by 'Everybody around here is dying,' Shelburne retirement home devastated by outbreak By barrie.ctvnews.ca Published On :: Thu, 7 May 2020 17:17:00 -0400 The Shelburne Retirement Residence has been devastated by an outbreak of COVID-19, with 90 per cent of its residents becoming infected. Full Article
by Campers must clear out of Oppenheimer Park by noon Saturday By bc.ctvnews.ca Published On :: Fri, 8 May 2020 11:29:00 -0700 With the eviction date looming for campers to leave Oppenheimer Park, B.C.'s social development minister says everyone is still expected to be out of the park by Saturday. Full Article
by Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function. Full Article
by Libya Needs an Economic Commission to Exit From Violence By feedproxy.google.com Published On :: Wed, 20 Nov 2019 14:11:20 +0000 20 November 2019 Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn A new effort to manage the economy, one that brings together both sides of the war with international partners, is an essential step forward. 2019-11-20-LD.jpg Angela Merkel greets Fayez al-Serraj, prime minister of the Government of National Accord of Libya, in May. Photo: Getty Images. There has been a stark contrast between messaging coming from the international community and trends on the ground as Libya’s latest bout of civil war enters its eighth month.Led by Germany, some states have been trying to build consensus for a ceasefire ahead of a summit that is expected to be held in Berlin in the next few months. Today marks the date of one of the final planning meetings for the summit.The increasing use of drone technology, airstrikes and further influxes of fighters trend points in the opposite direction. Warring groups in Libya continue to receive support from external states, undermining international efforts to de-escalate the conflict. A UN arms embargo goes largely unenforced. As the Berlin process unfolds, there is little evidence to suggest that these external states will shift their positions.The launch of Field Marshal Khalifa Haftar’s Libyan Arab Armed Forces (LAAF) offensive on Tripoli in April sunk a UN-planned ‘national conference’, intended to be held less than two weeks later, to negotiate a framework for transition out of Libya’s governance crisis. Yet, Haftar has so far failed in his objective of capturing Tripoli. While his offensive continues, had he the capacity to capture the city, he would have done so already.This has created a conundrum for peace talks: there appears to be little chance of negotiating a deal with Haftar, while it is also hard to see how a deal could be reached without him.The field marshal has little interest in accepting a withdrawal, even a partial one, of his forces. His opponents – who have found unity in their shared efforts to defeat Haftar’s forces – will not accept a ceasefire that leaves the LAAF on the hinterlands of the capital. Similarly, a deal apparently agreed in Abu Dhabi between Haftar and Prime Minister Fayez al-Serraj in February is also dead in the water.Amid this logjam, there has been an increasing interest in the economic content of the Berlin summit. Countries supportive of Haftar argue that his alliance has legitimate concerns over the management of Libya’s economy and, particularly, the dominant role of the Tripoli-based central bank and its governor in supporting armed groups.For some within these countries, changing the leadership of the central bank and a finding means of limiting the dominance of the UN-backed Government of National Accord (GNA) over the state’s resources – thus reducing flows of funding to armed groups fighting Haftar – could present a point of agreement in Berlin.But their focus on financial management in Tripoli is not mirrored by interest in holding the rival central bank in the eastern city of Bayda – an institution unrecognized by the international community – to account for its pursuit of its own monetary policy. This is built on approximately $23 billion of unsecured debt from commercial banks and $11 billion of currency supplied by Russia.Indeed, very few of the conversations surrounding parameters for Berlin contain details of what would be asked of eastern-based actors beyond pursuit of an audit of the Tripoli and Bayda central banks (only the Tripoli bank is recognized by the international community).Clearly, the GNA and its allies would have no incentive to accept provisions that limit their means to mobilize resources for the war while its opponents do not receive the same scrutiny. However, it is possible to capitalize on the broad interest in economic content to reach some points of agreement over the management of the economy and state institutions. Rather than seeking to replace individuals aligned with one faction for those aligned with another, or expecting asymmetrical concessions from the GNA and its allies, this effort must instead focus on structures and processes that exacerbate the conflict and represent major grievances for the warring parties.Importantly, this would include the establishment of a system of transparency and accountability for the management of Libya’s finances. The opacity of current processes enables the support of patronage-based networks with no effective oversight.Linked to this, the development of effective processes for budgeting and allocating funds could help to reduce graft.And, finally, rationalizing the role of state institutions to agree their roles and responsibilities, creating the room for reforms to Libya’s system of state employment and subsidies through provision of direct payments to Libyan citizens, is essential. An economic commission that comprises members from across political and institutional divides – receiving political support from international powers and technical support from international financial institutions – could be an effective approach. Such a commission could match an inclusive, Libyan-led process with international support to progressively harmonize economic and financial policy between rival authorities and develop consensus for a process of institutional reunification in Libya.This would constitute a major element of an eventual political settlement and reduce the risk of a limited set of actors capturing the system at the expense of the others – an outcome which would likely result in future bouts of violence.Such a commission would offer a means of addressing a key driver of the conflict by decentralizing aspects of Libya’s governance, moving away from the dominance of Tripoli and the current winner-take-all system. These issues cannot be put to one side, to follow progress on the security front. The remarkable resilience that Libya’s economy has shown over the last seven months should not be taken for granted. It has become increasingly difficult for Libya’s institutions to insulate themselves from the conflict as both sides seek to mobilize resources to sustain their war effort.The LAAF is increasingly looking to sideline civilian authorities in eastern Libya. On the other side, the GNA has found means of routing funds to armed groups fighting Haftar.In September, a dispute over the supply of jet fuel between the LAAF and the National Oil Corporation resulted in the establishment of a parallel Brega Petroleum Marketing Company, the state-owned company that possesses a monopoly over fuel distribution.Meanwhile, other major problems lurk under the surface. The banking sector is in an increasingly perilous state and debts continue to mount all around, with those in the east not accounted for by Tripoli’s official authorities. Through the establishment of an economic commission, the Berlin process provides an opportunity and – most importantly – a mechanism to address these problems while also helping to maintain the basic functionality of the state. Even if a ceasefire deal does not materialize, initiating negotiations about the future shape of the state and its economy would be a significant step forward. Full Article
by Local Pathways Towards De-escalation of Libya's Conflict By feedproxy.google.com Published On :: Wed, 22 Jan 2020 10:20:01 +0000 Invitation Only Research Event 28 January 2020 - 3:00pm to 4:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Usama Otman Essed, Libya Center for Strategic & Future StudiesChair: Tim Eaton, Middle East and North Africa Programme, Chatham House A shaky truce remains broadly in place among rival Libyan forces fighting for control of Tripoli. However, a durable ceasefire to bring an end to the current bout of conflict, which was initiated by Khalifa Haftar’s Libyan Arab Armed Forces’ (LAAF) offensive on the capital in April 2019, has not been reached. In recent weeks attention has focused on talks hosted in Moscow and Berlin, with the former aimed at agreeing a ceasefire and the latter seeking to reach agreement among international actors to bring an end to external military support for Libyan warring actors, and to craft a way forward for future intra-Libyan talks. Yet, there has been little emphasis on Libyan actors – beyond Haftar and prime minister Fayez al-Serraj – in this process. This roundtable will bring together experts and policymakers to discuss means of de-escalating the conflict and seeking a lasting resolution through the development of interconnected intra-Libyan social and security negotiation tracks. Mr Usama Otman Essed of the Libya Center for Strategic and Future Studies (LCSFS) will present his research group’s ideas on these issues and discuss their ongoing efforts to promote dialogue among social and security actors.Attendance at this event is by invitation only. Event attributes Chatham House Rule 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
by Prospects for Reforming Libya’s Economic Governance: Ways Forward By feedproxy.google.com Published On :: Mon, 27 Jan 2020 15:45:02 +0000 Invitation Only Research Event 6 February 2020 - 10:30am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Jason Pack, Non-Resident Fellow, Middle East InstituteTim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseChair: Elham Saudi, Director, Lawyers for Justice Libya There is a broad consensus that Libya’s rentier, patronage-based system of governance is a driver, and not only a symptom, of Libya’s continuing conflict. The dysfunction of Libya’s economic system of governance has been exacerbated by the governance split that has prevailed since 2014 whereby rival administrations of state institutions have emerged. Despite these challenges, a system of economic interdependence, whereby forces aligned with Field Marshal Haftar control much of the oil and gas infrastructure and the UN-backed Government of National Accord controls the means of financial distribution, has largely prevailed. Yet, at the time of writing, this is under threat: a damaging oil blockade is being implemented by forces aligned with Haftar and those state institutions that do function on a national basis are finding it increasingly difficult to avoid being dragged into the conflict.This roundtable will bring together analysts and policymakers to discuss these dynamics and look at possible remedies. Jason Pack, non-resident fellow at the Middle East Institute, will present the findings of his latest paper on the issue which recommends the formation of 'a Libyan-requested and Libyan-led International Financial Commission vested with the requisite authorities to completely restructure the economy.' Tim Eaton, who has been leading Chatham House’s work on Libya’s conflict economy, supporting UNSMIL’s efforts in this field, will act as respondent.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Libya’s Conflict Economy Full Article
by POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Wed, 04 Mar 2020 14:15:01 +0000 Invitation Only Research Event 18 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham HouseEmaddedin Badi, Non-Resident Scholar, Middle East InstituteTim Eaton, Senior Research Fellow, MENA Programme Chatham HouseValerie Stocker, Independent Researcher Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country, armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Countering Conflict Economies in MENA, Libya’s Conflict Economy Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
by The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Mon, 16 Mar 2020 17:25:16 +0000 17 March 2020 This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics. Read online Download PDF Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn Abdul Rahman Alageli Associate Fellow, Middle East and North Africa Programme @abdulrahmanlyf Emadeddin Badi Policy Leader Fellow, School of Transnational Governance, European University Institute Mohamed Eljarh Co-founder and CEO, Libya Outlook Valerie Stocker Researcher Amru_24-2_13.jpg Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien SummaryLibya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive. Department/project Middle East and North Africa Programme, Chaos States, Countering Conflict Economies in MENA, Libya’s Conflict Economy Full Article
by NAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling [Microbiology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell. Full Article
by Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function. Full Article
by By enabling formal trade, Nigeria can unleash its vast potential By feedproxy.google.com Published On :: Mon, 07 Dec 2015 16:18:19 +0000 3 December 2015 20151207Nigeriabooming.jpg Nigeria’s booming informal trade is costly for society, business and government, yet a critical opportunity exists to formalize such trade and drive more sustainable and less volatile growth, argues a new report from Chatham House.According to one estimate, informal activity accounts for up to 64 per cent of Nigeria’s GDP. Nigeria's Booming Borders: The Drivers and Consequences of Unrecorded Trade finds that this is a result of obstacles that impede trading through formal channels. These drivers include bureaucratic burdens and other factors, such as:The need for Nigerian businesses to produce at least nine documents in order to send an export shipment and at least 13 in order to bring in an import consignment.Rigid and dysfunctional foreign-exchange regulations that push most smaller traders into the incompletely regulated parallel exchange market.Corruption and unofficial ‘taxation’, especially on major border highways, which delegitimize formal channels and encourage the use of smuggling routes.As a result, the state loses direct tax revenues that would be generated by formal cross-border trade. This is not just siphoned into the informal economy; some is lost entirely. For example, many shippers opt to dock in neighbouring countries rather than deal with the expense and difficulty of using Nigeria’s ports.Informal trade also undermines the social contract between the private sector and government. The state lacks tax revenues to pay its officials, improve infrastructure or implement reforms, while traders feel the government provides no services in return for any taxes they might pay.‘Every day tens of thousands of unofficial payments are made, none destined for the government. Policy-makers need to create an environment that encourages trade to flow through formal channels and capture lost revenue’, says co-author Leena Koni Hoffmann.‘Formalization would assist Nigeria to pursue more high-quality, high-tech economic activity at a time when rising labour costs in Asia are creating scope for Nigerian manufacturers to compete’, she adds.The report makes a number of recommendations for how Nigeria could encourage more formal trade, including:Strengthening the resources and capacity of the Federal Ministry of Industry, Trade and Investment to coordinate action across key government ministries, departments and agencies, as well as public and private stakeholders.Prioritizing engagement in the development of Economic Community of West African States (ECOWAS) trade policies and fully implementing the ECOWAS Protocol on Free Movement of Persons to reduce harassment at borders.Allowing banks to operate simple services for small and medium-sized businesses to make trade payments directly from Nigerian naira to CFA francs and vice versa.Improving basic facilities that support traders, including improving the efficiency of border posts, installing truck parks and all-weather surfacing on market access roads, and introducing online booking for trucks to enter ports.Separating responsibilities for assessing duty and tariff liabilities from revenue collection in order to reduce opportunities for corruption, an approach already tested with success by the Lagos State Internal Revenue Service.Increasing funding and technical support for the National Bureau of Statistics, which has a significant role to play in measuring and capturing more of Nigeria’s external trade.Interviews conducted for the report reveal that business people would welcome the opportunity to pay taxes, but only if they received assurance that these payments would represent a contract with government guaranteeing that conditions for business would be improved.‘As Africa’s largest economy, formalizing external trade would allow Nigeria to fulfil its potential as the trading engine of the West and Central African economy and shape the business landscape across the region,’ says co-author Paul Melly. Editor's notes Read Nigeria's Booming Borders: the Drivers and Consequences of Unrecorded Trade (embargoed until 17:00 GMT on Monday 7 December).To request an interview with the authors, contact the press office.Nigeria’s recorded external trade for 2014 was $135.8 billion.Estimate of informal activity as a percentage of GDP from Jonathan Emenike Ogbuabor and Victor A. Malaolu, ‘Size and Causes of the Informal Sector of the Nigerian Economy: Evidence from Error Correction Mimic Model’, Journal of Economics and Sustainable Development, Vol. 4, No. 1, 2013. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
by Supporting the US Economy by Improving the Mobility of High-skilled Labour Across the Atlantic By feedproxy.google.com Published On :: Wed, 20 Sep 2017 10:33:17 +0000 27 September 2017 US policymakers should give special consideration to a more open immigration policy for highly skilled professionals from the EU. This would ultimately benefit the US economy. Read online Download PDF Marianne Schneider-Petsinger Senior Research Fellow, US and the Americas Programme @mpetsinger 2017-09-25-labour-mobility-us-economy.jpg Businessman on bicycle passing skyline of La Defense business district in Paris, France. Photo: Getty Images. SummaryThe United States and the European Union are deeply integrated economically in terms of movement of goods, services and capital across the Atlantic, but this is not matched by the mobility of labour. Freer movement of high-skilled workers across the Atlantic has a potentially critical role to play in maintaining and strengthening the bilateral economic relationship.Both the US and EU seek to attract high-skilled labour through the use of temporary visa programmes. Various routes are available for highly skilled workers from the EU to temporarily work in the US (for instance, through the H-1B visa for foreign nationals in ‘specialty occupations’, as well as other visa categories for treaty traders and investors, intra-company transferees, and international students seeking work authorization in the US before or after graduation). The main ways for highly skilled workers from the US to temporarily work in EU member states are through EU-wide schemes that apply in 25 out of the 28 member states (for holders of EU Blue Cards or intra-company transferees); or via member states’ parallel national schemes.The experiences of US and EU employers and workers under the US H-1B programme and the EU’s Blue Card scheme differ greatly. The EU Blue Card scheme avoids many of the drawbacks of the H-1B visa. It does not have an annual cap on the number of visas issued. It also grants greater autonomy to the worker by not requiring the employer to sponsor long-term residence, by providing greater flexibility to switch employment, and by having a longer grace period for visa-holders to find new employment after dismissal.The US visa system hampers America’s economic growth. Restrictive policies such as an annual limit on the number of H-1B visas issued, and the associated uncertainty for employees and employers, hinder the ability of US companies to expand and innovate. The complex and costly visa application process is a particular burden for small and medium-sized enterprises. Problems around the timely availability of visas frustrate investors both from the US and from abroad (including from the EU). European firms face difficulties in acquiring visas for intra-company transferees, and not all EU member states have access to the treaty trader and treaty investor visa categories. At times, this impedes foreign direct investment and restricts US job creation. In addition, current policies hinder the economy’s retention of EU and other graduates of US universities. This is of particular concern given that skilled graduates have a critical role to play in addressing the US’s growing shortage of workers in the science, technology, engineering and mathematics (STEM) fields.Given the comparability of US and EU wages and labour markets, US concerns about foreign workers ‘stealing’ their jobs or depressing wages generally do not apply to EU citizens. On the contrary, a more open immigration policy for high-skilled workers – in particular for EU citizens – would benefit the US economy.Efforts to reform visa systems for high-skilled labour are under way in both the US and EU. In order to facilitate the movement of highly skilled workers across the Atlantic, this research paper recommends (1) creating a special visa for highly skilled EU citizens to work temporarily in the US; (2) extending the availability of treaty trader and investor visas to all EU member states; and (3) increasing efforts to eliminate fraud and abuse in the H-1B system. These measures could potentially help to create more investment, jobs and economic growth in the US. Department/project International Security Programme, US and the Americas Programme Full Article
by Professor Robyn Alders, AO By feedproxy.google.com Published On :: Thu, 05 Dec 2019 13:29:42 +0000 Senior Consulting Fellow, Global Health Programme Biography Robyn Alders is a senior consulting fellow with the Chatham House Global Health programme focusing on policy opportunities to support sustainable livestock strategy implementation and sustainable food and nutrition security through a One Health lens.Robyn is also an honorary professor with the Development Policy Centre within the Australian National University, an adjunct professor in the Department of Infectious Disease and Global Health, School of Veterinary Medicine, Tufts University, and chair of the Kyeema Foundation and Upper Lachlan Branch of the NSW Farmers’ Association. For more than 30 years, she has worked closely with family farmers in sub-Saharan Africa, South East Asia and Australia and as a veterinarian, researcher and colleague, with an emphasis on the development of sustainable infectious disease control in animals in rural areas in support of food and nutrition security and systems. Areas of expertise Domestic and global food and nutrition security/systemsHealth securityOne/Planetary HealthGender equityScience communication Past experience 2019 - presentHonorary professor, Development Policy Centre, Australian National University, Canberra, Australia2012-18Professor of food and nutrition security, Faculty of Veterinary Science, University of Sydney, Australia +61 467 603370 Email @robynalders LinkedIn Google Scholar Full Article
by America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images. As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.Bewildering responseFor European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.Need for public oversightIn the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone. Full Article
by 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
by The Human Plasma Proteome: A Nonredundant List Developed by Combination of Four Separate Sources By feedproxy.google.com Published On :: 2004-04-01 N. Leigh AndersonApr 1, 2004; 3:311-326Research Full Article
by Distinct and Overlapping Sets of SUMO-1 and SUMO-2 Target Proteins Revealed by Quantitative Proteomics By feedproxy.google.com Published On :: 2006-12-01 Alfred C. O. VertegaalDec 1, 2006; 5:2298-2310Research Full Article
by In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy By feedproxy.google.com Published On :: 2008-01-01 Ivan MaticJan 1, 2008; 7:132-144Research Full Article
by Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution By feedproxy.google.com Published On :: 2007-12-01 Hasmik KeshishianDec 1, 2007; 6:2212-2229Research Full Article
by Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis By feedproxy.google.com Published On :: 2012-06-01 Ludovic C. GilletJun 1, 2012; 11:O111.016717-O111.016717Research Full Article
by Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics By feedproxy.google.com Published On :: 2005-10-01 William M. OldOct 1, 2005; 4:1487-1502Research Full Article
by Absolute Quantification of Proteins by LCMSE: A Virtue of Parallel ms Acquisition By feedproxy.google.com Published On :: 2006-01-01 Jeffrey C. SilvaJan 1, 2006; 5:144-156Research Full Article
by Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics By feedproxy.google.com Published On :: 2014-02-01 Linn FagerbergFeb 1, 2014; 13:397-406Research Full Article
by Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein By feedproxy.google.com Published On :: 2005-09-01 Yasushi IshihamaSep 1, 2005; 4:1265-1272Research Full Article
by Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ By feedproxy.google.com Published On :: 2014-09-01 Jürgen CoxSep 1, 2014; 13:2513-2526Technological Innovation and Resources Full Article
by Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics By feedproxy.google.com Published On :: 2002-05-01 Shao-En OngMay 1, 2002; 1:376-386Research Full Article
by 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions. Full Article
by The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining {alpha}-tubulin acetylation [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment. Full Article
by Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article
by Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis. Full Article
by A Legionella effector kinase is activated by host inositol hexakisphosphate [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis. Full Article
by NAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling [Microbiology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell. Full Article
by Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria By feedproxy.google.com Published On :: Thu, 07 May 2020 09:16:54 +0000 7 May 2020 , Volume 96, Number 3 Helle Malmvig Read online This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike. Full Article
by Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol By feedproxy.google.com Published On :: 1999-09-01 James M. NtambiSep 1, 1999; 40:1549-1558Reviews Full Article
by Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases By feedproxy.google.com Published On :: 2006-06-01 David A. MitchellJun 1, 2006; 47:1118-1127Thematic Reviews Full Article
by Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions By feedproxy.google.com Published On :: 1970-11-01 M. BursteinNov 1, 1970; 11:583-595Articles Full Article
by Gene expression regulation by retinoic acid By feedproxy.google.com Published On :: 2002-11-01 James E. BalmerNov 1, 2002; 43:1773-1808Reviews Full Article
by Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics By feedproxy.google.com Published On :: 2008-05-01 Vitali MatyashMay 1, 2008; 49:1137-1146Methods Full Article
by Bile salt biotransformations by human intestinal bacteria By feedproxy.google.com Published On :: 2006-02-01 Jason M. RidlonFeb 1, 2006; 47:241-259Reviews Full Article
by Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By feedproxy.google.com Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
by America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images. As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.Bewildering responseFor European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.Need for public oversightIn the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone. Full Article
by Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development. Full Article
by Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria By feedproxy.google.com Published On :: Thu, 07 May 2020 09:16:54 +0000 7 May 2020 , Volume 96, Number 3 Helle Malmvig Read online This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike. Full Article
by Undercurrents: Episode 7 - Libya's War Economy, and Is the United Nations Still Relevant? By feedproxy.google.com Published On :: Fri, 04 May 2018 00:00:00 +0100 Full Article
by Equality by 2030: The Press for Progress By feedproxy.google.com Published On :: Wed, 16 May 2018 00:00:00 +0100 Full Article
by Inside the Battle for the New Libya By feedproxy.google.com Published On :: Fri, 18 May 2018 00:00:00 +0100 Full Article
by How to Fix Finance by Reinforcing Human Rights By feedproxy.google.com Published On :: Wed, 11 Jul 2018 00:00:00 +0100 Full Article
by Sustainable Solutions to Challenges Faced by Displaced People and Refugees By feedproxy.google.com Published On :: Wed, 03 Apr 2019 00:00:00 +0100 Full Article
by Protecting the Environment in Areas Affected by Armed Conflict By feedproxy.google.com Published On :: Tue, 15 Oct 2019 00:00:00 +0100 Full Article
by Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Thu, 28 Nov 2019 00:00:00 +0000 Full Article