han Naked Mole Rat - More Than Meets The Eye By feedproxy.google.com Published On :: Sat, 22 Aug 2015 17:03:00 +0200 The naked mole rat (Heterocephalus glaber) is a rodent, known for its burrowing and is indigenous to East Africa. The mole rat possesses a number of characteristics which allow it to survive in underground and harsh environments. The average naked mole rat is between 3 to 4 inches (8 to 10 centimeters) in length and weighs between 1.1 and 1.2 ounces (30 to 35 grams). They have small eyes, poor sight, and have legs that are quite short and thin. They are also able to move backward and forward at the same quick pace and have large teeth that allow them to dip. The term "naked" comes from the fact that they have very little hair and gray-pink skin. The species is highly adapted to situations in which oxygen is limited within tunnels of their habitat. The lungs are small and their blood is greatly able to bond oxygen. They have very low metabolic and respiration rates. During periods of drought and hunger, the metabolic can decrease further to about 25% of its normal level. The naked mole rat lives predominantly in the dry tropical grasslands in East Africa with large concentrations being concentrated in Somalia, Kenya, and southern Ethiopia. Groups of around 80 individual mole rats (although it can be as few as 20 and as many as 200) live within a complex burrowing system within the African desert. These tunnel systems can be quite long, between two to three miles in length. There is a complex hierarchical structure where one queen and between 1 and 3 males reproduce, the other naked mole rats are workers and sterile. Dimorphism exists between the males, two forms of workers (tunnel digging/gathering and soldiers), and the breeding males. The breeding males and the queen can keep up their relationship for several years. The queens can live for a period of between 13 and 18 years and are quite hostile towards other females. Upon the death of the queen, another female will become queen in her place. The naked mole rat mostly eats large tubers that they find underground during their mining exhibitions. However, they are also known for eating their own fecal matter. One tuber, depending upon its size, can feed a colony for several months or years as they only eat the inside of the tuber. They leave the outer parts so that the tuber is able to regenerate. Naked mole rats are currently not a threatened species. Although their living conditions are tough, they are a widespread species. Naked mole rats help in cancer research, because they never get cancer (read here). Full Article default
han I Never Thought I’d Want (or Need) an Electric Folding Bike … But This Changed My Mind By feedproxy.google.com Published On :: Mon, 23 Sep 2019 18:44:13 +0000 If you've never had enough room to take your bike road-tripping, Oyama's origami-inspired folding electric bike is here to change your mind. The post I Never Thought I’d Want (or Need) an Electric Folding Bike … But This Changed My Mind appeared first on Vagabondish. Full Article Modern Vagabond Review
han My Faith in Nerds: Stronger Than Any Gelatinous Cube By feedproxy.google.com Published On :: Fri, 10 Sep 2010 20:01:57 +0000 dConstruct 2010: Merlin Mann - "Kerning, Orgasms & Those Goddamned Japanese Toothpicks" (NSFW) ME - Kerning, Orgasms And Those Goddamned Japanese Toothpicks on Huffduffer Download the audio | Huffduff it Let's be honest. I don't go...mmmm...places very often. I sit in this chair. I go to the Safeway with my daughter. Sometimes, I take the train downtown to get a haircut. I check the mail. But, by and large, like most nerds, I'm without question, a bit of a shut-in. Which makes it more than a little ironic that my first trip off the North American continent brought me all the way to Brighton, England's wonderful dConstruct Conference. Which wonderful conference placed me inside a very royal complex, alone on a very large stage, 90 seconds after being informed I'd better be entertaining, because I'd be conducting my oration on the same spot where, a scant 36 years earlier, ABBA had become international stars by singing an up-tempo number about giving up. So, y'know. No pressure. Commanded to this location by two of my web heroes, I was told I could speak about whatever I wanted. So, wow, to quote the ladies of ABBA, how could I ever refuse? Thus, I stood on that stage for over 35 minutes, rambling to 800 talented, creative people about Dungeons & Dragons, japanese toothpicks, torrenting Photoshop, as well as what I used to find myself doing after a long evening of shooting mutants in Stargate.1 But, mostly? Yes. Mostly, I stood on a stage thousands of miles from the chair from which I barely move, and I told a lot of really smart people that they were nerds. I also told them they should get out more. I swear: it made sense at the time. Some Serious Talent My talk about the challenges and opportunities of being a giant nerd seemed well received. Honestly, I'm very happy with how it turned out. But--oh, brother--was I ever up against some heavy hitters. Serious Lou Gehrig shit. I'll leave it to other, more eloquent folks to tell you what a wonderful day this was. But I will very much suggest you learn this for yourself by listening to the audio of the fantastic talks. Because every one of them is a corker. Additionally, like I said, Tom Coates put on one of the loveliest slide decks it's ever been my pleasure to see (56MB PDF). Great speakers, great hosts, wonderful attendees (who aren't above buying a yank a pint [thanks, everybody]). And, Thanks, dConstruct I have to admit, I'm kind of over conferences as a thing, which makes it even more crazy when I go to one, and it blows me out of the water with the care and quality of the event, the speakers, and the attendees. dConstruct was absolutely one of those blown-out-of-the-water events. (photo: happy.apple) As I learned over and over again--yes, like me--these folks are nerds. But, brother are they ever talented nerds who care and care. Which I just love so much. I'll take a nerdy bunch of fontdorks and cellists over a splashy mega-conference full of VC pitches and skanks pushing free Red Bull anytime. Anytime. dConstruct was simply a top-notch operation from end-to-end, and I'm insanely grateful that I was invited to participate. Thanks, Clearleft. And, you, the reader? If you get the chance next time, go. Heck, I might even leave this chair and go there, myself. Maybe. I suppose when Dr. Who's over, I could just let these 20-sided dice decide for me. Lemme see...what's my Armor Class and Hit Points...? Listen for Yourself2 dConstruct Podcast MARTY NEUMEIER - The Designful Company The Designful Company on Huffduffer Download the audio | Huffduff it BRENDAN DAWES - Boil, Simmer, Reduce Boil, Simmer, Reduce on Huffduffer Download the audio | Huffduff it DAVID MCCANDLESS - Information Is Beautiful Information Is Beautiful on Huffduffer Download the audio | Huffduff it SAMANTHA WARREN - The Power and Beauty of Typography The Power and Beauty of Typography on Huffduffer Download the audio | Huffduff it JOHN GRUBER - The Auteur Theory Of Design The Auteur Theory Of Design on Huffduffer Download the audio | Huffduff it HANNAH DONOVAN - Jam Session: What Improvisation Can Teach Us About Design Jam Session: What Improvisation Can Teach Us About Design on Huffduffer Download the audio | Huffduff it JAMES BRIDLE - The Value Of Ruins The Value Of Ruins on Huffduffer Download the audio | Huffduff it TOM COATES - Everything The Network Touches Everything The Network Touches on Huffduffer Download the audio | Huffduff it Kerning, Orgasms And Those Goddamned Japanese Toothpicks ME - Kerning, Orgasms And Those Goddamned Japanese Toothpicks on Huffduffer Download the audio | Huffduff it Hint: Number Three. ↩ Code for these was stolen wholesale from the dConstruct site. Jeremy, et al - don't hesitate to tell me if that's a problem.Srsly. ↩ ”My Faith in Nerds: Stronger Than Any Gelatinous Cube” was written by Merlin Mann for 43Folders.com and was originally posted on September 10, 2010. Except as noted, it's ©2010 Merlin Mann and licensed for reuse under CC BY-NC-ND 3.0. "Why a footer?" Full Article dConstruct Geeks Knowledge Workers Nerds Speaking NSFW
han VIDEO: AG Barr criticizes Mueller’s handling of Steele dossier By dennismichaellynch.com Published On :: Sat, 09 May 2020 15:50:00 +0000 The DML News App offers the best in news reporting. The post VIDEO: AG Barr criticizes Mueller’s handling of Steele dossier appeared first on Dennis Michael Lynch. Full Article News Feed Powered by DMLNewsApp.com
han 'Where is that compassion?': Closing tent cities a chance to change housing policy, advocates say By bc.ctvnews.ca Published On :: Fri, 8 May 2020 06:49:00 -0700 T.J. Lovell had just 30 minutes to pack up his belongings from the tent city in Oppenheimer Park if he wanted access to a hotel room that he could share with his father. Full Article
han BREAKING: CBS News Allegedly Staged Fake COVID19 Testing In MI…Makes Dem Gov Whitmer Look Like She’s Doing More To Help Citizens Than Fed Government [VIDEO] By 100percentfedup.com Published On :: Wed, 06 May 2020 15:57:46 +0000 The following article, BREAKING: CBS News Allegedly Staged Fake COVID19 Testing In MI…Makes Dem Gov Whitmer Look Like She’s Doing More To Help Citizens Than Fed Government [VIDEO], was first published on 100PercentFedUp.com. Project Veritas founder James O’Keefe has done it again. He’s uncovered yet another deceitful piece of coverage on the Wuhan coronavirus pandemic in America by CBS News. O’Keefe begins his interview with a man whose identity is being hidden, “You’re telling me—you’re 100% certain, that CBS News, CBS News Corporation national—staged a fake event. They […] Continue reading: BREAKING: CBS News Allegedly Staged Fake COVID19 Testing In MI…Makes Dem Gov Whitmer Look Like She’s Doing More To Help Citizens Than Fed Government [VIDEO] ... Full Article Featured Left News Political Correctness Politics
han Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn By 100percentfedup.com Published On :: Fri, 08 May 2020 19:54:46 +0000 The following article, Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn, was first published on 100PercentFedUp.com. Yesterday, after 3 1/2 years of having his character and integrity called into question, President Trump's first NSA, General Michael Flynn was finally... Continue reading: Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn ... Full Article Featured Politics
han Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity. Full Article
han Iraq's Reconstruction: In Conversation with Governor of Anbar Ali Farhan Hamid By feedproxy.google.com Published On :: Mon, 09 Dec 2019 16:30:01 +0000 Invitation Only Research Event 18 December 2019 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Ali Farhan Hamid, Governor of Anbar ProvinceChair: Dr Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House In the aftermath of the liberation from ISIS, the government of Iraq was left to count the cost of three years of brutal conflict, only the most recent phase in the ongoing cycle of conflict and stabilization that has plagued Iraq for 16 years. While reconstruction has been a focus of both the Iraqi government and international policymakers since 2003, billions of dollars in pledged funds have continually failed to reach the places they are most needed. At this roundtable, Ali Farhan Hamid will discuss the efforts of his provincial government to rebuild the cities and towns worst-hit by the conflict. He will provide insights into the practical and structural impediments to reconstruction efforts in both Anbar and neighbouring provinces such as Ninewah where the worst damage was sustained under ISIS but where little in the way of reconstruction has been achieved thereby leaving the door open to the potential resurgence of conflict.The roundtable is part of the Chatham House Iraq Initiative. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Iraq Initiative Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
han Can Morocco Effectively Handle the COVID-19 Crisis? By feedproxy.google.com Published On :: Mon, 06 Apr 2020 09:10:24 +0000 6 April 2020 Dr Mohammed Masbah Associate Fellow, Middle East and North Africa Programme @MasbahMohammed LinkedIn Google Scholar Anna Jacobs Senior Research Assistant, Brookings Doha Center The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long. GettyImages-1208907580.jpg A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images. In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.Call for national unityIn times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.Public trust issuesThis pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.A vulnerable economyThere is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.Moving forward?Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long. Full Article
han 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
han Mohamed El Dahshan By feedproxy.google.com Published On :: Sat, 02 May 2020 09:17:19 +0000 Associate Fellow, Middle East and North Africa Programme Biography Mohamed El Dahshan is an associate fellow with the Chatham House Middle East and North Africa Programme, where he focuses on economic development, regional cooperation, and fragile states.He is also managing director of OXCON, a public sector consulting firm, advising governments and international organisations on Africa and the Middle East. Prior to this, he was senior cooperation advisor at the African Development Bank, and senior research fellow at Harvard University.He is an award-winning writer and columnist, and the co-author of Diaries of the Revolution (2012), a memoir of the Egyptian revolution, as well as several book chapters, academic papers, and more than 100 media articles for outlets such as Foreign Policy the New York Times, and the Guardian, among others.He was honoured as an Archbishop Desmond Tutu fellow, a fellow of the United Nations Alliance of Civilisations, and is listed among the 100 Africa Future Economic Leaders by the Institut Choiseul.Mohamed holds Master degrees from Oxford, Harvard and Sciences-Po Paris. Areas of expertise Economic developmentEgyptSMEs and private sector developmentFragile states Past experience 2017 - presentManaging director, OXCON Frontier Markets & Fragile States Consulting2014-15Regional economist / Senior cooperation officer, African Development Bank2012-13Middle East manager, Senior research fellow, Center for International Development, Harvard University Email @eldahshan LinkedIn Google Scholar Full Article
han Significant political change is coming to the Gulf By feedproxy.google.com Published On :: Thu, 19 Feb 2015 10:31:55 +0000 19 February 2015 20150212GCCKinninmont.jpg Photo by ArabianEye / Getty Images Significant political change is coming to the Gulf monarchies, often seen in the West as bastions of stability, argues a new Chatham House report entitled Future Trends in the Gulf.The Gulf states are already undergoing dramatic demographic and economic changes – changes which are being accelerated by lower oil prices.The current political systems in the Gulf have been defined by the oil era, enabling governments to provide extensive economic benefits and no taxation, while maintaining a monopoly over political power. As the economic role of the state changes, its political role will change too.Even at a time of plenty, pressures for political change have been rising. Significant changes in the availability of information, the surge in social media and women’s education are driving new demands for transparency.Political protests have been most visible in Bahrain, but calls for change and reform have been growing in all of the Gulf countries. Raif Badawi, the blogger recently flogged in Saudi Arabia, is hardly an isolated case: campaigners for constitutional monarchies and elected parliaments have been facing severe punishments for years. The report author, Jane Kinninmont, says:'The US and UK underestimate the significant leverage that they still have in the Gulf compared with most other countries, even if it is less than in the 20th century. As much as Asian countries are strengthening their trade links with the Gulf, they are reluctant to step forward as the security allies that the Gulf countries need.' Combating instability, extremism and sectarianism in the wider region requires looking hard at the pressures for change and insecurities inside the Gulf states. These help explain, for instance, why Qatar and the UAE have backed different sides in the intensifying civil conflict in Egypt.The report, based on three years of research, argues that: It is time for the GCC countries to seize the opportunity to carry out gradual and consensual political and social reforms towards more constitutional forms of monarchy. Western countries, especially the US and UK, need to diversify the base of relations with the Gulf beyond the existing elite – and reach out to a broader base among the increasingly well-educated and aspirational new generation.Defence cooperation with the Gulf needs to be placed in a wider political context, where respect for human rights is not seen as being at odds with security imperatives, but as part of ensuring sustainable security. The UK and US policy of expanding their military bases in Bahrain has sent a strong signal that political reform is not their priority. A fresh discourse on Gulf security needs to take account of the need for people to feel secure vis-à-vis their own governments, for instance by ensuring the police are held accountable by independent judiciaries, and ending lengthy detention without trial.In partnering with Gulf countries against extremism, Western allies need to broach sensitive issues such as religious education in Saudi Arabia, or the impact on Western publics and Muslim communities outside the region of flogging a blogger for insulting Islam. Editor's notes Read the report Future Trends in the Gulf by Jane Kinninmont, MENA Programme. Embargoed until Thursday 19 February, 00:01 GMT. Read the executive summary here. When linking to this report, please use this link, which will go live when the embargo is lifted. This report will be launched at an event at Chatham House on 19 February. For all enquiries, please contact the press office. To contact the author directly, please use:Email: jkinninmont@chathamhouse.orgPhone: +44 (0)7967 325 993Twitter: @janekinninmont Full Article
han Asia-Pacific security is about more than just China and the US By feedproxy.google.com Published On :: Fri, 09 Oct 2015 14:22:43 +0000 21 September 2015 20150924AsiaPacific.jpg Photo: Jacob Parakilas/Chatham House. Seeing geo-strategic rivalry between the US and China as the sole variable in Asia-Pacific security risks becoming a self-fulfilling prophecy, according to a forthcoming Chatham House paper. As Xi Jinping’s visit to the US approaches, The Asia-Pacific Power Balance: Beyond the US–China Narrative, warns against deploying Cold War-type narratives that pit the two countries against each other. Such narratives not only misunderstand the complexity of the region and the growing influence of India, Japan and Indonesia, but also risk increasing the likelihood of conflict and of missing vital opportunities for future cooperation. The paper, by John Nilsson-Wright, Tim Summers and Xenia Wickett argues that by focusing too heavily on the US and China, policymakers risk narrowing the aperture through which they evaluate policy choices regarding major regional challenges. Some of the key findings include the following:MilitaryDespite rapidly rising defence spending across Asia, the relative importance of traditional military means is declining relative to instruments such as development assistance and cyber offence.The militaries of Japan and India are becoming – in very different ways – more versatile and potentially expanding their remits. In the future, there will be a larger number of more capable military powers in the region, including South Korea and Vietnam.Current perceptions that the main dynamic is China’s rising military capabilities outstripping others in the region, therefore, need to be tempered. India’s defence spending, for example, as a percentage of GDP has surpassed China’s for the past several decades.EconomicsAlthough China has the world’s second-largest economy and – despite recent problems – is growing faster than most major economies, its growth rate is in secular decline. China has gone from near-constant double-digit growth over the past four decades to 7.4 per cent in 2014 and could dip below 7 per cent this year.Whilst India’s economy remains notably smaller than those of China, the US and Japan, it will surpass China’s growth rate this year and has a lot of potential.If the Trans-Pacific Partnership (TPP) is successfully negotiated, the potential for integration and growth between the United States, Japan and the other 10 TPP members may reduce their current trade dependence on China.DemographyThe demography of Asia is another reason to look beyond the US-China nexus, as China faces the challenge of an aging society, while countries such as India have the advantage of a younger population and decades of demographic dividend ahead of them.Likewise populations across much of Southeast Asia, such as the Philippines and Indonesia are growing rapidly and expanding their middle classes. Editor's notes Read the report The Asia-Pacific Power Balance: Beyond the US–China Narrative from Chatham House.For all enquiries, including requests to speak with the authors of this paper, please contact the press office. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
han Transatlantic Strategy Group on the Future of US Global Leadership: Transatlantic Security Policy Towards a Changing Middle East By feedproxy.google.com Published On :: Thu, 05 Mar 2015 11:45:02 +0000 Invitation Only Research Event 6 February 2015 - 8:45am to 4:30pm Residence of the British Ambassador to France, Paris Meeting Summarypdf | 95.65 KB With the Middle East in chaos and the future of many states increasingly uncertain, there is a large amount of attention as to how policy-makers in Europe and the US should respond. In particular, many in Europe are unsure of long-term US policy in light of competing American priorities, budgetary constraints and a public adverse to committing further resources abroad. In this context, it is important that European and American policy-makers understand each other’s positions.At this all-day event, a group of experts will discuss how US policy towards the Middle East is changing, what this means for Europe and, subsequently, how Europe should respond. Attendance at this event is by invitation only.The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Delegation of Strategic Affairs of the French Ministry of Defence and the British Embassy in Paris. Event attributes External event Department/project US and the Americas Programme Full Article
han Beneath the Bluster, Trump Offers the Chance to Rethink Trade By feedproxy.google.com Published On :: Mon, 12 Dec 2016 14:58:53 +0000 12 December 2016 Marianne Schneider-Petsinger Senior Research Fellow, US and the Americas Programme @mpetsinger Trump’s trade policy may not be as radical in practice as he described it on the stump, and his win is an opportunity to address the shortcomings in the current global trade system. 2016-12-12-TrumpTrade.jpg Trump has pointed to some valid concerns about the current trading system. Photo by Getty Images. With Donald Trump in the White House, US trade policy will probably look very different from the past 70 years - seven decades across which successive Republican and Democratic administrations have participated in and led global trade liberalization initiatives. If the president-elect delivers on his major campaign promises on trade, the negative effects on the American economy would be severe and the United States would give up its role in shaping the global trading system.But there is no need to panic. Trump will likely leave behind the rhetoric of the campaign trail once he sits in the Oval Office. Trump will probably moderate his proposals, because a faction of the Republican-dominated Congress continues to support free trade. He might also be reined in by his team, though that depends on who best catches the ear of the president: individuals such as Vice-President-elect Mike Pence, who has supported free-trade agreements in the past, or trade-skeptical advisors such as Dan DiMicco, who now heads the transition team for the Office of the United States Trade Representative. So what does the Trump presidency actually mean for trade?Trump won’t likely follow through on his most extreme plans, such as leaving the World Trade Organization. But he will lead a more protectionist United States that focuses on its trade deficits – with particular attention being paid to China and Mexico. Trump will probably impose tariffs on imports from those countries; however, duties will be lower than the mooted 45 per cent and 35 per cent, respectively. With regards to China, Trump will probably bring trade cases against Beijing’s subsidy arrangements and look into alleged currency manipulation (even though most economists accept that the renminbi is no longer undervalued).Given the prominence of the North American Free Trade Agreement on the campaign trail, Trump will have to address the deal with Canada and Mexico. Whether that means renegotiating or pulling out remains to be seen. One thing is certain: Trump will not move forward with mega-regional trade accords such as the Trans-Pacific Partnership or the US-EU Transatlantic Trade and Investment Partnership. Those would-be pacts are a lost opportunity, but this is not the end of the trade world. Trump will focus instead on striking trade deals with individual countries. One such potential bilateral trade deal could be a US–UK agreement, which Trump and his advisers, despite the prognostications of the current president, see at the front of the queue. Opportunity to rethink the trade frameworkThe fact that Trump is not necessarily against free trade per se bears hope. And there is another silver lining in the dark cloud hanging over trade. Trump has pointed to some valid concerns about the current trading system. His victory can be an opportunity to address these shortcomings. NAFTA does need an update. The agreement entered into force in 1994 - before the internet took off. Thus, provisions to include standards to protect digital freedoms could modernize NAFTA and expand its scope to cover 21st century economic issues. In addition, labour rights and environmental protections were not included in NAFTA but were incorporated into side agreements with weak, unenforceable provisions. By better addressing labour and environmental issues, NAFTA could be significantly upgraded.Trump will aim to tackle unfair competition and look to enforce existing trade deals more vigilantly. This is another important and legitimate issue, and could be tackled in conjunction with European allies. The European Commission has recently proposed redesigning and updating its trade defence instruments because non-market economy practices and state intervention by some WTO countries - for example, China’s overcapacity in the steel sector - have hurt domestic industries. Without action by major players such as the United States or the European Union, China would have no incentive to reform its distortionary policies. Trust in the rules-based trading system requires that existing trade agreements are properly and fairly enforced.Trump’s win highlights the need for better compensation for those who have felt the adverse effects of trade. His victory was partly fuelled by tapping into economic anxieties and appealing to voters who feel left behind by globalization. Better mechanisms to cushion the blows to the losers of globalization are indeed required. In the United States, Trade Adjustment Assistance has been insufficiently funded and is ineffective. More needs to be done to replace the wages of workers whose jobs have been lost due to trade and to provide them with skills training for re-employment. This reconsideration of assistance for those who are hurt by free trade could provide a foundation for the future. Once the current wave of anti-trade sentiment subsides, new trade agreements can be struck that don’t leave so many citizens feeling left behind. Instead of worrying about how Trump might blow up the underpinnings of the global trading system, this is an opportunity to rethink what a new trade framework might look like.This piece was published in collaboration with Real Clear World.To comment on this article, please contact Chatham House Feedback Full Article
han The oversecuritization of global health: changing the terms of debate By feedproxy.google.com Published On :: Wed, 04 Sep 2019 14:01:47 +0000 4 September 2019 , Volume 95, Number 5 Read online Clare Wenham Linking health and security has become a mainstream approach to health policy issues over the past two decades. So much so that the discourse of global health security has become close to synonymous with global health, their meanings being considered almost interchangeable. While the debates surrounding the health–security nexus vary in levels of analysis from the global to the national to the individual, this article argues that the consideration of health as a security issue, and the ensuing path dependencies, have shifted in three ways. First, the concept has been broadened to the extent that a multitude of health issues (and others) are constructed as threats to health security. Second, securitizing health has moved beyond a rhetorical device to include the direct involvement of the security sector. Third, the performance of health security has become a security threat in itself. These considerations, the article argues, alter the remit of the global health security narrative; the global health community needs to recognize this shift and adapt its use of security-focused policies accordingly. Full Article
han SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes. Full Article
han ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling. Full Article
han Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity. Full Article
han DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension. Full Article
han The Escherichia coli cellulose synthase subunit G (BcsG) is a Zn2+-dependent phosphoethanolamine transferase [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes. Full Article
han Roles of active-site residues in catalysis, substrate binding, cooperativity, and the reaction mechanism of the quinoprotein glycine oxidase [Enzymology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The quinoprotein glycine oxidase from the marine bacterium Pseudoalteromonas luteoviolacea (PlGoxA) uses a protein-derived cysteine tryptophylquinone (CTQ) cofactor to catalyze conversion of glycine to glyoxylate and ammonia. This homotetrameric enzyme exhibits strong cooperativity toward glycine binding. It is a good model for studying enzyme kinetics and cooperativity, specifically for being able to separate those aspects of protein function through directed mutagenesis. Variant proteins were generated with mutations in four active-site residues, Phe-316, His-583, Tyr-766, and His-767. Structures for glycine-soaked crystals were obtained for each. Different mutations had differential effects on kcat and K0.5 for catalysis, K0.5 for substrate binding, and the Hill coefficients describing the steady-state kinetics or substrate binding. Phe-316 and Tyr-766 variants retained catalytic activity, albeit with altered kinetics and cooperativity. Substitutions of His-583 revealed that it is essential for glycine binding, and the structure of H583C PlGoxA had no active-site glycine present in glycine-soaked crystals. The structure of H767A PlGoxA revealed a previously undetected reaction intermediate, a carbinolamine product-reduced CTQ adduct, and exhibited only negligible activity. The results of these experiments, as well as those with the native enzyme and previous variants, enabled construction of a detailed mechanism for the reductive half-reaction of glycine oxidation. This proposed mechanism includes three discrete reaction intermediates that are covalently bound to CTQ during the reaction, two of which have now been structurally characterized by X-ray crystallography. Full Article
han COP26 Diplomatic Briefing Series: Climate Change and National Security By feedproxy.google.com Published On :: Tue, 21 Apr 2020 13:25:01 +0000 Research Event 25 March 2020 - 9:00am to 10:30am Event participants Lieutenant General Richard Nugee, Departmental Lead for Climate Change and Sustainability in the UK Ministry of DefenceRear Admiral Neil Morisetti, Vice Dean (Public Policy) Engineering Sciences at the University College London and Associate Fellow at Chatham HouseDr. Patricia Lewis, Research Director for Conflict, Science and Technology, and Director of the International Security Programme at Chatham HouseProfessor Yacob Mulugetta, Professor of Energy and Development Policy at the University College LondonChair: Glada Lahn, Senior Research Fellow, Chatham House Extreme weather, rising sea levels and a melting Arctic - the effects of climate change are posing an increasingly large threat to national security worldwide. Although the issue has gained traction within the international community in recent years, including within the UN Security Council, it is urgent that governments act more decisively to mitigate and respond to the threat, not least given that climate change is happening faster and in a more powerful way than originally anticipated. The third event in the Chatham House COP26 Diplomatic Briefing Series – 'Climate Change and National Security' - will analyze how climate change acts as a threat multiplier, fuelling instability and endangering economic, social and political systems across the globe. The briefing will also provide recommendations of what governments and other stakeholders should do to develop effective responses. Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
han Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
han Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth By feedproxy.google.com Published On :: 1980-07-01 MS BrownJul 1, 1980; 21:505-517Reviews Full Article
han 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
han Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol By feedproxy.google.com Published On :: 1964-10-01 William R. MorrisonOct 1, 1964; 5:600-608Articles Full Article
han 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
han Arturo Sarukhan By feedproxy.google.com Published On :: Wed, 12 Feb 2020 11:57:22 +0000 Associate Fellow, US and the Americas Programme (based in the US) Biography Ambassador Arturo Sarukhan is the founder and president of Sarukhan + Associates. Now a consultant and public speaker, he was a career diplomat in the Mexican foreign service for 22 years, receiving the rank of career ambassador in 2006.From 2007 to 2013, he served as Mexico's ambassador to the US. Previously, he served, among other positions, as consul general in New York, chief of policy planning and deputy director general for inter-American affairs.In 2006 he requested a leave of absence from the foreign service to become foreign policy advisor and international spokesperson for the Calderon presidential campaign. He subsequently led the foreign policy transition team.A digital diplomacy pioneer, he became the first ambassador accredited in Washington to use Twitter as a public diplomacy tool. He publishes regularly and appears frequently on US and international media.He sits on several non-profit and corporate boards, and has several academic and think-tank affiliations in the US.He holds a BA in international relations from El Colegio de Mexico and an MA in American Foreign Policy from SAIS-Johns Hopkins. Areas of expertise US foreign and domestic policyMexican foreign and domestic policy; US-Mexico and North American relationsDigital Diplomacy/Public DiplomacyInter-American affairsNew global challenges: migration; transnational organized crime; disinformation and weaponization of social media Past experience 2014 - presentPresident and founder, Sarukhan + Associates, LLC 2007-13Mexican Ambassador to the US 2006Coordinator, Presidential Foreign Policy Transition Team2006Foreign Policy Advisor and international spokesperson, Calderon presidential campaign2003-06Consul General, New York City2000-03Chief for Policy Planning, Mexican Foreign Ministry1989-2000Senior Advisor to the Foreign Minister1995-98Head of the Counternarcotics section, Mexican Embassy USA1993-95Chief of Staff to the Ambassador, Mexican Embassy USA1992-93Deputy Director General for Inter-American Affairs1992Admission to the Foreign Service, Instituto Matias Romero1989-91MA, School of Advanced International Studies, Johns Hopkins University1987-89Executive Assistant, Ford Foundation Bilateral Commission on the Future of US-Mexico Relations1984-88BA, International Relations, El Colegio de México1982-84BA studies, History, Universidad Nacional Autónoma de México +(202) 4132005 Email @Arturo_Sarukhan LinkedIn Full Article
han Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
han Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. Full Article
han ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling. Full Article
han S-Palmitoylation of the sodium channel Nav1.6 regulates its activity and neuronal excitability [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions. Full Article
han 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
han Mohamed El Dahshan By feedproxy.google.com Published On :: Sat, 02 May 2020 09:17:19 +0000 Associate Fellow, Middle East and North Africa Programme Biography Mohamed El Dahshan is an associate fellow with the Chatham House Middle East and North Africa Programme, where he focuses on economic development, regional cooperation, and fragile states.He is also managing director of OXCON, a public sector consulting firm, advising governments and international organisations on Africa and the Middle East. Prior to this, he was senior cooperation advisor at the African Development Bank, and senior research fellow at Harvard University.He is an award-winning writer and columnist, and the co-author of Diaries of the Revolution (2012), a memoir of the Egyptian revolution, as well as several book chapters, academic papers, and more than 100 media articles for outlets such as Foreign Policy the New York Times, and the Guardian, among others.He was honoured as an Archbishop Desmond Tutu fellow, a fellow of the United Nations Alliance of Civilisations, and is listed among the 100 Africa Future Economic Leaders by the Institut Choiseul.Mohamed holds Master degrees from Oxford, Harvard and Sciences-Po Paris. Areas of expertise Economic developmentEgyptSMEs and private sector developmentFragile states Past experience 2017 - presentManaging director, OXCON Frontier Markets & Fragile States Consulting2014-15Regional economist / Senior cooperation officer, African Development Bank2012-13Middle East manager, Senior research fellow, Center for International Development, Harvard University Email @eldahshan LinkedIn Google Scholar Full Article
han How is Saudi Arabian Society Changing? By feedproxy.google.com Published On :: Fri, 09 Mar 2018 00:00:00 +0000 Full Article
han 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
han Argentina: Political Change and the G20 Presidency By feedproxy.google.com Published On :: Tue, 05 Jun 2018 00:00:00 +0100 Full Article
han The United States in Afghanistan and Pakistan By feedproxy.google.com Published On :: Mon, 09 Jul 2018 00:00:00 +0100 Full Article
han The Kremlin Letters: Wartime Exchanges of the Big Three By feedproxy.google.com Published On :: Wed, 07 Nov 2018 00:00:00 +0000 Full Article
han Frosty Neighbours? Unpacking Narratives of Afghanistan-Pakistan Relations By feedproxy.google.com Published On :: Mon, 03 Dec 2018 00:00:00 +0000 Full Article
han Afghanistan in 2018: A Survey of the Afghan People By feedproxy.google.com Published On :: Thu, 07 Feb 2019 00:00:00 +0000 Full Article
han Radical Change? New Political Paradigms in Brazil and Mexico By feedproxy.google.com Published On :: Tue, 12 Feb 2019 00:00:00 +0000 Full Article
han Chatham House Primer: Making Change By feedproxy.google.com Published On :: Thu, 04 Apr 2019 00:00:00 +0100 Full Article
han 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
han Iran, Islam and Democracy: The Politics of Managing Change 20 Years On By feedproxy.google.com Published On :: Tue, 02 Jul 2019 00:00:00 +0100 Full Article
han The Climate Briefing: Episode 3 - Climate Change and National Security By feedproxy.google.com Published On :: Wed, 29 Apr 2020 00:00:00 +0100 Full Article
han X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
han Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc. Full Article
