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MMP activation-associated aminopeptidase N reveals a bivalent 14-3-3 binding motif [Protein Structure and Folding]

Aminopeptidase N (APN, CD13) is a transmembrane ectopeptidase involved in many crucial cellular functions. Besides its role as a peptidase, APN also mediates signal transduction and is involved in the activation of matrix metalloproteinases (MMPs). MMPs function in tissue remodeling within the extracellular space and are therefore involved in many human diseases, such as fibrosis, rheumatoid arthritis, tumor angiogenesis, and metastasis, as well as viral infections. However, the exact mechanism that leads to APN-driven MMP activation is unclear. It was previously shown that extracellular 14-3-3 adapter proteins bind to APN and thereby induce the transcription of MMPs. As a first step, we sought to identify potential 14-3-3–binding sites in the APN sequence. We constructed a set of phosphorylated peptides derived from APN to probe for interactions. We identified and characterized a canonical 14-3-3–binding site (site 1) within the flexible, structurally unresolved N-terminal APN region using direct binding fluorescence polarization assays and thermodynamic analysis. In addition, we identified a secondary, noncanonical binding site (site 2), which enhances the binding affinity in combination with site 1 by many orders of magnitude. Finally, we solved crystal structures of 14-3-3σ bound to mono- and bis-phosphorylated APN-derived peptides, which revealed atomic details of the binding mode of mono- and bivalent 14-3-3 interactions. Therefore, our findings shed some light on the first steps of APN-mediated MMP activation and open the field for further investigation of this important signaling pathway.




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A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications [Neurobiology]

Abnormal changes of neuronal Tau protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer's disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remain ill-defined. Tau contains ∼85 potential phosphorylation sites, which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, methodological limitations (e.g. in MS of phosphopeptides, or antibodies against phosphoepitopes) led to conflicting results regarding the extent of Tau phosphorylation in cells. Here we present results from a new approach based on native MS of intact Tau expressed in eukaryotic cells (Sf9). The extent of phosphorylation is heterogeneous, up to ∼20 phosphates per molecule distributed over 51 sites. The medium phosphorylated fraction Pm showed overall occupancies of ∼8 Pi (± 5) with a bell-shaped distribution; the highly phosphorylated fraction Ph had 14 Pi (± 6). The distribution of sites was highly asymmetric (with 71% of all P-sites in the C-terminal half of Tau). All sites were on Ser or Thr residues, but none were on Tyr. Other known posttranslational modifications were near or below our detection limit (e.g. acetylation, ubiquitination). These findings suggest that normal cellular Tau shows a remarkably high extent of phosphorylation, whereas other modifications are nearly absent. This implies that abnormal phosphorylations at certain sites may not affect the extent of phosphorylation significantly and do not represent hyperphosphorylation. By implication, the pathological aggregation of Tau is not likely a consequence of high phosphorylation.




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Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood [Microbiology]

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.




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COVID-19: The Hidden Majority in India's Migration Crisis

13 July 2020

Dr Champa Patel

Director, Asia-Pacific Programme
While the social and economic costs of coronavirus lockdowns, travel bans and social distancing initially focused on international migrants, there has been increasing attention paid to the plight of internal migrants.

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Migrant workers plant paddy in a field at Jhandi village in Patiala, India. Photo by Bharat Bhushan/Hindustan Times via Getty Images.

The World Bank estimates that the magnitude of internal migration is about two‐and‐a‐half times that of international migration. Within India, an estimated 40 million internal migrant workers, largely in the informal economy, were severely impacted by the government’s COVID-19 lockdown.

With transportation systems initially shut down, many had no recourse to travel options back to homes and villages, resulting in harrowing journeys home. Those who were able to make it home found, in some instances, villages refusing entry because of fears of transmission.

The shocking images of migrants forced to walk in desperation showed the enormity of the crisis as well as some of the challenges posed by an extended lockdown in India where so many people live hand to mouth and cannot afford not to work.

Migrant workers and the informal economy

The complete failure of the government to anticipate the needs of this group, and the subsequent distress caused, has made visible a large workforce who experience precarity of work and often live hand to mouth.

One key challenge is the lack of robust data on the scale of internal migration. While estimates abound, there is no proper data collection system in place to accurately record temporary, seasonal and circular migration patterns. However, it is estimated that more than 90% of working people in India are engaged in the informal economy, with states such as Uttar Pradesh and Bihar accounting for more than 80% of workers in this sector.

A recent government labour force survey estimated that more than 71% of people with a regular salary working in non-agricultural industries had no written job contract. Nearly half of workers are not eligible for social security benefits.

Daily-wage workers are particularly vulnerable, with limited or no access to social security and most living in poverty. Living hand to mouth, their loss of livelihoods has led to a lack of money to pay rents or pay for food. Women are impacted whether because of their gender, responsibilities as caregivers, or as members of disadvantaged castes and communities.

COVID-19 has massively impacted this group of workers. Stranded Workers Action Network found that 50% of workers had rations left for less than one day; 74% had less than half their daily wages remaining to survive for the rest of the lockdown period; and 89% had not been paid by their employers at all during the lockdown.

According to Supreme Court proceedings, relief camps are housing some 660,000 workers; some 2.2 million people also rely on emergency food supplies. Job losses, and home and food insecurity have left this group highly vulnerable.

In March 2020, in response to COVID-19, the Indian government instituted the Pradhan Mantri Garib Kalyan Package (PMGKB), a $22.6 billion relief package. The World Bank announced $1 billion funding to accelerate social protection support, in part through the PMGKB.

This support would work alongside pre-existing initiatives such as the Public Distribution System (PDS), which covers 800 million people, and Direct Benefit Transfers (DBT). This cash injection could help address one of the key challenges facing India’s piecemeal and uneven social protection programmes – inadequate funding. India’s spending on public social protection excluding health is just 1.3% of the GDP.

However, there are still other challenges to overcome. One is how to ensure coordination and coverage within, and across, differing states. The second is how to transition multiple schemes into one integrated system that can be accessed anywhere within the country, particularly important when many workers are on the move. There is an urgent need for a comprehensive system, which is adaptive and flexible to needs and provides adequate social and income support.

Another coverage issue relates to the use of direct cash transfers (DCTs) to support people impacted by the loss of livelihoods, where funds are deposited within bank accounts. Such measures fail to consider the significant numbers of people who do not have access to banks and will not be able to access this support.

Wider impact on livelihoods and remittances

​There is a risk, with extended lockdown and risks of further waves of infection, that labour shortages could negatively impact the economy. There is a wider need to support re-entry back into the workforce and support livelihoods. National Survey Sample data shows that between 2007 and 2008, internal remittances amounted to US$10 billion. These domestic transfers financed over 30% of all household consumption in remittance-receiving households.

But future migration for work is likely to be severely impacted. As restrictions begin to ease, employers and businesses cannot necessarily rely on cheap available labour. Having faced destitution and hardship, many may wish to stay closer to families and local support networks.

As Irudaya Rajan notes in The New Humanitarian, it is likely ‘there will be a reduction in long-distance migration in India after this’, as many migrants will be wary of being stranded again. This would be hugely detrimental to stimulating the economy as reverse migration could push down wages and subsequently demand.

Another issue may be returning migrant workers, who have been working overseas, over half of whom work in the Gulf. It is unclear if, or when, migrants will be able to return to work, with the World Bank estimating that remittances from this group could fall by about 23%.

However, what is striking has been India’s support for this group - the Vande Bharat Mission has deployed flights and naval ships to help return migrant workers, especially vulnerable groups - in marked contrast to the lack of preparation and care for internal migrants.

One factor for this may be the volume of remittances these migrant workers bring to the Indian economy, but it overlooks the contribution of internal remittances, on which there is far less robust data.

But the current challenges can also be an opportunity. The scale of the migrant crisis has made visible an often-overlooked population of workers. With political will, and investment at federal and state levels, this could be an opportunity to transform livelihoods.

As thoughts will turn to how to stimulate economies and get people back to work, it is imperative that those in authority turn their minds to how to create a more just society, that invests in healthcare, and has a social protection system that supports the most vulnerable in society.

Migrants are not just objects of charity that need support. Internal migrants are key income generators that play a vital role in Indian society and should never be overlooked again.

This article was originally published in Routed Magazine.




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Emerging Economies: Where is the Debt Problem?

16 July 2020

David Lubin

Associate Fellow, Global Economy and Finance Programme
Just two months ago it appeared self-evident that emerging economies faced a devastating inability to service their foreign debt, mostly denominated in dollars. That has turned out to be wrong, for now at least.

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Yes Bank branch of Malcha Marg, in New Delhi, India. Photo by Vipin Kumar/Hindustan Times via Getty Images.

Back in April, nervousness about external debts reached its peak when highly-respected economists Carmen Reinhart and Kenneth Rogoff suggested emerging economies with less than a AAA credit rating be offered a moratorium on all their external debt service payments.

Although such a proposal might make sense if emerging economies were actually facing any serious shortage of access to foreign exchange, it is a difficult case to make. What we should worry about is not the external debt of emerging economies, but rather the large increases in government debts denominated in their own currencies.

In the first six months of 2020, borrowers from emerging economies issued more than $400 billion of Eurobonds to international investors, up by one-fifth over the same period in 2019. Most of these bonds were sold by borrowers with relatively high credit ratings, but many of the poorest countries do not fear for their access to international capital markets - largely because the US Federal Reserve increased global supply of dollars to a point where their availability is beyond question.

Much of the panic about emerging economies’ external debt comes from ‘sticker shock’ - the bald fact that developing countries’ external debt rose by $4.1 trillion in the decade to 2018 generates much hand-wringing.

But the increase in gross external debt of developing countries looks a lot scarier than the net increase in debt, which sets off a country’s foreign assets - mostly foreign exchange reserves - against its liabilities. And it is net that counts.

At the end of 2018, foreign exchange reserves covered 70% of the external debt of low and middle income developing countries - much lower than a decade ago, when that coverage was above 100%. But in the 1980s and 1990s – two decades of financial instability largely because of excessive foreign debt – the coverage was 15%. By that measure, we are far from crisis territory.

Complacency about the external debt burden of developing countries is quite wrong. But, if complacency is misplaced, so is panic.

The debt growing most worryingly is the domestic debt of governments. There are large, systemically important emerging economies who will suffer eye-watering increases in public debt this year thanks to a combination of collapsing GDP and the fiscal effort needed to save lives.

In Brazil, public debt is rising from 75% GDP last year to a level that could top 100% in 2020. South African public debt is rising from just over 60% last year to something close to 80% GDP. These are truly unprecedented levels of debt.

So why worry about a government’s domestic debt? These are debts which are denominated in these countries’ own currency. So surely the central bank can just print the currency needed to repay their obligations if more conventional solutions – such as tax increases – will not work.

But it is one thing for the US Federal Reserve to increase supply of dollars on a massive scale, since the world is hungry for them - it is quite another thing if emerging economies do the same with their currencies which almost entirely lack the many attractions of the dollar. That remains the currency of the pre-eminent global superpower whose capital markets offer legal certainty and depth of liquidity. And other highly developed economies have a similar privilege.

And yet printing money – in effect, asking the central bank to finance budget deficits – does seem as though it could become a more attractive option for many emerging countries. Importantly, international fund managers have lost interest in buying bonds issued by emerging economy governments in their local currencies. Just a few years ago, foreign investors owned more than 40% of South Africa’s public debt. That has fallen sharply to 30% and is unlikely to rise.

Monetising budget deficits was once anathema, since it was routinely associated with uncontrolled rates of inflation - bad news not only for firms trying to decide whether to invest but also for the poor, who suffer disproportionately when inflation accelerates.

Right now there are emerging economies – such as Indonesia – whose central banks lend directly to the government, and the sky has not fallen in. The rupiah has been remarkably stable this year. However, there are other examples – Argentina, Turkey – where central bank financing of government deficits has been associated with uncomfortably high inflation rates.

This needs careful watching. The biggest risk is the accumulation of public debt threatening longer-term growth. If firms stop investing because they worry about the risks to the value of their currency as domestic public debt explodes, emerging economies will have a tough time growing their way out of these debts.

It could be this, rather than the external debt of emerging economies, that is the biggest risk to the post-coronavirus economic environment in the developing world.




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Domestic Violence in Russia: The Impact of the COVID-19 Pandemic

20 July 2020

Ekaterina Aleynikova

Research Assistant, Russia and Eurasia Programme
The COVID-19 pandemic has made Russia’s domestic violence problem more visible, with shifting public opinion potentially incentivizing the government to change its approach, argues Ekaterina Aleynikova.

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Campaigners during a rally held in 2019 in support of a Russian law on domestic violence. Photo: Getty Images

Russia is one of the few countries in the region to have no legal definition of domestic violence and, as a result, there are no protective measures specific to domestic violence such as restraining orders or compulsory anger management training for abusers. In fact, the government has taken steps in recent years to remove any legal distinction between assault happening in one’s home, and elsewhere, with battery among family or household members for first-time offences decriminalized in 2017.

The Russian Ministry of Justice explicitly defended this position in its response to an enquiry into Russian domestic violence cases by the European Court of Human Rights (ECtHR) in November 2019. The ministry claimed existing legislation adequately protects citizens from domestic violence, ‘even though it has never been considered a separate offence’, reiterating that there is ‘no need’ for adopting specific legislation.

However, the four cases that led to the ECtHR’s enquiry demonstrate that current legislation is not sufficient. The most prominent case is that of Margarita Gracheva whose ex-husband severed her hands in 2017 despite her having made multiple complaints to the police ahead of the act being committed. If Russian legislation had mechanisms in place to isolate victims from their abusers, then Gracheva could have been protected by the law.

Instead, systemic impunity for abusers is supported by statements from people in power excusing domestic violence. The most recent of such statements came from the head of the Chechen Republic, Ramzan Kadyrov, in June 2020. When meeting with the family of a young woman allegedly murdered by her husband, Chechnya’s leader said, husbands beating their wives ‘happens’ and that the young woman should have tried harder to hold on to her marriage. These statements send clear signals to abusers that their actions are justified, and to the victims, that they won’t be protected if they were to come forward.

Similarly, to other parts of the world, civil society organizations in Russia have reported an increase in the number of cases of domestic violence during the COVID-19 pandemic. On a personal level, the pandemic has often exacerbated many of the factors that can lead to domestic violence such as stress, economic anxiety or social isolation.

On a systemic level, many of the provisions intended to protect victims of violence, which were already ineffective in Russia, have been worsened during the lockdown. Where police may not have rapidly responded to reports of domestic violence previously, under lockdown, they have become focused on  other priorities and, where shelters and support networks for the victims may have been scarce in the past, they have been further constrained.

Unsurprisingly, the strategy of the Russian state so far has been to deny that there is a problem of domestic violence, with the Ministry of Interior reporting that, according to their statistics, the number of domestic violence cases have gone down during the lockdown. Indeed, Chairwoman of the Federation Council, Valentina Matvienko, has said she does not believe lockdown has increased domestic violence because, on the contrary, families have been  ‘brought together’, reflecting wishful thinking at best and negligence at worst.

The pandemic has also been used as an excuse to postpone discussion of a federal law on domestic violence, drafted by civil society, that was submitted for review by the Duma last year. This bill would have introduced different types of domestic violence such as psychological and economic violence and transferred domestic violence offences from private to public prosecutions to make it easier for victims to seek justice.

The government’s disregard for domestic violence reflects, in part, the patriarchal mindsets of those in power but perhaps, more significantly, the Kremlin’s belief that conservative social groups constitute its main support base. This has been made evident by the politicization of Russia’s ‘traditional’ values in recent years which was vigorously deployed throughout the constitutional amendments campaign. While it is clear that the true purpose of amending the constitution has always been to allow Vladimir Putin to stay in power beyond 2024, amendments relating to this were absent from the government’s campaign. Instead, Russians were encouraged to vote by populist socially-conservative messages, hence why respect for traditional values has been added to the constitution.

Despite this, attitudes in Russian society are changing. A February 2020 survey by the Levada Centre showed that 61 per cent of Russians – and 74 per cent of Russian women – think domestic violence is a serious problem.

Moreover, the survey shows that women are much more aware of domestic violence than men – with every third woman in Russia admits being aware of domestic violence in their social circles while only every fifth man admits the same. This could be a sign that Russian men and women, on average, have a different understanding of what constitutes domestic violence. If so, adopting a law that defines domestic violence and holding a public awareness campaign is of paramount importance to eliminate any misunderstanding.

The difference could also be a sign that victims of domestic violence are more likely to confide in women hence making domestic violence less visible to men. This awareness gap perhaps explains the difference between men’s and women’s assessments of how serious the issue in Russia is.

The pandemic has provoked a new wave of discussions of domestic violence among Russia’s population with stories and statistics widely shared in the media and on the internet. As domestic violence becomes more visible, public perceptions are likely to shift further towards recognizing, and hopefully condemning, it. But, while legislation is crucial, the experience of other countries in the region, such as Armenia or Kazakhstan, shows that adopting laws on domestic violence is not enough. Measures are needed to ensure implementation of the law including training police officers and state officials and instituting disciplinary action for negligence of victims’ complaints.

Nevertheless, admitting there is a problem with domestic violence in Russia, and introducing laws, are an essential first step. The Russian government seems to have placed its bet on the support of conservative social groups but changing public opinion may prove this strategy unsustainable.




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EU Budget Battle Could Undermine its International Ambitions

17 July 2020

Alice Billon-Galland

Research Associate, Europe Programme

Vassilis Ntousas

Stavros Niarchos Foundation Academy Fellow, Europe Programme
EU’s heated budget negotiations risk producing a compromise at the expense of its longer-term international agenda.

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German Chancellor Angela Merkel (L) talks with French President Emmanuel Macron (C) and President of European Council Charles Michel (R) during an EU summit on 17 July 2020 in Brussels, Belgium. Photo by Thierry Monasse/Getty Images.

With all EU economies still reeling from COVID-19, the ongoing heated deliberations on the bloc’s next budget, which will determine the amount of money matching its priorities for the next seven years, have taken on an urgency rarely felt in Brussels.

Relying in part on an unprecedentedly large volume of jointly issued debt, the European Commission’s plan for a €750 billion coronavirus recovery instrument is embedded within a revamped proposal for the EU’s long-term budget, of €1.1 trillion for the 2021-27 period. 

Now the ball is in the member states’ court. All seem to agree that getting the EU budget right is crucial to fostering an economic recovery and ensuring the Union is on the right track towards its long-term pre-COVID objectives, from increasing its strategic autonomy to reaching climate neutrality by 2050. However, stark differences persist as to what that means in practice.

Most of the core divisions predate the pandemic’s outbreak. In a special European Council meeting in February, leaders failed to find common ground on the Union’s first post-Brexit budget. Net contributor countries, such as Austria, Denmark, Sweden and the Netherlands — the so-called ‘Frugal Four’— refused to agree to higher overall spending and instead advocated for cuts in the Common Agricultural Policy or cohesion funds, meeting the resistance of states like France and Portugal.

These early divisions foreshadowed the risk of a budget compromise that would leave little space for new policy priorities. The COVID-induced economic crisis has made a traditionally fraught political process even more difficult, putting the squeeze on what were previously priority areas of funding.

The Frugal Four agree on the need for the coronavirus recovery plan but vehemently oppose the volume of grants or the issuance of too much common debt in the proposed instrument, reflecting the unpopularity of these proposals with their domestic audiences. Hungary has also threatened to derail progress on the EU’s rescue plan if rule of law criteria are weaved into mechanisms for the allocation of EU funding.

As European leaders reconvene at the 17-18 July Council meeting, EU Council President Michel proposed a revised 'negotiating box' in preparation for the discussions. The document, which tries to bridge these intra-bloc divisions, bolts the demands for short-term recovery onto the EU’s longer-term ambitions. For instance, it sets an increased target of 30 per cent of funding to go toward climate-related projects, which is necessary for the Union’s green transformation. It also retains the link between the rule of law and EU funding — despite Budapest’s opposition — which is critical for the bloc’s internal accountability and transparency, and external credibility. Furthermore, it proposes a set of new mechanisms through which the EU can sustainably raise its own revenue, including a plastics levy as well as more controversial carbon border tax and digital levy.

Yet in several other critical ways, Michel’s proposals fall short. This is particularly true for some of the more ‘geopolitical’ goals of the Union, as previously expressed by Commission president Ursula von der Leyen, or the repeated calls by the Union’s high representative that the EU should learn to use the language of power.

For all the rhetoric around the EU’s need to boost its ability to act more autonomously in the field of security and defence, reductions in important thematic programmes in this domain could result in a critical loss of momentum, if confirmed. For instance, in Michel’s proposals, flagship defence initiatives such as the European defence fund and the military mobility plan are facing cuts of about 39 per cent and 74 per cent respectively (to some €7 billion for the former and €1.5 billion for the latter) compared with the initial Commission proposal of 2018.

Moreover, the tragic developments at the Greece-Turkey border in the beginning of the year might have brought migration back to the forefront of the EU’s attention, but the overall funding for migration and border management is also significantly lower compared to initial proposals. This serves as another example of a discrepancy between the figures on the table today and those that the EU commission had previously regarded as necessary to address the challenges the bloc faces.

Similarly, under the Council president’s latest proposal, the combined funding allocated for the EU’s external action (under the ‘Neighbourhood and the World’ heading) is lower than the figures in the Commission’s May announcements – from €118.2 billion to €113.9 billion overall. This represents an increase compared to the previous EU budget, but it is not in line with the elevated ambitions recognized by the Commission in May, which have only been made more compelling by the pandemic.

Brokering a deal in EU budget negotiations has always been a brutal affair, requiring sacrifices and compromise under the pressure of a ticking clock. 2020 was never likely to be an exception to this rule; but the pandemic has complicated the politics and raised the stakes.

The risk is that the budget negotiations lead to a compromise which, while delivering a historic coronavirus package, does not adequately support some of the key elements of the Union’s long-term agenda, especially its international ambitions.




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Nigeria’s Recovery Means Rethinking Economic Diversification

14 August 2020

Iseoluwa Akintunde

Mo Ibrahim Foundation Academy Fellow, Energy, Environment and Resources Programme
With more than half its revenue derived from oil exports, Nigeria’s economic fortunes are tied to the boom and bust cycles of the oil market. Those fortunes have waned way below expectations this year and, with more than one-quarter of its labour force jobless, it is time to question the country’s economic pathway.

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Yahaya Musa, 19-year old local mason, inspects a wall of a 'plastic bottle house' in Sabongarin Yelwa village, near Kaduna, Nigeria. Photo by AMINU ABUBAKAR/AFP via Getty Images.

For decades, the mantra of ‘economic diversification’ characterized attempts to reverse Nigeria’s dependence on oil with little real progress. Despite numerous reforms, international loans and restructuring programmes, 85 million Nigerians live in deteriorating conditions of poverty. The current coronavirus pandemic combined with mounting debt obligations and declining GDP gives new urgency to this issue.

The fall in international oil prices, which led government to slash its oil benchmark price from $57 to $30 a barrel and cut 20% of the capital budget, worsens these problems, but it is far from the only factor. Biomass, which drives household pollution and contributed to the death of 114,000 people in Nigeria in 2017, is the most dominant source of energy in Nigeria, amounting to more than 80% of the total energy mix, followed by fossil fuels (18%), and a negligible amount of renewable energy.

Although a diversified energy sector with a strong emphasis on renewables is known to reduce health and economic risks of combustion, there has been little emphasis on the role a diversified energy mix could play in ensuring sustainable development – even though the estimated potential of 427,000MW of solar power and photovoltaic generation means Nigeria has enormous renewable energy opportunities.

The global economy is also undergoing tectonic structural changes that will affect demand for Nigeria’s oil, leaving a fossil fuel-dependent economy more vulnerable. Improvements in global fuel efficiency, the ascent of electricity as a substitute for oil in the transport sector, and the falling prices of renewables and storage technologies all lead to a reduction in demand for fossil fuel products.

Creating structures for transition

This is not a ‘get out of oil’ prescription, and energy transition is complex. But it is inevitable. There are no universal strategies applicable to all countries; local contexts and political realities inform what is possible. Nigeria can take advantage of its abundant natural gas deposit as a ‘transition fuel’ to buy it time for putting the appropriate transition structures in place. The country has made progress in reducing the amount of gas flared, but much remains to be done for Nigeria to meet the 2030 global deadline to end flaring, after failing to meet its 2020 national target.

The first step to proper transition is to align Nigeria’s international obligations with its domestic policies and legislations - the distance between words and action must be bridged and the institutional capacity to implement raised. And, while they contain symbolic green gestures, the economic recovery and growth plan developed in response to the 2016 recession, and the post-COVID-19 economic sustainability plan, do not espouse green growth as a fundamental objective.

Nigeria must start looking inwards, investing its resources in designing and funding a green transition strategy. Its leadership role in floating Africa’s first Sovereign Green Bonds should be followed with non-debt funding options. Faced with a pandemic that has shattered the boundaries of what is politically possible, the Buhari government has overcome initial inertia to announce a halt in oil subsidy payments, although whether it will see through that policy is yet to be seen.

If it does, how it uses the savings will be significant. The money could provide support for Nigeria’s renewable sector to counteract the price disparity with fossil fuels and encourage rapid research and development. The Nigerian Ecological Fund — which is 3% of the Federation Account — should be reformed and expanded beyond its current scope of addressing ‘serious ecological problems’ to cover climate change with a strong emphasis on mitigation and resilience. That would increase Nigeria’s climate finance and minimize reliance on multilateral climate funds.

Beyond public investments in green infrastructure, the government can also incentivize the private sector to drive a green economy. As the largest purchaser of goods and services in the country, it can leverage purchasing power to green the procurement process. With the release of about $421 million to the Ministry of Works, the 2020 budgetary allocation for road projects has been fully disbursed to the Ministry, making procurement in the construction sector ripe for green reforms. The application of sustainable building techniques and materials could reduce Nigeria’s 17 million housing deficit and create more jobs.

But the task of greening the Nigerian economy is too important to be left to the federal government alone. It also requires mainstreaming climate change and sustainable development into the operations, governance, and budgets of government ministries, departments, and private entities at the sub-national and national levels.

There has been much focus on reviving agriculture, which is laudable, but agrarian practices have radically changed from the 1970s when the sector accounted for 57% of Nigeria’s GDP and generated 64.5% of export earnings. Beset by a loss of biodiversity, drought, and desertification, extreme weather events, rise in sea levels and variable rainfall, it is no longer smart for Nigeria to invest in this area without due regard for the significant climate risks. Any effort to revive agriculture and its export potential must be green-centred and integrate regenerative and climate-smart practices.

The right policy mix combined with aggressive funding can position the country as a renewable energy leader, both on the African continent and globally. And it will reap the benefits in technology development, foreign investment, decreased emissions, poverty reduction, and energy for the 80 million people currently without access to the national grid – all of which could ripple into millions of clean energy jobs in manufacturing and installation across the country.

The road to a green future must be paved with deliberate and consistent policies. Reforms hatched because oil prices have plunged should not be ditched when there is a boom. On the brink of a second recession in four years, Nigeria has learnt that the economic turmoil caused by COVID-19 is only the latest warning that pinning economic growth on a boom-bust market and the generosity of foreign donors and creditors is a failing strategy. There is another way and there is an opportunity for Nigeria to lead.




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By Inventing Military Threats, Lukashenka Is Playing with Fire

20 August 2020

Keir Giles

Senior Consulting Fellow, Russia and Eurasia Programme
In a bid to reassert control in Belarus, Aliaksandr Lukashenka is trying to stir the worst fears of his supporters by playing the war card. But overplaying his hand could prove disastrous if it leads to confrontation with either Russia or NATO.

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A mass rally in Grodno, Belarus where factory workers went on strike in protest against the election results and actions of law enforcement officers. Photo by Viktor DrachevTASS via Getty Images.

Having failed to swiftly translate popular support into tangible political achievements, there are signs the protests against the fraudulent presidential election in Belarus may be losing momentum in the face of the state’s resilience and still-confident security and enforcement apparatus.

Attempts to blame the unrest on the West have focused on groups Lukashenka and Russia can both call enemies. And now Aliaksandr Lukashenka is not only inventing anti-Russian policies supposedly held by the opposition, such as suppressing the Russian language and closing the border with Russia, but also a supposed military threat from NATO.

Border movements

Increased military activity inside Belarus does give Lukashenka a wider range of options. Unscheduled activation of military units includes airspace defence practice with missiles and aircraft, electronic warfare (EW) units put on round-the-clock alert, and a number of infantry brigades preparing for live firing exercises.

Lukashenka is drawing attention to the north-west corner of Belarus, singling out the city of Grodno near the border with Poland and Lithuania as a supposed target for Western efforts at destabilization. Grodno is also the destination for an airborne brigade moving from the east to the west of the country and the focus of military exercises under way on the country’s western borders.

All this feeds Lukashenka’s narrative that Belarus is in danger from NATO and the West who are supposedly both stirring up the protests and seeking to exploit disorder - and that this danger extends to possible military clashes.

The Belarusian exercises are over the border from where NATO troops - including elements of the Light Dragoons, a British reconnaissance unit - have been in place in Poland as part of NATO's enhanced forward presence (eFP) since 2017. Pointing to NATO activity in Poland and Lithuania, Lukashenka said on Wednesday ‘we have to follow their movements and plans’ and that ‘they will answer for it if something happens’.

The danger is that having invented a tense situation in Grodno, Lukashenka may now need to be proved right. There may be staged incidents or ‘provocations’ against Belarus military forces, either supposedly instigated by protesters or even by NATO forces on the border - all aimed at bolstering the narrative that NATO, the EU, and the West in general are hostile to Belarus and that more drastic measures are necessary for protection.

Russia’s options still open

Although initial fears of a Russian move into Belarus have receded, Lukashenka’s complaints about NATO also bolster the case for Moscow to intervene. The military exercises fit the narrative that Belarus is under threat from the West - which is exactly the pretext Russia would need.

If this is believed in Moscow, where foreign minister Sergey Lavrov has already described events in Belarus as part of a ‘struggle for the post-Soviet space’, this makes a Russian intervention more likely. Moving forces away from their base near the border with Russia to the other end of the country near Poland and Lithuania also means any Russian entry into Belarus could go more smoothly, with fewer wild cards of possible Belarusian opposition to consider.

There are plenty of sensible, rational, logical reasons why a Russian military intervention in Belarus would be disastrous and counter-productive. But what seems sensible and rational in Europe and North America does not always carry weight in Moscow, which may see the situation completely differently and measure options by completely different standards.

One key area of doubt is the sympathies of the Belarus armed forces. Although some elements of the Belarusian army - particularly airborne and special forces - work closely with their Russian counterparts, more general suggestions that the Belarusian military is merely an extension of Russia’s and is not capable of taking decisions for itself are an over-simplification.

The Belarus armed forces do know that hosting Russian ground troops, airbases or air defence systems would fatally undermine the country’s hopes of avoiding being caught up in any confrontation between Russia and NATO.

And although the great majority of Belarusian officers are Russian-speaking and many have been trained and educated in Russia, there may be sufficient pride in national identity and resentment at heavy-handed treatment by Russia to lead to substantial obstruction of Russian initiatives.

The Belarus General Staff has already refused permission for a Russian aircraft carrying 155 personnel from the Rosgvardiya militarized security force and three tonnes of cargo ‘for the Belarusian interior ministry’ to land in Belarus. This could indicate not only tension between Russia and Belarus, but even between ministries within Belarus itself.

Like Russia, Lukashenka has plenty of options in reserve if his situation deteriorates further. Announcing a state of emergency would allow the Belarusian army to support the security forces in dealing with protests. If the army is on the move with their equipment they are better prepared to be brought into action if needed, but testing the loyalty of the armed forces could prove dangerous if the sympathies of army units turn out to lie more with civilians than with their oppressors from the interior ministry.

The military preparations against fictitious threats and a patiently-waiting Russia is a toxic mix and Belarus’s friends abroad must tread carefully. A key task for the European Union (EU) is to help the Belarusian people without providing a pretext for further violence and Russian intervention.

The right level of engagement needs to be carefully calibrated, avoiding disasters of strategic communication such as European Commissioner Thierry Breton being translated into English as saying Belarus is not part of Europe – with the lack of EU interest that that implies. Although the EU statement promising sanctions and offering funds received a mixed reception, at least it cannot be used by Lukashenka and Vladimir Putin as evidence that their warnings of a Western military threat are genuine.




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Can the International Criminal Court Help Belarus?

26 August 2020

Kateryna Busol

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
A referral of election violence in Belarus to the International Criminal Court could enhance the support for the Belarusian people at other crucial platforms.

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A protester carries a former Belarusian flag during an opposition rally by the Minsk Hero City Obelisk. Photo by Valery SharifulinTASS via Getty Images.

Making the case

The recent election results in Belarus have triggered revolution in yet another post-Soviet country and Aliaksandr Lukashenka’s response has been devastatingly brutal. However, the Belarusian people’s resilience and Western sanctionsadopted on 14 August – have proved effective. As some of the 6,700 jailed protesters were released, accounts of horrific treatment by law enforcement emerged: overcrowded cells, no food, torture, forced confessions, severe beatings , and threats of rape.

With reports of mounting violence, Polish MEP Radosław Sikorski warned Lukashenka to expect not just sanctions but also the possible intervention of the International Criminal Court (ICC), an idea supported by the opposition-led Belarus’ National Salvation. While there are significant impediments to the Court’s involvement, the impact of such an initiative could be ground-breaking.

Legal framework

The ICC considers criminal responsibility of top civilian or military leaders for only the most serious atrocities - war crimes, genocide, crimes against humanity and, in certain cases, the crime of aggression. In the context of Belarus, the Court’s jurisdiction over crimes against humanity might be relevant. According to the Rome Statute, the ICC’s founding treaty, crimes against humanity include widespread or systematic abuses directed against a civilian population. Atrocities relevant to Belarus include arbitrary imprisonment, torture, inhuman treatment, sexual violence, and enforced disappearances.

The ICC is a last resort. It can intervene only if states are unable or unwilling to properly investigate and prosecute serious crimes themselves. Although Belarus’s Criminal Code punishes crimes against humanity, as Lukashenka himself is implicated, impartial trials in the country are impossible while he is still in power. Other countries may investigate specific atrocities in Belarus under the universal jurisdiction principle. Universal jurisdiction greenlights investigations into the most serious crimes regardless of where they are perpetrated. German, Swedish and French proceedings on Syria are illustrative examples of this. Protesters may also file individual complaints of abuse to UN bodies under the protocols of the International Covenant on Civil and Political Rights and the Convention on the Elimination of All Forms of Discrimination against Women. The European Court of Human Rights is not an option for the protesters because Belarus is not a member of the Council of Europe.

As the UN mechanisms are yet to be triggered and there has not yet been any talk of universal jurisdiction proceedings, the question of recourse to the ICC remains. But as Belarus is not party to the Rome Statute, the only way to trigger the Court’s jurisdiction is a referral by the UN Security Council (UNSC). Even though it would be vetoed by Russia –  and, almost certainly, China – it could be worth pursuing.

The importance of symbolism

So far, the UNSC has referred to the ICC two situations in non-party states – Sudan and Libya. But for cases that do not end up being referred to the Court, the UNSC debates are as significant for what they manage to agree upon as they are for what they do not. Regarding Belarus, two impeded UNSC accountability initiatives are relevant: on Syria and MH17.

In 2014, Russia and China vetoed the referral of cases of violence in Syria to the ICC. In 2015, Russia was the only country to block the creation by the UNSC of a special tribunal to investigate Malaysian Airlines flight MH17, downed by a Russian missile over war-affected eastern Ukraine. In both cases, the vetoes delayed justice, but they did not prevent it. For Syria, special independent mechanisms to collect evidence for adjudication were developed. Although justice has yet to be done, except in states like Germany, the evidence is ready for any future court. For MH17, a proceeding at a domestic Dutch court became an alternative. Parallel to that, new evidence of Russia’s role in both Syria and the downing of MH17 emerged - contextualising its UNSC vetoes.

Russia’s stakes in the Belarusian elections are probably even higher: the victory of democracy in Belarus will deprive it of one of its closest and most dependent post-Soviet allies.

Even if Russia destroys any chance of Belarusian citizens using the ICC, the attempted ICC-Belarus discussion will not have been in vain. Russia’s opposition to the respective UNSC resolution would be a self-defeating validation of Lukashenka’s atrocities against his own people, unashamedly restated at one of the world’s top diplomatic negotiation tables. Similar to Syria and MH17, the UNSC would reconfirm its self-imposed impotency to defend basic human rights amid political conjuncture. This would bring more attention to the issue and catalyse action through other platforms, including the discussions across UN bodies and the consideration of Belarusians’ individual complaints of abuse, and could lead to tougher sanctions. It could also further make the case for universal jurisdiction proceedings in other countries.      

Supporting civil society

Belarusian civil society will need stronger support from democratic governments and human rights organizations in reporting and documenting the crimes. Other countries, neighbouring states in particular, should be ready to welcome Belarusian protesters through refugee schemes, so they are able to continue their activities from abroad.

When nationwide strikes enveloped Belarus, singers from the Minsk Opera supported protesters by singing Va, pensiero, the famed chorus of the Hebrew slaves from Verdi’s Nabucco – and a symbol of united Italy’s revival. The people of Belarus also want to live in a democratic state ‘where the mind is without fear and the head is held high’. And they deserve all the support they can get. The inevitable fall of Lukashenka’s regime might take time but it should not take more lives.




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Rage Against the Algorithm: the Risks of Overestimating Military Artificial Intelligence

27 August 2020

Yasmin Afina

Research Assistant, International Security Programme
Increasing dependency on artificial intelligence (AI) for military technologies is inevitable and efforts to develop these technologies to use in the battlefield is proceeding apace, however, developers and end-users must ensure the reliability of these technologies, writes Yasmin Afina.

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F-16 SimuSphere HD flight simulator at Link Simulation in Arlington, Texas, US. Photo: Getty Images.

AI holds the potential to replace humans for tactical tasks in military operations beyond current applications such as navigation assistance. For example, in the US, the Defense Advanced Research Projects Agency (DARPA) recently held the final round of its AlphaDogfight Trials where an algorithm controlling a simulated F-16 fighter was pitted against an Air Force pilot in virtual aerial combat. The algorithm won by 5-0. So what does this mean for the future of military operations?

The agency’s deputy director remarked that these tools are now ‘ready for weapons systems designers to be in the toolbox’. At first glance, the dogfight shows that an AI-enabled air combat would provide tremendous military advantage including the lack of survival instincts inherent to humans, the ability to consistently operate with high acceleration stress beyond the limitations of the human body and high targeting precision.

The outcome of these trials, however, does not mean that this technology is ready for deployment in the battlefield. In fact, an array of considerations must be taken into account prior to their deployment and use – namely the ability to adapt in real-life combat situations, physical limitations and legal compliance.

Testing environment versus real-life applications

First, as with all technologies, the performance of an algorithm in its testing environment is bound to differ from real-life applications such as in the case of cluster munitions. For instance, Google Health developed an algorithm to help with diabetic retinopathy screening. While the algorithm’s accuracy rate in the lab was over 90 per cent, it did not perform well out of the lab because the algorithm was used to high-quality scans in its training, it rejected more than a fifth of the real-life scans which were deemed as being below the quality threshold required. As a result, the process ended up being as time-consuming and costly – if not more so – than traditional screening.

Similarly, virtual environments akin to the AlphaDogfight Trials do not reflect the extent of risks, hazards and unpredictability of real-life combat. In the dogfight exercise, for example, the algorithm had full situational awareness and was repeatedly trained to the rules, parameters and limitations of its operating environment. But, in a real-life dynamic and battlefield, the list of variables is long and will inevitably fluctuate: visibility may be poor, extreme weather could affect operations and the performance of aircraft and the behaviour and actions of adversaries will be unpredictable.

Every single eventuality would need to be programmed in line with the commander’s intent in an ever-changing situation or it would drastically affect the performance of algorithms including in target identification and firing precision.

Hardware limitations

Another consideration relates to the limitations of the hardware that AI systems depend on. Algorithms depend on hardware to operate equipment such as sensors and computer systems – each of which are constrained by physical limitations. These can be targeted by an adversary, for example, through electronic interference to disrupt the functioning of the computer systems which the algorithms are operating from.

Hardware may also be affected involuntarily. For instance, a ‘pilotless’ aircraft controlled by an algorithm can indeed undergo higher accelerations, and thus, higher g-force than the human body can endure. However, the aircraft in itself is also subject to physical limitations such as acceleration limits beyond which parts of the aircraft, such as its sensors, may be severely damaged which in turn affects the algorithm’s performance and, ultimately, mission success. It is critical that these physical limitations are factored into the equation when deploying these machines especially when they so heavily rely on sensors.

Legal compliance

Another major, and perhaps the greatest, consideration relates to the ability to rely on machines for legal compliance. The DARPA dogfight exclusively focused on the algorithm’s ability to successfully control the aircraft and counter the adversary, however, nothing indicates its ability to ensure that strikes remain within the boundaries of the law.

In an armed conflict, the deployment and use of such systems in the battlefield are not exempt from international humanitarian law (IHL) and most notably its customary principles of distinction, proportionality and precautions in attack. It would need to be able to differentiate between civilians, combatants and military objectives, calculate whether its attacks will be proportionate against the set military objective and live collateral damage estimates and take the necessary precautions to ensure the attacks remain within the boundaries of the law – including the ability to abort if necessary. This would also require the machine to have the ability to stay within the rules of engagement for that particular operation.

It is therefore critical to incorporate IHL considerations from the conception and throughout the development and testing phases of algorithms to ensure the machines are sufficiently reliable for legal compliance purposes.

It is also important that developers address the 'black box' issue whereby the algorithm’s calculations are so complex that it is impossible for humans to understand how it came to its results. It is not only necessary to address the algorithm’s opacity to improve the algorithm’s performance over time, it is also key for accountability and investigation purposes in cases of incidents and suspected violations of applicable laws.

Reliability, testing and experimentation

Algorithms are becoming increasingly powerful and there is no doubt that they will confer tremendous advantages to the military. Over-hype, however, must be avoided at the expense of the machine’s reliability on the technical front as well as for legal compliance purposes.

The testing and experimentation phases are key during which developers will have the ability to fine-tune the algorithms. Developers must, therefore, be held accountable for ensuring the reliability of machines by incorporating considerations pertaining to performance and accuracy, hardware limitations as well as legal compliance. This could help prevent incidents in real life that result from overestimating of the capabilities of AI in military operations. 




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Economic Diplomacy in the Era of Great Powers

17 September 2020

Dr Linda Yueh

Associate Fellow, Global Economy and Finance Programme and US and the Americas Programme
The 21st-century global economy has different drivers from those in the previous century. Amid ever more politicized trade relations, economic diplomacy needs a more transparent framework.

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US president Donald Trump at the World Economic Forum in Davos, Switzerland, on January 22, 2020. Photo by JIM WATSON/AFP via Getty Images.

The emergence of a multipolar global economy in which the US is no longer the main engine of growth has boosted the role of economic diplomacy, the setting of foreign economic policy. While the EU remains the world’s biggest economic bloc and the US is still an economic powerhouse, it is Asia – China in particular – which has created hundreds of millions of new middle-class consumers, helping to drive global economic growth.

This shift has ignited an era of competition between the US and China and, by implication, a debate about the merits of different political and legal systems. The difficulty for the rest of the world is how best to navigate this highly polarized climate – in recent history, only the Cold War comes close to having matched the adversarial dynamics of such a divided international community.

In conducting economic diplomacy, governments should consider their economic strengths, the importance of transparency, and how best to operate in a fragmented international system.

First, the setting of trade and investment policy should take into account developments in the global economy. One trend worth noting is the rising importance of services – in particular digital services – in international trade. The expanding cross-border trade in intangibles such as business services and data means the negotiation, definition and enforcement of standards to regulate these are of growing importance for the global economy, and for policymakers in many countries.

In contrast, negotiations around merchandise trade are likely to take a somewhat lower profile. Under the World Trade Organization (WTO), tariffs on manufactured goods have dropped significantly in any case – though there is still scope to lower them. Contemporary diplomacy, as well as disputes, around the lowering or raising of barriers to international trade will increasingly concern non-tariff measures applicable to services rather than those, such as tariffs, that traditionally apply to goods.

For service-based economies, it is vital free-trade agreements (FTAs) encompass regulations and standards for intangibles. But this is difficult in a multipolar global economy where the US, China and the EU all have different legal and regulatory systems, and raises the prospect of a fragmented global trading system divided into blocs of countries adhering to different standards.

A pluralistic or mini-multilateral approach to trade such as the stalled Trade in Services Agreement (TiSA) could help resolve elements of this division. TiSA was launched in 2013 by a group of advanced economies, not the entirety of the WTO, to further opening up global services trade. However, talks have been on hold since 2016 and, in the current climate, it is near impossible to conclude negotiations when the major economies do not come to the table and instead promote their own standards with their closest trading partners.

Second, policymakers should consider that, in an era of heightened trade tensions, any framework for economic diplomacy needs to be transparent if it is to be trusted and credible. Such a framework could centre on commercial openness and consistency with a country’s foreign and intelligence policy aims. For example, clearly spelling out how a country reviews prospective foreign investment and applying this consistently would demonstrate that all projects are treated equally without singling out any individual country. This would be an improvement over an ad hoc and less transparent approach .

A major challenge in creating a ‘principle-based’ economic diplomacy framework of this kind is reconciling competing policy aims. To this end, several key questions need answering. Should trade agreements encompass non-economic elements, such as foreign policy aims? Do concerns over national security mean that trade and investment agreements should favour allies? Could such a framework assess a trading or investment partner in terms of national security as well as potential economic benefit?

A country should also re-think how to undertake a wider international role when embarking on economic diplomacy. The inability of the major powers to set new global rules has had a detrimental impact on an international system under significant strain. The stalling of multilateral trade talks and urgency of international coordinated action on global public goods, such as health and the environment, shows there is a pressing need for a new approach to international relations.

Economic diplomacy could, and should, bolster the rules-based multilateral system. The challenge is engaging the major powers without whom widespread adoption of global policies and standards is less likely. Yet the chances of wider adoption might actually be better if a proposal does not come from either the US or China. This opens up the opportunity for other countries to be ‘honest brokers’ and potentially improve their own international standing.

In an era of increasing tension between great powers, economic diplomacy requires re-tooling. It should consider not just economic considerations, but also broader foreign policy aims, greater transparency, and a pluralistic approach to global rules to strengthen the multilateral system.




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Inhibition of mitochondrial oxidative metabolism attenuates EMCV replication and protects {beta}-cells from virally mediated lysis [Immunology]

Viral infection is one environmental factor that may contribute to the initiation of pancreatic β-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate β-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the β-cell response to viral infection. We show that nitric oxide protects β-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS-derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated β-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in β-cells functions to limit viral replication and subsequent β-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide–dependent manner.




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Ascertaining the biochemical function of an essential pectin methylesterase in the gut microbe Bacteroides thetaiotaomicron [Metabolism]

Pectins are a major dietary nutrient source for the human gut microbiota. The prominent gut microbe Bacteroides thetaiotaomicron was recently shown to encode the founding member (BT1017) of a new family of pectin methylesterases essential for the metabolism of the complex pectin rhamnogalacturonan-II (RG-II). However, biochemical and structural knowledge of this family is lacking. Here, we showed that BT1017 is critical for the metabolism of an RG-II–derived oligosaccharide ΔBT1017oligoB generated by a BT1017 deletion mutant (ΔBT1017) during growth on carbohydrate extract from apple juice. Structural analyses of ΔBT1017oligoB using a combination of enzymatic, mass spectrometric, and NMR approaches revealed that it is a bimethylated nonaoligosaccharide (GlcA-β1,4-(2-O-Me-Xyl-α1,3)-Fuc-α1,4-(GalA-β1,3)-Rha-α1,3-Api-β1,2-(Araf-α1,3)-(GalA-α1,4)-GalA) containing components of the RG-II backbone and its side chains. We showed that the catalytic module of BT1017 adopts an α/β-hydrolase fold, consisting of a central twisted 10-stranded β-sheet sandwiched by several α-helices. This constitutes a new fold for pectin methylesterases, which are predominantly right-handed β-helical proteins. Bioinformatic analyses revealed that the family is dominated by sequences from prominent genera of the human gut microbiota, including Bacteroides and Prevotella. Our re-sults not only highlight the critical role played by this family of enzymes in pectin metabolism but also provide new insights into the molecular basis of the adaptation of B. thetaiotaomicron to the human gut.




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Climate migration: Ways ahead from the next generation

Climate migration: Ways ahead from the next generation The World Today rsoppelsa.drupal 25 May 2022

Ella Dennis and Mike Higgins talk to young activists seeking solutions as global warming wreaks havoc in sub-Saharan Africa

Africa has the lowest carbon emissions per capita yet the highest rate of temperature increase in the world. Rising levels of desertification, drought and flooding are already forcing millions of Africans to relocate to find more stable livelihoods. 

The continent’s youth will bear the brunt of this climate migration problem. It is estimated that by 2050, Africa will be home to 86 million internal climate migrants.

How is climate migration already affecting sub-Saharan Africa and what frameworks could tackle it? To begin to answer those questions, five young activists from across the region, who are members of Chatham House’s Common Futures Conversations, took part in a panel discussion at the world’s first youth-led Conference on Climate Migration, convened in April by the Alliance for Citizen Engagement, a nonpartisan think tank based in the US. 

[Farmer-herder] conflicts will pose even larger security concerns as climate migration intensifies

Laura Mukhwana, Kenyan PhD candidate

The conversation and follow-up discussions focused on a common problem – climate migration brings people into conflict and puts pressure on infrastructure. 

In Kenya, droughts have left 3.5 million people hungry and the chronic flooding of several lakes in the Rift Valley has displaced hundreds of thousands, said Gerald Muchiri, 29, a social scientist from Kenya. One result has been outbreaks of violence between pastoralists such as the Orma people and the farmers of the Pokomo community, said Laura Mukhwana, 33, a PhD student in Kenya. She believes this violence is likely to worsen. ‘Inter-group conflicts will pose even larger security concerns for surrounding communities as climate migration intensifies,’ she said.

Suleman Nuhu, 24, a farmer and veterinary student from Nigeria, said farmer-herder conflicts were his country’s most significant climate-migration issue. The movement of nomadic tribes from the north had affected him personally: ‘Nomads have trespassed on [my family’s] farms many times while moving with their livestock, destroying our crops.’ 

Changes in climate also force people to move from rural to urban areas. Nigeria, for instance, struggles with the so-called ‘Lagos problem’, said Temiloluwa Lawal, 25, a lawyer and researcher from Nigeria. An estimated 22 million people, a number that is rising fast, are crammed into a city smaller than Greater London. While not on the same scale, Zimbabwe experiences comparable challenges, said Tinotenda Dube, 29, a Zimbabwean finance director. Thanks to drought, unemployed rural migrants arriving in cities ‘put excessive pressure on service delivery against a low tax base,’ he said. ‘People, including close family members of mine, are crowded in dilapidated homes because they cannot afford to pay rent for decent housing.’ 

But there is hope, say the activists. Dube believes that affordable housing is an ‘integral component of [tackling] the climate migration crisis’. 

In Zimbabwe, he has developed a low-cost home finance model that, he said, has helped more than 250 low-income households find good-quality accommodation. Alongside this initiative, Dube has co-founded a property and construction company, Solinfra Zimbabwe Private Ltd, to provide low-cost housing. 

Muchiri is taking action in Kenya, founding an NGO called Social Assistance Welfare to tackle public health issues, he said: ‘As climate migration becomes more intense, I expect preventable health issues to increase throughout the region, and thus see Social Assistance Welfare as an important mitigation.’

To mitigate food security problems, we must reduce reliance on rain-fed agriculture through irrigation schemes

Suleman Nuhu, farmer and veterinary student from Nigeria

In Nigeria, Nuhu noted that to help reduce conflict between farmers and herders social-media campaigns are encouraging pastoralists to move from nomadic livestock farming to more efficient intensive systems, using ranching and grazing reserves. ‘As for food security problems, the best mitigation is to reduce reliance on rain-fed agriculture through irrigation schemes,’ he said. 

All five agreed that, in their experience, the youth of sub-Saharan Africa could be better informed about climate migration. But they took encouragement from the fact the young are passionate about tackling issues arising from the broader climate crisis. 

In Kenya, Mukhwana pointed to successful youth projects around agro-forestry and tree-planting. She added that there is ‘a growing movement of urban youth who are advocating for climate justice, such as the Kenyan Youth Environmental Network and Fridays for the Future Kenya’. It was pleasing too, she said, that when the Kenyan government revised its contributions to the Paris Climate Accords it staged a week-long youth conference to include their opinions.

‘Overall, I am quite hopeful about how the youth are mobilizing themselves in Kenya,’ she added.

Find out more about Chatham House’s Common Futures Conversations
 




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A booming tech sector can unleash pan-African trade

A booming tech sector can unleash pan-African trade The World Today mhiggins.drupal 31 July 2022

The new African Continental Free Trade Area must embrace hyperscale data centres, cross-border digital payments and other innovations to realise its potential.

The Africa Continental Free Trade Area (AfCFTA) not only lays the groundwork for a single market across the continent, it can act as a driving force to unleash the full potential of the technology revolution that is under way across the African continent. 

To help achieve this, the AfCFTA must go beyond simply lowering barriers to the movement of goods and services, to what the World Bank calls an ‘FDI [foreign direct investment] deep scenario’. This requires harmonizing policies on investment, competition, intellectual property rights and e-commerce to encourage FDI at a greater scale. 


The World Bank estimates that the AfCFTA could increase income across the continent by 7 per cent by 2035 (an additional $445 billion), mainly by boosting intra-regional trade in manufactured goods and lifting approximately 40 million people from extreme poverty. Under an FDI deep scenario, the projected income growth jumps to 9 per cent by 2035, supporting 50 million people out of extreme poverty. 

The initial focus of the AfCFTA is on movement of goods and services and the associated financial flows through the establishment of the Pan-African Payment and Settlement System (PAPSS), a technology that enables instant local currency payment across Africa without first converting to a hard currency. In addition, harmonizing policies and easing the movement of data could enable technology to accelerate the anticipated AfCFTA income growth.

Global venture capital is pouring in

There is no doubt the African tech industry is growing. In 2021, 681 African technology companies raised $5.2 billion in equity venture funding, up from $2 billion in 2019, according to Partech Partners’ annual Africa Tech Venture Capital report. 

It is understandable why the industry has attracted global venture capital. While tech businesses are often initially focused on meeting needs in their home markets, most have a strong desire to tap into the pan-African market, with its 1.3 billion consumers across 54 countries and a combined GDP of $3.4 trillion. This in turn should attract global venture capital to invest in Africa. 


Regulatory constraints mean African data centres are less competitive than those in America and China


The AfCFTA has created a framework for technology-led companies to scale across the continent in a way that will impact digital infrastructure, logistics, energy and much else. For example, Africa’s hyperscale data centre capacity would benefit from the ability to locate centres in the lowest cost jurisdiction with the best energy availability and to use that to power cloud storage across the continent.

Yet various regulatory constraints, including the desire for each state to own its population’s data on local servers, prevent that. As a result, African data centres are less competitive than those in America and China. 

Similarly, logistics and other sectors would be transformed if the information on goods in transit, such as digital customs documentation, could move easily across borders while being tracked across all 54 countries. Financial services would also benefit from the ability to pay across borders in a low-cost, frictionless way.

Fintech companies should be encouraged to build technology solutions linking to PAPSS and other initiatives to accelerate the adoption-of-use cases that PAPSS supports – such as intra-Africa instant payment, embedded finance and remittances services.

AfCFTA may also unlock mergers and acquisitions (M&A) activity among African and international firms. Technology companies are using M&A to enter new markets, as the international payments platform Stripe did when it acquired the Nigerian business Paystack, and the payments business MFS Africa did when it took over the fintech start-up Baxi. 

Governments and regulators must support innovation

Given the difficulty of a country-by-country organic growth strategy across Africa, M&A is likely to increase in various technology sectors over the next few years. With the anticipated ease of doing business that the AfCFTA could facilitate, we are likely to witness further welcome consolidation, creating larger corporates that create more jobs and increase tax revenues. 

To unlock the benefits that technology will bring, governments and regulators need to play a supportive role in encouraging innovation. They will need to ensure the appropriate consumer protections are in place without stifling creativity through regulation, inefficiencies or rent-seeking. 

At the same time, governments and regulators should not permit themselves to be held to ransom by dominant incumbents, such as banks and mobile operators in the fintech space, at the expense of stifling technology companies looking to disrupt their respective industries. 

Only then will the AfCFTA allow Africa to benefit from its tech potential. 

Risana Zitha writes this article in a personal capacity




mi

Culture notes: Europe's broken promises to Africa

Culture notes: Europe's broken promises to Africa The World Today mhiggins.drupal 1 August 2022

Europe’s ‘gas grab’ in Africa is just the latest abuse of its relationship with the continent, says Catherine Fieschi.

When Emmanuel Macron made one of his first visits to Africa as France’s recently elected young president in 2017, his speech at Ouagadougou University in Burkina Faso was designed to set the tone for a new relationship between his country and African countries. 

‘There no longer is a French policy for Africa,’ he said.

This was a signal away from ‘la Françafrique’, with its post-colonial accents and the propping up of regimes friendly to France, to something that was more strategic, equitable and transparent – more partnership and less tutelage. 

And Europe seemed to be following suit. In March 2020 the European Union and Africa decided that they would redefine their relationship. The European Commission unveiled its vision for a ‘comprehensive strategy with Africa’. The roadmap would give Africa significantly more say over the nature and extent of the relationship, more choice and more political agency.

Despite repeated statements, Europe seems to be saying one thing and doing another when it comes to Africa

But what, today, is left of these aspirations? Despite repeated statements, Europe seems to be saying one thing and doing another. 

Earlier this year, after the long-awaited 6th annual EU-African Union summit in Brussels, South African president Cyril Ramaphosa was frank when he summed up the gap between stated ambitions and the current relationship. The pandemic-weary Global South had reason to be wary. Ramaphosa laid out missed opportunities, disappointment and the low expectations that act as self-fulfilling prophecies. 

Europe’s changing focus in Africa 

From the apparent high point of the Ouagadougou speech, Macron has now turned to the Organization Internationale de la Francophonie (OIF) in Africa for geopolitical purposes. His primary aim is to combat the rise of Islamist militants and terrorism in the Sahel as well as to tackle the growing influence of China and Russia in the region. 

Russian inroads – via the security firm Wagner in Mali, for instance – have given France further cause to use the OIF to counter destabilization activities. Both the United Kingdom and France train African military in the Sahel, but now, with the end of France’s anti-insurgent Operation Barkhane in Mali, the subsequent withdrawal of French troops and the increasingly established presence of the Wagner group, the security situation in the region is expected to deteriorate dramatically and become increasingly impermeable to European interests and forces.

As for development aid, Britain’s Integrated Review of Security, Defence, Development and Foreign Policy makes no bones about the fact that Asia is now a priority over Africa.

The relationship between Africa and Britain is being transformed as a result, most obviously through the cuts in development aid, with African aid cut by 66 per cent in 2021. But the nature of the relationship, which has become both more conditional and more transactional, has also changed. 

The UK is emphasizing human rights and ‘free societies’, but also pushing for free market principles rather than the kind of state involvement that some African countries often prefer as a road to accelerated and more autonomous development. 

The future of energy exports and COP27

The issue of energy exports points to what will most likely trigger the greatest disappointment in the next few years – climate and climate finance. 

Green energy deals, like the $8.5 billion COP26 package from the EU, United States and UK to South Africa, look far more problematic now in the light of Europe’s African gas-grab. Indeed, Europe is importing as much African gas as it can after the invasion of Ukraine by Russia reduced supplies. Yet African countries are still being told to curb their own use of ‘dirty’ energy. 

As an illustration, Nigeria holds 3 per cent of the world’s gas reserves, but has barely tapped them, while 40 per cent of its output is exported to Europe. In April, Italy closed deals to buy gas from Angola and the Republic of Congo, while Germany did the same with Senegal.
 

At COP15 in Copenhagen in 2009, developed countries pledged an annual $100 billion in climate finance to developing countries for both adaptation and mitigation. But pledges have never really materialized. The aid agency Oxfam estimates that only about a third of the money has been delivered. Climate finance was again the main focus of COP26 – and dismissed by Greta Thunberg as more ‘blah, blah, blah’.

This series of repeated resets, pledges and disappointments tells a story – indeed, several stories. First and foremost, it is one of arrogance and betrayal. That much is obvious. But it is also a story about stories – about how the narratives elaborated by various European countries and leaders never amount to more than a sum of transactions. 

Climate change places Europe, and other rich nations, at a crossroads in its relationship with Africa: the former holds the wealth, but also some of the keys and threats to the transition. COP27, to be held in Egypt in November, will be the next chapter in the story. 




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Africa in 2023: Continuing political and economic volatility

Africa in 2023: Continuing political and economic volatility Expert comment NCapeling 6 January 2023

Despite few African trade and financial links with Russia and Ukraine, the war in Ukraine will cause civil strife in Africa due to food and energy inflation.

Africa’s economy was recovering from the COVID-19 pandemic in 2022 when a range of internal and external shocks struck such as adverse weather conditions, a devastating locust invasion, and the Russian invasion of Ukraine – all of which worsened already rapidly-rising rates of inflation and borrowing costs.

Although the direct trade and financial linkages of Africa with Russia and Ukraine are small, the war has damaged the continent’s economies through higher commodity prices, higher food, fuel, and headline inflation.

The main impact is on the increasing likelihood of civil strife because of food and energy-fuelled inflation amid an environment of heightened political instability.

Key African economies such as South Africa and Nigeria were already stuck with low growth and many African governments have seen their debt burdens increase – some such as Ethiopia and Ghana now have dollar debt trading at distressed levels – and more countries will follow in 2023.

On average the public sector debt-to-GDP ratio of African countries stood at above 60 per cent in 2022. The era of Chinese state-backed big loans and mega-projects which started 20 years ago in Angola after the end of its civil war may be coming to an end but Chinese private sector investments on the continent will continue through its Belt and Road Initiative and dual circulation model of development.

Great and middle powers building influence

Geopolitical competition in Africa has intensified in 2022, particularly among great powers such as China, Russia, the US, and the EU but also by middle powers such as Turkey, Japan, and the Gulf states.

The sixth AU-EU summit held in Brussels in February 2022 agreed on the principles for a new partnership, although the Russian invasion of Ukraine which followed disrupted these ambitions. Japan’s pledge of $30 billion in aid for Africa at TICAD 8 in August 2022 was clearly made due to the $40 billion pledged at the China–Africa summit in November 2021.

The geopolitical and geoeconomic ramifications of the war in Ukraine has directly impacted the African continent by contributing to food and cooking oil inflation and humanitarian aid delivery

The US also launched a new strategy to strengthen its partnership and held a second US-Africa Leaders’ summit in Washington in December, the first since 2014. Russia’s ambition has been curtailed by its invasion of Ukraine, postponing its second summit with African states to 2023.

The imposition of international sanctions complicated its trade and investments, and military support such as that provided by Russian paramilitary group Wagner focused on Mali, Libya and the Central African Republic (CAR) has been curtailed.

The strategic importance of Africa has resulted in all the UN P5 members calling on the G20 to make the African Union (AU) its 21st member in 2023 under India’s presidency.

International competition to secure Africa’s critical and strategic minerals and energy products intensified in 2022 and, in the energy sector, European countries are seeking to diversify away from Russian oil and gas with alternative supplies, such as those from Africa.

Western mining companies and commodity traders are also increasingly seeking alternative supplies from Africa. Decarbonization is becoming a driver of resource nationalism and geopolitical competition in certain African mining markets, home to large deposits of critical ‘transition minerals’ such as copper, cobalt, graphite, lithium, or nickel.

COP27 was hosted in Egypt in November and gave African leaders an opportunity to shape climate discussions by pushing priority areas such as loss and damage, stranded assets, access to climate finance, adaptation, and desertification. Climate adaptation in Africa is a key condition to preserving economic growth and maintaining social cohesion.

The Horn of Africa, particularly Somalia, is suffering from one of the worst droughts in memory. The geopolitical and geoeconomic ramifications of the war in Ukraine has directly impacted the African continent by contributing to food and cooking oil inflation and humanitarian aid delivery.

Thoughout 2022 the AU was undergoing intensive reform and it struggled to respond to the growing number of security crises across the continent. Hotspots in 2023 will be in the western Sahel and Lake Chad Basin, eastern DRC, and northern Mozambique, all of them crossing state borders.

In Mozambique, a 2019 peace deal assisted by the United Nations (UN) will see the last ex-guerrillas from Renamo demobilized in 2023 to reintegrate into civilian life – some having been recruited in 1978.

Jihadist activity may spread further into coastal states which has resulted in international partners such as France and the UK redesigning their security assistance strategies for the region

In eastern Congo, M23 – one of around 120 armed groups – resumed its conflict against the central government. After lying dormant for several years, it took up arms again in 2021 and has been leading an offensive in eastern DRC against the Congolese army.

According to the UN, Rwanda has been supporting M23, and Kenya’s parliament approved in November the deployment of about 900 soldiers to the DRC as part of a joint military force from the East African Community (EAC) bloc – DRC joined the EAC in March.

In the Horn of Africa, Ethiopia saw an uneasy ceasefire agreed between the federal government and the Tigray People’s Liberation Front (TPLF).

Islamist militant groups in Africa further expanded their territorial reach in 2022, particularly in the western Sahel where al-Qaeda and Islamic State affiliates are competing for influence and continued to make inroads.

The drawdown and exit of western forces from Mali, both the French Operation Barkane and international contributions for the UN’s MINUSMA mission there, adds new dimensions to regional security challenges.

Mali’s decision in May to withdraw from the G5 Sahel has also eroded the regional security architecture. Jihadist activity may spread further into coastal states which has resulted in international partners such as France and the UK redesigning their security assistance strategies for the region.

Coups on the increase again

Since 2020, there have been successful military coups in Burkina Faso (twice), Chad, Guinea, Mali (twice), and Sudan, and failed ones in the CAR, Djibouti, Guinea-Bissau, Madagascar, Niger, and possibly Gambia and São Tomé and Príncipe.

Three national elections illustrate the state of African democracy in 2022. In Angola’s August elections, the ruling MPLA lost its absolute majority with the opposition UNITA winning the majority in Luanda for the first time.




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SNMMI Procedure Standard/EANM Practice Guideline for Brain [18F]FDG PET Imaging, Version 2.0

PREAMBLE

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.

The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.

Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.

These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.

The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.

The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.

Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.




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