sin '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
sin MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out By 100percentfedup.com Published On :: Wed, 06 May 2020 01:49:01 +0000 The following article, MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out, was first published on 100PercentFedUp.com. Last week, we reported about how Shelley Luther, owner of the Salon Á La Mode in North Dallas, Texas, who opened up her business in defiance of lockdown orders in the city. The salon owner said that she was ignoring a citation and a cease and desist order from the city to shut down. This one […] Continue reading: MI Barber Shop Owner Defies Gov. Whitmer Shutdown Order…Opens Business…Police Officer Walks In…Says, “I love you!”…Walks Out ... Full Article Featured Politics
sin NY Shame: Workers Who Tested Positive For COVID-19 Were Allowed To Remain On The Job At Nursing Homes, As Death Toll For Nursing Home Patients Exceeds 3,000 By 100percentfedup.com Published On :: Wed, 06 May 2020 21:44:54 +0000 The following article, NY Shame: Workers Who Tested Positive For COVID-19 Were Allowed To Remain On The Job At Nursing Homes, As Death Toll For Nursing Home Patients Exceeds 3,000, was first published on 100PercentFedUp.com. The coronavirus crisis at New York’s nursing homes is even worse than previously thought. Monday night, the state Department of Health issued new data, adding more than 1,600 people who were presumed to have died of the virus in nursing homes, but did not have a confirmed diagnosis, to the official toll. As of May […] Continue reading: NY Shame: Workers Who Tested Positive For COVID-19 Were Allowed To Remain On The Job At Nursing Homes, As Death Toll For Nursing Home Patients Exceeds 3,000 ... Full Article Featured Politics
sin Texas Gov Abbott Frees Salon Owner Shelley Luther: “Criminals shouldn’t be released to prevent COVID-19 just to put business owners in their place” By 100percentfedup.com Published On :: Thu, 07 May 2020 15:50:22 +0000 The following article, Texas Gov Abbott Frees Salon Owner Shelley Luther: “Criminals shouldn’t be released to prevent COVID-19 just to put business owners in their place”, was first published on 100PercentFedUp.com. Texas Governor Greg Abbott just changed the coronavirus order to free Salon A La Mode owner Shelley Luther from jail. Abbott tweeted out a comment about the poor treatment of the business owner: Throwing Texans in jail whose biz’s shut down through no fault of their own is wrong. I am eliminating jail for violating […] Continue reading: Texas Gov Abbott Frees Salon Owner Shelley Luther: “Criminals shouldn’t be released to prevent COVID-19 just to put business owners in their place” ... Full Article Breaking Featured Government Politics
sin Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China” By 100percentfedup.com Published On :: Thu, 07 May 2020 16:55:44 +0000 The following article, Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China”, was first published on 100PercentFedUp.com. During a recent interview on CNN, Obama-Biden ambassador to China (2014-2017) Max Baucus compared standing up to China on the coronavirus to “Hitler in the ’30s.” Baucus has proven himself to be sympathetic to China in recent interviews, where he puts down America and praises the Chinese. The MSNBC video via The Washington Free Beacon […] Continue reading: Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China” ... Full Article Breaking Featured Government Politics
sin Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity. Full Article
sin 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
sin Five Lessons From the New Arab Uprisings By feedproxy.google.com Published On :: Tue, 12 Nov 2019 09:11:56 +0000 12 November 2019 Dr Georges Fahmi Associate Fellow, Middle East and North Africa Programme @GeorgesFahmi Georges Fahmi examines how protesters across the region have adapted their tactics after the experiences of the Arab Spring. 2019-11-12-Lebanon.jpg The second wave of Arab uprisings that started in Sudan in December last year and extended to Algeria, Lebanon and Iraq this year have built on past experiences of political transitions during the Arab Spring, both its mistakes and achievements. Protesters from this new wave have already learned five lessons from previous transitions.The first lesson is that toppling the head of a regime does not mean that the political regime has fallen. In Tahrir Square on 11 February 2011, Egyptian protesters celebrated the decision of Hosni Mubarak to step down and left the square, thinking his resignation was enough to allow a democratic transition to take place. In contrast, in Sudan and Algeria, protesters continued to demonstrate after the resignation of Abdelaziz Bouteflika and the military-led ousting of Omar al-Bashir.Protesters understood the lesson that the regime is found not only in the head of the state, but rather in the rules that govern the political sphere. By extension, political change requires changing the rules, not just the names of those in charge of implementing them.The second lesson is that resorting to violence is the fastest way to end any hope for democratic change. Protesters who decided to take up arms offered their regimes the chance to reframe the political uprisings as civil war, as was the case in Syria. Even when armed groups manage to bring down the regime, their presence endangers the transitional phase afterwards, as is the case in Libya.Although protesters in Sudan and Iraq have been faced with government violence and repression, they have insisted on their non-violent approach. In Sudan, the protesters responded to the massacre outside of the General Command of the Armed Forces on 3 June by organizing a mass demonstration on 30 June, which put pressure on the military to resume talks with the revolutionary forces. The third lesson is that once the old regime has fallen, the transition period must be a collective decision-making process in which the opposition has, at least, veto power. The example of Tunisia after 2011 is a case in point. The Higher Authority for Realization of the Goals of the Revolution, Political Reform and Democratic Transition, which formulated the planned course of the transition, included representatives from across the political spectrum and civil society.Although the military forces in Algeria and Sudan will not cease to play a political role any time soon, this does not have to mean exerting complete control over the transitional period. Sudan could offer a positive example in this regard, if it succeeds in implementing a power-sharing deal according to which a joint civilian-military sovereign council will govern Sudan during the transitional period.The fourth lesson is that political transitions should achieve agreement on the rules of the game before proceeding to elections. In Egypt after 2011, rushed elections served to divide the political opposition and dramatically increase polarization in society. In this second wave, protesters have perceived elections as a trap which enable old regimes to reproduce themselves with new names.In both Algeria and Sudan, protesters have resisted attempts by the military to hold elections as soon as possible. In Sudan, the agreement between the revolutionary forces and the military council postponed the elections until after the end of a three-year transitional period of technocratic rule. In Algeria, protesters are taking to the streets every Friday to demonstrate against the authorities’ decision to hold presidential elections in December.The fifth and final lesson is that the call for change in the region goes beyond electoral democracy and extends to deep socioeconomic reforms. Iraq and Lebanon show this clearly: relatively free and fair elections have already been held but have served only to reinforce corrupt sectarian regimes.According to the fifth wave of the Arab Barometer, the economic situation and corruption are perceived as the main challenge for Algerians (62.2%), Sudanese (67.8%), Lebanese (57.9%), and Iraqis (50.2%), while democracy is perceived as the main challenge for only 2.3%, 3.9%, 5% and 1.4% respectively. The experience of the Arab Spring has shown people that democratic measures are only a means to an end.Unlike in 2011, when the Arab Spring revolts enjoyed broad international support, this second wave is taking place in a hostile environment, with stronger Russian and Iranian presences in the region and an indifferent international climate. But where protesters have the advantage is in experience, and across the region they are clearly adapting their tactics to lessons learned from the early part of the decade. Full Article
sin How the Soleimani Assassination Will Reverberate Throughout the Middle East By feedproxy.google.com Published On :: Mon, 06 Jan 2020 12:59:23 +0000 6 January 2020 Dr Sanam Vakil Deputy Director and Senior Research Fellow, Middle East and North Africa Programme @SanamVakil Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Dr Lina Khatib Director, Middle East and North Africa Programme @LinaKhatibUK Regional experts examine how Iran benefits from the fallout of the killing, the implications for politics in Iraq and how Tehran might respond with its proxies in the region. 2020-01-06-Soleimani.jpg Protesters hold up an image of Qassem Soleimani during a demonstration in Tehran on 3 January. Photo: Getty Images. An unexpected bounty for IranSanam VakilThe assassination of Qassem Soleimani has been an unexpected bounty for the Islamic Republic at a time when Iran was balancing multiple economic, domestic and regional pressures stemming from the Trump administration’s maximum pressure campaign.Coming on the heels of anti-Iranian demonstrations in Iraq and Lebanon, and following Iran’s own November 2019 protests that resulted in a brutal government crackdown against its own people, the Soleimani killing has helped the Iranian government shift the narrative away from its perceived regional and domestic weaknesses to one of strength. The massive funeral scenes in multiple Iranian cities displaying unending waves of mourners chanting against the United States has provided the Islamic Republic with a unique opportunity to showcase its mobilizing potential. This potential is not limited to Iran but also extends to Iraq and Lebanon, where Tehran’s transnational summoning power has also been visible. The Iraqi parliamentary vote to end the American military presence is one early negative consequence. While the region awaits Iran’s response, further anti-American rallying cries will continue to reverberate. Domestically, Soleimani’s death and President Donald Trump’s continued provocations on Twitter, including threats to attack 52 Iranian cultural sites, are being used as a nationalist rallying cry. This sentiment should not be seen solely as Islamic or ideological, but rather an opportunity for the state to pivot to an Iranian-based nationalism that is more inclusive and empowering for much of the country’s disgruntled youth.Iran’s notoriously divided political factions have also unified in the face of this crisis. With parliamentary elections looming in February and turnout previously expected to be low, the political establishment is likely to use this crisis to mobilize voters in favour of conservative candidates. How Tehran chooses to respond to Qassem Soleimani’s death will very much determine its ability to continue to control the narrative and manage its swell of domestic and regional support. For these benefits to continue to manifest, it is important for Tehran to balance the mix of public sympathy and international anxiety and not overplay its hand in its quest for revenge.A reset for Iraqi politicsRenad MansourThe US strike which killed Qassem Soleimani and Abu Mehdi al-Muhandis has grave implications for Iraq. The act jeopardizes Iraq’s recently stabilized security situation, and threatens to reshape the country’s political environment, moving backwards to the days of anti-Americanism and sect-based mobilization. If Baghdad loses relations with the US and other diplomatic representations, it risks turning into a pariah state. Over the past few years, and notably since October 2019, young Iraqis have taken to the streets demanding reform and the downfall of the political establishment, and its main external backer Iran. The political establishment, including political parties and militias close to Tehran, failed to appease or suppress these protests. Now, these political elites are using the deaths of Muhandis and Soleimani to (re)gain popularity from their own population, by drawing on the old tool of anti-Americanism. Following the attacks, Shia populist cleric Muqtada al-Sadr – who until recently had called for an end to Iranian and pro-Iranian militia influence in Iraq – has called to revamp the Mehdi Army that he led until 2008 and is calling for ‘Islamic resistance’ to the US. In seeking to regain control of his former movement, he is coming closer to former Shia foes.For years, pro-Iranian groups attempted to push the US out of Iraq. Their calls often fell on deaf ears, as public opinion in Iraq did not consider the US as a threat and some even supported the US and international effort against ISIS. Following the attacks, however, anti-American voices have gained more ammunition.A complete American withdrawal would not only have direct security implications but force other countries and organizations, from European states to NATO, to reconsider their positions and role.Limited options for ‘revenge’ in the LevantLina KhatibIran’s use of Lebanon and Syria as spaces for revenge against the US is unlikely.On Sunday, Hezbollah leader Hassan Nasrallah vowed revenge for Soleimani’s death by singling out American soldiers as a target. However, Hezbollah’s options are limited. Lebanon is in the middle of wide-ranging protests against the country’s ruling political class, of which Nasrallah is a key figure.Unlike in 2006, when Hezbollah’s military actions against Israel rallied the public around it, today there is no public appetite for dragging Lebanon into a war. Were Hezbollah to instigate one, it would incur public anger, if only for the economic repercussions that would exacerbate an already severe financial crisis in Lebanon. Lebanon also does not have any US military bases that could be a target for Hezbollah.In theory, Hezbollah or other Iranian-backed groups could attack American bases in Syria. But these bases are staffed by multinational forces from the international anti-ISIS coalition. Attacking them would therefore put Iran in confrontation with other countries besides the US, which is not in Iran’s interest.Attacking US soldiers in northeast Syria would also go against Kurdish interests because it would weaken the anti-ISIS coalition front of which Kurdish forces are part. It would, furthermore, anger Arab tribes in the area, opening up possibilities for ISIS to take advantage of public dissent to stage a comeback. Iran would then find itself fighting on several fronts at once, which it does not have the capacity to handle. More likely, Iran’s allies and proxies in the Levant are going to engage in strong rhetoric without taking hasty actions. When a key Hezbollah leader, Imad Mughniyeh, was assassinated in Damascus on 2008, there were strong words and public vows to seek revenge for his killing, but ultimately there was no response. Full Article
sin After Latest Turn, Is Muqtada al-Sadr Losing Influence in Iraq? By feedproxy.google.com Published On :: Wed, 12 Feb 2020 14:23:04 +0000 12 February 2020 Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Ben Robin-D'Cruz Researcher on Iraqi Politics, University of Edinburgh The populist cleric has repositioned himself in Iraqi politics multiple times, but his recent shift against youth-led protestors may signal his decline as an autonomous political force. 2020-02-12-Sadr.jpg Muqtada al-Sadr in Najaf in October. Photo: Getty Images. Following the US strike on Qassem Solaimani and Abu Mehdi al-Muhandis, populist cleric Muqtada al-Sadr has violently cracked down on youth-led protests in Iraq.His paramilitaries and ‘blue hats’ – supposedly created to protect protestors from state and allied parastatal security forces – sought to end the months-long demonstrations by attacking the places where protesters have camped since October. In Baghdad’s Tahrir Square, they successfully captured the famous Turkish restaurant which had become a symbol of Iraq’s ‘October revolution’. Once the champion of Iraq’s protest movement, Sadr has seemingly changed course and now leads the counter-protests. This reversal has mystified many, from Iraqis who saw Sadr as an ally in their struggle for reform against an impenetrable elite to foreign diplomats who hoped Sadr could help pushback against Iranian influence in Iraq. Yet this is not the first time that Sadr has drastically redefined his position. Since 2003, he has gone from Shia sectarian militia leader to pro-democracy reformist and Iraqi nationalist.And in the past few months, he has given mixed signals, both supporting and criticising the protesters. The most recent incidents of Sadrist violence targeting demonstrators provoked a societal backlash, prompting Sadr to change tack once more and announce that he would disband the blue hats and investigate their crimes against protesters.Sadr and the paramilitariesSadr’s latest change of course may seem to flow directly from the US assassination of Qassem Soleimani and Abu Mahdi al-Muhandis and the ensuing vacuum in the Shia paramilitary sphere. Prior to this move, the Sadrists were on the defensive, outflanked and outgunned by the growing coercive and political power of a constellation of Shia armed groups coalescing under Muhandis’s de facto leadership. Many of these groups competed for Sadr’s base, including Qais al-Khazali’s Asa’ib ahl al-Haq and Akram al-Kaabi’s Harakat Hezbollah al-Nujaba. With Muhandis out of the picture, Sadr could reclaim the space by pushing his own right hand, Kadhem al-Issawi (Abu Do’a), to be the new centre of the paramilitary field and forcing competitors, including Khaza’li and Kaabi, to rally around his leadership.Iran, in the short term, appears to be going along with this solution to bring more coherence to its allied forces in Iraq as it seeks to counter what it regards as US aggression. Iran also hopes that bringing Sadr back in will help neutralize the protest movement which threatens its stake in Iraqi politics. The most visible sign of this Iran-brokered rapprochement was the 13 January meeting in Qom attended by Sadr, Issawi and several senior militia commanders including Laith al-Khazali (Qais al-Khazali’s brother). Following the Qom meeting, a pattern of tit-for-tat violence and assassinations between the Sadrists’ Saraya al-Salam and Asa’ib Ahl al-Haq – ongoing since the start of the October protests in Iraq – ceased.A fragmented movement?However, while the US strikes certainly changed Sadr’s political calculations, there are more persistent fundamentals at work that help explain his change of course. The first of these relates to long-standing fragmentation within the movement. This exists not only within Sadrist paramilitaries, but within the movement’s clerical networks, and also applies to the ties that bind the Sadrist leadership to its popular base. This fragmentation makes it difficult for Sadr to impose a coherent politics on his followers from the top down.There are signs that Sadr’s recent shift in position has exacerbated this fragmentation. His attempt to reposition the movement’s base within the ‘resistance axis’ that supports the Shia militias in Iraq has only been partially successful. On 24 January, responding to the US assassinations, Sadr called for a million-man march focused on expelling US forces from Iraq. However, turnout was poor, especially given the huge logistical support for the march, and it lasted only a few hours.Equally revealing, when Sadr called on his supporters to vacate the squares, many refused. One Sadrist protester in Baghdad’s Tahrir Square told the authors: ‘We’ve been camping with our brothers and sisters for four months. Why should we leave them to die?’Meanwhile, fissures have also opened up within the Sadrists’ clerical elite. One senior Sadrist cleric, for example, is openly defying Sadr’s authority and siding with the revolutionaries in Nasiriyah. Sadr’s attempt to dominate the paramilitary sphere is also unlikely to prove any more successful than his many previous failed attempts since 2003. He is neither trusted nor respected by the leaders of other groups. The Iran-brokered rapprochement is already showing signs of weakness. Two recent assassinations of Saraya al-Salam leaders in Basra and Maysan indicate a potential renewal of power struggles between the Sadrist militia and Asa’ib Ahl al-Haq. Sadr is not a revolutionarySadr has never been a revolutionary, but someone who seeks to leverage a role as both ‘spoiler’ and ‘stabilizer’ to maximise his political leverage. This strategy is ultimately oriented towards sustaining Iraq’s extant political system, not its overthrow. Forced to choose between the roles of revolutionary or maintainer of the status quo, he has opted for the latter. The protests that erupted in 2019 were not the same movement that Sadr led from 2015. The 2015 protests were an elite-driven phenomenon, integrated into the political field and carefully calibrated to exert pressure on the elite towards gradual reform. By contrast, the 2019 demonstrations spring from a youth-led, bottom-up mobilization that rejects politicization and seeks a more radical form of change. Chatham House surveys in a forthcoming paper reveal that the protesters are younger that those who protested in 2015-16. Fewer have permanent employment. Instead of demanding better services or jobs, they are focusing wholesale transformation of the post-2003 political system.A Sadrist official told the authors that their movement initially joined the protests in October 2019 expecting a similar reform-orientation to the protests which Sadr had previously led. However, according to him, the protesters failed to come forward with reasonable demands or alternative names for prime minister. He believed the protests would fade, and many would regret the ‘wasted time and blood’. Sadr’s relations with IranA final long-term factor at play is Sadr’s receding autonomy from Iran. Ever since his movement’s electoral victory in May 2018, Sadr came under enormous pressure to reconcile with the political wing of the Iranian-allied parastatal armed groups in the formation of a new government acceptable to Iran.Over the last year, Sadr has moved even closer to Iran, spending more time in Qom. Iran has offered Sadr security from his paramilitary rivals (such as Asa’ib ahl al-Haq), convincing Sadr that he is safer in Iran than Iraq. Moreover, Sadr is undertaking religious training in Qom, and may see this as a chance to enhance his standing in the Shia religious field as many look towards a future beyond the elderly Najaf-based marja Ali al-Sistani.By keeping Sadr in Qom, Iran appears to be trying to isolate him from what they regard as negative influences. As tensions between the Sadrists and other protest groups intensified, efforts were made by some protest leaders and allied political groups to reach Sadr in Qom and try to persuade him to change course or restrain the worst abuses of his forces. However, this delegation was unable to make contact with Sadr. Those involved told the authors they have resorted to communicating with local Sadrist leaders in Najaf, Babil, Basra and Baghdad. Crossing a lineThis is a transformative moment for the Sadrists. Sadr is now defying the popular sentiments driving protests across central and southern Iraq. The sense of betrayal among former allies and friends of the Sadrists is palpable. One senior activist involved in cooperation with the Sadrists wrote that, no matter what moves Sadr makes next, the cleric has ‘terminated all partnership with the protesters,’ and ‘shattered the framework for cooperation’. A line has thus been crossed that Sadr cannot reverse; he will not be able to recover what he has now lost. Iran, also, does not see Sadr as a dependable ally, and will look to isolate and side-line the cleric when the opportunity arises. Thus, in seeking to exploit a crisis for short-term gain, Sadr may well have sealed his fate – in the long term – as a declining force in Iraqi politics. Full Article
sin Expanding Sino–Maghreb Relations: Morocco and Tunisia By feedproxy.google.com Published On :: Wed, 26 Feb 2020 12:49:01 +0000 26 February 2020 Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia. Read online Download PDF Yahia H. Zoubir Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center 2020-02-26-Xi-Jinping-King-Mohammed.jpg Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images. SummaryChina’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa. Department/project Middle East and North Africa Programme, Economic Transformation in North Africa Full Article
sin POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Wed, 04 Mar 2020 14:15:01 +0000 Invitation Only Research Event 18 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham HouseEmaddedin Badi, Non-Resident Scholar, Middle East InstituteTim Eaton, Senior Research Fellow, MENA Programme Chatham HouseValerie Stocker, Independent Researcher Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country, armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Countering Conflict Economies in MENA, Libya’s Conflict Economy Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
sin The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Mon, 16 Mar 2020 17:25:16 +0000 17 March 2020 This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics. Read online Download PDF Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn Abdul Rahman Alageli Associate Fellow, Middle East and North Africa Programme @abdulrahmanlyf Emadeddin Badi Policy Leader Fellow, School of Transnational Governance, European University Institute Mohamed Eljarh Co-founder and CEO, Libya Outlook Valerie Stocker Researcher Amru_24-2_13.jpg Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien SummaryLibya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive. Department/project Middle East and North Africa Programme, Chaos States, Countering Conflict Economies in MENA, Libya’s Conflict Economy Full Article
sin COVID 19: Assessing Vulnerabilities and Impacts on Iraq By feedproxy.google.com Published On :: Tue, 07 Apr 2020 14:33:01 +0000 7 April 2020 Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Dr Mac Skelton Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics Dr Abdulameer Mohsin Hussein President of the Iraq Medical Association Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic. 2020-04-07-Iraq-COVID-spray Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images. Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.Iraq’s myriad vulnerabilitiesCertain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.This analysis was produced as part of the Iraq Initiative. Full Article
sin Webinar: Assessing the Twists and Turns in the US-Iran Stalemate By feedproxy.google.com Published On :: Thu, 23 Apr 2020 10:35:01 +0000 Research Event 28 April 2020 - 2:00pm to 3:30pm Event participants Esfandyar Batmanghelidj, Founder and Publisher, Bourse & BazaarNasser Hadian, Professor of Political Sciences, Faculty of Law and Political Sciences, University of TehranAzadeh Zamirirad, Deputy Head, Middle East and Africa Division, SWP BerlinAriane Tabatabai, Middle East Fellow, Alliance for Securing Democracy, US German Marshall Fund; Adjunct Senior Research Scholar, SIPAModerator: Sanam Vakil, Deputy Head and Senior Research Fellow, Middle East and North Africa Programme, Chatham House The webinar will be livestreamed on the MENA Programme Facebook page.Since the start of 2020, Iran has been beset with multiple challenges including the spread of COVID-19, economic pressure from US sanctions, parliamentary elections in February, the killing of Qassem Soleimani and an increase in tensions in Iraq. The Trump administration interprets these domestic and regional challenges faces by Iran as evidence that its maximum pressure campaign is proving to be effective.In this webinar, speakers will examine the economic and political impact of the Trump administration's policy towards Iran. Panelists will consider how these events are impacting internal dynamics in Iran and examine the economic impact of sanctions. They will also evaluate European diplomatic efforts to preserve the Iran nuclear agreement, and consider the future trajectory of US Iran policy and the potential for escalation in the region. This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record. Department/project Middle East and North Africa Programme, Iran Forum 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
sin COVID-19 Crisis – Business as Usual for Gaza? By feedproxy.google.com Published On :: Wed, 06 May 2020 14:48:14 +0000 6 May 2020 Mohammed Abdalfatah Asfari Foundation Academy Fellow @mhalabi258 LinkedIn The COVID-19 pandemic has brought unprecedented challenges, economic collapse and strict lockdowns in many parts of the world. For the people of Gaza, this reality is nothing new. 2020-05-06-covid-19-gaza.jpg Palestinians light fireworks above the rubble during the Muslim holy month of Ramadan amid concerns about the spread of the coronavirus disease (COVID-19), in Gaza City , 30 April 2020. Photo by Majdi Fathi/NurPhoto via Getty Images. In August 2012, when the UN released its report Gaza in 2020: A liveable place?, they could not have imagined what the world would look like in 2020: cities under lockdown, restrictions on movement, border closures, widespread unemployment, economic collapse, fear and anxiety and, above all, uncertainty about what the future holds.For Gaza’s population of 2 million people this reality is nothing new. The conditions that the rest of the world are currently experiencing as a result of the COVID-19 pandemic is similar to the tight blockade Gaza has been living under ever since Hamas took over in 2007. Israel has imposed severe restrictions on the movement of people and goods, youth unemployment has reached 60 per cent, and over 80 per cent of Gaza’s population are now dependent on international aid.The people of Gaza are having to face the COVID-19 crisis already at a disadvantage, with poor infrastructure, limited resources and a shortage of the most basic services, such as water and power supply. It also has a fragile health system, with hospitals lacking essential medical supplies and equipment, as well as the capacity to deal with the outbreak as there are only 84 ICU beds and ventilators available. Meanwhile, intra-Palestinian divisions have persisted and were evident in the initial reaction to the pandemic. When President Mahmoud Abbas announced a state of emergency, it took two days for the Hamas-led government in Gaza to follow suit and shut down schools and universities. They later made a separate emergency appeal to address the crisis and prepare for a COVID-19 response in Gaza. This lack of coordination is typical of the way the Palestinian Authority and Hamas approach crisis situations.After the initial uncoordinated response, Hamas, as the de-facto ruler of Gaza, has asserted its ability to control Gaza’s borders by putting in place quarantine measures for everyone who enters the strip, whether through the Erez checkpoint with Israel or the Rafah border with Egypt. They have also assigned 21 hospitals, hotels, and schools as compulsory quarantine centres for all arrivals from abroad, who have to stay in quarantine for 21 days. In comparison, there are 20 quarantine centres in the West Bank. These strict measures have prevented the spread of the virus in the community and confined it to the quarantine centres, with only 20 confirmed cases of COVID-19 as of 6 May. Gaza’s de-facto authorities have also been able to monitor markets and prices to ensure the availability of essential goods.Faced with a major crisis, Al-Qassam Brigades – the armed wing of Hamas – have tried to play the role of a national army by participating in efforts to fight the pandemic. They have relatively good logistical capacity and have contributed to the construction of two quarantine facilities with a total capacity of 1,000 units to prepare for more arrivals into Gaza. At the local level, municipalities have been disinfecting public spaces and facilities in addition to disseminating information about the virus and related preventative and protective measures. Other precautionary measures put in place include closing the weekly open markets, and restricting social gatherings like weddings and funerals.Despite COVID-19, it’s business as usual when it comes to international dealings with Gaza. The key parties in the conflict – Israel, Hamas and the Palestinian Authority – along with the main external actors – Egypt, the United Nations and Qatar – have continued to stick to their policies aimed at keeping the security situation under control and preventing further escalation. Although Israel has allowed entry of pharmaceutical supplies and medical equipment into Gaza during the pandemic, it has kept its restrictions on the movement of goods and people in place, while keeping a close eye on the development of the COVID-19 outbreak in Gaza – a major outbreak here would be a nightmare scenario for Israel.Meanwhile, Qatar has continued to address the humanitarian and economic needs of Gaza in an attempt to ease the pressure and prevent further escalation. It has pledged $150 million over the next six months to help families in Gaza from poorer backgrounds. Gaza has also been discussed by the Middle East Quartet, as Nickolay Mladenov, the UN special coordinator for the Middle East Peace Process, expressed his concern about the risk of a disease outbreak in Gaza during a call with the members of the Quartet.Amid the pandemic, threats are still being exchanged between Israel and Hamas. The Israeli defence minister, Naftali Bennett, requested that in return for providing humanitarian aid to Gaza, Hamas agrees to return the remains of two Israeli soldiers killed in the 2014 war. While openly rejecting Bennett's statement, the leader of Hamas in Gaza, Yahya Sinwar, has offered to move forward with a prisoner swap deal if Israel agrees to release elderly prisoners and detainees in addition to detained women and children. Though dealing with its own COVID-19 outbreak, Egypt has started to mediate between the two parties in an attempt to stabilize the situation and reach a prisoner swap deal.In the wake of this pandemic, lessons should be learned and policies should be examined, by all parties. Firstly, Israel should re-evaluate its security measures towards Gaza by easing restrictions on movement and trade which would have a positive impact on living conditions for Gaza’s population. The current measures have proven to be unsustainable and have contributed to the endless cycle of violence. Secondly, the intra-Palestinian division should end, to save Palestinians from contradictory policies and insufficient capacity on both sides. In fact, all previous attempts have failed to end this self-destructive division and this is due to the absence of political will on both sides. Elections seem to be the only viable path towards unity. Finally, efforts by the international community should go beyond stabilizing the security situation and ongoing crisis inside Gaza, where disruption of normal life is the norm.While the world has reacted to this pandemic with a whole host of new policies and emergency measures, it has remained business as usual when dealing with Gaza. Should COVID-19 spread in Gaza, its people – who have already paid the price of a continuous blockade and intra-Palestinian division for 13 years – will pay a heavy price yet again. However, this time it is not a crisis that they alone will have to face. Full Article
sin The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability. Full Article
sin Radical new business model for pharmaceutical industry needed to avert antibiotic resistance crisis By feedproxy.google.com Published On :: Mon, 12 Oct 2015 09:19:24 +0000 7 October 2015 20151009Antibiotics.jpg High-level complex of physiologically active antibiotic substance extracted from blastema at the Arctic Innovation Center (AIC) of Ammosov, North-Eastern Federal University (NEFU) in Yakutsk. Photo: Yuri Smityuk/ITAR-TASS Photo/Corbis. Revenues for pharmaceutical companies need to be 'delinked' from sales of antibiotics to avoid their over-use and avert a public health crisis, says a new report from the think-tank Chatham House.Over-use of antibiotics is contributing to the growing resistance of potentially deadly bacteria to existing drugs, threatening a public health crisis in the near future. The report notes that, by 2050, failing to tackle antibiotic resistance could result in 10 million premature deaths per year. Novel antibiotics to combat resistant pathogens are thus desperately needed, but market incentives are exacerbating the problem. Towards a New Global Business Model for Antibiotics: Delinking Revenues from Sales states that, 'The current business model requires high levels of antibiotic use in order to recover the costs of R&D. But mitigating the spread of resistance demands just the opposite: restrictions on the use of antibiotics.' To tackle this catch-22 problem, the Centre on Global Health Security at Chatham House recommends the establishment of a global body to implement a radical new business model for the industry, which would encourage investment and promote global access to - and conservation of - antibiotics. The current business model has several perverse effects. As R&D is an inherently risky and costly endeavour, the industry is chronically under-investing in new treatments. Today, few large pharmaceutical companies retain active antibacterial drug discovery programmes. Re-stoking the industry's interest in antibiotics would be one of the primary roles of the new body. Secondly, the need to recover sunk cost under the current business model encourages both high prices and over-marketing of successful drugs, making potentially life-saving treatments unaffordable to many in developing countries, while simultaneously encouraging over-use in developed markets and increasing resistance. The new global body would address these challenges by ‘delinking’ pharmaceutical revenues from sales of antibiotics. It would do this by directly financing the research and development of new drugs, which it would then acquire at a price based on production costs rather than the recovery of R&D expenses. Acquisition could take the form of procurement contracts with companies, the purchase of full IP rights or other licensing mechanisms. This would enable it to promote global access to antibiotics while simultaneously restricting over-use. Conservation would be promoted through education, regulation and good clinical practice, with the report recommending that 'proven conservation methods such as antibiotic stewardship programmes… be incentivized and implemented immediately.'Priorities for R&D financing would be based on a comprehensive assessment of threats arising from resistance. Antibiotics would qualify for the highest level of financial incentives if they combat resistant pathogens posing a serious threat to human health. Finance for the new body would come from individual nation states, with the report noting that this could 'begin with a core group of countries with significant research activity and large antibiotic markets, (though) it is envisaged that all high income countries should make an appropriate financial contribution.' It is not yet clear exactly how much funding would be necessary to combat resistance, but with inaction expected to cost $100 trillion in cumulative economic damage, the report argues that 'an additional global investment of up to $3.5 billion a year (about 10 per cent of the current value of global sales of antibiotics) would be a bargain.' Editor's notes Towards a New Global Business Model for Antibiotics: Delinking Revenues from Sales, is a Chatham House report edited by Charles Clift, Unni Gopinathan, Chantal Morel, Kevin Outterson, John-Arne Røttingen and Anthony So.The report is embargoed until 00.01 GMT Friday 9 October.For more information, or to request an interview with the editors, contact the press office. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
sin Britain should treat Europe as its ‘inner circle’ or risk losing international influence By feedproxy.google.com Published On :: Mon, 19 Oct 2015 09:05:23 +0000 13 October 2015 20151019BritanEuropeWorld.jpg British Prime Minister David Cameron sits with other world leaders at the G20 summit in Brisbane, Australia on 15 November 2014. Photo by Getty Images. Given the international context, it is in Britain’s best interests to treat Europe as the ‘inner circle’ of its foreign, security and international economic policy, argues Dr Robin Niblett, director of Chatham House, in a new paper.The British government’s approach since 2010 of seeking to enhance the UK's relations with the world’s emerging powers while balancing these with relationships with the United States and Europe has had only limited success. With constrained resources, and in the face of intense global economic competition, mounting security challenges and decaying international institutions, trying to commit the UK equally on all three fronts will not succeed in the future.Britain, Europe and the World: Rethinking the UK’s Circles of Influence calls for a different mindset and strategy towards the UK’s place in the world – one in which Britain is surrounded by three concentric circles of influence:The first or ‘inner circle’ is the EU, the region with which the UK’s relationships need to be strongest and most active.The ‘second circle’ consists of the protective and enabling set of economic and security relationships with the US.Finally, an ‘outer circle’ comprises the UK’s other key bilateral and institutional relationships.Should the UK vote to remain in the EU, policy-makers should commit to placing the EU at the centre of Britain's foreign policy, using the country’s economic weight, diplomatic skills and networks to play a leading role in leveraging more effective EU-wide policies. Should the country vote to leave, the UK and the EU would enter an extended period of dislocation before arriving at a new, mutually diminished settlement. British policy-makers would be forced to deal and negotiate with the EU on critical policy issues from the outside. It is hard to see, argues Dr Niblett, how that could lead to EU policies or an international context more in line with British interests. Despite its structural flaws and competing national interests, the EU offers the best prospects for managing the rapidly changing global context, for three main reasons:First, it allows the UK to leverage the EU’s global economic weight to enhance the UK’s economic interests internationally, including securing beneficial trade agreements and contributing to EU and global standard-setting and rule-writing. Conversely, leaving would require the UK to renegotiate over 100 trade agreements, and would disadvantage UK interests in EU markets, including making EU governments less likely to liberalize services. Second, it gives the UK a say in designing new EU initiatives to strengthen both British and European security in the face of diverse threats, whether managing the flow of refugees and other emigrants; combatting terrorism; or managing a more assertive Russia and the fallout from a disintegrating Middle East. Third, cooperating with other EU members offers a way of maximizing opportunities to find joint solutions to shared problems, whether in terms of responding to climate change; managing growing cyber insecurity; reversing the decay of governance in failing states; or combating the rise of dangerous non-state actors.Dr Robin Niblett said:‘Britain is likely to be richer, safer and more influential in the coming decades if it treats Europe as the ‘inner circle’ of its foreign policy. For a mid-sized country like the UK, being a major player in a strong regional institution can offer a critical lever for international influence. In the UK’s case, this means choosing to be a leading player in the world’s principal civilian power, the European Union.’ Editor's notes Read Britain, Europe and the World: Rethinking the UK's Circles of InfluenceChatham House will host a press briefing with Dr Robin Niblett on Monday 19 October at 11:00-11:45 BST. To register, or for interview requests, please contact the press office.The views expressed in this paper are those of the author. Chatham House experts will publish a series of papers and commentaries in the run up to the UK’s referendum on its membership of the EU. The institute will also offer a platform for debate on the referendum and Britain’s role in Europe via a series of events and meetings.Read more about the EU referendum. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
sin The Transatlantic Business Response to Foreign Policy Challenges By feedproxy.google.com Published On :: Tue, 10 Jun 2014 15:00:02 +0000 Invitation Only Research Event 12 June 2014 - 8:00am to 9:15am Chatham House, London Meeting Notepdf | 97.01 KB Event participants Myron Brilliant, Executive Vice President and Head of International Affairs, US Chamber of CommerceChair: James Nixey, Head, Russia and Eurasia Programme, Chatham House The speaker will outline a number of foreign policy challenges facing transatlantic business, such as China’s increasing economic power, turmoil in the Middle East, and Russia’s recent actions in eastern Europe. He will examine how these issues can provide obstacles to cooperation and development, and restrict access to markets, and how they can be addressed. The event is part of our series on US and European Perspectives on Common Economic Challenges. Conducted with the support of Bank of America Merrill Lynch, this series examines some of the principal global challenges that we face today and the potentially differing perspectives from the US and across Europe. Attendance at this event is by invitation only. Department/project US and the Americas Programme, US Geoeconomic Trends and Challenges Rory Kinane +44 (0) 20 7314 3650 Email Full Article
sin One Year of Donald Trump: Assessing the Future of the Transatlantic Relationship By feedproxy.google.com Published On :: Mon, 11 Dec 2017 14:00:00 +0000 Members Event Webinar 18 January 2018 - 11:30am to 12:00pm Online Event participants Xenia Wickett, Head, US and the Americas Programme; Dean, The Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House Events over the past 18 months, in particular with the UK’s decision to leave the European Union and the election of Donald Trump, have elevated concerns among many Europeans and Americans over the health of the transatlantic relationship. With the EU looking inward and President Trump’s rejection of a number of historically common US-European interests, such as NATO, the JCPOA on Iran, and the Paris Agreement, the continuation of close transatlantic collaboration is in question.Xenia Wickett will discuss the future of the transatlantic relationship. Is there a clear structural divergence between the US and the UK or is the partnership merely going through a temporary hiccup? She will explore the importance of recent events as well as structural, long-term factors that affect the US and Europe similarly. And what actions, if any, can be taken to mitigate differences and best manage the current situation of uncertainty?Please note, this event is online only. Members will be able to watch the webinar from a computer or other internet-ready device and do not need to come to Chatham House to attend. Full Article
sin Making the Business Case for Nutrition Workshop By feedproxy.google.com Published On :: Thu, 05 Dec 2019 12:15:01 +0000 Invitation Only Research Event 28 January 2020 - 9:30am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A ground-breaking research project from Chatham House, supported by The Power of Nutrition, is exploring the business case for tackling undernutrition, micronutrient deficiencies and overnutrition. Companies across all sectors hold huge, transformative power to save countless lives and transform their own financial prospects. To act, they need more compelling evidence of the potential for targeted investments and strategies to promote better nutrition and create healthier, more productive workforces and consumers.At this workshop, Chatham House will engage business decision-makers in a scenario exercise that explores different nutrition futures and their commercial prospects in each before examining what different strategies business can pursue to maximize future profitability through investments in nutrition.Attendance at this event is by invitation only. Department/project Energy, Environment and Resources Programme Full Article
sin RNA helicase-regulated processing of the Synechocystis rimO-crhR operon results in differential cistron expression and accumulation of two sRNAs [Gene Regulation] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts. Full Article
sin On the measure of maximal entropy for finite horizon Sinai Billiard maps By www.ams.org Published On :: Tue, 10 Mar 2020 10:59 EDT Viviane Baladi and Mark F. Demers J. Amer. Math. Soc. 33 (2020), 381-449. Abstract, references and article information Full Article
sin Lysine Acetylation Is a Highly Abundant and Evolutionarily Conserved Modification in Escherichia Coli By feedproxy.google.com Published On :: 2009-02-01 Junmei ZhangFeb 1, 2009; 8:215-225Research Full Article
sin Lysine Propionylation and Butyrylation Are Novel Post-translational Modifications in Histones By feedproxy.google.com Published On :: 2007-05-01 Yue ChenMay 1, 2007; 6:812-819Research Full Article
sin Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules By feedproxy.google.com Published On :: 2005-09-01 Yi ZhangSep 1, 2005; 4:1240-1250Research Full Article
sin Trypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues By feedproxy.google.com Published On :: 2004-06-01 Jesper V. OlsenJun 1, 2004; 3:608-614Technology Full Article
sin Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns By feedproxy.google.com Published On :: 2005-07-01 Martin R. LarsenJul 1, 2005; 4:873-886Technology Full Article
sin Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents By feedproxy.google.com Published On :: 2004-12-01 Philip L. RossDec 1, 2004; 3:1154-1169Research Full Article
sin Reply to Cosgrove: Non-enzymatic action of expansins [Letters to the Editor] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 In our computational study, we use molecular simulations to substantiate a hypothetical mechanism for glycosidic bond cleavage in the presence of a single catalytic acid at the active site of the mutant D10N HiCel45A. In addition to discussing this plausible mechanism from the context of structurally related MltA lytic transglycosylase and subfamily C GH45s, we also suggest the implications of the plausible mechanism for our current understanding of the action of expansins and lytic transglycosylases. As correctly pointed out by Professor Cosgrove (1), there is large body of evidence, a significant portion of which was regrettably not discussed in our paper, that suggests that expansins are incapable of lytic action on polysaccharide substrates. Whereas these insights do not change the results or the conclusions of our article, we would like to thank Professor Cosgrove for these additional insights. In particular, our main point with respect to expansins is that our results suggest the possibility that expansins are capable of nonhydrolytic lytic activity. Our intention was not to suggest this was the mechanism of expansins, but that it should be considered based on our results and the similarity of the active sites.The molecular mechanisms of how expansins enable cell wall expansion remains to be fully understood. Whereas our proposed mechanism resulting in the formation of the 1,6-anhdro product might be found in expansins and might contribute to the mode of action of expansins, we would like to emphasize that the intent of this study was only to suggest this as a... Full Article
sin Non-enzymatic action of expansins [Letters to the Editor] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 From their simulations of endoglucanase Cel45A, Bharadwaj et al. (1) propose that structurally related expansins and MltA may cut glycan backbones without generating reducing ends. This is tenable for MltA, a peptidoglycan lytic transglycosylase whose action produces nonreducing 1,6-anhydro products, but is untenable for expansins.Expansins loosen plant cell walls and induce wall expansion. Contrary to the assertion by Bharadwaj et al., the conclusion that expansins are not lytic is not merely based on lack of new reducing ends but is supported by multiple (negative) tests for polysaccharide cleavage that do not rely on detection of reducing ends. At least eight studies with three divergent groups of expansins document this point. For instance, α-expansin did not reduce the viscosity of various wall polysaccharide solutions, an endolytic assay that does not rely on measuring reducing ends (e.g. see Ref. 2 and other studies).Walls treated with α-expansin did not release saccharide fragments, measured by pulsed amperometric detection, which can detect nonreducing saccharides (3).In the case of β-expansins, protein treatments did not cleave the backbones of a wide range of dye-coupled cross-linked wall polysaccharides; nor did they cleave backbones of polysaccharides extracted from plant cell walls, measured by gel permeation chromatography (4).For five microbial expansins, tests with a range of dye-coupled cross-linked polysaccharides likewise did not detect lytic activity (e.g. see Ref. 5). Thus, extensive published evidence argues against lytic action by expansins, as proposed by Bharadwaj (1), and attempts to identify 1,6-anhydro products seem unlikely to succeed. Full Article
sin Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs. Full Article
sin G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis. Full Article
sin 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
sin Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article
sin Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
sin A single amino acid substitution uncouples catalysis and allostery in an essential biosynthetic enzyme in Mycobacterium tuberculosis [Enzymology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery. Full Article
sin Unpacking the role of religion in political transnationalism: the case of the Shi'a Iraqi diaspora since 2003 By feedproxy.google.com Published On :: Wed, 04 Mar 2020 12:58:04 +0000 4 March 2020 , Volume 96, Number 2 Oula Kadhum Read Online This article explores the role of religion in political transnationalism using the case of the Shi'a Iraqi diaspora since 2003. The article focuses on three areas that capture important trends in Shi'a transnationalism and their implications for transnational Shi'a identity politics. These include Shi'a diasporic politics, transnational Shi'a civic activism, and the cultural production of Iraqi Shi'a identity through pilgrimages, rituals and new practices. It is argued that understanding Shi'a Islam and identity formation requires adopting a transnational lens. The evolution of Shi'a Islam is not only a result of the dictates of the Shi'a clerical centres, and how they influence Shi'a populations abroad, but also the transnational interrelationships and links to holy shrine cities, Shi'i national and international politics, humanitarianism and commemorations and rituals. The article demonstrates that Shi'a political transnationalism is unexceptional in that it echoes much of the literature on diasporic politics and development where diaspora involve themselves from afar in the politics and societies of their countries of origin. At the same time, it shows the exceptionalism of Shi'a diasporic movements, in that their motivations and mobilizations are contributing to the reification of sectarian geographical and social borders, creating a transnationalism that is defined by largely Shi'a networks, spaces, actors and causes. The case of Shi'a political transnationalism towards Iraq shows that this is increasing the distance between Shi'is and Iraq's other communities, simultaneously fragmenting Iraq's national unity while deepening Shi'a identity and politics both nationally and supra-nationally. Full Article
sin Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era By feedproxy.google.com Published On :: Tue, 21 Apr 2020 23:55:01 +0000 Invitation Only Research Event 7 May 2020 - 3:00pm to 4:30pm Event participants Anneli Ahonen, Head, StratCom East Task Force, European External Action ServiceKeir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham HouseThomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown FoundationChairs:James Nixey, Programme Director, Russia and Eurasia, Chatham HouseGlen Howard, President, The Jamestown Foundation The COVID-19 pandemic provides the ideal environment for malign influence to thrive as it feeds on fear and a vacuum of authoritative information. What are the current challenges posed by Russian disinformation, and how should Western nations be responding? In this discussion, jointly hosted by the Jamestown Foundation and the Chatham House Russia and Eurasia Programme, the speakers will consider what best practice looks like in safeguarding Western societies against the pernicious effects of disinformation. This event will be held on the record. Department/project Russia and Eurasia Programme, Russia's Domestic Politics Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
sin Webinar: Assessing the Twists and Turns in the US-Iran Stalemate By feedproxy.google.com Published On :: Thu, 23 Apr 2020 10:35:01 +0000 Research Event 28 April 2020 - 2:00pm to 3:30pm Event participants Esfandyar Batmanghelidj, Founder and Publisher, Bourse & BazaarNasser Hadian, Professor of Political Sciences, Faculty of Law and Political Sciences, University of TehranAzadeh Zamirirad, Deputy Head, Middle East and Africa Division, SWP BerlinAriane Tabatabai, Middle East Fellow, Alliance for Securing Democracy, US German Marshall Fund; Adjunct Senior Research Scholar, SIPAModerator: Sanam Vakil, Deputy Head and Senior Research Fellow, Middle East and North Africa Programme, Chatham House The webinar will be livestreamed on the MENA Programme Facebook page.Since the start of 2020, Iran has been beset with multiple challenges including the spread of COVID-19, economic pressure from US sanctions, parliamentary elections in February, the killing of Qassem Soleimani and an increase in tensions in Iraq. The Trump administration interprets these domestic and regional challenges faces by Iran as evidence that its maximum pressure campaign is proving to be effective.In this webinar, speakers will examine the economic and political impact of the Trump administration's policy towards Iran. Panelists will consider how these events are impacting internal dynamics in Iran and examine the economic impact of sanctions. They will also evaluate European diplomatic efforts to preserve the Iran nuclear agreement, and consider the future trajectory of US Iran policy and the potential for escalation in the region. This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record. Department/project Middle East and North Africa Programme, Iran Forum 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
sin Human Development as Positive Freedom: A World View Since 1870 By feedproxy.google.com Published On :: Mon, 10 Feb 2014 15:33:29 +0000 Invitation Only 26 February 2014 - 8:15am to 9:30am Chatham House, London Event participants Leandro Prados de la Escosura, Professor, Economic History, Universidad Carlos III de Madrid This meeting will see the launch of the Chatham House-CAGE briefing paper ‘Human Development as Positive Freedom: A World View since 1870’. The author of the paper will argue that while substantial gains in world human development have been achieved since 1870, the main period of improvement actually occurred between World War I and 1970. He will further argue that, despite initial successes in lifting human development, the socialist experiments of the 20th century failed to sustain momentum and then (with the exception of Cuba) stagnated and fell behind prior to the socialist model's ultimate demise. Finally, he will contend that since 1970, while most OECD countries have experienced a second (later life) health transition, all developing regions have fallen behind in this dimension.The briefing paper is the 12th publication in the Chatham House-CAGE series, published in partnership with the Centre for Competitive Advantage in the Global Economy (CAGE) at the University of Warwick.Attendance at this event is by invitation only. Department/project Global Economy and Finance Programme Full Article
sin Human Development as Positive Freedom: A World View Since 1870 By feedproxy.google.com Published On :: Thu, 27 Feb 2014 15:32:11 +0000 1 February 2014 Substantial gains in world human development have been achieved since 1870, but research shows that the main improvement actually occurred between the First World War and 1970. Leandro Prados de la Escosura 20140200CAGEhumandevelopmentW.jpg Photo by 1xpert /iStock. Summary points:Substantial gains in world human development have been achieved since 1870, but research shows that the main improvement actually occurred between the First World War and 1970. Across-the-board advances took place in life expectancy and education between 1920 and 1950, a phase during which there was a major backlash against economic globalization. This is evidence of a development puzzle: economic growth and human development do not always go hand in hand. Between 1913 and 1970 the absolute gap between most countries in the OECD and the rest of the world widened, with different regions experiencing mixed success in catching up. Since the 1970s the performance of developing regions has varied greatly. Despite initial successes in lifting human development, the socialist experiments of the 20th century failed to sustain momentum and then (with the exception of Cuba) stagnated and fell behind prior to the socialist model’s ultimate demise. Education has been the driving force behind the limited catching-up of developing regions in terms of long-term human development. In terms of life expectancy,these regions achieved significant gains only during the first (early-life) health transition. Since 1970, while most OECD countries have experienced a second (later-life) health transition, all developing regions have fallen behind.Project: Shifting Competitive Advantage in the Global Economy Launch eventHuman Development as Positive Freedom: A World View Since 187026 February 2014 Related documents Briefing Paper: Human Development as Positive Freedom: A World View Since 1870pdf | 666.29 KB Department/project Global Economy and Finance Programme, Shifting Competitive Advantage in the Changing Global Economy Full Article
sin Make It Awesome — Three Tips for Impressing Your Readers By mythicscribes.com Published On :: Mon, 04 May 2020 20:35:47 +0000 You’re a fantasy writer. You’ve created an amazing and original world, full of wondrous magic, mind-blowing monsters, and fascinating new cultures. You’ve got powerful heroes, menacing villains, and mysterious mentors. There’s just the right amount of romance. In short, you’ve got all that good stuff you’d expect to find in a fantasy novel. Only, somehow it’s still not coming out quite as awe-inspiring as you’d envisioned it. Today, I’ve got three tips for you on how to make your awesome stuff seem more awesome. Establish the Norm “When everything is awesome, awesome becomes average.” Every now and then, I come across a book that begins with the writer very obviously trying to impress me with how cool their main character is, and what an amazing world they have created, and how scary the villain is. All at once. In the first chapter. It rarely works. Let’s say there’s a ballroom full of ultra-rich and mega-powerful vampires, and then someone flies in on a golden unicorn and starts shooting fireballs the shape of grinning skulls. That would probably look rather spectacular as an introduction to a movie, but does it work in a book? Continue reading Make It Awesome — Three Tips for Impressing Your Readers at Mythic Scribes. Full Article Writing Craft & Technique
sin A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent By feedproxy.google.com Published On :: 1989-04-01 M el-SaadaniApr 1, 1989; 30:627-630Articles Full Article
sin Harnessing the Potential of Cities By feedproxy.google.com Published On :: Fri, 22 Nov 2019 11:55:02 +0000 Corporate Members Event 13 December 2019 - 12:30pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Penny Abeywardena, Commissioner for International Affairs, New York CityChair: Dr Beyza Unal, Senior Research Fellow, International Security Department, Chatham House Cities are strong engines of growth and job creation accounting for some 85 per cent of global GDP. By 2030, more than 60 per cent of people worldwide will live in cities and they will be on the front lines of managing issues transcending borders such as climate, migration and sustainability. International organizations like the United Nations are striving to meet these challenges but relying on traditional multilateral agreements is growing ever more unpredictable. If cities and local governments are key to global prosperity, how can their power and influence be harnessed to accelerate impact for their citizens?Drawing on the pioneering work of New York City in the area of foreign policy leadership at a municipal level, Penny Abeywardena will discuss how the influence of subnational leadership and diplomacy is more important than ever as national governments are abdicating their responsibility at the multilateral level. How can the Sustainable Development Goals be localized among cities on policy issues that impact communities? And what can large cities, beyond the capital, do to remain influential and harness job growth? This event will be preceded by an informal sandwich reception from 12.30pm-1pm. The roundtable discussion to follow will take place from 1pm-2pm.This event is corporate members only. If you'd like to attend, please RSVP to Linda Bedford.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Members Events Team Email Full Article
sin Chile After the October Uprising By feedproxy.google.com Published On :: Fri, 07 Feb 2020 15:10:01 +0000 Invitation Only Research Event 13 February 2020 - 8:00am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Andrés Velasco, Dean of the School of Public Policy, London School of Economics and Political ScienceRobert Funk, Assistant Professor of Political Science, University of Chile; Visiting Senior Fellow at the School of Public Policy, London School of Economics and Political ScienceChair: Melissa MacEwen, Manager, Energy, Environment and Resources Programme The outbreak of popular discontent in Chile in October of last year caught many observers by surprise. What began as a protest against a metro fare hike has transformed into widespread rejection of the economic and political model in place since the return to democracy in 1990, accompanied with unprecedented violence which raises questions about the state's ability to maintain rule of law. Professor Andrés Velasco, Dean of the School of Public Policy at the LSE, and Dr Robert Funk, Assistant Professor of Political Science at the University of Chile will join us for a discussion on the causes of the current protest.What are the prospects for reform and a return to normality? Is this the end of the much-lauded Chilean model? Event attributes Chatham House Rule Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
sin G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis. Full Article
sin A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates. Full Article
sin Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article