em 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
em Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 An experimental and computational approach for identification of protein-protein interactions by ex vivo chemical crosslinking and mass spectrometry (CLMS) has been developed that takes advantage of the specific characteristics of cyanurbiotindipropionylsuccinimide (CBDPS), an affinity-tagged isotopically coded mass spectrometry (MS)-cleavable crosslinking reagent. Utilizing this reagent in combination with a crosslinker-specific data-dependent acquisition strategy based on MS2 scans, and a software pipeline designed for integrating crosslinker-specific mass spectral information led to demonstrated improvements in the application of the CLMS technique, in terms of the detection, acquisition, and identification of crosslinker-modified peptides. This approach was evaluated on intact yeast mitochondria, and the results showed that hundreds of unique protein-protein interactions could be identified on an organelle proteome-wide scale. Both known and previously unknown protein-protein interactions were identified. These interactions were assessed based on their known sub-compartmental localizations. Additionally, the identified crosslinking distance constraints are in good agreement with existing structural models of protein complexes involved in the mitochondrial electron transport chain. Full Article
em 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
em Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity. Full Article
em Targeting the polyamine pathway—“a means” to overcome chemoresistance in triple-negative breast cancer [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Triple-negative breast cancer (TNBC) is characterized by its aggressive biology, early metastatic spread, and poor survival outcomes. TNBC lacks expression of the targetable receptors found in other breast cancer subtypes, mandating use of cytotoxic chemotherapy. However, resistance to chemotherapy is a significant problem, encountered in about two-thirds of TNBC patients, and new strategies are needed to mitigate resistance. In this issue of the Journal of Biological Chemistry, Geck et al. report that TNBC cells are highly sensitive to inhibition of the de novo polyamine synthesis pathway and that inhibition of this pathway sensitizes cells to TNBC-relevant chemotherapy, uncovering new opportunities for addressing chemoresistance. Full Article
em Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC. Full Article
em DHS herding people on to an imperfect system in myGov By www.smh.com.au Published On :: Mon, 10 Aug 2015 14:17:52 GMT Over the past few weeks I have been answering calls for the myGov helpdesk. Full Article
em Memo to Australia Post: Sendle has arrived By www.smh.com.au Published On :: Mon, 17 Aug 2015 14:00:00 GMT From aspiring spaceship builder to CSIRO bigwig, James Chin Moody has taken an unlikely route to creating a parcel delivery start-up. Full Article
em Victorian Premier Daniel Andrews announces 175 new tech jobs for Melbourne By www.smh.com.au Published On :: Mon, 09 Nov 2015 01:57:04 GMT State government commits to five-year funding round as software company launches community centre and new jobs. Full Article
em Anonymous group hacks Islamic State, tells them to chill out: reports By www.smh.com.au Published On :: Fri, 27 Nov 2015 00:42:23 GMT Terrorists' propaganda appears to be shifting to the Dark Web so that it will be harder to shut down. Full Article
em Australian public service failing to share information: Public Sector Data Management report By www.smh.com.au Published On :: Tue, 08 Dec 2015 02:59:08 GMT A report has revealed stunning examples of public service inefficiency when it comes to releasing and managing data. Full Article
em Telstra privacy breach leaves customer's voicemail exposed By www.smh.com.au Published On :: Fri, 22 Jan 2016 05:56:14 GMT Richard Thornton did a factory reset on his second-hand iPhone 5, but the buyer kept receiving his voicemail. Full Article
em Remembering the failed Aussie start-ups of yesteryear By www.smh.com.au Published On :: Thu, 18 Feb 2016 00:13:08 GMT Failed start-ups are a dime a dozen. But you wouldn't know it from the Australian market which, unlike that of our American cousins, prefers to hide its failures and slink quietly into that good night instead of exploring the lessons gleaned from failure. Full Article
em Digital public service means ditching control and embracing 'we' By www.smh.com.au Published On :: Mon, 01 Aug 2016 13:45:00 GMT Collaborating with the public is the key for a more engaging government experience. Full Article
em $212,000 per public service IT contractor, and we're hiring more of them By www.smh.com.au Published On :: Tue, 20 Dec 2016 08:47:58 GMT Contractors cost 80 grand more than public servants, Finance Departments says, and the public service hires more of them. Full Article
em Auditor-general exposes weaknesses in ACT government's IT systems By www.smh.com.au Published On :: Mon, 08 May 2017 02:35:19 GMT Electronic sexual health records and the births, deaths and marriages registry have been left exposed. Full Article
em Latest ATO online system failure hits at peak tax time By www.smh.com.au Published On :: Wed, 05 Jul 2017 10:54:02 GMT Outages have hit the Tax Office's IT system on Wednesday. Full Article
em Tax time IT problems strike again at Australian Taxation Office By www.smh.com.au Published On :: Mon, 21 Aug 2017 06:34:06 GMT Slow internet is causing headaches during a busy time at the Tax Office. Full Article
em Public service bosses to be schooled in digital following IT problems By www.smh.com.au Published On :: Wed, 10 Jan 2018 06:56:05 GMT Public service bosses will take lessons aiming to improve their leadership in all things digital. Full Article
em ACT police emailing speeding tickets could be 'ripe for scammers' By www.smh.com.au Published On :: Sat, 27 Jan 2018 23:16:02 GMT Nigel Phair said experts had spent years warning Australians about dodgy email scams. Full Article
em Latin America: Shifting Political Dynamics and the Implications for the Global System By feedproxy.google.com Published On :: Mon, 09 Sep 2019 13:20:01 +0000 Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates 26 September 2019 - 8:00am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House In the past 12 months, a series of highly-anticipated elections throughout Latin America have demonstrated that deep political shifts are underway. This has occurred at a time when economic growth across the region is slowing and a number of countries face growing social crises. How will these political shifts and social challenges affect growth and foreign direct investment (FDI)?Christopher Sabatini will outline how the shifting political dynamics across the region have, and will, continue to influence trade and investment in the coming months and years across the continent and what regional developments mean for the international community in light of Brexit, global trade tensions and the rise of China and other emerging powers. How can businesses and governments provide a platform to overcome mutual obstacles faced by Latin American investors? What impact have Chinese development projects had in Latin America? And are medium and small economies in Latin America vulnerable to a global trade war?This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you would like to register your interest, please RSVP to Linda Bedford. We will contact you to confirm your attendance.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Members Events Team Email Full Article
em Influencing the social impact of financial systems: alternative strategies By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:35:39 +0000 4 March 2020 , Volume 96, Number 2 Lee-Anne Sim Read Online The social impact of the global financial crisis brought global and domestic financial systems into public focus. While over the last ten years governments have introduced a range of regulatory reforms, there are still low levels of public trust in financial sectors, and academics continue to express their concerns about financial systems and their desire for more influence. This is particularly the case for those framing their evaluation of the quality of financial systems in terms of social values. This article offers those seeking more influence over the social values of financial systems, a fresh perspective on their available strategic options for influencing outcomes. It argues that they should consider strategies aimed at making allies of financial sectors and regulators in influencing change. The main advantage of these alliance strategies is that they address key constraints to influence, as identified in existing scholarship, which are difficult to relax because they are tied to features inherent in financial systems. By addressing these constraints, alliance strategies could increase the likelihood that financial system outcomes align more closely with their preferred social values. Full Article
em 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
em The G20’s Pandemic Moment By feedproxy.google.com Published On :: Tue, 24 Mar 2020 16:57:35 +0000 24 March 2020 Jim O'Neill Chair, Chatham House The planned emergency meeting of the G20 leaders could be the beginning of smart, thoughtful, collective steps to get beyond this challenging moment in history. 2020-03-24-COVID-Vaccine A researcher works on a vaccine against coronavirus COVID-19 at the Copenhagen University research lab. Photo by THIBAULT SAVARY/AFP via Getty Images. Having chaired the independent (and global) Antimicrobial Resistance (AMR) Review for David Cameron, I know a similar approach should have been taken quickly about COVID-19.Similar not in precise nature but - in so far as incorporating infectious disease modelling, and using economic analysis to try to contain and solve it - it should be applied in parallel.The AMR Review is well-known for highlighting the potential loss of life as well as the economic costs of an escalating growth of resistance to antimicrobials, and the inaction to prevent it.In particular we showed that, by 2050, there could be around 10 million people each year dying from AMR, and an accumulated $100trn economic cost to the world from 2015 to 2050.Horrendous outcomesWhat is less focused on, as we showed in our final report, is that to prevent these horrendous outcomes, a 'mere' $42bn would need to be invested globally. This would give an investment return of something like 2,000%.I shudder to think what policymakers could do if we don’t make these investments and we reach a situation - possibly accelerated itself by escalating the inappropriate use of antibiotics in this COVID-19 crisis - where we run out of useful antibiotics. It will be a much longer time period to find new vaccines to beat COVID-19.In addition to this crisis, requiring G20 policymakers to back up their generous words about combatting AMR would mean they need to spend around $10bn instigating the generally agreed Market Incentive Awards to promote serious efforts by pharmaceutical companies.In fact, given that the financial crisis we are also now in means companies are greatly dependent on our governments for their future survival, perhaps the pharma Industry will finally understand the real world concept of 'Pay or Play', where companies that don’t try to find new antibiotics are taxed to provide the pool of money for others that are bold enough to try. And realise there is a world coming of different risk-rewards for all, including them.When applied to the COVID-19 challenge, it is useful to look at the required investment in accelerating as much as possible the efforts to find useful vaccines to beat it, but also to immediately introduce the therapeutics and diagnostics in countries that are so poorly prepared.Those Asian countries affected early include a number that seem to have coped so far in keeping the crisis to a minimum because they had the appropriate therapeutics and diagnostics, despite not having vaccines. A sum of approximately $10 bn from the G20 would be sufficient to cover all these vital areas.Now consider the economics of social distancing. As soon as it became apparent that our policymakers were heeding the Chinese method of trying to suppress COVID-19, it was immediately obvious that our economies would - at least for a short period - sustain the collapse of GDP that China self-imposed in February. From industrial production and other regular monthly data, the Chinese economy has declined by around 20%.It is quite likely many other economies - probably each of the G7 countries - will experience something not too dissimilar in March. And, to stop our complex democracies from further immediate pressure including social disharmony, governments in many countries have needed to undertake dramatic unconventional steps.Here in the UK, our new chancellor effectively had three budgets within less than a fortnight. And outside of the £330bn loan policy he has announced, at least £50bn worth of economic stimulus has been announced.Many other G20 countries have undertaken their own versions of what I call 'People’s QE', many of them bigger packages - the US appears to be contemplating a stimulus as much as $2 trillion.But, for the sake of illustration, if the UK package were the price for three months social distancing and this was repeated across the G20, then the total cost for all G20 countries - adjusted for relative size - would be in the vicinity of $1trillion.If this isn’t accompanied by steps involving the best therapeutics and diagnostics, and we have to keep everyone isolated for one year, it would become at least $4trillion.This may be 'back of the envelope' calculations which ignores the almost inevitable challenges for social cohesion in so many nations. But the G20 must spend something around $10bn immediately to put in absolute best standards all over the world, and another $10 bn to kickstart the market for new antibiotics.This is a version of an article that first appeared in Project Syndicate. Full Article
em Emerging Lessons From COVID-19 By feedproxy.google.com Published On :: Thu, 02 Apr 2020 14:49:54 +0000 2 April 2020 Jim O'Neill Chair, Chatham House Exploring what lessons can be learned from the crisis to improve society and the functioning of our economic model going forward. 2020-04-02-COVID-Italy A man with a protective mask by the Coliseum in Rome during the height of Italy's COVID-19 epidemic. Photo by ALBERTO PIZZOLI/AFP via Getty Images. As tentative evidence emerges that Italy and Spain may have reached - or are close to - the peak of the curve, this could demonstrate that not only can Asian countries get to grips with COVID-19, but so can western democracies. And, if so, this offers a path for the rest of us.The last few weeks does demonstrate there is a role for governments to intervene in society, whether it be health, finance or any walk of life, as they have had to implement social distancing. Some have been forced, and the interventions are almost definitely only temporary, but perhaps some others may be less so.Governments of all kinds now realise there is a connection between our health system quality and our economic capability. On an index of global economic sustainability that I presided over creating when I was at Goldman Sachs, the top ten best performing countries on growth environment scores includes eight of the best performing ten countries - so far- in handling the crisis in terms of deaths relative to their population.Health system qualityThe top three on the index (last calculated in 2014) were Singapore, Hong Kong and South Korea, all of which are exemplary to the rest of us on how to deal with this mess. This suggests that once we are through this crisis, a number of larger populated countries - and their international advisors such as the IMF - might treat the quality of countries' health systems just as importantly as many of the other more standard indicators in assessing ability to deal with shocks.Policymakers have also been given a rather stark warning about other looming health disasters, especially antimicrobial resistance, of which antibiotic resistance lies at the heart. An independent review I chaired recommended 29 interventions, requiring $42 bn worth of investment, essentially peanuts compared to the costs of no solution, and the current economic collapse from COVID-19. It would seem highly likely to me that policymakers are going to treat this more seriously now.As a clear consequence of the - hopefully, temporary - global economic collapse, our environment suddenly seems to be cleaner and fresher and, in this regard, we have bought some time in the battle against climate change. Surely governments are going to be able to have a bigger influence on fossil fuel extractors and intense users as we emerge from this crisis?For any industries requiring government support, the government can make it clear this is dependent on certain criteria. And surely the days of excessive use of share buy backs and extreme maximisation of profit at the expense of other goals, are over?It seems to me an era of 'optimisation' of a number of business goals is likely to be the mantra, including profits but other things too such as national equality especially as it relates to income. Here in the UK, the government has offered its strongest fiscal support to the lower end of the income earning range group and, in a single swoop, has presided over its most dramatic step towards narrowing income inequality for a long time.This comes on top of a period of strong initiatives to support higher levels of minimum earnings, meaning we will emerge later in 2020, into 2021, and beyond, with lower levels of income inequality.The geographic issue of rural versus urban is also key. COVID-19 has spread more easily in more tightly packed cities such as London, New York and many others. More geographically remote places, by definition, are better protected. Perhaps now there will be some more thought given by policymakers to the quality and purpose of life outside our big metropolitan areas.Lastly, will China emerge from this crisis by offering a mammoth genuine gesture to the rest of the world, and come up, with, unlike, in 2008, a fiscal stimulus to its own consumers, that is geared towards importing a lot of things from the rest of the world? Now that would be good way of bringing the world back together again.This is a version of an article originally published in The Article Full Article
em Webinar: Global Economic Recovery and Resilience to Systemic Shocks By feedproxy.google.com Published On :: Fri, 17 Apr 2020 16:15:01 +0000 Corporate Members Event Webinar 20 May 2020 - 5:00pm to 5:45pmAdd to CalendariCalendar Outlook Google Yahoo Francesca Viliani, Consultant Researcher, Global Health Programme, Chatham House; Director, Public Health, International SOSSven Smit, Co-Chair, McKinsey Global Institute and Senior Partner, McKinsey & Company, AmsterdamChair: Creon Butler, Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme, Chatham House The outbreak of COVID-19 has demonstrated the wide-ranging and immediate impact a systemic shock can have on the global economy including the financial loss caused by the emergency shutdown of many retail operations, the loss of income for individuals who are forced to stay indoors and the major disruption to supply chains. The longer term impacts are still being realized and depend heavily on the ability of industry and the government to respond effectively to the direct economic shock caused by the pandemic.Systemic shocks like the COVID-19 pandemic demand immediate responses, but should also encourage governments and industries to re-examine their recovery processes, their resilience and their forward planning. In this webinar, the panellists will discuss the short and long-term impacts of the current crisis and explore how industry can help ensure that the global economy is able to recover from, and build resilience to, future systemic shocks. How do business leaders move from making decisions to reimagining a ‘new normal’ and reforming their practices? What are the critical decisions that businesses should consider when planning for this 'new normal'? And how far can these decisions be based on expected changes to governmental or intergovernmental regulation of different sectors? This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members and giving circles.Not a corporate member? Find out more. Full Article
em Webinar: European Democracy in the Last 100 Years: Economic Crises and Political Upheaval By feedproxy.google.com Published On :: Thu, 23 Apr 2020 10:25:01 +0000 Members Event Webinar 6 May 2020 - 1:00pm to 2:00pm Event participants Pepijn Bergsen, Research Fellow, Europe Programme, Chatham HouseDr Sheri Berman, Professor of Political Science, Barnard CollegeChair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House In the last 100 years, global economic crises from the Great Depression of the 1930s to the 2008 financial crash have contributed to significant political changes in Europe, often leading to a rise in popularity for extremist parties and politics. As Europe contends with a perceived crisis of democracy - now compounded by the varied responses to the coronavirus outbreak - how should we understand the relationship between externally-driven economic crises, political upheaval and democracy?The panellists will consider the parallels between the political responses to some of the greatest economic crises Europe has experienced in the last century. Given that economic crises often transcend borders, why does political disruption vary between democracies? What can history tell us about the potential political impact of the unfolding COVID-19-related economic crisis? And will the unprecedented financial interventions by governments across Europe fundamentally change the expectations citizens have of the role government should play in their lives?This event is based on a recent article in The World Today by Hans Kundnani and Pepijn Bergsen who are both researchers in Chatham House's Europe Programme. 'Crawling from the Wreckage' is the first in a series of articles that look at key themes in European political discourse from the last century. You can read the article here. This event is open to Chatham House Members. Not a member? Find out more. Full Article
em Sphingolipids distribution at mitochondria-associated membranes (MAM) upon induction of apoptosis. By feedproxy.google.com Published On :: 2020-04-29 Vincent MignardApr 29, 2020; 0:jlr.RA120000628v1-jlr.RA120000628Research Articles Full Article
em Phosphatidylinositol Metabolism, Phospholipases, Lipidomics, and Cancer:In Memoriam of Michael J. O. Wakelam (1955-2020) By feedproxy.google.com Published On :: 2020-04-28 Edward A DennisApr 28, 2020; 0:jlr.T120000868v1-jlr.T120000868Tribute Full Article
em In Memoriam: Lina M. Obeid (1957-2019) By feedproxy.google.com Published On :: 2020-04-01 Ashley J. SniderApr 1, 2020; 61:466-467Tribute Full Article
em A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound By feedproxy.google.com Published On :: 2020-04-27 Timothy D RohrbachApr 27, 2020; 0:jlr.D120000809v1-jlr.D120000809Methods Full Article
em LDL subclass lipidomics in atherogenic dyslipidemia:Effect of statin therapy on bioactive lipids and dense LDL By feedproxy.google.com Published On :: 2020-04-15 M John ChapmanApr 15, 2020; 0:jlr.P119000543v1-jlr.P119000543Patient-Oriented and Epidemiological Research Full Article
em Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. By feedproxy.google.com Published On :: 2020-04-14 Inês Magro dos ReisApr 14, 2020; 0:jlr.RA120000632v1-jlr.RA120000632Research Articles Full Article
em Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes By feedproxy.google.com Published On :: 2020-03-10 Inga NilssonMar 10, 2020; 0:jlr.RA120000654v1-jlr.RA120000654Research Articles Full Article
em Membrane domains beyond the reach of microscopy By feedproxy.google.com Published On :: 2020-05-01 Ilya LeventalMay 1, 2020; 61:592-594Commentary Full Article
em Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation By feedproxy.google.com Published On :: 2020-05-01 Henry J. PownallMay 1, 2020; 61:595-597Commentary Full Article
em A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice By feedproxy.google.com Published On :: 2020-05-01 Chelsea DeLeonMay 1, 2020; 61:767-777Research Articles Full Article
em Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope By feedproxy.google.com Published On :: 2020-04-15 Souad AmiarApr 15, 2020; 0:jlr.ILR120000753v1-jlr.ILR120000753Images in Lipid Research Full Article
em Episode 22 - The Internet of Ultra Balls (IoUB) Pokemon Go, Playstation VR and iOS 10 By play.acast.com Published On :: Fri, 08 Jul 2016 11:24:25 GMT In Matt Egan's absence first time host Henry Burrell heroically steps in to chat about Pokemon Go with producer Chris. Then fellow staff writer Chris Minasians discusses iOS 10 beta and all of the rumoured features for the latest Apple operating system, including dark mode (10:30). Finally, Lewis Painter, staff writer at PC Advisor, talks about Playstation VR being released for the PS4, pricing and games (23:30). See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 23 - The Internet of Top Tech Topics (IoTTT) Brexit, Pokemon Go & Tesla By play.acast.com Published On :: Fri, 15 Jul 2016 13:19:19 GMT For the second week running hosting duties are taken by Henry Burrell, who is joined by Techworld.com editor Charlotte Jee to discuss the impact of Brexit on the UK's startups. Producer Chris then jumps in to discuss the Pokemon Go launch in the UK and a debate breaks out over whether it is for adults (13:00) Finally, online editor at Computerworld UK Scott Carey brings the latest news around driverless cars, from Tesla's recent struggles and how it may affect the industry in general (25:00) See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 27 - The Internet of No Man's Sky (IoNMS) NMS hype, open banking and emojis By play.acast.com Published On :: Fri, 12 Aug 2016 14:50:59 GMT Host Matt Egan is joined by the world's number one authority on No Man's Sky, producer Chris, to discuss the hype around the vast Playstation and PC game, how it was made and parallel universes. Scott Carey, online editor at Techworld.com jumps in to speak about the government's Open Banking report and how technology could change the way we bank in the future (16:00). Finally, acting editor at Macworld UK David Price is talking water pistol emojis and the strange politics of Apple (27:00). See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 42 - The Internet of Chinese Boogie Men (IoCBM) Black Friday, Facebook and Autumn Statement By play.acast.com Published On :: Fri, 25 Nov 2016 07:00:00 GMT Matt Egan is in the presenter chair this week as he chats about Black Friday and the changing face of online retail with acting editor at Macworld UK, David Price. Then online editor at Techworld.com Scott Carey talks Facebook and its recent issues with fake news and Chinese censorship (12:00). Finally, online editor at Computerworld UK Tamlin Magee brings us up to date with the Government's Autumn Statement and what it means for the technology sector (26:00). See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 69 - The Internet of internal memos (IoIM) Google sexism row and iPhone 8 leaks By play.acast.com Published On :: Fri, 11 Aug 2017 11:35:44 GMT Join Miriam Harris, David Price and Henry Burrell as they dissect the weird internal memo row at Google. Was a male engineer genuinely trying to help Google and make a point about the company being too Left, or is he just an arsehole? Then we describe the iPhone 8 dummy we received this week (take a look at it here: https://www.youtube.com/watch?v=PRNIwh61j_E ) and the revelations that came from the Homepod firmware leak. We also debate the usefulness of an LTE Apple Watch and try to make puns work. Magic. See acast.com/privacy for privacy and opt-out information. Full Article podcast technology tech apple watch iphone 8 pod smartphone
em Episode 71: The Internet of iPhone X (IoiX) Plus Apple Watch 3 and Apple TV announcements By play.acast.com Published On :: Wed, 13 Sep 2017 15:41:20 GMT This week it is all about Apple as the company announces its eagerly awaited iPhone X and iPhone 8/8 Plus smartphones, a new Apple watch (yawn) and Apple TV news. Macworld UK editor Karen Haslam is our host this week, as she chats to a distinctly unconvinced Dominic Preston about the latest iPhone, followed by David Price on the Apple Watch Series 3, which he likes but not as much as its predecessor. Then everyone piles in together to discuss the quite-good iPhone 8, the quite-late Apple TV 4K, and all the rest of the evening's festivities. See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 90 - The Internet of Meaty Topics (IoMT) Digital afterlife, net neutrality and GDPR emails By play.acast.com Published On :: Wed, 23 May 2018 10:43:08 GMT Oh boy what a meaty session we have for you as Christina Mercer, Somrata Sarkar, David Price and Henry Burrell tackle three whopics (whopping topics) head on.Somrata takes us into the sometimes scary thoughts of our own digital afterlives. Should we be worried that we'll end up as misrepresentative chat bots one day? Who will have the authority to police the companies that harvest our data?Then Christina explains the knife edge America is on when it comes to net neutrality. Despite recent hope, there's still a chance the web across the pond will be ruthlessly metered and segmented.Finally David asks us if we've checked our unused email accounts recently, as there might be a lot of desperate noodle companies in there begging you to stay on their mailing lists. See acast.com/privacy for privacy and opt-out information. Full Article
em Episode 99 - The Internet of Redemption (IoR) Google tracking, Red Dead Redemption 2 and the iMac at 20 By play.acast.com Published On :: Fri, 17 Aug 2018 13:15:50 GMT This week our host Scott Carey is joined by Techworld editor Charlotte Jee to discuss the revelation that Google is still tracking users, even if you have that feature disabled, and the wider topic of privacy.Then games editor at Tech Advisor, Lewis Painter, joins to talk about one of the most hotly anticipated games of the year: Red Dead Redemption 2.Lastly Macworld UK editor Karen Khan talks about the enduring legacy of the iMac PC 20 years on and how it set Apple on a historic trajectory. See acast.com/privacy for privacy and opt-out information. Full Article
em WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews] By feedproxy.google.com Published On :: 2018-10-15T08:42:37-07:00 This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98. Full Article
em Fatty acid oxidation and photoreceptor metabolic needs [Thematic Reviews] By feedproxy.google.com Published On :: 2020-02-24T12:30:36-08:00 Photoreceptors have high energy-demands and a high density of mitochondria that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) of fuel substrates. Although glucose is the major fuel for central nervous system (CNS) brain neurons, in photoreceptors (also CNS), most glucose is not metabolized through OXPHOS but is instead metabolized into lactate by aerobic glycolysis. The major fuel sources for photoreceptor mitochondria remained unclear for almost six decades. Similar to other tissues (like heart and skeletal muscle) with high metabolic rates, photoreceptors were recently found to metabolize fatty acids (palmitate) through OXPHOS. Disruption of lipid entry into photoreceptors leads to extracellular lipid accumulation, suppressed glucose transporter expression, and a duel lipid/glucose fuel shortage. Modulation of lipid metabolism helps restore photoreceptor function. However, further elucidation of the types of lipids used as retinal energy sources, the metabolic interaction with other fuel pathways, as well as the crosstalk among retinal cells to provide energy to photoreceptors is not yet known. In this review, we will focus on the current understanding of photoreceptor energy demand and sources, and potential future investigations of photoreceptor metabolism. Full Article
em Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes [Research Articles] By feedproxy.google.com Published On :: 2020-03-10T09:30:25-07:00 Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport. Full Article
em Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. [Research Articles] By feedproxy.google.com Published On :: 2020-04-14T06:30:26-07:00 Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1nih), creating a dysfunctional NPC1 protein. Npc1nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease. Full Article