10 August 2020

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16 September 2020

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.

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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.

Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1β, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring β-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated β-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for β-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in β-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a β-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis.

Africa Aware: Relations between Ethiopia and Sudan Audio bhorton.drupal 9 April 2022

This episode of Africa Aware examines the relationship between Ethiopia and Sudan.

Ahmed Soliman provides an overview of the Africa Programme’s work on cross-border conflict as part of the XCEPT project.

First, we speak to Kholood Khair on the steady deterioration in relations between Sudan and Ethiopia. Then Abel Abate Demissie discusses how recent political developments in Ethiopia and Sudan have impacted relations between the two countries.

This podcast was produced with support from the Cross-Border Conflict Evidence, Policy and Trends (XCEPT) project, funded by UK Aid from the UK government. The views expressed do not necessarily reflect the UK government’s official policies.

It is also part of a series of outputs on Ethiopia’s political transition.

Will Africans’ calls for better democracy be met? The World Today mhiggins.drupal 29 July 2022

Voters want the continent’s ageing leaders to step aside to usher in a new age of political engagement and robust democracy, say the experts of Afrobarometer.

Across Africa, recent years have been marked by both encouraging democratic highs and troubling anti-democratic lows. Notable advances from last year include the Gambia’s successful presidential election, a ruling-party transition in Zambia and the first democratic transfer of power in Niger. In the lead up to this, add Malawi’s retake of its flawed presidential election in 2020 and an earlier succession of oustings of long-serving autocrats in Sudan, Zimbabwe and the Gambia. 

Contrast these gains, though, with setbacks elsewhere, including increasing restrictions on opposition parties in Benin, Senegal and Tanzania; the use of violence and intimidation during elections in Côte d’Ivoire and Uganda; and military coups, with the latest in Burkina Faso this year and last year in Chad, Mali, Sudan and Guinea.

These contradictory developments join dire warnings from experts that democracy is losing ground on the continent. But what can we learn about the state of democracy on the continent from Africans themselves?

Afrobarometer, a pan-African, non-partisan research network, has been surveying people about their views on democracy, governance and quality of life for more than 20 years. After interviewing nearly 50,000 citizens across 34 countries during Afrobarometer Round 8, which spans 2019-2021, we find that despite the efforts of some leaders to undermine democratic norms, Africans remain committed to democracy and democratic institutions.

They believe that the military should stay out of politics, that political parties should freely compete for power, that elections are an imperfect but essential tool for choosing their leaders, and that it is time for the old men who cling to power to step aside.

But their political reality falls short of these expectations. The perception of widespread and worsening corruption is particularly corrosive, leaving people increasingly dissatisfied with political systems that are yet to deliver on their aspirations to live in societies that are democratically and accountably governed. And although citizens find myriad ways to voice their concerns, they feel that their governments are not listening.

Simply put, Africans want more democratic and accountable governance than they think they are getting.

Africans’ democratic aspirations

Over the past decade, democracy watchers have been alarmed by declining trends in Africa. Concerns have been exacerbated in the past two years as some governments have taken advantage of the Covid pandemic to limit freedoms, restrict fair campaigning or postpone elections. Activists fear that supposedly temporary rollbacks in hard-won governance reforms could become permanent.

But for the most part, African citizens remain committed to democracy and democratic institutions. Across 30 countries that Afrobarometer has surveyed consistently since Round 5 (2011–2013), most indicators are strong and quite steady.

For example, seven in 10 Africans say that ‘democracy is preferable to any other kind of government’. While this is down modestly from 73 per cent a decade ago, more specific indicators seem to affirm popular commitment to democracy. Large and steady majorities consistently reject authoritarian alternatives, including one-person or ‘strongman’ rule (82 per cent), one-party rule (77 per cent) and military rule (75 per cent), which is clearly rejected even in many of the countries rocked by recent military coups.

Africans also express strong support for a limit to presidential terms, a feature of democratic governance that researchers and activists argue nurtures political participation, demonstrates that change via the ballot box is possible, and reduces the risk of personality cults, authoritarianism, corruption and coups. Across 34 countries, an average of 76 per cent favour limiting their presidents to two terms, including a majority (54 per cent) who ‘strongly’ support this rule. Term limits enjoy majority support in every surveyed country. 

The public’s democratic commitment is undergirded by strong and in some cases growing support for core democratic institutions. Support for multiparty competition and parliamentary oversight of leaders remains steady, while expectations that governments should be accountable to the courts have increased significantly over the past decade.

In addition, growing numbers of people say it is more important to have a government that is accountable to the people rather than one that just ‘gets things done’, an especially strong indicator of deepening commitment to democratic norms among citizens. 

Trouble at the polling booth

Elections remain a central, though controversial, institution of democracy for Africans. They have served as the foundation for real change, as in Zambia last year. But in other cases, such as Uganda’s January 2021 poll, they have been marred by violence and human rights abuses, as well as the weaponization of Covid to justify restrictions on campaigning.

The public is also sceptical about the capacity of elections to bring about real change: fully 50 per cent say they do not think elections are effective in enabling voters ‘to remove from office leaders who do not do what the people want’.

At the same time, large majorities report positively on their country’s election environment. Asked about their most recent election, at least eight in 10 say they did not observe intimidation (87 per cent) or interference (81 per cent) by security forces and did not fear violence (80 per cent).

We must keep in mind that these encouraging averages can obscure deep problems in some countries. For example, while only 3 per cent of Namibians say votes are ‘often’ not counted fairly, between a quarter and one-third cite inaccurate counts as a frequent problem in Zimbabwe, Sudan and Gabon. 

In addition, confidence in the fairness of the media environment is drastically lower, on average just 36 per cent.

But perhaps most importantly, almost nine in 10 Africans (87 per cent) say they are free to vote as they choose, including sizeable majorities in every surveyed country. And a solid majority of 63 per cent rate their most recent election as completely or mostly free and fair. 

All of this may help to explain still-strong support for competitive elections as the best system for selecting leaders. A robust three-quarters confirm their commitment to elections, though this has fallen slightly over the past decade, probably reflecting disillusionment with electoral processes that are too often torn by violence and produce contested results. 

A growing number of people may also be recognizing that elections, especially poor-quality ones, are not enough to guarantee democracy and better governance, and that a healthy democracy must include such other features as government accountability, respect for the rule of law, responsiveness and citizen participation.

The ‘democratic disappointment’ gap

To what extent does political reality align with Africans’ democratic aspirations? Our findings suggest that it is falling well short of expectations.

While a slim majority has steadily reported that their country is a ‘full democracy’ or one ‘with minor problems’ over the past decade, satisfaction, however, has dropped to 43 per cent in that time. 

What explains this growing dissatisfaction? Other indicators of democratic supply offer some clues. While ratings of election quality have held steady, favourable public assessments of presidential accountability to parliament and to the courts have both declined.

The rising scourge of corruption

But one of the most significant driving factors may be burgeoning corruption, a trend that appears to parallel declining democratic satisfaction. On average across 34 countries, around six in 10 say both that corruption in their country increased over the past year, and that their government is doing a poor job of controlling it.

These perceptions matter. Over time, when perceptions of corruption rise or fall, levels of dissatisfaction with democracy tend to follow suit. 

In South Africa, dissatisfaction with democracy grew steadily alongside scandals involving President Jacob Zuma, and has continued to rise under his successor, Cyril Ramaphosa, whose office has been tainted by ‘Farmgate’ and a major Covid-relief scandal. The ‘Fishrot’ scandal in Namibia has had similar consequences.

Are governments listening?

African citizens are raising their voices, calling on their governments to fulfil their democratic aspirations. Since April 2017, the Carnegie Endowment for International Peace has recorded more than 70 episodes in 35 African countries of protests focused on issues ranging from demands for democracy in eSwatini to resisting police brutality, presidential third-term attempts and Covid restrictions. 

Citizen participation and government responsiveness are cornerstones of democracy. But are governments listening?

Voting is the most obvious and popular way for citizens to express themselves, and Africans take advantage of this opportunity. Two-thirds said they voted in their most recent national election. But elections occur only occasionally, and they force individuals to compress a wide array of views into very few choices. How do Africans find their voice during the long intervals between elections?

Many invest in personal efforts to act as agents of change. In fact, nearly half say they joined with others to raise an issue at least once in the past year, and a third contacted a political leader. A quarter report they acted with others to request government action. Less common but still important modes of engagement include asking for help from or lodging a complaint with government, contacting the media, and joining a demonstration.

These robust levels of citizen engagement suggest that people feel they can make a difference. Unfortunately, decision-makers aren’t always receptive or responsive to citizen voices. Less than a quarter of people think local government officials listen to them – and even fewer think their members of parliament do. 

What is more troubling is that fully two-thirds say they are at risk of retaliation or some form of negative consequences if they take action by reporting incidents of corruption. 

Lack of government responsiveness and respect for popular voices may have direct implications for both citizen engagement and citizen satisfaction. For example, we find that people are more likely to contact leaders or take other actions to solve problems if they believe that government officials respect and listen to them; that they will get a response if they raise an issue; and if they do not need to fear retaliation. 

Similarly, when we compare country averages for government responsiveness to the percentage of citizens who are satisfied with democracy, we again find positive associations. 

When governments are responsive, citizens are more likely to engage in addressing community needs and to be satisfied with their political system and optimistic about the future. Respectful and responsive governance has the potential to spur citizen action to solve critical development challenges – and may be the cure for what ails democracy.

Why Africa needs to be in space The World Today mhiggins.drupal 1 August 2022

From agriculture and navigation to banking and tele-education, satellite technology can have a huge impact on rapidly developing societies, says Val Munsami.

Africa’s socio-economic and environmental development is widely acknowledged as being crucial to its growth and long-term sustainability – and the prosperity of its more than one billion residents. 

Increasingly, though, attention is also turning to the contribution that the space industry can make to progress on the continent. Space-based products and services have a critical role to play in meeting national and continental priorities, as underpinned by the UN’s Sustainable Development Goals and the African Union’s Agenda 2063 – the bloc’s strategic framework for development, democracy and peace. 

With this in the mind of policymakers, the African Union’s space policy and strategy is embedded in Agenda 2063 as one of its 15 key programmes. It guides the sector’s development and the nascent African Space Agency, to become operational later this year from its headquarters in Egypt.

The continental agency is expected to leverage the benefits of space science and technology for socio-economic and environmental development. It will lead on bridging the space divide, especially for those countries that do not have a focus on, or activities in, space science and technology – and simultaneously inject some momentum into improving capabilities of existing national space programmes.

The African Union’s commitment to space has accelerated the growth of the African space industry. More than 20 national space agencies or space-related institutions have been established on the continent over the past five or so years. 

Our modern lifestyles are intimately dependent on space products and services. Meteorological and communication satellites are placed in geostationary orbits at an altitude of 36,000km above the equator. At this point above the Earth, they complete one orbit every 24 hours in the direction of the planet’s rotation, appearing, essentially, motionless – and providing a constant gaze on the same geographic location.

They provide a wealth of information that fuels the everyday services we take for granted, but that are essential for our everyday lives, from health to education to the economy.

From their vantage point, geostationary orbit satellites provide our daily weather reports, monitor climate-related cycles and offer a platform for near-instantaneous communications across the globe to relay multimedia, live sporting events and up-to-the-minute global news. 

This lightning-fast communication is also indispensable for tele-education and tele-medicine, by which professionals in urban areas can deliver educational content and health services to rural schools and clinics, respectively. Banking transactions also rely on telecommunication satellites to communicate between an automated teller machine and the data servers located at the bank. 

How satellites can detect disease

Other satellites are placed in low Earth orbits. These complete on average one polar orbit around the Earth every 100 minutes. Because the planet rotates across the plane of the orbit, such a satellite eventually covers the whole Earth, which is immensely useful for remote sensing and navigation and positioning applications. 

Remote sensing applications provide a myriad of products and services, including monitoring the state of our natural resources, observing ship traffic in our coastal economic zones and providing information for precision farming that can help a farmer decide, for example, when to irrigate and how much fertilizer to use.

They can also detect changes that might indicate encroaching water-borne diseases, aid peacekeeping missions and help ensure public safety and security. Navigation applications are vital for aviation and marine navigation, whereas positioning applications are important for safety-of-life services. 

Another way that positioning applications in developing countries are put to good use is the assignment of geolocation addresses to dwellings in informal settlements where postbox addresses do not exist. This then allows the overlaying of key vector data about populations on to geophysical base maps. This type of data is vital for town planning in terms of how many schools and clinics are needed to serve the population, and the extent of the road, water, sanitation and electrical infrastructure needed.

The rich source of information derived from satellites, overlaid with in-situ data, is vital for evidence-based decision and policymaking. Datasets accessed from historical archives can be used to observe the time evolution of environmental and statistical data. 

When policy decisions are taken, we can utilize the same satellite and in-situ platforms to monitor progress after their implementation. The utility of data to inform decision-making is being enhanced through the adoption of AI and big-data analytics, which is placing key information at our disposal in near real time. 

It is therefore not surprising to notice the increasing focus on space science and technology activities on the continent. However, to ensure the effective uptake and utilization of space products and services, certain building blocks are needed to establish robust national and regional space ecosystems. 

Africa’s route into space

These ecosystems must include four primary elements to function: the human capital required to establish and operate the space initiatives; a significant industry base to capitalize on the commercial aspects of the space sector; the requisite infrastructure needed to support the space value chain; and international cooperation to ensure knowledge transfer and diffusion – so that we don’t have to reinvent the wheel.

The applications and problem-solving innovations provided by space products and services are endless. To take advantage of this, Africa needs strong governance and institutional architectures. 

The evolution of the space ecosystem on the continent must be premised on key instruments such as a space policy – which areas to focus on and why – and a space strategy that outlines which programmes and performance indicators to pursue. 

The conceptualization of a space ecosystem is by no means a simple endeavour and there is certainly a dearth of skills and experience on the African continent to establish effective and relevant space ecosystems. 

There are many institutions leading efforts to build space capacity and skills on the continent, such as the International Space University in France, which offers programmes that provide a holistic overview of the complex global space sector, and the African Space Leadership Institute, which has been recently created to develop capacity in space policy, law and strategy. 

With the right approach, commitment and investment, Africa can rapidly change the fate of its citizens by effectively using space science and technology to support and drive its developmental agenda.

Eight ways to build better African cities The World Today mhiggins.drupal 2 August 2022

Young professionals from across the continent tell Emmanuel Adegboye how city life could be improved: from high-speed rail to people-centred urban planning.

Ahmed Elsawy, 33, Director of Talent
Cairo, Egypt
We must amend employment law in Egypt to support individual contractors to match with the global demand for short-term and project-based assignments within the tech and service industries. While we have a new, decent education system, I think we should care more about foreign languages to have a higher rank when it comes to the global competition of skilled workers.

Iman Abubaker, 31, Urban Mobility Project Manager, WRI Africa
Addis Ababa, Ethiopia
Rapid urbanization and increased motorization have exacerbated the city’s urban challenges. Addis Ababa would benefit from safer street design and people-centred city planning. Urban amenities should be located within walking and cycling distances. For longer trips, the city needs to invest in improving the accessibility, safety, integration and multimodality of its public transport system. I would love to see more pockets of green spaces and parks all around the city. 

Bree, 31, Project Manager
Nairobi, Kenya
I have a love-hate relationship with Nairobi. I spent four years smack in the middle of the city while attending the University of Nairobi. Being in the middle of all the hustle and bustle made the transition to a sleepy-ish coastal town easy. I would happily trade matatus [shared taxis] for tuktuks any day. I do miss the conveniences that come with a big city like a 24-hour grocery store and delivery services on those lazy days.

Mfon Bassey, 30, Co-Founder, TalentX Africa
Lagos, Nigeria
The government should improve the road networks and public transport systems, because the common challenge most Lagosians face is commuting from point A to B without traffic. There are so many private cars on the road because the public transport system isn’t optimally efficient yet. Once you take away the commute time most workers spend just to get work done, we’ll surely have happier Lagosians.

Olga Kiconco, 32, Innovation Strategist
Kampala, Uganda
As one of Africa’s fastest-growing cities with a projected 112 per cent population growth by 2035, there are a number of critical changes that need to be made in preparation for this. Our leaders should embrace coherent policies that will catalyze socio-economic transformation. We need to hold them accountable for better infrastructure and delivery of public services, while taking personal responsibility to protect our environment against the prevalent threat of climate change.

Etienne Amougou, 30, Curator/Arts Project Manager
Yaounde, Cameroon
What would make Yaounde better would be a good ecosystem that provides more opportunities for young people. If it was possible, I would like to see the creation of more cultural spaces, like parks, zoos, cinemas and sport areas. Also, we could use a more effective approach to waste management – sometimes we have trash everywhere in the ’hood.

Valentino Fernandez, 23, Writer
Johannesburg, South Africa
 We need better transportation to bridge the inequality gap and allow the youth to access spaces to be inspired and create change. Apartheid spatial planning is still affecting us. People of colour were relegated to the outskirts of the city, and very little has changed. It’s virtually impossible to move out of your childhood home, which means you’re looking at a two-hour commute every morning and two more hours to get home. I would like a reliable, affordable, high-speed rail system.

Jean-Louis Mbaka, 34, Co-Founder and Director, Education at Kinshasa Digital
Kinshasa, DRC
Our youth must receive a sufficient education that is in line with the strategic requirements of their future workplaces. By 2030, more than 130 million jobs in Africa will require digital skills, according to the International Finance Corporation. To close the gap between the conventional educational system and the labour market, our organisation is providing training for digital jobs. Initiatives like ours must be supported if the current and next generations are to have the means for their economic and social advancement. Scaling up investments in vital facilities like the internet is also necessary.

Africa’s maritime agency cannot be overlooked Expert comment LJefferson 3 November 2022

Increasing maritime awareness has already delivered impact, but consistency and continental leadership are needed to realize the sector’s full potential.

Africa’s 48,000 kilometres of coastline, shared among 38 coastal states, are resource rich and hold some of the world’s most strategic sea lanes, including the approaches to the Suez Canal, which carries 12 per cent of worldwide trade, and the Gulf of Guinea, a critical route for global energy. But despite the vast potential this represents, piracy and maritime insecurity have dominated the narrative of Africa’s coasts, and further propagated the image of African states as beholden to external intervention.

Yet African agency is established and evolving in the sector, with African littoral states enhancing their capacity to face collective security threats and exercising increasing autonomy in responding to the recent rush of external actors looking for port facilities and military bases. Enhanced continental coordination, consistency and leadership can help Africa’s maritime endowment become a resource that can bring sustainable benefit across the continent.  

Agency beyond piracy: the Gulf of Aden and Western Indian Ocean

Piracy became the dominant frame of reference for the East African maritime space as a result of the crisis off the coast of Somalia, which peaked between 2008 and 2012. In 2008, the UN Security Council (UNSC) took the unprecedented step of authorizing international naval operations in Somali territorial waters, contributing to a gradual reduction in attacks. There have been no successful hijackings reported since 2017.

But progress has not just been down to international assistance. Somalia is prioritizing increased domestic enforcement capacity – as demonstrated in the establishment of  a new specialized maritime unit and the wider region enhanced collaboration and information sharing through the Djibouti Code of Conduct of 2009, amended in 2017.

South Africa’s recent admission as a new signatory demonstrates its continued relevance. In March 2022, the UNSC authorization lapsed, following pressure from the Somali government. Although it is not yet clear whether Somali efforts will be sufficient to repress piracy in the long term, this reverse was a clear statement of Somalia’s agency at a level unthinkable during the outset of the crisis.

As the immediate threat of piracy has quietened, broader geopolitical dynamics have come to the fore, notably in a surge by external actors to establish strategic ports and military bases. Here too, African states have demonstrated enhanced agency, for better or worse. Consider Djibouti’s unilateral seizure of a container terminal from an Emirati firm, Sudan’s review of Russian and Turkish deals for maritime facilities, Tanzania’s rejection of a Chinese-led port investment, or the Seychelles withdrawing agreement for an Indian naval base.

Such examples point to a growing awareness of the value of maritime resources within African states, alongside a willingness and ability to push back against external imposition – and indeed to innovate in finding solutions beyond infrastructure and ‘hard’ security. In 2018, the Seychelles launched the world’s first sovereign blue bond to fund sustainable marine projects. That other countries are seeking to replicate this model points to the potentially global impact of African leadership on maritime issues.

Regional cooperation or competition in the Gulf of Guinea?

The Gulf of Guinea is likewise resource rich and geographically strategic, and has faced diverse maritime security threats including piracy, smuggling, illegal fishing, oil theft and pollution. Gulf of Guinea states put in place several initiatives to promote security, including the Yaoundé Code of Conduct (YCoC), signed by 25 states in 2013, that led to information-sharing and cooperation on interdiction, investigation and prosecution. But crime in the Gulf of Guinea nonetheless reached an all-time high in 2020, suffering 130 of the 135 maritime kidnappings recorded worldwide, due to the non-binding nature of the YCoC and gaps in capacity and finance.

Though external actors have become increasingly engaged, including the EU, US, France, Denmark, and the G7++ Group of Friends of the Gulf of Guinea (FOGG), states within the region, especially those most affected by piracy and armed robbery, have nonetheless demonstrated leadership. Nigeria, Ghana, and Cote D’Ivoire have all developed maritime security strategies; Nigeria launched its Deep Blue Project to secure Nigerian waters; Ghana has strengthened its navy; and Togo has changed its laws and judicial system to allow the arrest and prosecution of ships and persons. Maritime security incidents have consequently reduced in 2022.

Visual Abstract

On October 24 and 25, SophosAI presents ideas on how to use models large and small—and defend against malignant ones.

Make the most of your Sophos Firewall.

The Internet is full of cats—and in this case, malware-delivering fake cat websites used for very targeted search engine optimization.

Felicia Grasso
Dec 1, 2020; 19:1986-1996
Research

Tricia Rowlison
Dec 1, 2020; 19:2090-2103
Research

Alison M. Kurimchak
Dec 1, 2020; 19:2068-2089
Research

Weixian Deng
Dec 22, 2020; 0:RA120.002411v1-mcp.RA120.002411
Research

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor and lymphoid enhancer factor (TCF/LEF) serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor-suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2–AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)–dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. In contrast, glucose stimulation induces cell spreading, actin remodeling, and point-like adhesions that contain phospho-FAK and phosphopaxillin, located in small protrusions. Rat primary β-cells and mouse insulinomas showed an adhesion remodeling during GSIS resulting from autocrine insulin/IGF2 and AKT1 signaling. However, under starving conditions, the maintenance of stress fibers and the large adhesion phenotype required autocrine IGF2-IGF1 receptor signaling mediated by AKT2 and elevated FAK-kinase activity and ROCK-RhoA levels but low levels of paxillin phosphorylation. This starved adhesion phenotype prevented excessive insulin granule release to maintain low insulin secretion during fasting. Thus, deregulation of the IGF2 and adhesion-mediated signaling may explain dysfunctions observed in diabetes.

Transient receptor potential vanilloid 1 (TRPV1) channel is a multimodal receptor that is responsible for nociceptive, thermal, and mechanical sensations. However, which biomolecular partners specifically interact with TRPV1 remains to be elucidated. Here, we used cDNA library screening of genes from mouse dorsal root ganglia combined with patch-clamp electrophysiology to identify the voltage-gated potassium channel auxiliary subunit Kvβ1 physically interacting with TRPV1 channel and regulating its function. The interaction was validated in situ using endogenous dorsal root ganglia neurons, as well as a recombinant expression model in HEK 293T cells. The presence of Kvβ1 enhanced the expression stability of TRPV1 channels on the plasma membrane and the nociceptive current density. Surprisingly, Kvβ1 interaction also shifted the temperature threshold for TRPV1 thermal activation. Using site-specific mapping, we further revealed that Kvβ1 interacted with the membrane-distal domain and membrane-proximal domain of TRPV1 to regulate its membrane expression and temperature-activation threshold, respectively. Our data therefore suggest that Kvβ1 is a key element in the TRPV1 signaling complex and exerts dual regulatory effects in a site-specific manner.

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response, and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria-associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an up-regulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1β secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection.

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in ∼80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain.

Alice Santonastaso
Dec 1, 2020; 61:1687-1696
Research Articles

Daphne E.C. Boer
Dec 23, 2020; 0:jlr.RA120001043v1-jlr.RA120001043
Research Articles

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles

Natalie Bruiners
Dec 1, 2020; 61:1617-1628
Research Articles

Julia V Busik
Dec 23, 2020; 0:jlr.TR120000981v1-jlr.TR120000981
Thematic Reviews

Jenny E. Kanter
Dec 8, 2020; 0:jlr.ILR120001217v1-jlr.ILR120001217
Images in Lipid Research

For data that is being loaded from a SAS Stored Process Server, an insertion process might fail to a MySQL database with a warning, as well as an error message that says "During insert: Incorrect datetime value…"

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Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.