rn A kainate receptor-selective RNA aptamer [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2'-OH group with 2'-fluorine. These 2'-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits. Full Article
rn 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
rn Coronavirus Vaccine: Available For All, or When it's Your Turn? By feedproxy.google.com Published On :: Mon, 04 May 2020 15:39:19 +0000 4 May 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain. 2020-05-04-Vaccine-COVID-Brazil Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images. When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.From roulette to a horse raceOur game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020. Full Article
rn Victory and Memory: WW2 Narratives in Modern Day Russia and Ukraine By feedproxy.google.com Published On :: Tue, 05 May 2020 09:20:01 +0000 Invitation Only Research Event 11 May 2020 - 4:00pm to 5:30pmAdd to CalendariCalendar Outlook Google Yahoo Nina Tumarkin, Kathryn Wasserman Davis Professor of Slavic Studies; Professor of History; Director, Russian Area Studies Program, Wellesley CollegeGeorgiy Kasianov, Head, Department of Contemporary History and Politics, Institute of History of Ukraine, National Academy of Sciences of UkraineChair: Robert Brinkley, Chairman, Steering Committee, Ukraine Forum, Chatham House In 2020 the world commemorates the 75th anniversary of the end of World War II. The Russian government has organized a wide range of activities to mark the USSR’s victory, aiming to raise the already prominent role of the USSR to a new level. Moscow also uses its narrative about the war as a propaganda tool. Ukraine, which suffered disproportionally huge human losses and material destruction during WWII, is departing from its Soviet legacy by focusing commemorative efforts on honouring the victims of WWII rather than on glorifying victory. This event will analyze the evolution of the WWII narratives in Russia and Ukraine in recent years. The panellists will discuss the role of those narratives in shaping national discourses and their implications for the countries' respective futures. This event will be held on the record. Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Department/project Russia and Eurasia Programme Full Article
rn Virtual Roundtable: Land Reform in Ukraine: Is Zelenskyy's Government Getting it Right? By feedproxy.google.com Published On :: Thu, 07 May 2020 00:05:01 +0000 Invitation Only Research Event 14 May 2020 - 12:00pm to 1:30pmAdd to CalendariCalendar Outlook Google Yahoo Ihor Petrashko, Minister of Economic Development and Trade, UkraineAndriy Dykun, Chair, Ukrainian Agricultural CouncilVadim Tolpeco, Ukrlandfarming PlcChair: Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House Ukraine is known as the ‘breadbasket of Europe’ thanks to its grain exports. On 31 March 2020, the Ukrainian parliament passed a landmark law ending a 19-year ban on the sale of privately owned agricultural land. Due to come into force in July 2021, the law applies to 41.5 million hectares of farmland and economists predict substantial economic gains from this liberalization. This event will discuss the impact of the law on Ukraine’s agricultural sector and food security. How can the government best implement this reform and ensure that small and medium-sized agricultural companies increase their productivity? What does this change mean for Ukraine’s capacity to export grain? Can the country’s food supply withstand crises such as the COVID-19 pandemic? What role could foreign direct investors play in boosting production? This event will be held on the record. Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Department/project Russia and Eurasia Programme, Ukraine Forum Full Article
rn It's a man's world: carnal spectatorship and dissonant masculinities in Islamic State videos By feedproxy.google.com Published On :: Thu, 07 May 2020 08:41:04 +0000 7 May 2020 , Volume 96, Number 3 Manni Crone Read Online Islamic State videos have often been associated with savage violence and beheadings. An in-depth scrutiny however reveals another striking feature: that female bodies are absent, blurred or mute. Examining a few Islamic State videos in depth, the article suggests that the invisibility of women in tandem with the ostentatious visibility of male bodies enable gendered and embodied spectators to indulge in homoerotic as well as heterosexual imaginaries. In contrast to studies on visual security and online radicalization which assert that images affect an audience, this article focuses on the interaction between video and audience and argues that spectators are not only rational and emotional but embodied and gendered as well. Islamic State videos do not only attract western foreign fighters through religious–ideological rhetoric or emotional impact but also through gendered forms of pleasure and desire that enable carnal imagination and identification. The article probes the analytical purchase of carnal aesthetics and spectatorship. Full Article
rn Webinar: International Humanitarian Law Amid Coronavirus By feedproxy.google.com Published On :: Thu, 07 May 2020 09:20:01 +0000 Members Event Webinar 15 May 2020 - 1:00pm to 2:00pmAdd to CalendariCalendar Outlook Google Yahoo Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseChair: Chanu Peiris, Programme Manager, International Law Programme, Chatham HouseFurther speakers to be announced. In April 2020, UN Secretary General Antonio Guterres called for a global ceasefire in order for communities and states to focus efforts on responding to the coronavirus outbreak. The consequences of armed conflict – including displacement, detention, lack of access to health services and disrupted social infrastructures – mean that those in conflict-ridden areas are amongst the most vulnerable to the virus. Observing international humanitarian law (IHL) could be one way of safeguarding against, at least, the provision of vital medical supplies and personnel for vulnerable groups. Against the backdrop of a growing health and economic emergency that is otherwise dominating government agendas, how do we emphasise the importance of humanitarian action and guarantee - or improve - compliance?The panellists will discuss the remit and limitations of international humanitarian law and how the pandemic might complicate compliance. What is the framework for humanitarian action under international humanitarian law? What are the challenges to delivering relief? And how has COVID-19 impacted humanitarian action in conflict-ridden areas?This event is for Chatham House members only. Not a member? Find out more. Full Article
rn Power and Story: What is the Future for Journalism? By feedproxy.google.com Published On :: Mon, 26 Feb 2018 00:00:00 +0000 Full Article
rn Can Old Economics Help Solve Modern Economic Problems? By feedproxy.google.com Published On :: Wed, 04 Apr 2018 00:00:00 +0100 Full Article
rn Undercurrents: Episode 5 - Chokepoints in Global Food Trade, and How the Internet is Changing Language By feedproxy.google.com Published On :: Thu, 05 Apr 2018 00:00:00 +0100 Full Article
rn Undercurrents: Episode 6 - Tribes of Europe, and the International Women's Rights Agenda at the UN By feedproxy.google.com Published On :: Thu, 19 Apr 2018 00:00:00 +0100 Full Article
rn Stopping the Use of Chemical Weapons in Modern Conflicts By feedproxy.google.com Published On :: Fri, 25 May 2018 00:00:00 +0100 Full Article
rn The Western Balkans Before the Berlin Process Summit By feedproxy.google.com Published On :: Wed, 13 Jun 2018 00:00:00 +0100 Full Article
rn Undercurrents: Episode 10 - Artificial Intelligence in International Affairs, and Women Drivers in Saudi Arabia By feedproxy.google.com Published On :: Fri, 15 Jun 2018 00:00:00 +0100 Full Article
rn The Failed Marshall Plan: Learning from US Foreign Policy Missteps By feedproxy.google.com Published On :: Mon, 10 Sep 2018 00:00:00 +0100 Full Article
rn The Belt and Road Initiative: Modernity, Geopolitics and the Global Order By feedproxy.google.com Published On :: Fri, 28 Sep 2018 00:00:00 +0100 Full Article
rn Trump’s America: Domestic and International Public Opinion By feedproxy.google.com Published On :: Fri, 12 Oct 2018 00:00:00 +0100 Full Article
rn International Security Institutions: A Closer Look By feedproxy.google.com Published On :: Tue, 13 Nov 2018 00:00:00 +0000 Full Article
rn Can Europe Save the Liberal International Order? By feedproxy.google.com Published On :: Fri, 23 Nov 2018 00:00:00 +0000 Full Article
rn 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
rn International Law Podcast: Starvation in Armed Conflict By feedproxy.google.com Published On :: Wed, 12 Dec 2018 00:00:00 +0000 Full Article
rn China and the Future of the International Order - The Belt and Road Initiative By feedproxy.google.com Published On :: Thu, 13 Dec 2018 00:00:00 +0000 Full Article
rn The Great Delusion: Liberal Dreams vs International Realities By feedproxy.google.com Published On :: Mon, 21 Jan 2019 00:00:00 +0000 Full Article
rn China and the Future of the International Order – Peace and Security By feedproxy.google.com Published On :: Tue, 12 Feb 2019 00:00:00 +0000 Full Article
rn Rethinking the Governance of Solar Geoengineering By feedproxy.google.com Published On :: Thu, 21 Feb 2019 00:00:00 +0000 Full Article
rn Undercurrents: Episode 27 - Financing for Developing Countries, and Investigative Journalism in West Africa By feedproxy.google.com Published On :: Thu, 28 Feb 2019 00:00:00 +0000 Full Article
rn Cybersecurity Series: Exploring Methods of Internet Censorship and Control By feedproxy.google.com Published On :: Thu, 14 Mar 2019 00:00:00 +0000 Full Article
rn Serbia-Kosovo Dialogue: The Future of Peace and Security in the Western Balkans By feedproxy.google.com Published On :: Fri, 05 Apr 2019 00:00:00 +0100 Full Article
rn Weak States: Rebel Governance and War Economies By feedproxy.google.com Published On :: Mon, 15 Apr 2019 00:00:00 +0100 Full Article
rn The Kremlin Spectrum: Western Approaches Towards Russia By feedproxy.google.com Published On :: Tue, 14 May 2019 00:00:00 +0100 Full Article
rn Undercurrents: Bonus Episode - How Technology is Changing International Affairs By feedproxy.google.com Published On :: Mon, 20 May 2019 00:00:00 +0100 Full Article
rn Our Shared Humanity: Governance, Youth and Leadership By feedproxy.google.com Published On :: Tue, 04 Jun 2019 00:00:00 +0100 Full Article
rn Africa’s Economic Outlook in a Challenging External Environment By feedproxy.google.com Published On :: Mon, 10 Jun 2019 00:00:00 +0100 Full Article
rn Zimbabwe’s International Engagement By feedproxy.google.com Published On :: Fri, 12 Jul 2019 00:00:00 +0100 Full Article
rn Podcast: International Law, Security and Prosperity in the Asia-Pacific By feedproxy.google.com Published On :: Fri, 01 Nov 2019 00:00:00 +0000 Full Article
rn Who Runs the Internet: Internet Consolidation and Control By feedproxy.google.com Published On :: Tue, 10 Dec 2019 00:00:00 +0000 Full Article
rn Investigating Violations of International Humanitarian Law By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 Full Article
rn The Use of Sanctions to Protect Journalists By feedproxy.google.com Published On :: Thu, 13 Feb 2020 00:00:00 +0000 Full Article
rn How Concerning Is the New Coronavirus Outbreak? By feedproxy.google.com Published On :: Wed, 26 Feb 2020 00:00:00 +0000 Full Article
rn Virtual event: Global Forum on Forest Governance Number 30 By feedproxy.google.com Published On :: Mon, 20 Jan 2020 13:15:01 +0000 Research Event 13 July 2020 - 9:00am to 14 July 2020 - 5:00pmAdd to CalendariCalendar Outlook Google Yahoo Chatham House | 10 St James's Square | London | SW1Y 4LE The 30th Global Forum on Forest Governance will take place remotely online on 13-14th July 2020. Online registration, with further details, will follow in due course. Melissa MacEwen Project Manager, Energy, Environment and Resources Programme Email Department/project Energy, Environment and Resources Programme, Improving Forest Governance and Tackling Illegal Logging and Deforestation Full Article
rn Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’ By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:00:22 +0000 4 March 2020 , Volume 96, Number 2 Emma Tomalin Read Online In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this. Full Article
rn Episode 15: The Perks of Being a Wallflower/Beasts of the Southern Wild By feedproxy.google.com Published On :: Sun, 09 Dec 2012 17:29:00 +0000 The Perks of Being A Wallflower ReviewBeasts of the Southern Wild ReviewWhat We WatchedDownload Episode 15 here. (right click to save) Next episode is our Caveman episode. We will be discussing Quest For Fire, 10,000 B.C. and Ice Man. Full Article
rn Episode 39: American Hustle/The Hobbit 2/Anchorman 2/Out of the Furnace By feedproxy.google.com Published On :: Fri, 27 Dec 2013 07:32:00 +0000 American HustleThe Hobbit: The Desolation of SmaugAnchorman 2: The Legend ContinuesOut of the Furnace2014 Bucket List FilmsWhat We Watched: Bully, Prisoners, Powwow Highway, Miss Representation, The Spectacular Now, Knuckle, Shut Up And Play The Hits, Mike Birbiglia: My Girlfriend's Boyfriend and The Act of Killing. You can download the episode here. (right click to save) Next Episode: Martin Scorcese's The Wolf of Wall Street and Spike Jonze's Her. Full Article
rn New Coronavirus Outbreak: Concern Is Warranted, Panic Is Not By feedproxy.google.com Published On :: Thu, 23 Jan 2020 12:03:21 +0000 23 January 2020 Professor David Heymann CBE Distinguished Fellow, Global Health Programme Lara Hollmann Research Assistant, Global Health Programme @lara_hollmann LinkedIn Whenever there is a new infection in humans, such as the novel coronavirus, it is appropriate to be concerned because we do not know enough about its potential. Explainer: Coronavirus - What You Need to Know World-renowned global health expert Professor David Heymann CBE explains the key facts and work being done on the Coronavirus outbreak. When it comes to emerging infectious diseases – those newly recognized in humans or in new locations – it is not only what we know that matters but also what we do not know.An outbreak of a new coronavirus first reported in Wuhan, China, which has so far led to more than 500 confirmed cases and multiple deaths across five countries (and two continents) has prompted the question from several corners of the world: Should we be worried?Although expert teams coordinated by the World Health Organization (WHO) are working on key questions to get answers as soon as possible, the level of uncertainty is still high.We do not yet know exactly how deadly the disease is, how best to treat those who get sick, precisely how it is spreading, nor how stable the virus is. It is thought that the virus spread from an animal source, but the exact source is yet to be confirmed and the disease is now in human populations and appears to be spreading from human to human.It is such uncertainty, inherent in emerging infectious disease outbreaks, that warrants concern. Until they are resolved, it is appropriate for the world to be concerned. It is useful to remember that most established scourges of humanity such as HIV, influenza and tuberculosis likely started as emerging infectious diseases that jumped the species barrier from animals to humans.Shortly after the Chinese authorities reported the first cases of ‘mystery pneumonia’ in Wuhan, China, to WHO, the virus causing the disease was isolated and identified as being part of the coronavirus family. It belongs to the same virus family as SARS, a highly contagious and life-threatening coronavirus that caused a nine-month epidemic in 2003 that affected 26 countries and resulted in more than 8,000 infections and nearly 800 deaths.A second novel coronavirus that emerged in 2012 and persists today – MERS, or Middle East Respiratory Syndrome – is less contagious (spread by close contact rather than coughing and sneezing).The differences between the SARS coronavirus and the MERS coronavirus highlight that, despite belonging to the same virus family, pathogens do not necessarily behave in the same way. It is as yet unknown whether the new virus is, or will turn out to be, more like SARS or MERS, or neither. Chinese authorities have confirmed that there is human-to-human transmission. However, it is not yet established whether it is sustained, which would make the outbreak more difficult to control. As of 23 January, the number of cases range from 500 confirmed cases up to an estimated 1,700 cases, according to a disease outbreak model by Imperial College London.Likewise, we do not know to what extent the virus is able to mutate and if so, how rapidly. Generally, coronaviruses are known to be able to mutate, with the risk that a less contagious form of the virus becomes highly contagious. This could have an impact not only on the transmission pattern and rate but also the death rate. The virus could change in either direction, to become either more or less of a threat.It is important to take a precautionary approach while uncertainty persists. It is also important not to overreact and for measures to be scientifically sound. Concern over this outbreak is due, but panic is not.Three virtual networks of experts supporting the response – one of virologists, one of epidemiologists and one of clinicians – are working on the key pieces of the jigsaw puzzle: watching the virus, watching the transmission patterns, and watching the people who have been infected. It is crucial to maintain the ongoing investigation of the disease, stay focused on the science and to keep sharing the necessary information. Full Article
rn The Hurdles to Developing a COVID-19 Vaccine: Why International Cooperation is Needed By feedproxy.google.com Published On :: Thu, 23 Apr 2020 09:26:36 +0000 23 April 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Dr Champa Patel Director, Asia-Pacific Programme @patel_champa While the world pins its hopes on vaccines to prevent COVID-19, there are scientific, regulatory and market hurdles to overcome. Furthermore, with geopolitical tensions and nationalistic approaches, there is a high risk that the most vulnerable will not get the life-saving interventions they need. 2020-04-23-Covid-Vaccine.jpg A biologist works on the virus inactivation process in Belo Horizonte, Brazil on 24 March 2020. The Brazilian Ministry of Health convened The Technological Vaccine Center to conduct research on COVID-19 in order to diagnose, test and develop a vaccine. Photo: Getty Images. On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. Vaccine developmentFirstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.Vaccine manufacturingDevelopers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine. There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. Vaccine distributionGlobal leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. The need for global leadership There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles. Full Article
rn Coronavirus Vaccine: Available For All, or When it's Your Turn? By feedproxy.google.com Published On :: Mon, 04 May 2020 15:39:19 +0000 4 May 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain. 2020-05-04-Vaccine-COVID-Brazil Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images. When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.From roulette to a horse raceOur game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020. Full Article
rn Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD. Full Article
rn Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction. Full Article
rn Iraq is trying yet again to form a government. Why is it so hard? By feedproxy.google.com Published On :: Wed, 06 May 2020 17:33:52 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/04/15/iraq-is-trying-yet-again-form... Release date 15 April 2020 Expert Dr Renad Mansour In the news type Op-ed Hide date on homepage Full Article
rn The insurgency in northern Mozambique has got worse. Why? By feedproxy.google.com Published On :: Wed, 06 May 2020 17:41:31 +0000 Source Mail & Guardian URL https://mg.co.za/article/2020-03-31-the-insurgency-in-northern-mozambique-has-go... Release date 31 March 2020 Expert Dr Alex Vines OBE In the news type Op-ed Hide date on homepage Full Article