als Four Theories and a Philosophy: Self-Management Education for Individuals Newly Diagnosed With Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2003-04-01 T. Chas SkinnerApr 1, 2003; 16:Lifestyle and Behavior Full Article
als New Research Reveals Dramatic Shifts in US Household Spending By www8.gsb.columbia.edu Published On :: Fri, 01 May 2020 00:00:00 -0400 Data from March shows similarities in spending across various demographics. Full Article
als Migration Deals Risk Undermining Global Refugee Protection By feedproxy.google.com Published On :: Fri, 13 Apr 2018 09:53:48 +0000 13 April 2018 Amanda Gray Meral Associate Fellow, International Law Programme @AmandaLouGray While some aspects of agreements like that between the EU and Turkey reflect a genuine effort to cooperate in addressing the needs of refugees, other elements risk undermining the very essence of the global refugee protection regime. 2018-04-13-Lesbos.jpg A boat carrying migrants approaches shore after making the crossing from Turkey to the Greek island of Lesbos in November 2015. Photo: Getty Images. Last month the European Commission proposed that the EU should mobilize the next tranche of funding for Turkey (€3 billion) under the EU–Turkey deal agreed in 2016. The deal is part of a rapidly developing strategy on the part of the EU to improve cooperation on migration issues with countries of origin as well as those through which migrants and refugees transit en route to Europe. Since 2015, the EU has ramped up negotiations, with the New Partnership Framework underpinning arrangements with countries such as Niger, Mali and Ethiopia, and endorsing a memorandum of understanding between Italy and Libya in February 2017.A common thread that runs across all of these deals is their focus on containment in exchange for funding, rather than a principled approach to refugee protection. For example, the EU has committed around €6 billion to Turkey as a contribution towards the cost of humanitarian assistance for the over 3 million Syrian refugees residing there. This funding also operates as an incentive for Turkey to take back all refugees and migrants who have irregularly arrived in Greece via Turkey since the deal entered effect.Similarly, the EU is providing financial support to Libya in exchange for its cooperation in reducing the flow of migrants and refugees towards Europe, while the New Partnership Framework aims to reduce the number of migrants and refugees departing for Europe in exchange for EU aid. While financial incentives geared towards containment do not amount to new policy, with the increasing number of deals being negotiated, the use of such a strategy appears to be both accelerating and becoming more explicit.An effective investment?Implementation of these deals has been hindered by obligations under international law, raising questions not only as to their legality but also their value for money.Under the EU–Turkey deal, refugees arriving in Greece irregularly were to be returned to Turkey, with an equal number of Syrian refugees resettled to Europe in exchange. However, implementation of this aspect of the deal has been limited.Under EU asylum law, Greece is obliged to provide access to asylum procedures for those arriving on its shores. Given that most arrivals from Turkey came from refugee-producing countries (including Syria, Afghanistan and Iraq), an individualized assessment of ‘safe third country’ is required before any possible return to Turkey can take place. This requires a finding that Turkey can guarantee effective access to protection for the individual in question, including protection against refoulement (i.e. forced return to a country where he or she is at risk of serious harm or persecution). By the end March 2018, only 2,164 people had been returned to Turkey.As for Italy, with EU support, under the MOU with Libya it has been training as well as providing funding and logistical support to the Libyan coastguard – including an Italian naval presence in Libyan waters – to intercept boats in the Mediterranean. Given the mounting evidence of abuse of migrants and refugees, whether by Libyan coastguards or inside Libyan detention centres, this raises questions as to whether the support being provided by Italy and the EU amounts to a breach of international law.Despite concerns about the protection risks for refugees, advocates of such deals claim they have the potential to prevent dangerous journeys, saving lives and interrupting the business model of smugglers. Numbers crossing the Mediterranean have indeed dropped since the deals were agreed. However, in Libya it has created an ‘anti-smuggling’ market which, despite leading to a reduction of migration in the short term, may not be sustainable in the long term if it drives conflict between various non-state actors.In the case of the EU–Turkey deal, while it has led to a fall in arrivals to the Greek islands in the first six months of 2017, there is also evidence that smugglers were already adapting their routes, forcing refugees and migrants to travel on the more dangerous central Mediterranean route.For now, at least, these deals appear to have gained significant popular support within the EU. Italy’s approaches in Libya, for example, have been broadly backed by the Italian public – unsurprising given that some polls indicate 50 percent of the Italian population believe migrants to be a threat to public security. However, the drivers of public attitudes towards refugees and migration are complex and, as noted in a policy brief published under the Chatham House–ODI Forum on Refugee and Migration Policy, influenced in part by narratives driven by politicians and the media.What some of these deals have achieved is the significant flow of aid money towards job creation and economic opportunities for refugees, incentivizing policy change in some contexts and producing real benefits for the refugees concerned (while reducing pressures on them to move onwards via dangerous journeys).A prominent example is the Jordan Compact, a 2016 agreement between Jordan, the EU and international financial institutions including the World Bank to improve the livelihoods and education of Syrian refugees inside Jordan. While challenges in its implementation remain, including concerns about labour rights, the Jordan Compact has resulted in real improvements in education and access to the labour market for Syrian refugees. The Jordanian government has made policy concessions on access to work permits for Syrian refugees, removing some of the barriers that prevented refugees accessing jobs, while the EU has committed to ease trade barriers for goods produced in Jordanian factories on condition they hire a percentage of Syrian refugees.Likewise, the EU–Turkey deal’s most successful component has been its financial contribution of €3 billion of aid under the EU Facility for Refugees towards support for the 3.7 million Syrian refugees currently being hosted by Turkey. This includes €1 billion allocated to the Emergency Social Safety Net, described by the European Commission as the ‘largest single humanitarian project in the history of the EU’, directly impacting the livelihoods of some 1.1 million vulnerable refugees.Moving aheadWhile some aspects of these deals reflect a genuine effort to cooperate in addressing the needs of refugees, other elements risk undermining the very essence of the global refugee protection regime.The diplomatic squabble over a proposed refugee ‘swap’ of 1,250 refugees between the US and Australia in February 2017 highlights the danger of refugees becoming bargaining chips. Similarly, the Kenyan government’s announcement that it would close Dadaab refugee camp in late November 2016 cited the EU-Turkey deal as justification. Migration partnerships which emphasise the securing of EU borders against refugee arrivals may diminish the willingness of states in the Global South to continue to host large numbers of refugees.While the positive aspects of such deals deserve acknowledgement, understanding their impact on refugee protection must be given greater attention. This is vital not only to ensure their workability but also to ensure that those countries who spearheaded the creation of the global refugee protection regime do not end up undermining its existence. Full Article
als Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part One By feedproxy.google.com Published On :: Mon, 29 Oct 2018 16:37:47 +0000 17 April 2014 As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) jointly organized this four-day meeting at Chatham House for international lawyers to discuss a wide range of issues related to public international law and the rights of individuals. Download PDF Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For China University of Political Science and Law, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The roundtable had a total of 22 participants, 10 Chinese (from universities and other academic institutions in Beijing and Shanghai) and 12 non-Chinese (from Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).All discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
als Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Two By feedproxy.google.com Published On :: Tue, 30 Oct 2018 08:46:37 +0000 15 November 2014 As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) held a two-day roundtable meeting in Beijing on public international law and the rights of individuals. Download PDF Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting in Beijing was hosted by CUPL and involved 20 participants, 10 Chinese (from universities and other academic institutions in Beijing) and 10 non-Chinese (from Australia, the Netherlands, South Africa, Switzerland, the United Kingdom and the United States).To ensure continuity while also expanding the experts network being built, the second meeting included a mix of participants from the first meeting and some new participants.All discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
als Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Three By feedproxy.google.com Published On :: Tue, 30 Oct 2018 08:55:48 +0000 6 March 2016 As part of a roundtable series, Chatham House, China University of Political Science and Law (CUPL) and the Graduate Institute Geneva held a two-day roundtable meeting in Geneva on public international law and the rights of individuals. Download PDF Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting in Geneva was co-hosted by the Graduate Institute Geneva and involved 19 participants, 9 Chinese (from six research institutions in Beijing and Shanghai) and 11 non-Chinese (from eight research institutions in Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).To ensure continuity while also expanding the expert network being built, the third meeting included a mix of participants from the first two meetings and some new participantsAll discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
als Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis By feedproxy.google.com Published On :: 2020-04-01 Beatriz RochaApr 1, 2020; 19:574-588Research Full Article
als Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 By feedproxy.google.com Published On :: 2020-04-01 Michael PlankApr 1, 2020; 19:655-671Research Full Article
als Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics By feedproxy.google.com Published On :: 2020-04-01 Patrick HerrApr 1, 2020; 19:608-623Research Full Article
als Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling By feedproxy.google.com Published On :: 2020-04-06 Samuel W EntwisleApr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946Research Full Article
als COVID-19 Impact on Refugees is Also Political By feedproxy.google.com Published On :: Tue, 31 Mar 2020 10:53:27 +0000 31 March 2020 Dr Lina Khatib Director, Middle East and North Africa Programme @LinaKhatibUK The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities. 2020-03-31-Covid19-lebanon The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images. As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece. Full Article
als Egypt and the Gulf: Allies and Rivals By feedproxy.google.com Published On :: Sun, 19 Apr 2020 20:38:18 +0000 20 April 2020 There is and will continue to be an edge of rivalry in Egypt’s relations with the dominant Gulf Arab powers. This paper will focus primarily on the Egypt–Gulf relationship during the Sisi era. Read online Download PDF David Butter Associate Fellow, Middle East and North Africa Programme @DavidCButter 2020-04-20-Egypt-Gulf.jpg Crown Prince of Abu Dhabi Mohammed bin Zayed is welcomed by Egypt’s President Abdel-Fattah el-Sisi in Cairo on 19 June 2017. Photo: Getty Images. Summary Egypt and the Gulf Arab region have long been important poles of political, military economic and cultural power and influence in the Middle East. Under the presidency of Gamal Abdel-Nasser, Egypt was the dominant force in the region, but the balance of power shifted towards the Gulf in the 1970s, as Egypt’s economy faltered and the Gulf Arab states reaped the benefits of resurgent oil prices in the wake of the 1973 OPEC embargo. The popular uprising against President Hosni Mubarak’s regime in 2011 elicited divergent reactions in the Gulf. The leaders of Saudi Arabia and the United Arab Emirates (UAE) were concerned about the risks of a movement for revolutionary change spreading to their own region, while Qatar saw an opportunity to strengthen its regional role through supporting the Muslim Brotherhood.The forcible removal of Egypt’s elected president, Mohammed Morsi of the Muslim Brotherhood, in July 2013 by the army commander, Abdel-Fattah el-Sisi, ushered in a new era in Egypt–Gulf relations. The UAE, Saudi Arabia and Kuwait quickly mobilized financial support for the new administration. Abu Dhabi’s crown prince, Mohammed bin Zayed, known for his intense opposition to the Muslim Brotherhood, signalled his strong support for the new regime by visiting Cairo only weeks after hundreds of Morsi’s supporters were killed.Between July 2013 and August 2016, the UAE, Saudi Arabia and Kuwait provided about $30 billion in aid to the Sisi regime through placing deposits with the Central Bank of Egypt and supplying petroleum products as grants. The UAE sought to link its aid to a programme of economic reforms, but the Egyptian government finally decided in mid-2016 to negotiate a loan agreement with the International Monetary Fund (IMF). Since the signing of the $12 billion loan with the IMF in November 2016, Egypt has no longer been reliant on Gulf Arab financial support, although some of the deposits placed previously have been rolled over on reaching maturity.During the Sisi era, Egypt has benefited from its economic links to the Gulf over a wide spectrum of activities. The UAE and Saudi Arabia in particular are increasingly important export markets for Egyptian companies, as well as major sources of foreign direct investment. The financial aid provided by Sisi’s Gulf allies in 2013–16 has also helped to underpin the surge in Egypt’s arms procurement. Another critical element in the economic relationship is the presence of millions of expatriate Egyptian workers in the Gulf, who are responsible for a large share of the annual inflow of about $25 billion in remittances.Egypt’s most important political relationships in the Gulf have been with Saudi Arabia and the UAE. Ties with Saudi Arabia were affected by the death of King Abdullah at the start of 2015 and by the subsequent emergence of Mohammed bin Salman as the most influential figure in the kingdom. During a visit by King Abdullah’s successor, King Salman, to Cairo in April 2016, Egypt announced a decision to cede sovereignty over two Red Sea islands, Tiran and Sanafir, to Saudi Arabia. Relations soured after this decision was challenged in the Egyptian courts, but the issue was resolved in favour of the deal. Egypt played no active role in the Saudi- and UAE-led intervention in Yemen, but joined its two principal Gulf allies and Bahrain in imposing sanctions on Qatar in mid-2017. Relations between Sisi and Crown Prince Mohammed bin Zayed have remained close throughout the past seven years. The UAE and Egypt have been among the most important external supporters of the Libyan National Army, commanded by Field Marshal Khalifa Haftar, although they have not created an overt alliance in this arena. Egypt has adopted a more prominent diplomatic profile in relation to Libya, while the UAE has been more deeply engaged militarily, to judge from assessments by the panel of experts tasked to monitor adherence to the UN embargo on the supply of weapons to Libya. The relationship between the Egyptian and Emirati leaders is underpinned by a strong shared ideological antipathy to the Muslim Brotherhood.Following the completion of the IMF programme in 2019, the Egyptian economy is in a much stronger position than it was in the early period of Sisi’s rule, even though this has exacted a harsh toll on the 60 per cent of the population classified by the World Bank as poor or vulnerable. There is no pressing need for direct financial support from the Gulf, but Egypt still depends on economic linkages through trade, investment, tourism and remittances. In this respect, the balance of power has tilted marginally back towards Egypt. However, Egypt is still beset by deep internal political contradictions, as reflected in the regime’s heavy reliance on coercion and repression, and the economy remains vulnerable to external shocks – of which the coronavirus pandemic is a prime example. Department/project Middle East and North Africa Programme Full Article
als Webinar: Egypt and the Gulf: Allies and Rivals By feedproxy.google.com Published On :: Tue, 21 Apr 2020 08:25:01 +0000 Research Event 23 April 2020 - 1:00pm to 2:00pm Event participants Speaker: David Butter, Associate Fellow, Middle East and North Africa Programme, Chatham HouseModerator: Mohamed El Dahshan, Associate Fellow, Middle East and North Africa Programme, Chatham House The webinar will be livestreamed on the MENA Programme Facebook page.Egypt and the Gulf Arab region have long been important poles of political, military, economic and cultural power and influence in the Middle East. A recently published Chatham House paper examines the strategic and economic relationship between Egypt and the Gulf, focusing in particular on the period since Abdel-Fattah el-Sisi came to power in Egypt. Author David Butter offers a detailed evaluation of these economic relationships, in the broader context of a strategic alliance that, since 2013, has been informed by a common commitment between Egypt and the UAE in particular to keep in check the Muslim Brotherhood and its regional state supporters, primarily Turkey and Qatar.In this webinar, the author will discuss the paper’s main argument, namely, that the degree of Egypt’s dependence on Gulf countries has fluctuated, and that by 2019, Egypt’s direct financial dependence on the Gulf was significantly reduced by comparison with the initial three years of the Sisi era, although other economic linkages such as investment, trade, remittances and tourism remained strong, with potential for growth. The speaker will also discuss the impact of the global crisis caused by the COVID-19 pandemic on Egypt’s and Gulf countries’ economies and will explore the implications for the relationship between Egypt and the Gulf.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 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
als Moving towards multicenter therapeutic trials in ALS: feasibility of data pooling using different TSPO positron emission tomography (PET) radioligands. By jnm.snmjournals.org Published On :: 2020-04-03T15:14:37-07:00 Rationale: Neuroinflammation has been implicated in Amyotrophic Lateral Sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, some challenges have to be overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudoreference analysis technique for 18F-DPA714. Methods: 7 ALS-Belgium (58.9±6.7 years,5M) and 8 HV-Belgium (52.1±15.2 years,3M); and 7 ALS-US (53.4±9.8 years,5M) and 7 HV-US (54.6±9.6 years,4M) from a previously published study (1) underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, US) PET-MR scans. For 18F-DPA714, volume of distribution (VT) maps were compared to standardized uptake value ratios (SUVR)40-60 calculated using the pseudoreference regions (1)cerebellum, (2)occipital cortex, and (3)whole brain without ventricles (WB-ventricles). Also for 11C-PBR28, SUVR60-90 using WB-ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0±5.6%) in primary motor cortices was observed in ALS, as measured by both VT and SUVR40-60 approaches. Highest sensitivity was found for SUVRWB-ventricles (average cluster 21.6±0.1%). 18F-DPA714 VT ratio and SUVR40-60 results were highly correlated (r>0.8, p<0.001). A similar pattern of increased uptake (average cluster 20.5±0.5%) in primary motor cortices was observed in ALS with 11C-PBR28 using the SUVRWB-ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together, resulted in a more extensive pattern of significant increased glial activation in the bilateral primary motor cortices. Conclusion: The same pseudoreference region analysis technique for 11C-PBR28 PET imaging can be extended towards 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these two tracers enables pooling of TSPO PET data across multiple centers and increase power of TSPO as biomarker for future therapeutic trials. Full Article
als Editor's Page: Unacceptable Denials By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 Full Article
als N-glycosylation Site Analysis Reveals Sex-related Differences in Protein N-glycosylation in the Rice Brown Planthopper (Nilaparvata lugens) [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Glycosylation is a common modification of proteins and critical for a wide range of biological processes. Differences in protein glycosylation between sexes have already been observed in humans, nematodes and trematodes, and have recently also been reported in the rice pest insect Nilaparvata lugens. Although protein N-glycosylation in insects is nowadays of high interest because of its potential for exploitation in pest control strategies, the functionality of differential N-glycosylation between sexes is yet unknown. In this study, therefore, the occurrence and role of sex-related protein N-glycosylation in insects were examined. A comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes at the glycopeptide level. N-glycopeptide enrichment via lectin capturing using the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans, resulted in the identification of over 1300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosylation sites were shown to be derived from proteins with a putative role in insect reproduction. In addition, differential glycan composition between males and females was observed for proteins shared across sexes. Both lectin blotting experiments as well as transcript expression analyses with complete insects and insect tissues confirmed the observed differences in N-glycosylation of proteins between sexes. In conclusion, this study provides further evidence for protein N-glycosylation to be sex-related in insects. Furthermore, original data on N-glycosylation sites of N. lugens adults are presented, providing novel insights into planthopper's biology and information for future biological pest control strategies. Full Article
als Peptidomic Analysis of Urine from Youths with Early Type 1 Diabetes Reveals Novel Bioactivity of Uromodulin Peptides In Vitro [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Chronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis are captured by the urinary peptidome. To elucidate the early kidney response to chronic hyperglycemia, we conducted a peptidomic investigation into urines from otherwise healthy youths with type 1 diabetes and their non-diabetic peers using unbiased and targeted mass spectrometry-based techniques. This cross-sectional study included two separate cohorts for the discovery (n = 30) and internal validation (n = 30) of differential peptide excretion. Peptide bioactivity was predicted using PeptideRanker and subsequently verified in vitro. Proteasix and the Nephroseq database were used to identify putative proteases responsible for peptide generation and examine their expression in diabetic nephropathy. A total of 6550 urinary peptides were identified in the discovery analysis. We further examined the subset of 162 peptides, which were quantified across all thirty samples. Of the 15 differentially excreted peptides (p < 0.05), seven derived from a C-terminal region (589SGSVIDQSRVLNLGPITRK607) of uromodulin, a kidney-specific protein. Increased excretion of five uromodulin peptides was replicated in the validation cohort using parallel reaction monitoring (p < 0.05). One of the validated peptides (SGSVIDQSRVLNLGPI) activated NFB and AP-1 signaling, stimulated cytokine release, and enhanced neutrophil migration in vitro. In silico analyses highlighted several potential proteases such as hepsin, meprin A, and cathepsin B to be responsible for generating these peptides. In summary, we identified a urinary signature of uromodulin peptides associated with early type 1 diabetes before clinical manifestations of kidney disease and discovered novel bioactivity of uromodulin peptides in vitro. Our present findings lay the groundwork for future studies to validate peptide excretion in larger and broader populations, to investigate the role of bioactive uromodulin peptides in high glucose conditions, and to examine proteases that cleave uromodulin. Full Article
als AMPK Interactome Reveals New Function in Non-homologous End Joining DNA Repair [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Adenosine monophosphate-activated protein kinase (AMPK) is an obligate heterotrimer that consists of a catalytic subunit (α) and two regulatory subunits (β and ). AMPK is a key enzyme in the regulation of cellular energy homeostasis. It has been well studied and is known to function in many cellular pathways. However, the interactome of AMPK has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we used tandem-affinity purification, coupled with mass spectrometry (TAP-MS) analysis, to determine the interactome of AMPK and its functions. We conducted a TAP-MS analysis of all seven AMPK subunits. We identified 138 candidate high-confidence interacting proteins (HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complexes. Five candidate AMPK-binding proteins were experimentally validated, underlining the reliability of our data set. Furthermore, we demonstrated that AMPK acts with a strong AMPK-binding protein, Artemis, in non-homologous end joining. Collectively, our study established the first AMPK interactome and uncovered a new function of AMPK in DNA repair. Full Article
als Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Male infertility is widespread and estimated to affect 1 in 20 men. Although in some cases the etiology of the condition is well understood, for at least 50% of men, the underlying cause is yet to be classified. Male infertility, or subfertility, is often diagnosed by looking at total sperm produced, motility of the cells and overall morphology. Although counting spermatozoa and their associated motility is routine, morphology assessment is highly subjective, mainly because of the procedure being based on microscopic examination. A failure to diagnose male-infertility or sub-fertility has led to a situation where assisted conception is often used unnecessarily. As such, biomarkers of male infertility are needed to help establish a more consistent diagnosis. In the present study, we compared nuclear extracts from both high- and low-quality spermatozoa by LC-MS/MS based proteomic analysis. Our data shows that nuclear retention of specific proteins is a common facet among low-quality sperm cells. We demonstrate that the presence of Topoisomerase 2A in the sperm head is highly correlated to poor head morphology. Topoisomerase 2A is therefore a potential new biomarker for confirming male infertility in clinical practice. Full Article
als Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases. Full Article
als Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 The cell cycle is a highly conserved process involving the coordinated separation of a single cell into two daughter cells. To relate transcriptional regulation across the cell cycle with oscillatory changes in protein abundance and activity, we carried out a proteome- and phospho-proteome-wide mass spectrometry profiling. We compared protein dynamics with gene transcription, revealing many transcriptionally regulated G2 mRNAs that only produce a protein shift after mitosis. Integration of CRISPR/Cas9 survivability studies further highlighted proteins essential for cell viability. Analyzing the dynamics of phosphorylation events and protein solubility dynamics over the cell cycle, we characterize predicted phospho-peptide motif distributions and predict cell cycle-dependent translocating proteins, as exemplified by the S-adenosylmethionine synthase MAT2A. Our study implicates this enzyme in translocating to the nucleus after the G1/S-checkpoint, which enables epigenetic histone methylation maintenance during DNA replication. Taken together, this data set provides a unique integrated resource with novel insights on cell cycle dynamics. Full Article
als Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis. Full Article
als Virtual Issue: Technological Innovations [Editorials] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Full Article
als Compliance Checklists No Longer Required at Initial Manuscript Submission [Editorials] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Full Article
als The Data Must Be Accessible to All [Editorials] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Full Article
als Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella. Full Article
als The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues. Full Article
als From AFL star to Big Apple start-up, Swift's Joel MacDonald is kicking goals By www.smh.com.au Published On :: Fri, 13 Nov 2015 05:53:09 GMT Two years ago Joel MacDonald was in Melbourne playing in the AFL; now he's kicking goals in New York. Full Article
als ATO fumes after cyber criminals attack myGov portal during last days of Tax Time 2016 By www.smh.com.au Published On :: Thu, 03 Nov 2016 13:15:00 GMT Tensions emerge between Tax Office and Human Services after hackers take down myGov Full Article
als Face scanning falls flat as part of digital credentials push By www.smh.com.au Published On :: Thu, 18 Jul 2019 01:14:02 GMT State government's facial recognition ID check is now required for those seeking solar rebates, but it failed 40 per cent of the time during the first two weeks. Full Article
als The Syrian Pound Signals Economic Deterioration By feedproxy.google.com Published On :: Thu, 26 Sep 2019 11:30:45 +0000 26 September 2019 Zaki Mehchy Senior Consulting Fellow, Middle East and North Africa Programme @mehchy LinkedIn The Syrian pound’s volatile exchange rate over the past month is not a short-term monetary crisis. It reflects the destruction of the economic foundations in Syria. 2019-09-26-SyriaBank.jpg The Syrian Central Bank building in 2008. Photo: Getty Images. The Syrian currency depreciated by 11% between mid-August and the first week of September, to reach an unprecedented level of SYP692 to the US dollar. According to the government, the main reasons behind this collapse are the international sanctions imposed on Syria and currency speculation.Accordingly, the government has forced speculators and local foreign exchange companies to sell the US dollar instead of holding it. Moreover, Syrian security agencies have pressured profiteers with close links to the regime to effectively participate in campaigns that support the local currency. Indeed, the Syrian pound appreciated in value in only a few days to reach an average of SYP615 for $1 in the second week of September.This high volatility in currency prices results in monetary uncertainty among traders, and thus, increases the possibility of other depreciations in the near future.Currency speculation could be the reason behind the high fluctuations. However, the fall in the exchange rate has been a continuous and steady trend ever since the beginning of the conflict. The Syrian currency is about 13 times less valuable than before conflict, and fell by 20% between January and September 2019. It is therefore more likely that the devaluation reflects a structural deterioration of the Syrian economy.There are a number of interlinked reasons behind this trend: Economic collapseThe conflict in Syria has led to a drastic decline in economic activity. By 2018, the total accumulated economic loss was estimated at about $428 billion, which equaled 6 times Syria’s GDP in 2010. The country’s GDP lost about 65% of its value compared to its level before the war. The conflict has also caused a reallocation of resources to destructive and war-related activities. This drop in economic productivity weighs on the Syrian pound’s stability. Dramatic export declineThe total value of Syrian exports contracted from $12.2 billion in 2010 to less than $700 million in 2018, whereas imports declined from $19.7 billion to $4.4 billion during the same period. Thus, the coverage ratio of exports to imports dropped from 62% to 16% in this period, indicating that the government has become very dependent on external trade partners. Almost all import payments are made in foreign currencies, which increases the devaluation pressure on the Syrian pound.Iran has provided the Syrian regime with credit lines estimated at about $6 billion to import oil and consumer goods from the Islamic Republic. These credit lines do not include all the Iranian financial support to the regime. Iranian oil exports to Syria are estimated at about 2 million barrels a month (a total of around $16 billion during the eight years of conflict). The increasing external debt to Iran, also due to military support, may contribute in stabilizing the Syrian pound for short period, yet it is bound to sustain the devaluation pressure in the long run. Damaging monetary policiesSince the beginning of the conflict, the Central Bank of Syria has issued a series of decisions that have contributed to the weakening of the Syrian pound. For instance, until 2015, the bank adopted a policy of selling hard currencies to local foreign exchange companies. This policy depleted their foreign currency reserves by about $1.2 billion, without halting the deterioration of the pound. The bank has also increased the money supply; there is three times the amount of currency in the local market as today compared to before the conflict, causing a surge in inflation and currency devaluation.The absence of foreign direct investmentBetween 2005 and 2010, Syria received an annual average of $1.5 billion as foreign direct investment (FDI); this amount has dropped almost to zero during the years of conflict. Russia and Iran have continued to invest in Syria, mainly in the mining sector, but the conditions of these investments have limited the inflows of foreign currency to Syria. FDI inflows were a major source of hard currency; their absence is an additional driver of currency depreciation.International sanctionsMany countries have imposed sanctions on various sectors in Syria, including energy and financial transactions. During the last two years, the US has tightened its sanctions by introducing the Caesar law, which aims to isolate the Syrian regime. These sanctions have increased the cost of the Syrian imports and therefore raised demand for foreign currencies. Remittances, estimated at $4.5 million per day as well as foreign investments and exports were also negatively affected, and this has reduced the supply side of hard currencies inside Syria.Currency speculationThe Syrian regime usually intervenes to manage currency speculation through government agencies and friendly business entities. But such speculations are very difficult to control in Syria given the poor economic conditions, the high level of business uncertainty and the lack of trust in institutions. This has driven the Syrian households, those who did not already lose their savings, to buy gold or hard currencies as safe investments.The Syrian pound’s depreciation and its high fluctuations reflect the fragile political and economic situation in the country. The government’s improvised decisions have failed to stabilize it, causing a rise in the prices of basic goods. This has left more than 90% of Syria’s population under the poverty line. Long-term stability in exchange rates requires an inclusive and sustainable development strategy, one that would need to be based on an accountable and transparent political landscape. That seems a long way off. Full Article
als To Advance Trade and Climate Goals, ‘Global Britain’ Must Link Them By feedproxy.google.com Published On :: Thu, 19 Mar 2020 17:12:54 +0000 19 March 2020 Carolyn Deere Birkbeck Associate Fellow, Global Economy and Finance Programme, and Hoffmann Centre for Sustainable Resource Economy @carolyndeere LinkedIn Google Scholar Dr Emily Jones Associate Professor, Blavatnik School of Government Dr Thomas Hale Associate Professor, Blavatnik School of Government COVID-19 is a sharp reminder of why trade policy matters. As the UK works to forge new trade deals, it must align its trade policy agenda with its climate ambition. 2020-03-19-Boris-Johnson-COP26.jpg Boris Johnson at the launch of the UK-hosted COP26 UN Climate Summit at the Science Museum, London on February 4, 2020. Photo by Jeremy Selwyn - WPA Pool/Getty Images. COVID-19 is a sharp reminder of why trade and climate policy matters. How can governments maintain access to critical goods and services, and ensure global supply chains function in times of crisis?The timing of many trade negotiations is now increasingly uncertain, as are the UK’s plans to host COP26 in November. Policy work continues, however, and the EU has released its draft negotiating text for the new UK-EU trade deal, which includes a sub-chapter specifically devoted to climate. This is a timely reminder both of the pressing need for the UK to integrate its trade and climate policymaking and to use the current crisis-induced breathing space in international negotiations - however limited - to catch up on both strategy and priorities on this critical policy intersection.The UK government has moved fast to reset its external trade relations post-Brexit. In the past month it formally launched bilateral negotiations with the EU and took up a seat at the World Trade Organization (WTO) as an independent member. Until the COVID-19 crisis hit, negotiations were also poised to start with the US.The UK is also in the climate spotlight as host of COP26, the most important international climate negotiation since Paris in 2015, which presents a vital opportunity for the government to show leadership by aligning its trade agenda with its climate and sustainability commitments in bold new ways.Not just an empty aspirationThis would send a signal that ‘Global Britain’ is not just an empty aspiration, but a concrete commitment to lead.Not only is concerted action on the climate crisis a central priority for UK citizens, a growing and increasingly vocal group of UK businesses committed to decarbonization are calling on the government to secure a more transparent and predictable international market place that supports climate action by business.With COP26, the UK has a unique responsibility to push governments to ratchet up ambition in the national contributions to climate action – and to promote coherence between climate ambition and wider economic policymaking, including on trade. If Britain really wants to lead, here are some concrete actions it should take.At the national level, the UK can pioneer new ways to put environmental sustainability – and climate action in particular - at the heart of its trade agenda. Achieving the government’s ambitious Clean Growth Strategy - which seeks to make the UK the global leader in a range of industries including electric cars and offshore wind – should be a central objective of UK trade policy.The UK should re-orient trade policy frameworks to incentivize the shift toward a more circular and net zero global economy. And all elements of UK trade policy could be assessed against environmental objectives - for example, their contribution to phasing out fossil fuels, helping to reverse overexploitation of natural resources, and support for sustainable agriculture and biodiversity.In its bilateral and regional trade negotiations, the UK can and should advance its environment, climate and trade goals in tandem, and implementation of the Paris Agreement must be a core objective of the UK trade strategy.A core issue for the UK is how to ensure that efforts to decarbonise the economy are not undercut by imports from high-carbon producers. Here, a ‘border carbon adjustment (BCA)’ - effectively a tax on the climate pollution of imports - would support UK climate goals. The EU draft negotiating text released yesterday put the issue of BCAs front and centre, making crystal clear that the intersection of climate, environment and trade policy goals will be a central issue for UK-EU trade negotiations.Even with the United States, a trade deal can and should still be seized as a way to incentivize the shift toward a net zero and more circular economy. At the multilateral level, as a new independent WTO member, the UK has an opportunity to help build a forward-looking climate and trade agenda.The UK could help foster dialogue, research and action on a cluster of ‘climate and trade’ issues that warrant more focused attention at the WTO. These include the design of carbon pricing policies at the border that are transparent, fair and support a just transition; proposals for a climate waiver for WTO rules; and identification of ways multilateral trade cooperation could promote a zero carbon and more circular global economy. To help nudge multilateral discussion along, the UK could also ask to join a critical ‘path finder’ effort by six governments, led by New Zealand, to pursue an agreement on climate change, trade and sustainability (ACCTS). This group aims to find ways forward on three central trade and climate issues: removing fossil fuel subsidies, climate-related labelling, and promoting trade in climate-friendly goods and services.At present, the complex challenges at the intersection of climate, trade and development policy are too often used to defer or side-step issues deemed ‘too hard’ or ‘too sensitive’ to tackle. The UK could help here by working to ensure multilateral climate and trade initiatives share adjustment burdens, recognise the historical responsibility of developed countries, and do not unfairly disadvantage developing countries - especially the least developed.Many developing countries are keen to promote climate-friendly exports as part of wider export diversification strategies and want to reap greater returns from greener global value chains. Further, small island states and least-developed countries – many of which are Commonwealth members – that are especially vulnerable to the impacts of climate change and natural disasters, need support to adapt in the face of trade shocks and to build climate-resilient, trade-related infrastructure and export sectors.As an immediate next step, the UK should actively support the growing number of WTO members in favour of a WTO Ministerial Statement on environmental sustainability and trade. It should work with its key trading partners in the Commonwealth and beyond to ensure the agenda is inclusive, supports achievement of the UN Sustainable Development Goals (SDGs) and helps developing countries benefit from a more environmentally sustainable global economy.As the UK prepares to host COP26, negotiates deals with the EU and US, and prepares for its first WTO Ministerial meeting as an independent member, it must show it can lead the way nationally, bilaterally, and multilaterally. And to ensure the government acts, greater engagement from the UK’s business, civil society and research sectors is critical – we need all hands on deck to forge and promote concrete proposals for aligning UK trade policy with the climate ambition our world needs. Full Article
als Episode 76 - The Internet of Deals (IoD) Black Friday, Mac root bug, Pixel Buds and Animal Crossing By play.acast.com Published On :: Fri, 01 Dec 2017 15:49:36 GMT It's a bumper pod! David Price leads Ashleigh Macro and Henry Burrell down the topical rabbit hole to discuss why Black Friday largely sucks, but is an interesting venture for publishers as well as consumers. Who else bought a Switch?We then tackle the Mac root issue that hit headlines worldwide before tearing the Pixel Buds a new one. And we all downloaded Animal Crossing: Pocket Camp to see what the fuss is about. See acast.com/privacy for privacy and opt-out information. Full Article
als To Advance Trade and Climate Goals, ‘Global Britain’ Must Link Them By feedproxy.google.com Published On :: Thu, 19 Mar 2020 17:12:54 +0000 19 March 2020 Carolyn Deere Birkbeck Associate Fellow, Global Economy and Finance Programme, and Hoffmann Centre for Sustainable Resource Economy @carolyndeere LinkedIn Google Scholar Dr Emily Jones Associate Professor, Blavatnik School of Government Dr Thomas Hale Associate Professor, Blavatnik School of Government COVID-19 is a sharp reminder of why trade policy matters. As the UK works to forge new trade deals, it must align its trade policy agenda with its climate ambition. 2020-03-19-Boris-Johnson-COP26.jpg Boris Johnson at the launch of the UK-hosted COP26 UN Climate Summit at the Science Museum, London on February 4, 2020. Photo by Jeremy Selwyn - WPA Pool/Getty Images. COVID-19 is a sharp reminder of why trade and climate policy matters. How can governments maintain access to critical goods and services, and ensure global supply chains function in times of crisis?The timing of many trade negotiations is now increasingly uncertain, as are the UK’s plans to host COP26 in November. Policy work continues, however, and the EU has released its draft negotiating text for the new UK-EU trade deal, which includes a sub-chapter specifically devoted to climate. This is a timely reminder both of the pressing need for the UK to integrate its trade and climate policymaking and to use the current crisis-induced breathing space in international negotiations - however limited - to catch up on both strategy and priorities on this critical policy intersection.The UK government has moved fast to reset its external trade relations post-Brexit. In the past month it formally launched bilateral negotiations with the EU and took up a seat at the World Trade Organization (WTO) as an independent member. Until the COVID-19 crisis hit, negotiations were also poised to start with the US.The UK is also in the climate spotlight as host of COP26, the most important international climate negotiation since Paris in 2015, which presents a vital opportunity for the government to show leadership by aligning its trade agenda with its climate and sustainability commitments in bold new ways.Not just an empty aspirationThis would send a signal that ‘Global Britain’ is not just an empty aspiration, but a concrete commitment to lead.Not only is concerted action on the climate crisis a central priority for UK citizens, a growing and increasingly vocal group of UK businesses committed to decarbonization are calling on the government to secure a more transparent and predictable international market place that supports climate action by business.With COP26, the UK has a unique responsibility to push governments to ratchet up ambition in the national contributions to climate action – and to promote coherence between climate ambition and wider economic policymaking, including on trade. If Britain really wants to lead, here are some concrete actions it should take.At the national level, the UK can pioneer new ways to put environmental sustainability – and climate action in particular - at the heart of its trade agenda. Achieving the government’s ambitious Clean Growth Strategy - which seeks to make the UK the global leader in a range of industries including electric cars and offshore wind – should be a central objective of UK trade policy.The UK should re-orient trade policy frameworks to incentivize the shift toward a more circular and net zero global economy. And all elements of UK trade policy could be assessed against environmental objectives - for example, their contribution to phasing out fossil fuels, helping to reverse overexploitation of natural resources, and support for sustainable agriculture and biodiversity.In its bilateral and regional trade negotiations, the UK can and should advance its environment, climate and trade goals in tandem, and implementation of the Paris Agreement must be a core objective of the UK trade strategy.A core issue for the UK is how to ensure that efforts to decarbonise the economy are not undercut by imports from high-carbon producers. Here, a ‘border carbon adjustment (BCA)’ - effectively a tax on the climate pollution of imports - would support UK climate goals. The EU draft negotiating text released yesterday put the issue of BCAs front and centre, making crystal clear that the intersection of climate, environment and trade policy goals will be a central issue for UK-EU trade negotiations.Even with the United States, a trade deal can and should still be seized as a way to incentivize the shift toward a net zero and more circular economy. At the multilateral level, as a new independent WTO member, the UK has an opportunity to help build a forward-looking climate and trade agenda.The UK could help foster dialogue, research and action on a cluster of ‘climate and trade’ issues that warrant more focused attention at the WTO. These include the design of carbon pricing policies at the border that are transparent, fair and support a just transition; proposals for a climate waiver for WTO rules; and identification of ways multilateral trade cooperation could promote a zero carbon and more circular global economy. To help nudge multilateral discussion along, the UK could also ask to join a critical ‘path finder’ effort by six governments, led by New Zealand, to pursue an agreement on climate change, trade and sustainability (ACCTS). This group aims to find ways forward on three central trade and climate issues: removing fossil fuel subsidies, climate-related labelling, and promoting trade in climate-friendly goods and services.At present, the complex challenges at the intersection of climate, trade and development policy are too often used to defer or side-step issues deemed ‘too hard’ or ‘too sensitive’ to tackle. The UK could help here by working to ensure multilateral climate and trade initiatives share adjustment burdens, recognise the historical responsibility of developed countries, and do not unfairly disadvantage developing countries - especially the least developed.Many developing countries are keen to promote climate-friendly exports as part of wider export diversification strategies and want to reap greater returns from greener global value chains. Further, small island states and least-developed countries – many of which are Commonwealth members – that are especially vulnerable to the impacts of climate change and natural disasters, need support to adapt in the face of trade shocks and to build climate-resilient, trade-related infrastructure and export sectors.As an immediate next step, the UK should actively support the growing number of WTO members in favour of a WTO Ministerial Statement on environmental sustainability and trade. It should work with its key trading partners in the Commonwealth and beyond to ensure the agenda is inclusive, supports achievement of the UN Sustainable Development Goals (SDGs) and helps developing countries benefit from a more environmentally sustainable global economy.As the UK prepares to host COP26, negotiates deals with the EU and US, and prepares for its first WTO Ministerial meeting as an independent member, it must show it can lead the way nationally, bilaterally, and multilaterally. And to ensure the government acts, greater engagement from the UK’s business, civil society and research sectors is critical – we need all hands on deck to forge and promote concrete proposals for aligning UK trade policy with the climate ambition our world needs. Full Article
als COVID-19 Impact on Refugees is Also Political By feedproxy.google.com Published On :: Tue, 31 Mar 2020 10:53:27 +0000 31 March 2020 Dr Lina Khatib Director, Middle East and North Africa Programme @LinaKhatibUK The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities. 2020-03-31-Covid19-lebanon The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images. As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece. Full Article
als Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis [13. Other] By feedproxy.google.com Published On :: 2010-02-10T02:51:33-08:00 Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment. Full Article
als Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling [Research] By feedproxy.google.com Published On :: 2020-04-06T05:35:14-07:00 Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR. Full Article
als Immunopeptidomic analysis reveals that deamidated HLA-bound peptides arise predominantly from deglycosylated precursors [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-05-01T11:35:42-07:00 The presentation of post-translationally modified (PTM) peptides by cell surface HLA molecules has the potential to increase the diversity of targets for surveilling T cells. Whilst immunopeptidomics studies routinely identify thousands of HLA-bound peptides from cell lines and tissue samples, in-depth analyses of the proportion and nature of peptides bearing one or more PTMs remains challenging. Here we have analyzed HLA-bound peptides from a variety of allotypes and assessed the distribution of mass spectrometry-detected PTMs, finding deamidation of asparagine or glutamine to be highly prevalent. Given that asparagine deamidation may arise either spontaneously or through enzymatic reaction, we assessed allele-specific and global motifs flanking the modified residues. Notably, we found that the N-linked glycosylation motif NX(S/T) was highly abundant across asparagine-deamidated HLA-bound peptides. This finding, demonstrated previously for a handful of deamidated T cell epitopes, implicates a more global role for the retrograde transport of nascently N-glycosylated polypeptides from the ER and their subsequent degradation within the cytosol to form HLA-ligand precursors. Chemical inhibition of Peptide:N-Glycanase (PNGase), the endoglycosidase responsible for the removal of glycans from misfolded and retrotranslocated glycoproteins, greatly reduced presentation of this subset of deamidated HLA-bound peptides. Importantly, there was no impact of PNGase inhibition on peptides not containing a consensus NX(S/T) motif. This indicates that a large proportion of HLA-I bound asparagine deamidated peptides are generated from formerly glycosylated proteins that have undergone deglycosylation via the ER-associated protein degradation (ERAD) pathway. The information herein will help train deamidation prediction models for HLA-peptide repertoires and aid in the design of novel T cell therapeutic targets derived from glycoprotein antigens. Full Article
als Proteomics of Campylobacter jejuni growth in deoxycholate reveals Cj0025c as a cystine transport protein required for wild-type human infection phenotypes [Research] By feedproxy.google.com Published On :: 2020-05-06T13:56:38-07:00 Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species. Full Article
als Egypt and the Gulf: Allies and Rivals By feedproxy.google.com Published On :: Sun, 19 Apr 2020 20:38:18 +0000 20 April 2020 There is and will continue to be an edge of rivalry in Egypt’s relations with the dominant Gulf Arab powers. This paper will focus primarily on the Egypt–Gulf relationship during the Sisi era. Read online Download PDF David Butter Associate Fellow, Middle East and North Africa Programme @DavidCButter 2020-04-20-Egypt-Gulf.jpg Crown Prince of Abu Dhabi Mohammed bin Zayed is welcomed by Egypt’s President Abdel-Fattah el-Sisi in Cairo on 19 June 2017. Photo: Getty Images. Summary Egypt and the Gulf Arab region have long been important poles of political, military economic and cultural power and influence in the Middle East. Under the presidency of Gamal Abdel-Nasser, Egypt was the dominant force in the region, but the balance of power shifted towards the Gulf in the 1970s, as Egypt’s economy faltered and the Gulf Arab states reaped the benefits of resurgent oil prices in the wake of the 1973 OPEC embargo. The popular uprising against President Hosni Mubarak’s regime in 2011 elicited divergent reactions in the Gulf. The leaders of Saudi Arabia and the United Arab Emirates (UAE) were concerned about the risks of a movement for revolutionary change spreading to their own region, while Qatar saw an opportunity to strengthen its regional role through supporting the Muslim Brotherhood.The forcible removal of Egypt’s elected president, Mohammed Morsi of the Muslim Brotherhood, in July 2013 by the army commander, Abdel-Fattah el-Sisi, ushered in a new era in Egypt–Gulf relations. The UAE, Saudi Arabia and Kuwait quickly mobilized financial support for the new administration. Abu Dhabi’s crown prince, Mohammed bin Zayed, known for his intense opposition to the Muslim Brotherhood, signalled his strong support for the new regime by visiting Cairo only weeks after hundreds of Morsi’s supporters were killed.Between July 2013 and August 2016, the UAE, Saudi Arabia and Kuwait provided about $30 billion in aid to the Sisi regime through placing deposits with the Central Bank of Egypt and supplying petroleum products as grants. The UAE sought to link its aid to a programme of economic reforms, but the Egyptian government finally decided in mid-2016 to negotiate a loan agreement with the International Monetary Fund (IMF). Since the signing of the $12 billion loan with the IMF in November 2016, Egypt has no longer been reliant on Gulf Arab financial support, although some of the deposits placed previously have been rolled over on reaching maturity.During the Sisi era, Egypt has benefited from its economic links to the Gulf over a wide spectrum of activities. The UAE and Saudi Arabia in particular are increasingly important export markets for Egyptian companies, as well as major sources of foreign direct investment. The financial aid provided by Sisi’s Gulf allies in 2013–16 has also helped to underpin the surge in Egypt’s arms procurement. Another critical element in the economic relationship is the presence of millions of expatriate Egyptian workers in the Gulf, who are responsible for a large share of the annual inflow of about $25 billion in remittances.Egypt’s most important political relationships in the Gulf have been with Saudi Arabia and the UAE. Ties with Saudi Arabia were affected by the death of King Abdullah at the start of 2015 and by the subsequent emergence of Mohammed bin Salman as the most influential figure in the kingdom. During a visit by King Abdullah’s successor, King Salman, to Cairo in April 2016, Egypt announced a decision to cede sovereignty over two Red Sea islands, Tiran and Sanafir, to Saudi Arabia. Relations soured after this decision was challenged in the Egyptian courts, but the issue was resolved in favour of the deal. Egypt played no active role in the Saudi- and UAE-led intervention in Yemen, but joined its two principal Gulf allies and Bahrain in imposing sanctions on Qatar in mid-2017. Relations between Sisi and Crown Prince Mohammed bin Zayed have remained close throughout the past seven years. The UAE and Egypt have been among the most important external supporters of the Libyan National Army, commanded by Field Marshal Khalifa Haftar, although they have not created an overt alliance in this arena. Egypt has adopted a more prominent diplomatic profile in relation to Libya, while the UAE has been more deeply engaged militarily, to judge from assessments by the panel of experts tasked to monitor adherence to the UN embargo on the supply of weapons to Libya. The relationship between the Egyptian and Emirati leaders is underpinned by a strong shared ideological antipathy to the Muslim Brotherhood.Following the completion of the IMF programme in 2019, the Egyptian economy is in a much stronger position than it was in the early period of Sisi’s rule, even though this has exacted a harsh toll on the 60 per cent of the population classified by the World Bank as poor or vulnerable. There is no pressing need for direct financial support from the Gulf, but Egypt still depends on economic linkages through trade, investment, tourism and remittances. In this respect, the balance of power has tilted marginally back towards Egypt. However, Egypt is still beset by deep internal political contradictions, as reflected in the regime’s heavy reliance on coercion and repression, and the economy remains vulnerable to external shocks – of which the coronavirus pandemic is a prime example. Department/project Middle East and North Africa Programme Full Article
als Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Lipid droplets (LDs) are energy-storage organelles that are coated with hundreds of proteins, including members of the perilipin (PLIN) family. PLIN5 is highly expressed in oxidative tissues, including the liver, and is thought to play a key role in uncoupling LD accumulation from lipotoxicity; however, the mechanisms behind this action are incompletely defined. We investigated the role of hepatic PLIN5 in inflammation and lipotoxicity in a murine model under both fasting and refeeding conditions and in hepatocyte cultures. PLIN5 ablation with antisense oligonucleotides triggered a pro-inflammatory response in livers from mice only under fasting conditions. Similarly, PLIN5 mitigated lipopolysaccharide- or palmitic acid-induced inflammatory responses in hepatocytes. During fasting, PLIN5 was also required for the induction of autophagy, which contributed to its anti-inflammatory effects. The ability of PLIN5 to promote autophagy and prevent inflammation were dependent upon signaling through sirtuin 1 (SIRT1), which is known to be activated in response to nuclear PLIN5 under fasting conditions. Taken together, these data show that PLIN5 signals via SIRT1 to promote autophagy and prevent FA-induced inflammation as a means to maintain hepatocyte homeostasis during periods of fasting and FA mobilization. Full Article
als The data must be accessible to all [Editorials] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Full Article
als Images in Lipid Research [Editorials] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
als A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease By diabetes.diabetesjournals.org Published On :: 2019-04-01T13:15:12-07:00 Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10–6) with replication at Bonferroni-corrected P < 8.6 x 10–4. Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10–4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood–derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat–associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups. Full Article
als The Metabolic Responses to 24-h Fasting and Mild Cold Exposure in Overweight Individuals are Correlated and Accompanied by Changes in FGF21 Concentration By diabetes.diabetesjournals.org Published On :: 2020-04-27T16:35:54-07:00 A greater decrease in 24-h energy expenditure (24EE) during 24h fasting defines a thriftier metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male, age: 36.6±11.4y, percentage body fat: 34.8±10.5%). Greater decrease in 24EE during fasting (thriftier phenotype) was associated with less increase in 24EE during COLD, i.e. less cold-induced thermogenesis. Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated and mediated by the liver-derived hormone FGF21. Thus, the 24EE response to COLD further identifies the thrifty versus spendthrift phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change. Full Article
als Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils [Computational Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis. Full Article
als Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis By feeds.bmj.com Published On :: Monday, December 5, 2016 - 14:46 Full Article
als Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019 By diabetescoreupdate.libsyn.com Published On :: Thu, 23 Apr 2020 18:00:00 +0000 Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019 This special issue is an audio version of the American Diabetes Associations Covid-19 leadership team discussing a range of issues on Covid-19 and Diabetes. Recorded March 31, 2020. Topics include: Access to medications Effect on Diabetes Self-management Can Patients take their own Supplies if they are an inpatient in the hospital – particularly insulin pumps and CGM Considerations for Specific Hypoglycemic Medications during Inpatient Hospitalization Differences in Management for Persons with Type 1 and Type 2 Diabetes SGLT-2 inhibitors and GLP-1 Receptor Agonists use During Covid-19 Infection Diabetes and Cardiovascular Disease during Covid-19 ACEs and ARBs Stress among Healthcare Professionals Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. Presented by: Robert Eckel, MD ADA President, Medicine & Science University of Colorado Mary de Groot, PhD ADA President, Health Care & Education Indiana University Irl Hirsch, MD University of Washington Anne Peters, MD University of Southern California Louis Philipson, MD, PhD ADA Past President, Medicine & Science University of Chicago Neil Skolnik, MD Abington Jefferson Health Full Article
als Covid-19: Nightingale hospitals set to shut down after seeing few patients By feeds.bmj.com Published On :: Thursday, May 7, 2020 - 13:50 Full Article
als US$10,000 gofundme launched to support animals at Hope Zoo By jamaica-gleaner.com Published On :: Fri, 08 May 2020 11:51:03 -0500 A gofundme account has been launched with the hope of keeping animals feed and to preserve endangered wildlife at the Hope Zoo in St Andrew. Curator, Joey Brown, organiser of the fundraiser, indicated that as a non-profit organisation,... Full Article