 per cent of GDP on defence by an unspecified date is all but meaningless – albeit prudent phrasing given fiscal uncertainties The choice of vocabulary reflects a long desire to balance forging commercial ties with an increasing wariness of data and security threats under President Xi’s leadership of China. The UK wants to support the US in its concerns but not to presume conflict is inescapable. The review does acknowledge the threat to Taiwan for the first time. Two years ago, it was fiercely criticized for not including any mention of that despite the potential disruption supposedly being ‘far more damaging than the renewed illegal invasion of Ukraine’ as MPs on the Foreign Affairs Select Committee put it. But again the question of resources is inescapable. The ‘Indo-Pacific tilt’ which the UK declared two years ago is offered not just as a recognition of the region’s political and economic heft in any vision of the future, but as a favour to the US. The UK lacks the resources to make that tilt credible in terms of substantial support to the US – nor, arguably, would it do the US any favours by neglecting the defence of Europe or the Middle East, which gets scant mention. The AUKUS announcement on the same day appears to fill that gap. UK prime minister Rishi Sunak was in San Diego, California to greet the declaration that Australia will draw on British designs for its new nuclear submarines – a decision which brings more British jobs and underpins an alliance of both symbolic and practical weight in the region. But for the UK to play its part fully, it may need to divert resources from elsewhere, and this review sidesteps that hard choice. More broadly, the UK would benefit from considering how to respond to the reality of China’s rise – analysing what happens to supply chains if tension disrupted them and how it might use membership of the Asia-Pacific CPTPP trading bloc, which appears likely to happen soon. The choice of vocabulary reflects a long desire to balance forging commercial ties with an increasing wariness of data and security threats under President Xi’s leadership of China One of the biggest omissions in the 2021 review was relations with Europe and that is somewhat remedied but more is needed. The UK has been a leader for Europe in its clear response to Russia’s invasion of Ukraine – almost the only common thread of passionate agreement between the three UK prime ministers since the invasion – but it should now consider if it wants to take part in joint development of military assets. And a clear statement of cooperation with European Union (EU) governments would be a boost to NATO. There is also now a Europe-shaped hole in the review’s discussion of trade. The 2021 version mentioned trade 79 times with the focus on new trade agreements outside Europe. It is now clear, if it was not before, these make little difference to GDP. The recent repairing of relations with the EU – and France in particular – may yield more practical results two years from now. UK power in the world is changing The review is also largely silent on another difficulty in the UK’s foreign policy which are the aims and size of its development aid – much changed from its original goal of poverty reduction to a focus on national interest with a reduced budget. This is sensitive political territory but must be better spelled out to count as a plan. The FCDO intends to appoint a second permanent under-secretary to deliver the government’s development priorities and the minister for international development will join the National Security Council. This acknowledges the disruption caused by the merger of the FCO with DFID and the need for development staff to have clear leadership as well as, hopefully soon, a clear policy. The pledge of a one-off payment of £20 million for the BBC World Service 42 foreign language channels for two years is welcome too as an acknowledgement of their ‘soft power’ value, especially in parts of the world where democracy is absent or in retreat. Full Article
mo Microtubule affinity-regulating kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and exacerbates neurodegeneration [Neurobiology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 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. Full Article
mo 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] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 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. Full Article
mo High temperature promotes amyloid {beta}-protein production and {gamma}-secretase complex formation via Hsp90 [Neurobiology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1. Full Article
mo How modular renewables can reduce the costs of relying on carbon capture By www.chathamhouse.org Published On :: Thu, 10 Oct 2024 09:57:06 +0000 How modular renewables can reduce the costs of relying on carbon capture Expert comment LToremark 10 October 2024 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. Related content COP28: What was achieved, and what needs to happen now 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. Related content To phase out or phase down? Why the debate on fossil fuels misses key point 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. Full Article
mo Moldova and Georgia face crucial elections – and diverging paths By www.chathamhouse.org Published On :: Wed, 16 Oct 2024 10:24:18 +0000 Moldova and Georgia face crucial elections – and diverging paths Expert comment LToremark 16 October 2024 The two countries face unusually consequential elections where their populations must choose between moving unambiguously towards the West – or towards closer ties with Russia. Moldova and Georgia both go to the polls at the end of October; Moldova for presidential elections on the 20th and Georgia for parliamentary elections on the 26th. The two countries share a number of similarities – beyond their justified reputation as world-class wine producers. They are both small, low- to middle-income countries that have struggled to consolidate their democracies and have experienced oligarchic political influence. Both are candidate countries for EU membership, with Moldova a step ahead having been invited to start negotiations. For both countries these elections represent a fork in the road: either move unambiguously into the Western world, or step back from it and become more closely tied to Russia again and its way of governance. However, the second option has caused yet-to-be-resolved territorial conflicts in both countries – Transnistria for Moldova, and Abkhazia and South Ossetia for Georgia. Related content Is Moldova a new battleground in Russia’s war? Some would say it should not be such a ‘zero sum’ choice. Why must a nation choose between Russia and the West? While that may be a fair statement for countries like India or South Africa, it does not work for Russia’s former colonies, which Moscow wishes to control. Moldova and Georgia’s final similarity is that they face Russian interference and attempts to manipulate votes in their elections. In Moldova this has been especially brazen with the uncovering in September of a $15 million vote-buying scheme, including instructions on who to vote for distributed to over 130,000 citizens. Russian interference in Georgia’s election is less overt but at the same time more endemic considering its government has in effect been captured by pro-Russia forces.Diverging pathsBut this is where the similarities end and the contrasts become clear.Moldova has a young, pro-Western and equality-conscious government, and 44 of the 100 MPs in its parliament are women. In this election, Maia Sandu is seeking her second and final term as president. The election is combined with a referendum asking the people if they wish to embed Moldova’s EU aspirations into the country’s constitution. The results of both the presidential election and the EU referendum will be close, reflecting a genuine split in attitudes (and debate) in the country. Related content Is the Kremlin behind Georgia’s foreign agents law? Georgia’s EU aspirations, meanwhile, are already embedded in its constitution – but that has not prevented Tbilisi from pivoting away from the West. Polls show that around 80 per cent of Georgia’s population desires EU (and NATO) membership – rising to 90 per cent among the under 30s – but its government seems determined to deny them that future. Its new ‘foreign agents’ law is seemingly copy-pasted from Russia – and incompatible with EU membership. The election can be seen as a de facto referendum on the EU too. Georgia’s accession is suspended until its political crisis is resolved. Georgia faces other challenges to its democracy. Due to the country’s limited presidential powers, Georgia is in effect run by the unelected Bidzina Ivanishvili – founder of the ruling Georgian Dream (GD) party – whose relationship with Russia is murky at best. Judging by his recent speeches, Ivanishvili now blames the Western world not just for igniting the war in Ukraine, but also for the war in Georgia 16 years ago which resulted in the loss of 20 per cent of its territory at the hands of Russia. This extraordinary position is both factually incorrect and out of step with the Georgian people. Georgia’s election looks like it is going to be messy. Both countries are now at a critical point. Whatever the outcome in Moldova, the election will pass off peacefully and competently. Its problems (Russia aside) are demographic and economic, and the country’s pro-Russian opposition is relatively weak.Georgia’s election looks like it is going to be messy. Ivanishvili’s party will likely manipulate the election to a win. There is still a chance that Georgia’s pro-Western but also weak opposition will regain power and return the country to its European path. But if the manipulation by the incumbency is heavy, people will likely take to the streets in protest, as in April this year – and in the 2003 Rose Revolution.Regime change via popular revolution shows political immaturity but the Georgian people may feel it is the only way they can have their views represented and their ambitions realised. Full Article
mo The Democratic Republic of the Congo’s foreign policy priorities By www.chathamhouse.org Published On :: Fri, 18 Oct 2024 19:42:13 +0000 The Democratic Republic of the Congo’s foreign policy priorities 29 October 2024 — 1:00PM TO 2:00PM Anonymous (not verified) 18 October 2024 Chatham House and Online The DRC’s Minister of Foreign Affairs discusses the country’s approach to regional stability and the role of international partnerships in securing economic prosperity. At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss DRC’s regional diplomatic priorities and international agency, including its ambitions around global critical mineral supply chains. The Democratic Republic of the Congo (DRC) faces foreign policy tests as it manages a complex security crisis and regional tensions, alongside global economic and trade partnerships.Entrenched conflict in eastern DRC continues to have wider regional implications. Troops from the Southern African Development Community (SADC) deployment are tackling a growing mandate as the UN’s peacekeeping mission prepares to withdraw. Tensions with Rwanda also remain high despite mediation efforts under the Luanda process.As a major producer of critical minerals for the global energy transition, the DRC seeks to benefit from growing international demand without sacrificing value addition. New and existing frameworks with international partners will remain key to this vision, including for the development of regional infrastructure networks such as the Lobito Corridor.At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss the DRC’s regional diplomacy and international agency, including the country’s positioning in global critical mineral supply chains.Please note that in-person attendance for this event will be balloted. Guests looking to join in-person must register interest in joining. Full confirmations to successful applicants will be sent on Friday 25 October. Full Article
mo Sinwar’s death does not make Hamas–Fatah reconciliation more likely, whoever his successor may be By www.chathamhouse.org Published On :: Tue, 22 Oct 2024 12:46:19 +0000 Sinwar’s death does not make Hamas–Fatah reconciliation more likely, whoever his successor may be Expert comment jon.wallace 22 October 2024 The killing may aid Hamas recruitment – but it will not make agreement with Fatah any easier to achieve. Western political leaders were quick to argue that Israel’s killing of Hamas leader Yahya Sinwar on 17 October presented an opportunity for a ceasefire in Gaza and the return of Israeli hostages.US President Joe Biden immediately called on Israeli prime minister Benjamin Netanyahu to seize the moment to negotiate, now that Israel has achieved one of its war aims.However, that ‘moment’ has already passed. Israel’s military assault on Gaza has intensified since Sinwar was killed, leading UN Peace Process Co-ordinator Tor Wennesland to say that ‘nowhere is safe in Gaza’. It is abundantly clear Netanyahu is intent on further degrading Hamas, resetting a new ‘power balance’ and carving out a buffer zone, no matter the cost in Palestinian lives or Israeli hostages. But there are other implications of Sinwar’s assassination beyond the zero-sum analysis of will there or won’t there be a ceasefire.Hamas’s ability to fightAt present, everyone has an opinion on how Sinwar’s killing will affect Hamas and its ability to resist and respond to Israel’s military. His death will have been a major blow – symbolically, operationally, and psychologically. Hamas has been downgraded and its capacity to respond compromised.But it will recover, regenerate and retaliate in time – and Sinwar’s death will have been no surprise to Palestinians in Gaza or elsewhere. Hamas is accustomed to seeing its leaders assassinated. Since its formation in 1987, it has been ‘decapitated’ many times, only to continue with its mission to ‘liberate Palestine’. Related content The killing of Yahya Sinwar won’t change the course of the Gaza war Hamas’s portrayal of Sinwar dying in his fatigues, head wrapped in a keffiyeh and resisting until the end will persuade many young Palestinians that he died as a martyr serving the Palestinian cause. Many will be inspired to join and fortify the ranks of Hamas as a result.The IDF’s release of drone footage showing Sinwar’s last moments will have done nothing to undermine his credibility. On the contrary, it will serve as a rallying call to disaffected and disenfranchised young Palestinians horrified by Israel’s bombing of civilian targets in Gaza and disaffected with Fatah’s inability to prevent Israeli settler expansion and violence in the West Bank.ReconciliationSome hope that if Sinwar is replaced by a more ‘moderate’ leader, his killing may smooth the path to Hamas–Fatah reconciliation – and that this could provide a foundation for a patchwork political solution when Israel and Gaza arrive at the ‘day after.’ Prospective new Hamas leaders such as Khaled al Meshaal and Khalil al-Hayya are based in Qatar (and) their ability to influence events on the ground in Gaza will be limited. But the idea that a downgraded and ‘leaderless’ Hamas will be susceptible to international pressure to reconcile with Fatah is divorced from reality. Prospective new Hamas leaders such as Khaled al Meshaal and Khalil al-Hayya are based in Qatar. They may be more pliable to external pressure to reconcile with Fatah in search of a political outcome, but their ability to influence events on the ground in Gaza will be limited. That was demonstrated by the Sinwar-orchestrated attacks on 7 October 2023, which took place without the blessing of the exiled leadership in Doha.Hamas has long gone to ground in Gaza and become far more decentralized than it was before 7 October. It is now more typical of an insurgency, where Hamas cadres exercise a great degree of operational autonomy.In other words, the disconnect between Hamas in Gaza and its political leadership in Qatar has only grown wider since this round of conflict started.International effortsThat will undermine international efforts made by Qatar, Egypt, Saudi Arabia, China, Russia and others to bring about a reconciliation. Moscow and Beijing already hosted reconciliation talks in February and April early this year but made no progress in closing the chasm between the two parties. Saudi Arabia has also hosted talks.The three Arab states, none of which have so far commented publicly on Sinwar’s killing, will likely view his death as an opportunity to bolster the political wing of Hamas – backing it with pledges of political, diplomatic and financial support. Hamas’s military wing is not about to concede ground and reconcile with Fatah. Saudi Arabia and Egypt will have next to no influence over the succession process, but Qatar’s long-established relationship with the political wing of Hamas affords it leverage over the organization, albeit limited. They may be able to strengthen the hand of those based in Doha by promising to work harder at securing a ceasefire, guaranteeing the provision of humanitarian relief, and working towards a political solution. Full Article
mo Trust in US democracy is at stake in this election By www.chathamhouse.org Published On :: Wed, 23 Oct 2024 08:50:44 +0000 Trust in US democracy is at stake in this election Expert comment rgold.drupal 23 October 2024 A narrow win for either side could make things worse. The rest of the world should be prepared for a disruptive transition. With less than two weeks to election day in the United States, polls suggest the gap between Harris and Trump has narrowed even further in the swing states where the election will be decided. A fierce contest has ensued as each campaign seeks to drive voter turnout. In such a tight race, this will be decisive. But in an election that many Americans perceive as being existential for the country’s future, a narrow victory by either side will heighten the risk of a contested election. Related content The US election will take place in a polluted information space Many Americans are pessimistic about the ability of democracy to deliver a reliable result. Two thirds of Republican voters continue to believe that the 2020 election was stolen from Donald Trump and for many of these, Biden’s inauguration may have demonstrated the weakness, not the strength, of US democracy. This environment has contributed to widespread anticipation of a contested election, as well as preparations for the possibility of a delayed result. Political disinformation and deep polarization across the country could mean that a narrow victory leads to more legal challenges and even political violence. 6 January, the anniversary of the assault on the US Capitol and the day Congress will certify the Electoral College has been designated a National Special Security Event. The issue of how quickly and reliably votes are certified has become an arena for argument. In the 2022 midterms, 22 county officials in key states voted to delay certification. Democrats have noted with alarm that this year, around 70 pro-Trump election ‘conspiracists’ are positioned to review the results in swing states.Those nervous about the possibility of a narrow vote being overturned will be watching to see if Republicans maintain or increase their majority in the House of Representatives, since the newly elected House will shape who holds the gavel when a joint session of Congress returns to certify the US presidential election result. Republican control of the House could give the former president more ability to influence this vote. A resilient democracyBut there should be room for optimism. Democracy in America has been remarkably resilient. In 2016, Democrats swallowed their unease with Donald Trump. Despite rumours of Russian interference in the election, they accepted the election result. If fears of another contested election materialise, it will be the third time in recent history that the US has struggled to confirm a result. Four years later, the US was far more polarized, trust in institutions had decreased, and challenges to the elections reflected this. The Trump campaign filed more than 60 lawsuits in 9 states challenging election processes and voter certification. In every single case, courts confirmed the results. After the 6 January insurrection on the US Capitol, Congress returned to its chambers and, on the very same day, confirmed the electoral results. If fears of another contested election materialise, it will be the third time in recent history that the US has struggled to confirm a result. In 2000, the Supreme Court intervened to decide on a recount in Florida, effectively delivering victory to George W Bush – a memory alongside the 6 January Capitol riots contributing to America’s anxiety ahead of polling day. International responseThe US’s partners and rivals may be ill-prepared for a contested election. If Trump or Harris, or both, claim victory before it is clearly settled, world leaders will need to decide how to react. Diplomatic protocol may dictate that leaders wait until the US confirms the results through official channels but there are concerns that not everyone will play by these rules. Full Article
mo The break-up of Scholz’s coalition government signals the end of Germany’s old economic model By www.chathamhouse.org Published On :: Tue, 12 Nov 2024 15:12:46 +0000 The break-up of Scholz’s coalition government signals the end of Germany’s old economic model Expert comment jon.wallace 12 November 2024 The coalition could not agree how to fund new support for Ukraine and failed to fully implement the ‘Zeitenwende’. A new government must push through reform. As Europeans were still processing Donald Trump’s victory in the 2024 US presidential election, an acrimonious break up occurred 4000 miles east of Washington DC.Reports had been circulating for weeks about the fragile state of Germany’s ‘traffic light’ coalition government led by German Chancellor Olaf Scholz, consisting of the centre-left Social Democratic Party (SPD), the Green Party, and liberal Free Democratic Party (FDP).The expectation had been that the coalition would hold on for a few more weeks and might even be given a new lease of life by Trump’s re-election. Instead, it collapsed on the day Trump’s win was confirmed. An unusually angry Scholtz announced in a live address that he had fired FDP Finance Minister Christian Lindner, effectively breaking up the coalition. Related content Independent Thinking: Can Germany lead in a divided Europe? At the heart of the dispute was the so-called ‘debt brake’ – a constitutional mechanism which restricts Germany’s annual public deficit to 0.35 per cent of GDP. Lindner proposed a set of reforms which were unpalatable to the SPD and the Greens. In response, Scholz suggested declaring an emergency, which would have suspended the debt brake. That in turn was unacceptable to Lindner, leading to his sacking by the Chancellor.Practically, this means the SPD and the Greens are now in a minority coalition, without agreement on the 2025 budget or the votes in parliament to pass it. They also still face the challenge of the debt brake.A vote of confidence will take place in December, with elections to be held before the end of February 2025 latest.The end of Germany’s economic modelAt the root of Germany’s political crisis is the country’s economic model. For decades, Germany relied on a system that depended on cheap Russian gas, cheap imports of consumer goods from China, high-value exports – particularly in the automotive sector – and the US security umbrella.With Russian energy no longer viable, the global economic landscape shifting, and Donald Trump on his way back to the White House, that model is no longer workable. And Germany’s economy is expected to contract by 0.2 per cent in 2024 – a contraction for the second year running. Germany has struggled to turn around its economic woes, with the car industry particularly affected. The ‘Zeitenwende’, announced by Scholz in the wake of Russia’s full-scale invasion of Ukraine, should have signalled a turnaround of both foreign and economic policy, given how much the two are interconnected. Yet on both fronts, too little changed.Germany’s reliance on Russian gas did come to an abrupt end in 2022. And Germany is Ukraine’s second largest military aid donor after the US, while accepting the most Ukrainian refugees.But the ‘Zeitenwende’ turnaround ended there. Scholz’s coalition government failed to prepare for long-term investment in defence at the levels required by creating an off-budget defence spending fund which would have run out in 2027. The draft budget for 2025 showed defence spending would have been cut, as would support for Ukraine.Germany has also struggled to turn around its economic woes, with the car industry particularly affected. Cheap Chinese EVs and new energy technologies are competing with Germany’s most powerful companies. Volkswagen, the country’s largest car manufacturer, has announced plant closures and layoffs due to shrinking profit margins. To the west, Trump’s threat to impose 10 to 20 per cent tariffs on all EU imports meant share prices of Volkswagen, BMW, Mercedez-Benz and Porsche all dropped between 4 to 7 per cent following news of his re-election.To the east, trade tensions between the EU and China are intensifying. Yet rather than choosing to diversify, German companies have doubled down on their bets in China, with German investment in the country rising from €6.5bn for the whole of 2023 to €7.3bn in the first half of 2024 alone – only exposing carmakers further.Germany’s support for UkraineLike French President Emmanuel Macron, Scholz had already been weakened by the results of the European Parliamentary elections in June. With the collapse of his traffic light coalition, the EU’s Franco-German ‘engine’ is now well and truly stalled – until new leadership can be found. This weakness comes at a perilous moment when clear, united European leadership, and much increased funding, is needed to shore up support for Ukraine. Full Article
mo Stopping the Use of Chemical Weapons in Modern Conflicts By f1.media.brightcove.com Published On :: Fri, 25 May 2018 00:00:00 +0100 Full Article
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mo France, the UK and Europe: New Partnerships and Common Challenges By f1.media.brightcove.com Published On :: Fri, 28 Feb 2020 00:00:00 +0000 Full Article
mo Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase By www.jlr.org Published On :: 2000-02-01 Jorge H. CapdevilaFeb 1, 2000; 41:163-181Reviews Full Article
mo Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells By www.jlr.org Published On :: 1978-11-01 W GambleNov 1, 1978; 19:1068-1070Articles Full Article
mo Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases By www.jlr.org Published On :: 2006-06-01 David A. MitchellJun 1, 2006; 47:1118-1127Thematic Reviews Full Article