For many Jamaicans, the deceased are more than just loved ones who have passed on; they are cherished family members who deserve to look as presentable as they did in life. In a culture where the appearance of the deceased is paramount, morticians...

Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15–25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host–pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.

Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.

High-throughput sequencing of hematologic malignancies and other cancers has revealed recurrent mis-sense mutations of genes encoding pre-mRNA splicing factors. The essential splicing factor U2AF2 recognizes a polypyrimidine-tract splice-site signal and initiates spliceosome assembly. Here, we investigate representative, acquired U2AF2 mutations, namely N196K or G301D amino acid substitutions associated with leukemia or solid tumors, respectively. We determined crystal structures of the wild-type (WT) compared with N196K- or G301D-substituted U2AF2 proteins, each bound to a prototypical AdML polypyrimidine tract, at 1.5, 1.4, or 1.7 Å resolutions. The N196K residue appears to stabilize the open conformation of U2AF2 with an inter-RNA recognition motif hydrogen bond, in agreement with an increased apparent RNA-binding affinity of the N196K-substituted protein. The G301D residue remains in a similar position as the WT residue, where unfavorable proximity to the RNA phosphodiester could explain the decreased RNA-binding affinity of the G301D-substituted protein. We found that expression of the G301D-substituted U2AF2 protein reduces splicing of a minigene transcript carrying prototypical splice sites. We further show that expression of either N196K- or G301D-substituted U2AF2 can subtly alter splicing of representative endogenous transcripts, despite the presence of endogenous, WT U2AF2 such as would be present in cancer cells. Altogether, our results demonstrate that acquired U2AF2 mutations such as N196K and G301D are capable of dysregulating gene expression for neoplastic transformation.

Bacterial low-copy-number plasmids require partition (par) systems to ensure their stable inheritance by daughter cells. In general, these systems consist of three components: a centromeric DNA sequence, a centromere-binding protein and a nucleotide hydrolase that polymerizes and functions as a motor. Type III systems, however, segregate plasmids using three proteins: the FtsZ/tubulin-like GTPase TubZ, the centromere-binding protein TubR and the MerR-like transcriptional regulator TubY. Although the TubZ filament is sufficient to transport the TubR-centromere complex in vitro, TubY is still necessary for the stable maintenance of the plasmid. TubY contains an N-terminal DNA-binding helix-turn-helix motif and a C-terminal coiled-coil followed by a cluster of lysine residues. This study determined the crystal structure of the C-terminal domain of TubY from the Bacillus cereus pXO1-like plasmid and showed that it forms a tetrameric parallel four-helix bundle that differs from the typical MerR family proteins with a dimeric anti-parallel coiled-coil. Biochemical analyses revealed that the C-terminal tail with the conserved lysine cluster helps TubY to stably associate with the TubR-centromere complex as well as to nonspecifically bind DNA. Furthermore, this C-terminal tail forms an amphipathic helix in the presence of lipids but must oligomerize to localize the protein to the membrane in vivo. Taken together, these data suggest that TubY is a component of the nucleoprotein complex within the partitioning machinery, and that lipid membranes act as mediators of type III systems.

Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset.

1 July 2020

10 August 2020

26 August 2020

10 September 2020

Cancer cachexia is characterized by reductions in peripheral lean muscle mass. Prior studies have primarily focused on increased protein breakdown as the driver of cancer-associated muscle wasting. Therapeutic interventions targeting catabolic pathways have, however, largely failed to preserve muscle mass in cachexia, suggesting that other mechanisms might be involved. In pursuit of novel pathways, we used untargeted metabolomics to search for metabolite signatures that may be linked with muscle atrophy. We injected 7-week–old C57/BL6 mice with LLC1 tumor cells or vehicle. After 21 days, tumor-bearing mice exhibited reduced body and muscle mass and impaired grip strength compared with controls, which was accompanied by lower synthesis rates of mixed muscle protein and the myofibrillar and sarcoplasmic muscle fractions. Reductions in protein synthesis were accompanied by mitochondrial enlargement and reduced coupling efficiency in tumor-bearing mice. To generate mechanistic insights into impaired protein synthesis, we performed untargeted metabolomic analyses of plasma and muscle and found increased concentrations of two methylarginines, asymmetric dimethylarginine (ADMA) and NG-monomethyl-l-arginine, in tumor-bearing mice compared with control mice. Compared with healthy controls, human cancer patients were also found to have higher levels of ADMA in the skeletal muscle. Treatment of C2C12 myotubes with ADMA impaired protein synthesis and reduced mitochondrial protein quality. These results suggest that increased levels of ADMA and mitochondrial changes may contribute to impaired muscle protein synthesis in cancer cachexia and could point to novel therapeutic targets by which to mitigate cancer cachexia.

Peptidoglycan (PG) is an essential constituent of the bacterial cell wall. During cell division, the machinery responsible for PG synthesis localizes mid-cell, at the septum, under the control of a multiprotein complex called the divisome. In Escherichia coli, septal PG synthesis and cell constriction rely on the accumulation of FtsN at the division site. Interestingly, a short sequence of FtsN (Leu75–Gln93, known as EFtsN) was shown to be essential and sufficient for its functioning in vivo, but what exactly this sequence is doing remained unknown. Here, we show that EFtsN binds specifically to the major PG synthase PBP1b and is sufficient to stimulate its biosynthetic glycosyltransferase (GTase) activity. We also report the crystal structure of PBP1b in complex with EFtsN, which demonstrates that EFtsN binds at the junction between the GTase and UB2H domains of PBP1b. Interestingly, mutations to two residues (R141A/R397A) within the EFtsN-binding pocket reduced the activation of PBP1b by FtsN but not by the lipoprotein LpoB. This mutant was unable to rescue the ΔponB-ponAts strain, which lacks PBP1b and has a thermosensitive PBP1a, at nonpermissive temperature and induced a mild cell-chaining phenotype and cell lysis. Altogether, the results show that EFtsN interacts with PBP1b and that this interaction plays a role in the activation of its GTase activity by FtsN, which may contribute to the overall septal PG synthesis and regulation during cell division.

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.

Now is the moment to launch an African vaccine industry The World Today mhiggins.drupal 31 July 2022

The continent plans to make 60 per cent of its vaccines by 2040. After the failure of the world to help in the pandemic, it’s high time, says Ngozi Erondu.

The lack of an African vaccine industry has been a glaring concern for decades. Before the pandemic, 99 per cent of Africa’s vaccines were manufactured outside the continent. As well as endangering the lives of millions, this situation has inhibited social and economic progress on the continent.

In response, the Africa Centres for Disease Control and Prevention (Africa CDC) has undertaken an ambitious plan, outlined in the Partnerships for African Vaccine Manufacturing (PAVM) Framework for Action, to develop the nascent African vaccine manufacturing sector into an end-to-end industry by 2040. The framework aims to raise the share of African-manufactured vaccines used across the continent to 60 per cent by 2040, or the equivalent to up to 1.7 billion doses annually.

Seven of every 10 vaccines used in Africa are currently donated through Gavi, the Vaccine Alliance. Most are administered within childhood immunization programmes and are largely manufactured either in India, or by  multinational vaccine manufacturers in North America or Japan.

Vaccine donations have inhibited the development in Africa of vaccines and other countermeasures against diseases.

Though the Ebola virus was discovered in Central Africa in 1976, vaccine development was not adequately funded until it emerged in Europe in 2014. Human monkeypox resurfaced in Nigeria in 2017, yet the global Coalition for Epidemic Preparedness Innovations only targeted it for vaccine development in July this year.

The pandemic highlighted Africa’s fatal dependency on imported vaccines. Only 20 per cent of Africans are fully vaccinated against Covid-19, due to the failure of countries in the Global North to ensure the equitable distribution of vaccines via the COVAX facility to 40 per cent of the world’s most vulnerable people. 

The pandemic also confirmed that Africa could not rely on fellow states of the Global South. At the height of the Delta variant outbreak in early 2021, India halted vaccine exports to Africa, where only 1.5 per cent of the population had at that time received any vaccine doses.

After decades of discussions, there are signs that Africa could soon succeed in creating its own vaccine industry. First, the 55-member African Union is in the process of establishing the African Medicines Agency, a regional regulatory body. 
 

‘The new public health order’

Additionally, the African Export-Import Bank and African Development Bank (AfDB) have established a foundation to provide financial and strategic support for the development of the pharmaceutical industry and the consolidation of regional vaccination programmes in Africa (the foundation would potentially negotiate intellectual property rights and licensing issues but that remains to be seen).

Second, studies show there is an emerging middle class in Africa. In a 2011 report by the AfDB, this was estimated at some 56 million households. Potentially, this means many people will be able to buy vaccines and medicines made in Africa.

About a third of African countries currently pay for their vaccine needs. According to PAVM forecasts, the value of the total African market could reach between $3 billion and $17 billion by 2040.

The recent entry into effect of the African Continental Free Trade Area should also prove conducive to African vaccine development. Through economic integration, free movement and harmonized regional standards, countries that invest in their biopharmaceutical and medical technology sectors may attract employees, regional and international businesses, and investment. Further, the pandemic has encouraged people to relocate to countries with, or planning for, universal healthcare.

Building an African pharmaceutical industry from the ground up could take much longer than two decades and cost tens of billions of dollars. Nevertheless, the moment seems ripe, and timely support has been forthcoming from influential regional actors, including Rwandan President Paul Kagame, South Africa’s Cyril Ramaphosa, and private sector business executives, including the Zimbabwean-born billionaire Strive Masiyiwa.

With a pandemic treaty embedding equity in prevention, preparedness and response some way off, and given the limitations surrounding the recent World Trade Organization compromise on the TRIPS waiver – which temporarily waives Covid-19 vaccine patent protections for poorer countries – it is doubly important for Africa to build up its own pharmaceutical industry and emergency systems. 

In 2021, John Nkengasong, then director of Africa CDC, wrote of the necessity of a post-pandemic ‘new public health order’ for Africa. Such a change may threaten the global health organizations, industries and institutes who derive payment from ‘saving Africa’ during emergencies. Additionally, through strengthening Africa CDC, other actors such as the World Health Organization may find that they have a diminished strategic role on the continent.
 
While Africa should not dismiss these valuable and long-standing partnerships, it must take the opportunity to advance its interests and to assume leadership in this important area.

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. 

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

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.

The online media changing African news The World Today mhiggins.drupal 2 August 2022

Africa’s news sites are gripping audiences with digital innovation and bold directions. Helen Fitzwilliam talks to editors at three platforms.

Lydia Namubiru
News editor of ‘The Continent’ (South Africa)

At the start of the pandemic, we realized a lot of fake news was being shared on WhatsApp. So, The Continent chose to launch on that platform to insert some real journalism in a way that could easily be shared. We now have about 100,000 readers across Africa and the rest of the world, but we had to dramatically change the way we write and edit stories: to compete with the likes of Twitter and Instagram, we try to keep stories tight at 300 words. 

There’s a real variety. We can run an investigation into corruption in the Democratic Republic of the Congo a week after a front page on the fashion designer who dresses Africa’s ‘big men’ [powerful leaders]. We cover feminist issues, the backlash against LGBT people in Ghana; we’ve had the Namibian first lady talking to us about misogyny. These are not the sort of topics a typical African newspaper is going to lead with.

With a story such as Ukraine, the war’s impact on the cost of living has been the most obvious angle for us. It has driven countries such as Malawi into crisis, forcing a devaluation of the currency.
 
As for the future, we see two issues looming. Workers’ economic rights and their treatment by multinationals will be a big story. There are refugees in camps in Kenya working in data operations and being paid a pittance to help create huge, potentially multimillion-dollar systems for US companies. 

Second, Africa has the world’s youngest population and the oldest leaders, so this will likely lead to activism and protests. The young are exposed to the global village, so they want different things and have different values. They speak a completely different language their leaders do not understand. It will be an interesting conflict, but could lead to real violence. 

John Githongo
Editor of ‘The Elephant’ (Kenya)

We set up this platform four years ago. Due to political and commercial pressures, mainstream media wasn’t doing much critical reporting. We have between 30,000 and 80,000 readers a week, the majority of them in Africa. 

The digital space reaches a completely different demographic. When The Elephant started, it was 80 per cent male and over 40, but we have gained more younger people and more women. Now it is 60 per cent men, 40 per cent women and that is something we have been working at. 

Our editorial approach is that as long as a piece has a strong argument and fits into our pan-African brief, we will publish it – even if we don’t agree with it.

The conflicts in Ethiopia and parts of the Sahel make the war in Ukraine pale in comparison. So many people have died in Ethiopia or been displaced and now we have the onset of a famine after four years of failed rain. During the 1960s and 1970s, when the Cold War found its way on to African soil, millions of people died – so there is caution about getting involved in a European fight.

There is always a lot of fake news around during elections. But people are beginning to be more sceptical. We go after those who attempt to change the level of debate with reputation-laundering and try to expose their actions. 
 
The future of democracy is going to be a big issue. When Africans were watching the attack on the US Capitol last year, they were hoping it was not a Black Lives Matter protest, which could have resulted in a ‘blackbath’. As soon as they saw the white guys wearing horns, people laughed with relief. 

There is an ongoing recalibration of Africa’s geopolitical relations with the rest of the world. A poll released in June showed China has overtaken the United States as the foreign power having the biggest positive influence in Africa in the eyes of young people across the continent. The younger generation is writing its own narrative. 

Wale Lawal
Editor of ‘The Republic’ (Nigeria)

Nigerian audiences are increasingly online and tend to read both local and international publications. They also know that the issues they care about are either under-reported or reported at lower quality levels. 

At The Republic, we provide political journalism that tends to require high levels of expertise. Yet online audiences also prioritize engagement: it is not enough for an issue to be important, it also needs to be interesting.

Some topics we have covered that Western media tend not to include how people experience blackness in different parts of the world; the waves of mostly female-led and youth-led movements rising up against autocratic governments across Africa; and relationships between countries within Africa itself. In the early days of the pandemic, we launched a Covid-19 and Africa series, having noticed a glaring lack of African expert voices in global media.
 
We also cover Africa’s evolving relations with Russia. Whenever we encounter a story like Russia’s invasion of Ukraine, the first thing we always ask ourselves is what missing voice can we add to the current discussion? All we were reading about after the invasion was how neighbouring countries were opening their borders and their homes to Ukrainians. Most people saw only that. 

But we knew that around 15,000 Africans were studying in Ukraine, that Africans routinely face harsh treatment at international borders, and that clearly their voices were missing from the discussion.

With fake news and information gaps on social media, our usual approach is to develop expert-led columns and circulate these as widely as possible.

Our next mission is to think about the role that independent media can play in supporting democracies, such as by increasing voter turnout. During the last election in Nigeria, less than 35 per cent of those who registered to vote eventually did so.

Not the same old African story The World Today mhiggins.drupal 2 August 2022

Nollywood studio boss Mo Abudu and author Dipo Faloyin discuss how Africans are redefining how the world sees them.

Mo Abudu
EbonyLife’s latest TV drama series, Blood Sisters, was in Netflix’s global top 10. It’s a thriller and it may be slightly melodramatic because we Nigerians are melodramatic. But it deals with universal themes. Nigerians are no different to anyone else. I want EbonyLife productions increasingly to appeal to anyone in the world, even if it’s in our language. Oloture, one of our films, was about human trafficking. It was all done in pidgin English and subtitled. I watch a lot of Korean dramas and Spanish dramas that are subtitled. A good story is a good story.

Dipo Faloyin
The influence that African countries have had on the West, from music, food and film to literature, science and technology, is something people find difficult to take seriously. So, it’s good to see Netflix and other production companies take it more seriously. How has your discussion with them changed since the early days?

Mo Abudu
I have been going to an entertainment market in Cannes called Mipcom for about 12 years, and at first no one had any interest in African content. So, we focused on doing local content for local markets. Now, different communities around the world want representation in content that speaks to them. Specific countries are also saying to streamers: ‘What’s your local content strategy?’ 

Netflix was the first of the streamers to come into Africa, and it now has an Africa office. Amazon has also made inroads recently. Disney is arriving. In the United States and Britain, they just need to maintain subscriber numbers, but real growth for them is going to be in Asia and Africa. 

I’m not telling broadcasters or distributors to commission original African content as a charity project – they can make money from this. Within five days of launch, Blood Sisters registered 11 million hours of viewing on Netflix around the world. It was made on a budget five times smaller than productions outside Africa. But we need to be among the gatekeepers, too. 

Moving beyond Hollywood

Dipo Faloyin
The challenge that many creatives across Africa have is that people [elsewhere] don’t necessarily feel like they relate to this continent. They see ‘Africa’ and its cultures as very distant. Instead of intricate, specific stories, simple stories of simple people have been pushed about the continent. 

I still get asked questions like, ‘But, what should we do about Africa’s problems?’ My response is, ‘Stop seeing Africa as just a problem.’ 

Mo Abudu
I was speaking at the Qatar Economic Forum recently and the panel started off talking about the ‘problems of Africa’ – and I had to jump in and say, ‘I get you guys talking about the problems, I’m not an economist, I’m just an entrepreneur, but from an entrepreneurial perspective, we have resources – like cobalt from the Democratic Republic of Congo that’s in all of our mobile phones.’ 

The problem is, we ship out all our resources and by the time they come back to us, they are 10-times more expensive than we can afford. I keep saying that they need to know they need us as much as we need them.
 
Dipo Faloyin
There are certainly issues within the continent like there are everywhere else; but more accurate stories will help people have a better sense of the context in which so many communities and their lives have been built up. 

Mo Abudu
The West doesn’t seem to have any interest in making films about Africa unless it’s about the worst of Africa: the slave trade, the Rwandan genocide, blood diamonds. That seems to be what has defined us. 

Dipo Faloyin
If you ask most people around the world to close their eyes and picture Africa, two images will come up: safari, and poverty and strife. Until the age of 12, I grew up in Lagos, a metropolis with no wild animals running around. There are slums, of course, but also traffic, shopping centres and overpriced restaurants. 

Writers who pitch ideas to Vice.com where I work often still don’t differentiate African countries. They’ll say, ‘There’s been a coup in Mali. Why can’t Africa get its head around democracy?’, and I remind them a small minority of countries on the continent is under any form of authoritarian rule. 

It’s frustrating that this perception hasn’t changed. For us to break through we need big cultural institutions – Hollywood, museums, literature – to allow people from across the regions to tell these stories. We are rarely portrayed as protagonists and forward thinkers. But I’m excited for the future.

Youth innovation can help shape the future of African cities Expert comment LToremark 16 August 2022

To meet the challenges of rapid urbanization, African governments must harness the potential of young innovators to help shape the future of African cities.

It is projected that 1.3 billion people will be living in Africa’s cities by 2050, an increase of almost 1 billion from today, and largely driven by young people migrating to urban centres in search of work. As the continent’s urban population grows, cities will need to adapt by nurturing new economic ecosystems to create jobs, while managing the environmental, social and political pressures that urbanization brings.

The evolution of Africa’s cities is critical for meeting the demands of its youth population and must be co-created with them. Africa’s young innovators are already proving to be an asset in shaping the future of African cities and, if they are allowed to flourish, they could be at the forefront of finding much-needed solutions to the continent’s vast urban challenges.

Growing tech hubs

African countries are increasingly benefitting from growth in technology ecosystems, which are often clustered within cities. There are currently more than 600 tech hubs helping to incubate innovative solutions across cities in Africa. Between 2015 and 2020, the number of start-ups receiving funding grew six times faster than the global average. In 2021 alone, start-ups raised over $4billion in funding – twice as much as in 2020.

But significant challenges remain. While the number of new start-ups is an encouraging indication of the entrepreneurialism and creativity of Africa’s youth, job creation on the level required will demand that they grow and scale up to generate more and higher quality jobs. Research on scaling up in Africa is sparse but research by Endeavor suggests that in Nairobi – one of Africa’s top tech ecosystems – only 5 per cent of companies are able to sustain growth of 20 per cent or more each year, yet they created 72 per cent of new jobs in the previous three years. For Africa to fully harness the potential of digital innovation, making cities the best place for young people to launch ideas and grow them into thriving businesses must become a priority policy for African governments. 

Barriers to scale

On the most basic level, business growth needs access to the services that make cities more liveable and help both urban residents and firms become more productive, such as healthcare, transport, water and sanitation. African cities already struggle to provide their residents – in particular the poorest and most vulnerable – with equitable, reliable, affordable and quality access to these services, in a sustainable manner. And these challenges will only get more acute as urban populations rise rapidly, often without any kind of integrated planning.

For example, an estimated 70-80 per cent of municipal solid waste in Africa is recyclable, yet only about 4 per cent is currently recycled, with more than 90 per cent of waste ending up in uncontrolled dumpsites and landfills. As Africa’s urban population grows, these conditions are likely to worsen – unless there is urgent action. New technology has the potential to help by creating a positive feedback loop between innovation, service delivery and growth. For example, to bridge the waste management gap, innovators are exploring various tech-enabled circular economy models. These solutions are often ground-breaking and have the potential to leapfrog traditional waste management infrastructure. Crucially, they are also formalizing a largely informal sector and creating new jobs.

Across the continent, start-ups like Kaltani, Mr Green Africa and Freetown Waste Transformers build processing facilities to turn waste into energy or reusable products, such as construction materials. Others, like Scrapays, Regenize and Soso Care, are helping households and businesses sell off their recycled materials for cash and virtual currencies or exchange them for critical services, such as micro health insurance premiums. Such start-ups help empower informal waste pickers or agents with tech-enabled tools and target low-income urban communities that would not normally prioritize recycling.

Help or hindrance from the top?

But Africa’s young people cannot do this alone – government decision-makers must become catalysts for entrepreneurial leadership. This requires nurturing a mindset that sees young innovators as Africa’s biggest resource, not a threat. While the importance of young people to Africa’s development is acknowledged in various high-level regional treaties, patterns of inhibition and outright hostility from political ‘elites’ suggest that the disruptive nature of technology start-ups and their access to significant capital through venture capital funding models – unlike existing rent-seeking business models with government control – threatens the political establishment.

The growing use of tech solutions also leads to increased transparency and efficiency of service delivery, which in turn leads to increased demand for government accountability and pressure to adopt more liberal policies. Until there is a shift towards catalysing entrepreneurial leadership, there is a stronger incentive for political elites to leverage their powers to co-opt successful technology businesses, or otherwise try to control them for political gain, than let them flourish. This shift in mindset will be critical to unlocking the full potential of Africa’s young innovators.

A new vision for African agency in sustainable development Expert comment LJefferson 18 October 2022

Change is necessary not only in global economic structures and attitudes – but in African governance too.

The conventional notion that Africa is mostly a consumer of norms and practices designed by the Global North has been repeatedly challenged and is increasingly being debunked. Increased African agency in international affairs is today a well-established and documented reality. But Africa’s influence still does not match the scale of the challenges that it faces on its pathway to sustainable development. 

Pushing for African agency in sustainable development also warrants a critical assessment of how ‘sustainable development’ should be defined, and how it can be achieved in terms of actual poverty reduction and real improvement in the lives of local poor Africans. Sustainable development has been a political catchphrase for over 30 years – but a genuine transition towards sustainability has yet to begin.

African agency today

Historically, there have been structural limitations on the agency of African stakeholders to shape development pathways. Chief among them, donor-recipient power dynamics have persistently promoted dependency and sustained institutional corruption. Many African countries are also challenged by economic incentives and infrastructure that have favoured the market demands and supply chains of former colonial powers, which largely remain reliant on natural resource extraction, and are marked by limited investment in value-addition activities and technology development.

Today, however, African agency is being exerted in a more assertive fashion. The African Union (AU), individual African states, civil society, the private sector and eminent and ordinary persons are all displaying Africa’s agency in steering global sustainable development priorities, namely by proposing their own development agenda, The African Union Agenda 2063, adopted in 2013. This was followed by the UN Sustainable Development Goals (Agenda 2030), which in many ways mirror Agenda 2063 – a clear demonstration of the influence of Africa in the global arena. 

Agenda 2063 is a strategic roadmap for Africa ‘to build an integrated, prosperous and peaceful Africa, driven and managed by its own citizens and development goals representing a dynamic force in the international arena’. Prepared following a broad-based participatory consultation, it advocates for inclusion and empowerment and provides an excellent vision for African countries and African people. The SDGs address several of the key shortcomings of their predecessor – the MDGs – and incorporate a broader and more transformative agenda that more adequately reflects the complex challenges of the 21st century and the need for structural reforms in the global economy and governance norms.

In international forums on sustainable development, African countries are increasingly using their collective voice to change the discourse on how development can and should be done. For instance, by championing innovative solutions for carbon markets, African policy leaders are enabling access to climate finance for development while preserving Africa’s natural wealth.

In the post-COVID era, championing investments in and leadership of Africa’s global health architecture demonstrates a desire that in the next pandemic, Africa CDC, AMA and continental manufacturers will play leading roles in determining Africa’s public health strategy and implementation.

In trade, building on the groundwork led by the regional economic commissions, the AfCFTA will catalyse and scale regional integration, trade and cooperation, leading to promising new modes of supply chain and self-sufficiency.

Encouraging signs, but persistent shortcomings

Encouraging signs that African agency is gaining momentum cannot disguise the fact that Africa has yet to move from rhetoric to implementation in the realm of sustainable development. Continental visions often fail to go beyond declarations of intent, and have only limited influence on governance systems or national structural transformation, and African states remain vulnerable to economic shocks emanating from the global system.

Change will require governance systems that are coordinated, transparent, efficient, and inclusive, as well as tools, processes, and means (material, technical, and human) for successful implementation. There is an urgent need for a new governance paradigm in Africa and internationally, dealing with long-term social change.

Notably, African agency should not be only seen as emanating from government, but also as being exerted by independent civil society organizations and committed ordinary individuals. Effective agency needs to be multi-faceted and multi-actor, and depends on the inclusiveness of African governments and their willingness to work with civil society in their strategic engagements with external partners.

Both Agenda 2063 and the SDGs hold the potential for transformation, but implementation will depend on continued advocacy to hold authorities to account and change the dominant discourse, logic and rules of engagement at global, regional, national, and local levels. There is a need for a dynamic new model of African ‘development’.

Time for a new vision

Africa’s economic landscape is changing rapidly, with new regional and local value chains, and integrated regional economic corridors to link countries, minimize the burden of high-cost production and logistics, and boost real incomes and international competitiveness. But Africa continues to face structural challenges, including the need for large investment projects – at a time when Africa remains a net exporter of capital.

Donors and development partners must reflect upon their prior modes of engagement and commit to genuine and equitable relationships with African states. Such partnerships must reflect mutual respect of ideas and accountability, and commit to making space in international forums and multi-lateral arrangements for African people and countries to realize their own visions for progress.

But African leaders and actors must also recognize that with the advent of resources and agency comes responsibility for results and outcomes, notably the need to improve governance. Gaps in accountability, widespread corruption, and lack of successful implementation and sustainability of projects must be addressed.

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.

Purpose: The ⁶⁸Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional ¹⁸F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and positive lesion number (135 vs. 95) of ⁶⁸Ga-PSMA PET/CT were higher than ¹⁸F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion: Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional ¹⁸F-FDG PET/CT.

Visual Abstract

Researchers use dynamic PET imaging with target-selective tracer molecules to probe molecular processes. Kinetic models have been developed to describe these processes. The models are typically fitted to the measured PET data with the assumption that the brain is in a steady-state condition for the duration of the scan. The end results are quantitative parameters that characterize the molecular processes. The most common kinetic modeling endpoints are estimates of volume of distribution or the binding potential of a tracer. If the steady state is violated during the scanning period, the standard kinetic models may not apply. To address this issue, time-variant kinetic models have been developed for the characterization of dynamic PET data acquired while significant changes (e.g., short-lived neurotransmitter changes) are occurring in brain processes. These models are intended to extract a transient signal from data. This work in the PET field dates back at least to the 1990s. As interest has grown in imaging nonsteady events, development and refinement of time-variant models has accelerated. These new models, which we classify as belonging to the first, second, or third generation according to their innovation, have used the latest progress in mathematics, image processing, artificial intelligence, and statistics to improve the sensitivity and performance of the earliest practical time-variant models to detect and describe nonsteady phenomena. This review provides a detailed overview of the history of time-variant models in PET. It puts key advancements in the field into historical and scientific context. The sum total of the methods is an ongoing attempt to better understand the nature and implications of neurotransmitter fluctuations and other brief neurochemical phenomena.

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

Simone Kurz
Dec 29, 2020; 0:RA120.002266v1-mcp.RA120.002266
Research

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

David Durán
Nov 19, 2020; 0:RA120.002276v1-mcp.RA120.002276
Research

Ka-Won Kang
Nov 30, 2020; 0:RA120.002169v1-mcp.RA120.002169
Research

Colin T. McDowell
Nov 24, 2020; 0:RA120.002256v1-mcp.RA120.002256
Research

Leandro Xavier Neves
Nov 11, 2020; 0:RA120.002227v1-mcp.RA120.002227
Research

Philipp Emanuel Geyer
Dec 17, 2020; 0:RA120.002359v1-mcp.RA120.002359
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.

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts. We were able to determine that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibit preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions. Further analysis revealed that these compounds target to redox systems such as GSH and thioredoxin and induce accumulation of reactive oxygen species in nutrient-deprived cancer cells, potentially contributing to apoptosis under nutrient-deprived conditions. Nutrient-deficient cancer cells are often deficient in GSH; thus, they are susceptible to redox system inhibitors. Targeting redox systems might be an attractive therapeutic strategy under nutrient-deprived conditions of the tumor microenvironment.

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

RAS genes are the most commonly mutated in human cancers and play critical roles in tumor initiation, progression, and drug resistance. Identification of targets that block RAS signaling is pivotal to develop therapies for RAS-related cancer. As RAS translocation to the plasma membrane (PM) is essential for its effective signal transduction, we devised a high-content screening assay to search for genes regulating KRAS membrane association. We found that the tyrosine phosphatase PTPN2 regulates the plasma membrane localization of KRAS. Knockdown of PTPN2 reduced the proliferation and promoted apoptosis in KRAS-dependent cancer cells, but not in KRAS-independent cells. Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling. Consistently, analysis of the TCGA database demonstrates that high expression of PTPN2 is significantly associated with poor prognosis of patients with KRAS-mutant pancreatic adenocarcinoma. These results indicate that PTPN2 is a key regulator of KRAS and may serve as a new target for therapy of KRAS-driven cancer.