ot Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions By feedproxy.google.com Published On :: 1970-11-01 M. BursteinNov 1, 1970; 11:583-595Articles Full Article
ot Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 By feedproxy.google.com Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1481-1494Articles Full Article
ot Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly By feedproxy.google.com Published On :: 2003-01-01 M. Mahmood HussainJan 1, 2003; 44:22-32Reviews Full Article
ot Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells By feedproxy.google.com Published On :: 1993-02-01 JL DixonFeb 1, 1993; 34:167-179Reviews Full Article
ot High density lipoprotein metabolism By feedproxy.google.com Published On :: 1984-10-01 S EisenbergOct 1, 1984; 25:1017-1058Reviews Full Article
ot Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans By feedproxy.google.com Published On :: 1993-10-01 JM DietschyOct 1, 1993; 34:1637-1659Reviews Full Article
ot Apolipoprotein-mediated removal of cellular cholesterol and phospholipids By feedproxy.google.com Published On :: 1996-12-01 JF OramDec 1, 1996; 37:2473-2491Reviews Full Article
ot Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host By feedproxy.google.com Published On :: 2004-07-01 Weerapan KhovidhunkitJul 1, 2004; 45:1169-1196Thematic Reviews Full Article
ot Identification of multiple subclasses of plasma low density lipoproteins in normal humans By feedproxy.google.com Published On :: 1982-01-01 Ronald M. KraussJan 1, 1982; 23:97-104Articles Full Article
ot Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein By feedproxy.google.com Published On :: 1997-11-01 DL BrasaemleNov 1, 1997; 38:2249-2263Articles Full Article
ot Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis By feedproxy.google.com Published On :: 2007-12-01 Dawn L. BrasaemleDec 1, 2007; 48:2547-2559Thematic Reviews Full Article
ot Plasma cholesteryl ester transfer protein By feedproxy.google.com Published On :: 1993-08-01 AR TallAug 1, 1993; 34:1255-1274Reviews Full Article
ot Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice By feedproxy.google.com Published On :: 1995-11-01 RK TangiralaNov 1, 1995; 36:2320-2328Articles Full Article
ot Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E By feedproxy.google.com Published On :: 1999-01-01 Robert W. MahleyJan 1, 1999; 40:1-16Reviews Full Article
ot Bile salt biotransformations by human intestinal bacteria By feedproxy.google.com Published On :: 2006-02-01 Jason M. RidlonFeb 1, 2006; 47:241-259Reviews Full Article
ot The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function By feedproxy.google.com Published On :: 1992-02-01 JP SegrestFeb 1, 1992; 33:141-166Reviews Full Article
ot Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis By feedproxy.google.com Published On :: 1996-04-01 IJ GoldbergApr 1, 1996; 37:693-707Reviews Full Article
ot Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By feedproxy.google.com Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
ot Harnessing the Potential of Cities By feedproxy.google.com Published On :: Fri, 22 Nov 2019 11:55:02 +0000 Corporate Members Event 13 December 2019 - 12:30pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Penny Abeywardena, Commissioner for International Affairs, New York CityChair: Dr Beyza Unal, Senior Research Fellow, International Security Department, Chatham House Cities are strong engines of growth and job creation accounting for some 85 per cent of global GDP. By 2030, more than 60 per cent of people worldwide will live in cities and they will be on the front lines of managing issues transcending borders such as climate, migration and sustainability. International organizations like the United Nations are striving to meet these challenges but relying on traditional multilateral agreements is growing ever more unpredictable. If cities and local governments are key to global prosperity, how can their power and influence be harnessed to accelerate impact for their citizens?Drawing on the pioneering work of New York City in the area of foreign policy leadership at a municipal level, Penny Abeywardena will discuss how the influence of subnational leadership and diplomacy is more important than ever as national governments are abdicating their responsibility at the multilateral level. How can the Sustainable Development Goals be localized among cities on policy issues that impact communities? And what can large cities, beyond the capital, do to remain influential and harness job growth? This event will be preceded by an informal sandwich reception from 12.30pm-1pm. The roundtable discussion to follow will take place from 1pm-2pm.This event is corporate members only. If you'd like to attend, please RSVP to Linda Bedford.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Members Events Team Email Full Article
ot 'The Truth is, Chile is Unequal': What's Behind Chile's Protests By feedproxy.google.com Published On :: Tue, 17 Dec 2019 19:33:39 +0000 18 December 2019 Dr Christopher Sabatini Senior Research Fellow for Latin America, US and the Americas Programme @ChrisSabatini LinkedIn Lyndsey Jefferson Digital Editor, Communications and Publishing Department @LyndseyLdn As part of a series on global protests, Dr Christopher Sabatini tells Lyndsey Jefferson why Chileans are taking to the streets. GettyImages-1177498531.jpg A demonstrator waves a Chilean flag during a protest in Santiago on 21 October 2019. Photo: Getty Images. Why are these protests happening now?The truth is, Chile is unequal, even though it actually reduced poverty from 1989, the time of the democratic transition, until today, from 40% to 16%.There are a number of reasons for the protests. One is the most proximate cause, which is the increase in the subway fares, but that really doesn’t explain the underlying tensions.One of those tensions is despite reductions in poverty, social mobility remains a large problem in Chile. It remains a very elitist country with limited social mobility. So, poverty may be reduced, but the likelihood that someone in the working middle class would reach the upper middle class has always been a stretch.The second issue is a lack of political change. The last four presidents were the same two people.Chile’s been governed, with the exception of Piñera, basically by the same political coalition, La Concertación, which is a combination of the Christian Democratic and Socialist parties. Piñera came from the right, an outside party, but even he has remained. There has been no renewal of the political leadership which again reinforces that lack of social mobility. Do the protesters have any other demands or grievances? The demands are amorphous and that’s part of the issue – they’re going to be difficult to meet. People are expressing a genuine desire for change but what would that change mean?Chileans don’t necessarily want to change the economic model; they simply want more mobility. That’s difficult to do and these are untested demands. Chileans also want political reform. What Piñera offered is to rewrite the constitution, which was created under military government in 1980. Other than some changes here and there in terms of the electoral system and reduction of military power, it has pretty much remained intact.Will constitutional change really address these demands? It’s simply a document that may create the rules for how power is allocated and conducted, but it’s not going to dramatically remake Chilean society.You mentioned inequality as a key driver of the protests. Can you expand a bit more on the current economic situation of ordinary Chileans?Chile is going to grow at only around 2-3%, but it was growing at around 4-5% earlier. A lot of those funds were ploughed into social programmes that have since been reduced. Chile’s economy really boomed in the early 2000s because of Chinese demands of Chilean imports. But as with any sort of commodities-based economy, the jobs it provides tend to be lower wage.As a result, despite the fact that Chile tried to diversify its economy by investing in entrepreneurship and innovation, it hasn’t grown in a way that provides jobs that many associate with upward mobility. As Chile's economy cooled, its ability to lift people out of poverty lagged as well. Demonstrators hold placards depicting eyes – in reference to police pellets hitting demonstrators' eyes – during a protest in Santiago on 10 December 2019. Photo: Getty Images. Two major issues for the protesters are education and pensions – can you explain why this is?These are two issues of the economic and social model that was held up at one time as being a model for the region, the neoliberal models that are really coming under question and are in some ways at the heart of this.One is the privatized pension system which is failing to produce the returns that retirees need to survive. The second is the education system. Chile created a voucher system where parents can shop around and send their kids to the best schools. The idea was to create competition among schools to improve.The problem was like any market, it created a certain amount of inequality among schools. There was a problem of some schools underperforming and being relegated poorer performing students, or students being forced to go to those schools because the more successful schools were already spoken for. At the end of October, the government announced a series of social reforms. Will this be enough to satisfy the protesters’ demands?Social reforms may address some of the issues of insufficient pensions or lack of quality education, but it will take a while for them to have an effect.The second thing is, social reforms don’t address the issues of power. At the heart of this is this idea of closed economic, political and social power. That comes about through economic growth and how you break up concentrations of wealth. Social reforms aren’t going to do that, although they’ll help on the margins. We’re seeing horrific scenes of police violence against protesters and dozens of people have died. Has this deterred the protesters in any way? No, in many ways it has sort of inspired them. It has, I think, sustained the protests.We’re not talking massive repression and tanks rolling in like Tiananmen Square. We’re talking about tear gas, rubber bullets, some injuries and deaths, and even credible reports of torture.It’s funny you should mention this – a class I’m teaching today is about social media and protests. One of the central arguments is that successful social protests need a martyr; they need a rallying cry.The deaths and the repression sort of help sustain that, but moreover, social media helps communicate what’s happening through videos and pictures. It really helps maintain this sense of righteousness, disdain for the government, and this idea of the need to demand change.Where do you see this going next?I don’t think we know. In the 60s and 70s, the political scientist Samuel Huntington argued in Political Order in Changing Societies that as economies grow, political institutions often strain to contain and channel demands. I think we’re seeing this now.This social ferment over political, economic and social demands is uncharted water. I don’t know where this will go, but I think we’ll see a change in the constitution. We’ve already seen a fragmenting of the party system, which I think will continue. Hopefully, that will lead to new leadership that can help reflect a change in Chile itself. Full Article
ot Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ot G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis. Full Article
ot Roles of the DOCK-D family proteins in a mouse model of neuroinflammation [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9−/−), DOCK10 (DOCK10−/−), or DOCK11 (DOCK11−/−) had been deleted and examined the phenotypic effects of these gene deletions in MOG35–55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10−/− mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10−/− and DOCK11−/− mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10−/− mice. No apparent phenotype was observed for DOCK9−/− mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10−/− mice. Up-regulation of C–C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10−/− astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis. Full Article
ot Brain manganese and the balance between essential roles and neurotoxicity [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity. Full Article
ot Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change? By feedproxy.google.com Published On :: Tue, 28 Apr 2020 14:07:38 +0000 29 April 2020 Dr Georges Fahmi Associate Fellow, Middle East and North Africa Programme @GeorgesFahmi The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do. 2020-04-28-covid-19-protest-movement-mena.jpg An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images. COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.Exposes economic vulnerabilityEconomic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism. Full Article
ot Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ot Chatham House Forum: Are Robots Prejudiced? By feedproxy.google.com Published On :: Tue, 13 Mar 2018 00:00:00 +0000 Full Article
ot Global Trade Landscape Series: US Trade in an Age of Protectionism By feedproxy.google.com Published On :: Fri, 15 Jun 2018 00:00:00 +0100 Full Article
ot Japan's Pivot in Asia By feedproxy.google.com Published On :: Wed, 27 Jun 2018 00:00:00 +0100 Full Article
ot Undercurrents: Bonus Episode - How Can Political Elites Reconnect With Voters? By feedproxy.google.com Published On :: Fri, 29 Jun 2018 00:00:00 +0100 Full Article
ot Undercurrents: Episode 19 - Green Building Projects in Jordan, and Qatar's Football World Cup By feedproxy.google.com Published On :: Thu, 18 Oct 2018 00:00:00 +0100 Full Article
ot Chatham House Prize 2018: The Committee to Protect Journalists By feedproxy.google.com Published On :: Wed, 28 Nov 2018 00:00:00 +0000 Full Article
ot China and the US: Through Each Other’s Eyes By feedproxy.google.com Published On :: Wed, 13 Feb 2019 00:00:00 +0000 Full Article
ot Negotiating With Terrorists By feedproxy.google.com Published On :: Wed, 10 Apr 2019 00:00:00 +0100 Full Article
ot Gender Inequality: Making Technology the Solution, Not the Problem By feedproxy.google.com Published On :: Thu, 11 Apr 2019 00:00:00 +0100 Full Article
ot Undercurrents: Episode 32 - Protecting Health Workers in Conflict By feedproxy.google.com Published On :: Thu, 02 May 2019 00:00:00 +0100 Full Article
ot Protection of the Wounded and Medical Care-Givers in Armed Conflict: Is the Law Up to the Job? By feedproxy.google.com Published On :: Thu, 16 May 2019 00:00:00 +0100 Full Article
ot Undercurrents: Episode 34 - Protecting Children in Conflict By feedproxy.google.com Published On :: Thu, 30 May 2019 00:00:00 +0100 Full Article
ot Protecting the Environment in Areas Affected by Armed Conflict By feedproxy.google.com Published On :: Tue, 15 Oct 2019 00:00:00 +0100 Full Article
ot Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 Full Article
ot Britain’s Soft Power Potential: In Conversation with Penny Mordaunt By feedproxy.google.com Published On :: Wed, 05 Feb 2020 00:00:00 +0000 Full Article
ot The Use of Sanctions to Protect Journalists By feedproxy.google.com Published On :: Thu, 13 Feb 2020 00:00:00 +0000 Full Article
ot Correction: Diversity in the Protein N-Glycosylation Pathways Within the Campylobacter Genus. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Full Article
ot Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella. Full Article
ot Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal. In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested. Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation. Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient. Full Article
ot Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Laser-capture microdissection (LCM) allows the visualization and isolation of morphologically distinct subpopulations of cells from heterogeneous tissue specimens. In combination with formalin-fixed and paraffin-embedded (FFPE) tissue it provides a powerful tool for retrospective and clinically relevant studies of tissue proteins in a healthy and diseased context. We first optimized the protocol for efficient LCM analysis of FFPE tissue specimens. The use of SDS containing extraction buffer in combination with the single-pot solid-phase-enhanced sample preparation (SP3) digest method gave the best results regarding protein yield and protein/peptide identifications. Microdissected FFPE human substantia nigra tissue samples (~3,000 cells) were then analyzed, using tandem mass tag (TMT) labeling and LC-MS/MS, resulting in the quantification of >5,600 protein groups. Nigral proteins were classified and analyzed by abundance, showing an enrichment of extracellular exosome and neuron-specific gene ontology (GO) terms among the higher abundance proteins. Comparison of microdissected samples with intact tissue sections, using a label-free shotgun approach, revealed an enrichment of neuronal cell type markers, such as tyrosine hydroxylase and alpha-synuclein, as well as proteins annotated with neuron-specific GO terms. Overall, this study provides a detailed protocol for laser-capture proteomics using FFPE tissue and demonstrates the efficiency of LCM analysis of distinct cell subpopulations for proteomic analysis using low sample amounts. Full Article
ot An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells. Full Article
ot The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Full Article
ot Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels. Full Article
ot Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation. Full Article