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An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics [Research]

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.




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Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions [Research]

HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions.




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The NBN satellite Malcolm Turnbull never wanted prepares for liftoff

In 34 days and counting down, Australia is set to blast a satellite weighing as much as an elephant one-tenth of the way to the moon.




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Malcolm Turnbull visits Sunshine Coast to view proposal for new undersea communications cable

A plan to make the Sunshine Coast a vital internet gateway is luring Communications Minister Malcolm Turnbull to the area on Friday to view the proposal in person.




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Digital Transformation Office chief executive Paul Shetler announces public service work schedule

Paul Shetler reveals the digital projects about to hit the federal bureaucracy. Starting with Canberra.




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How Australian public service's digital reforms will happen, according to the Digital Transformation Office

The millions of customers, the short deadline: how the public service's digital revolution will start.




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StartupWeek Sydney readies for launch

StartupWeek Sydney 2015 starts on Friday, and 5000 people are expected to attend more than 50 events to celebrate and strengthen the city's thriving start-up community.




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Public service to ban paper in boxes: New digital policy to make sweeping reforms across APS

One powerful agency head warns against "tyranny of small person" as sweeping reforms released for public service.




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Australian companies targeted by identity thieves for tax frauds

Australian companies are having their identities hijacked by international criminals who use them to try to defraud the Australian Taxation Office.




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Victorian Premier Daniel Andrews announces 175 new tech jobs for Melbourne

State government commits to five-year funding round as software company launches community centre and new jobs.




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Australian public service failing to share information: Public Sector Data Management report

A report has revealed stunning examples of public service inefficiency when it comes to releasing and managing data.




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Centrelink apologises for web welfare shutdown

Centrelink clients around Australia are furious over missing payments.




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Centrelink wrongly hits 70,000 families with bills for up to $726

Computer glitch blamed as welfare agency hits tens of thousands with bills for money that is not owed.




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Troubled myGov website to be taken from Human Services and given to Digital Transformation Office for streamlining

Malcolm Turnbull's DTO has been critical of myGov, now it has the chance to show it can do better.




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Hacking peak hour takes Aussies for a ride

Tuesday morning is peak hour for hackers as social engineering becomes their weapon of choice, shifting away from security exploits to focus on tricking people into doing their bidding.




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Branching out after death: where next for the 'Internet of Things'?

It turns out that even death needs the internet.




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Recruitment drive for cyber security specialists will bring challenges for government

Fear government's cyber security recruitment drive will lead to job cuts.




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Malcolm Turnbull promises $50 million reboot for troubled myGov

Takeover of troubled portal by Digital Transformation Office confirmed




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Call for a cyber security reserve corps to help fight major attacks

Experienced volunteers would help fight major online threats to governments, private industry and civil institutions.




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Centrelink apologises for new privacy breach

Rookie email error shares hundred of email addresses – twice.




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Digital Transformation Agency boss Paul Shetler resigns

Agile government takes a stumble as digital pioneer logs off after just six weeks.




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Centrelink debt debacle shows government is unprepared for digital revolution

The public service needs to embrace partnerships if it's to harvest big data's massive yields.




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Labor to push for Senate inquiry into $10b government IT spend and tech wrecks

The probe would investigate a trail of blunders that have shredded the government's reputation.




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ACT human rights commission 'concerned' about new app for ACT police

Canberrans' privacy rights could be threatened by the new app.




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ACT police emailing speeding tickets could be 'ripe for scammers'

Nigel Phair said experts had spent years warning Australians about dodgy email scams.




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Smart Energy Council calls for state to abandon facial recognition

Some users have been brought to tears by 'broken' facial recognition software now required to approve solar rebate applications.




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Brexit: What Now for UK Trade Policy? (Part 2)

Research Event

1 October 2019 - 12:30pm to 1:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Professor Jagjit S. Chadha, Director, NIESR
Dr Kamala Dawar, Senior Lecturer in Law, University of Sussex; Fellow, UKTPO
Dr Michael Gasiorek, Senior Lecturer in Economics, University of Sussex; Director, Interanalysis; Fellow, UKTPO
Chair: Professor Jim Rollo, Deputy Director, UKTPO; Associate Fellow, Chatham House

In the five months since the last extension of the Brexit deadline, the questions about the UK’s trading relationship with the EU remain as open as before, as do those about what sort of relationship it should seek with other partners.

The world has not stood still, however, and so the UKTPO is convening another panel to consider constructive ways of moving forward. The panel will discuss potential trajectories for UK trade policy, followed by a question and answer session.

The UK Trade Policy Observatory (UKTPO) is a partnership between Chatham House and the University of Sussex which provides independent expert comment on, and analysis of, trade policy proposals for the UK as well as training for British policymakers through tailored training packages.




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Latin America: Shifting Political Dynamics and the Implications for the Global System

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




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Could Brexit Open Up a New Market for Latin American Agriculture?

8 October 2019

Dr Christopher Sabatini

Senior Research Fellow for Latin America, US and the Americas Programme

Anar Bata

Coordinator, US and the Americas Programme
The demand will be there, but a range of barriers are likely to limit growth in agricultural trade links between the UK and Latin America.

2019-10-08-Brazil.jpg

An area of forest-pasture integration prepared to receive dairy cattle for feeding in Ipameri, Brazil. Photo: Getty Images.

Currently 73% of all UK agricultural imports come from the EU. That heavy dependence sparked a report by the British parliament expressing concern about the UK’s food security in the immediate aftermath of Brexit.

Meanwhile, Latin America’s agricultural powerhouses Brazil and Argentina only accounted for a total of 1.6% of the UK’s agricultural market across eight sectors in 2018. A growing relationship would seem to be an obvious fit post-Brexit – but a number of structural issues stand in the way.

There is certainly scope for increasing Latin American agricultural exports to the UK given current trade patterns. Two of the main agricultural imports that the UK buys from the EU are meat products, representing 82% of UK imports in that category, and dairy products and eggs; 98% of UK’s dairy- and egg-related external supply came from the EU. In both these areas, Brazil and Argentina could have comparative advantages, including lower prices.

But any improvement in agricultural trade links will depend on two factors: 1) how the UK leaves the EU: whether it crashes out, negotiates an easy exit or leaves at all; and 2) whether Latin American agricultural producers can improve their environmental practices and can meet the production standards established by the EU and likely maintained by a post-Brexit Britain.

Some of the key issues that will affect this are:

Tariff structures

On the UK side, there is pressure by domestic agricultural producers to raise UK tariffs to allow them to expand their local market share. Yet, despite the pressures from local farmers, the UK has laid out two scenarios.

In one case, the UK government has stated that in the event of a no-deal Brexit, tariffs will be lowered to 0%, but there is no firm commitment and this would likely be temporary. It is also unlikely that those would apply to all agricultural products. In the case of beef imports (of which Argentina and Brazil are major exporters), the UK has proposed that ‘no deal’ would bring a reduction on tariffs on a range of beef products of roughly half.

Meanwhile, tariffs on EU imports could go up. Even if the UK establishes 0% tariffs on EU products, it’s possible that the EU will not reciprocate, instead choosing to revert to the World Trade Organization’s most-favoured-nation tariffs. To take one example of what that would mean, under existing most-favoured-nation tariffs on beef, the tariffs range from €6.80 per 100 kilograms of full bovine carcasses or half carcasses all the way up to €161.10 for 160 kilograms of prepared or preserved meat, including sausages.

Free trade agreements between the EU and Latin American countries

The EU has free trade agreements with the Central American bloc of Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama; Mexico; Chile; and the Andean countries of Colombia, Ecuador, and Peru. In all those cases, the UK has expressed its desire to maintain its liberal trade framework with those countries.

Even if the UK leaves without a deal and tariffs do increase on EU agricultural exports, though, these Western Hemisphere economies are unlikely to see a large boost in their food exports to the UK. Chile and other large fruit producers are already locked into the Chinese market. And the real agricultural powerhouses, Argentina and Brazil, are now part of the EU trade agreement with Mercosur.

Since that agreement is not yet in force, the UK and Mercosur would need to negotiate a separate agreement. Such an agreement may be easier to ratify than the EU agreement since there is only one partner (the UK) for such a deal, but the likely change in government in Argentina after the 27 October elections may make it difficult to secure a deal on the Mercosur side.

Some EU trade agreements also include arrangements for tariff rate quotas. An EU quota with Argentina, for example, allows more than 280,000 tonnes of lamb to be imported to the EU duty free from Argentina, among other countries. It is unclear whether these quotas will be maintained or even expanded by the UK post-Brexit.  

Phytosanitary standards and rules governing the treatment of animals

Non-tariff barriers concerning production practices could play a key role. The large UK consumer organization Which? raised the concern before parliament that in the scramble to replace EU food imports, the UK could diverge from EU standards on animal cloning, the use of growth hormones and hygiene in poultry production. Pressure to maintain those standards would likely exclude many products from South America.

Beyond the regulatory barriers, there is also the possibility that UK consumers may reject agricultural products produced in less sustainable and humane conditions, or in countries (such as Brazil) that are seen by the public as abusing the environment.

In short, an increase in Latin American agricultural exports to the UK market may not happen as easily or as quickly as some hope after Brexit. In fact, it may not happen at all. But if Latin American countries – Argentina and Brazil in particular – want to capture this potential new market, the first step both should be to improve their environmental profile and standards at both the government and producer level.




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UK General Election 2019: What the Political Party Manifestos Imply for Future UK Trade

Research Event

4 December 2019 - 12:30pm to 1:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Michael Gasiorek, Professor of Economics, University of Sussex; Director, Interanalysis; Fellow, UK Trade Policy Observatory, University of Sussex
Julia Magntorn Garrett, Research Officer, UK Trade Policy Observatory, University of Sussex
Prof Jim Rollo, Deputy Director, UK Trade Policy Observatory, University of Sussex; Associate Fellow, Global Economy and Finance Department, Chatham House
Nicolo Tamberi, Research Officer in the Economics of Brexit, University of Sussex
L. Alan Winters, Professor of Economics, Director, UK Trade Policy Observatory, University of Sussex

The upcoming UK general election is arguably a 'Brexit election', and as such, whoever wins the election will have little time to get their strategy for Brexit up and running to meet the new Brexit deadline of 31 January 2020. But what are the political parties’ policies for the UK's future trade? This event will present and discuss what the five main parties’ manifestos imply for future UK trade. Each manifesto will be presented and analysed by a fellow of the UK Trade Policy Observatory (UKTPO) and will be followed by a Q&A session. 

Michela Gariboldi

Research Assistant, Global Economy and Finance Programme
02073143692




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The EU Cannot Build a Foreign Policy on Regulatory Power Alone

11 February 2020

Alan Beattie

Associate Fellow, Global Economy and Finance Programme and Europe Programme
Brussels will find its much-vaunted heft in setting standards cannot help it advance its geopolitical interests.

2020-02-11-Leyen.jpg

EU Commission President Ursula von der Leyen speaks at the European Parliament in Strasbourg in February. Photo: Getty Images.

There are two well-established ideas in trade. Individually, they are correct. Combined, they can lead to a conclusion that is unfortunately wrong.

The first idea is that, across a range of economic sectors, the EU and the US have been engaged in a battle to have their model of regulation accepted as the global one, and that the EU is generally winning.

The second is that governments can use their regulatory power to extend strategic and foreign policy influence.

The conclusion would seem to be that the EU, which has for decades tried to develop a foreign policy, should be able to use its superpower status in regulation and trade to project its interests and its values abroad.

That’s the theory. It’s a proposition much welcomed by EU policymakers, who know they are highly unlikely any time soon to acquire any of the tools usually required to run an effective foreign policy.

The EU doesn’t have an army it can send into a shooting war, enough military or political aid to prop up or dispense of governments abroad, or a centralized intelligence service. Commission President Ursula von der Leyen has declared her outfit to be a ‘geopolitical commission’, and is casting about for any means of making that real.

Through the ‘Brussels effect’ whereby European rules and standards are exported via both companies and governments, the EU has indeed won many regulatory battles with the US.

Its cars, chemicals and product safety regulations are more widely adopted round the world than their American counterparts. In the absence of any coherent US offering, bar some varied state-level systems, the General Data Protection Regulation (GDPR) is the closest thing the world has to a single model for data privacy, and variants of it are being adopted by dozens of countries.

The problem is this. Those parts of global economic governance where the US is dominant – particularly the dollar payments system – are highly conducive to projecting US power abroad. The extraterritorial reach of secondary sanctions, plus the widespread reliance of banks and companies worldwide on dollar funding – and hence the American financial system – means that the US can precisely target its influence.

The EU can enforce trade sanctions, but not in such a powerful and discriminatory way, and it will always be outgunned by the US. Donald Trump could in effect force European companies to join in his sanctions on Iran when he pulled out of the nuclear deal, despite EU legislation designed to prevent their businesses being bullied. He can go after the chief financial officer of Huawei for allegedly breaching those sanctions.

By contrast, the widespread adoption of GDPR or data protection regimes inspired by it may give the EU a warm glow of satisfaction, but it cannot be turned into a geopolitical tool in the same way.

Nor, necessarily, does it particularly benefit the EU economy. Europe’s undersized tech sector seems unlikely to unduly benefit from the fact that data protection rules were written in the EU. Indeed, one common criticism of the regulations is that they entrench the power of incumbent tech giants like Google.

There is a similar pattern at work in the adoption of new technologies such as artificial intelligence and the Internet of Things. In that field, the EU and its member states are also facing determined competition from China, which has been pushing its technologies and standards through forums such as the International Telecommunication Union.

The EU has been attempting to write international rules for the use of AI which it hopes to be widely adopted. But again, these are a constraint on the use of new technologies largely developed by others, not the control of innovation.

By contrast, China has created a vast domestic market in technologies like facial recognition and unleashed its own companies on it. The resulting surveillance kit can then be marketed to emerging market governments as part of China’s enduring foreign policy campaign to build up supporters in the developing world.

If it genuinely wants to turn its economic power into geopolitical influence – and it’s not entirely clear what it would do with it if it did – the EU needs to recognize that not all forms of regulatory and trading dominance are the same.

Providing public goods to the world economy is all very well. But unless they are so particular in nature that they project uniquely European values and interests, that makes the EU a supplier of useful plumbing but not a global architect of power.

On the other hand, it could content itself with its position for the moment. It could recognize that not until enough hard power – guns, intelligence, money – is transferred from the member states to the centre, or until the member states start acting collectively, will the EU genuinely become a geopolitical force. Speaking loudly and carrying a stick of foam rubber is rarely a way to gain credibility in international relations.

This article is part of a series of publications and roundtable discussions in the Chatham House Global Trade Policy Forum.




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A Credit-fuelled Economic Recovery Stores Up Trouble for Turkey

17 February 2020

Fadi Hakura

Consulting Fellow, Europe Programme
Turkey is repeating the mistakes that led to the 2018 lira crisis and another freefall for the currency may not be far off.

2020-02-17-TurCB.jpg

Headquarters of the Central Bank of the Republic of Turkey. Photo: Getty Images.

Since the 2018 economic crisis, when the value of the lira plummeted and borrowing costs soared, Turkey’s economy has achieved a miraculous ‘V-shaped’ economic recovery from a recession lasting three quarters to a return back to quarterly growth above 1 per cent in the first three months of 2019.

But this quick turnaround has been built on vast amounts of cheap credit used to re-stimulate a consumption and construction boom. This so-called ‘triple C’ economy generated a rapid growth spurt akin to a modestly able professional sprinter injected with steroids.

This has made the currency vulnerable. The lira has steadily depreciated by 11 per cent against the US dollar since the beginning of 2019 and crossed the rate of 6 lira versus the US dollar on 7 February. And there are further warning signs on the horizon.

Credit bonanza

Statistics reveal that Turkish domestic credit grew by around 13 per cent on average throughout 2019.  The credit bonanza is still ongoing. Mortgage-backed home sales jumped by a record high of 600 per cent last December alone and the 2019 budget deficit catapulted by 70 per cent due to higher government spending.

Turkey’s central bank fuelled this credit expansion by cutting interest rates aggressively to below inflation and, since the start of this year, purchasing lira-denominated bonds equivalent to around one-third of total acquisitions last year to push yields lower.

Equally, it has linked bank lending to reserve requirements – the money that banks have to keep at the central bank – to boost borrowings via state and private banks. Banks with a ‘real’ loan growth (including inflation) of between 5 and 15 per cent enjoy a 2 per cent reserve ratio on most lira deposits, which authorities adjusted from an earlier band of 10-20 per cent that did not consider double-digit inflation.

Cumulatively, bond purchases (effectively quantitative easing) and reserve management policies have also contributed to eased credit conditions.

Commercial banks have also reduced deposit rates on lira accounts to less than inflation to encourage consumption over saving. Together with low lending rates, the boost to the economy has flowed via mortgages, credit card loans, vehicle leasing transactions and general business borrowings.

Accordingly, stimulus is at the forefront of the government’s economic approach, as it was in 2017 and 2018. It does not seem to be implementing structural change to re-orient growth away from consumption towards productivity. 

In addition, governance is, again, a central issue. President Recep Tayyip Erdogan’s near total monopolization of policymaking means he guides all domestic and external policies. He forced out the previous central bank governor, Murat Cetinkaya, in July 2019 because he did not share the president’s desire for an accelerated pace of interest rate reductions.

New challenges

Despite the similarities, the expected future financial turbulence will be materially different from its 2018 predecessor in four crucial respects. 

Firstly, foreign investors will only be marginally involved. Turkey has shut out foreign investors since 2018 from lira-denominated assets by restricting lira swap arrangements. Unsurprisingly, the non-resident holdings of lira bonds has plummeted from 20 per cent in 2018 to less than 10 per cent today.

Secondly, the Turkish government has recently introduced indirect domestic capital controls by constraining most commercial transactions to the lira rather than to the US dollar or euro to reduce foreign currency demand in light of short-term external debt obligations of $191 billion.

Thirdly, the Turkish state banks are intervening quite regularly to soften Lira volatility, thereby transitioning from a ‘free float’ to a ‘managed float’. So far, they have spent over $37 billion over the last two years in a futile effort to buttress the lira. This level of involvement in currency markets cannot be maintained.

Fourthly, the Turkish state is being far more interventionist in the Turkish stock exchange and bond markets to keep asset prices elevated. Government-controlled local funds have participated in the Borsa Istanbul and state banks in sovereign debt to sustain rallies or reverse a bear market.  

All these measures have one running idea: exclude foreign investors and no crisis will recur. Yet, when the credit boom heads to a downturn sooner or later, Turks will probably escalate lira conversions to US dollars; 51 per cent of all Turkish bank deposits are already dollar-denominated and the figure is still rising.

If Turkey’s limited foreign reserves cannot satisfy the domestic dollar demand, the government may have to impose comprehensive capital controls and allow for a double digit depreciation in the value of the lira to from its current level, with significant repercussions on Turkey’s political stability and economic climate.

To avoid this scenario, it needs to restore fiscal and monetary prudence, deal the with the foreign debt overhang in the private sector and focus on productivity-improving economic and institutional reforms to gain the confidence of global financial markets and Turks alike.




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Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma

Long Xu
Apr 1, 2020; 61:560-569
Methods




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A Direct Fluorometric Activity Assay for Lipid Kinases and Phosphatases

Jiachen Sun
Apr 27, 2020; 0:jlr.D120000794v1-jlr.D120000794
Methods




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A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound

Timothy D Rohrbach
Apr 27, 2020; 0:jlr.D120000809v1-jlr.D120000809
Methods




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An LC/MS/MS method for analyzing the steroid metabolome with high accuracy and from small serum samples

Teng-Fei Yuan
Apr 1, 2020; 61:580-586
Methods




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Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease

Delphine Fontaine
Apr 7, 2020; 0:jlr.RA120000634v1-jlr.RA120000634
Research Articles




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A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice

Chelsea DeLeon
May 1, 2020; 61:767-777
Research Articles




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Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope

Souad Amiar
Apr 15, 2020; 0:jlr.ILR120000753v1-jlr.ILR120000753
Images in Lipid Research




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Dispersed lipid droplets: an intermediate site for lipid transport and metabolism in primary human adipocytes.

Björn Morén
Apr 15, 2020; 0:jlr.ILR120000808v1-jlr.ILR120000808
Images in Lipid Research




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GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells

Xia Meng
May 1, 2020; 61:591-591
Images in Lipid Research




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Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes [Molecular Bases of Disease]

Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations.




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Episode 36 - The Internet of Playstation pom-poms (IoPPP) Note 7, Playstation VR & Dreamforce

Matt Egan is back on hosting duties this week to break down the demise of the Samsung Galaxy Note 7 with producer Chris. Then staff writer at PC Advisor Lewis Painter comes on to talk about the Playstation VR release, games and pricing and compares it to the flagging Oculus Rift and HTC Vive (13:00). Finally, Scott Carey, online editor at Computerworld UK reports back from the biggest tech conference in the world, Dreamforce, chats about Salesforce's rumoured bid for Twitter and tries to make CRM interesting (25:00).  


See acast.com/privacy for privacy and opt-out information.




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Episode 77 - The Internet of Tulips (IoT) Bitcoin, the platform wars and Christmas tech gifts

We finally get the IoT acronym the pod has been waiting for as we discuss Bitcoin and 17th century Dutch finance. Charlotte Jee informs Henry Burrell, David Price and Scott Carey.


Scott then leads us down the winding road of the so-called platform wars, in a week when Google blocked the Amazon Echo Show from streaming YouTube. Is this a bump in the road or will services be cut from rival hardware?


And finally, led by David, the pod discusses its favourite tech of the year and what you might consider buying for friends and family for Christmas.

 

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Episode 78 - The Internet of the pod before Christmas (IotPBC) iMac Pro, Netflix's Twitter misstep and Apple buys Shazam

Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?


We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?


In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired?

 

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Episode 86 - The Internet of Education (IoE) New iPads for schools and the Huawei P20

Sheriff Scott Carey rounds up his two deputies in David Price and Henry Burrell for a quick-fire two topic pod. Apple launched a new cheaper iPad this week based around its education play - but can schools afford them and are Chromebooks a better option?


Then we discuss the new Huawei P20 and P20 Pro. Notches, three cameras but competitive pricing make the new Android flagship an interesting option.

 

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Episode 94 - The Internet of Screens (IoS) Netflix is huge and Fortnite is popular

This week it’s David Price in the hosting seat to dig into two meaty tech topics: how does Netflix buy and develop its massive content library, and why is Fortnite such a sensation?


Helping him dig into Netflix is Computerworld UK editor Scott Carey, with our new entertainment and lifestyle editor at Tech Advisor Dominic Preston joining in.


Then staff writer at Tech Advisor Sean Bradley is on hand to talk about how Fortnite has become such a sensation, and if it is built to last.

 

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Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease [Research Articles]

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions.




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Dispersed lipid droplets: an intermediate site for lipid transport and metabolism in primary human adipocytes. [Images in Lipid Research]




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Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope [Images in Lipid Research]