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.

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

Priorities for implementing Ethiopia's national dialogue 11 May 2022 — 1:00PM TO 3:00PM Anonymous (not verified) 3 May 2022 Online

Experts discuss challenges and priorities in shaping an inclusive and effective national dialogue in Ethiopia.

Ethiopia is grappling with numerous contentious national issues – not least persistent conflict in several parts of the country – which underscore the need for large-scale dialogue and reconciliation efforts to address the country’s deep-rooted societal and political divisions. Ethiopia’s newly established National Dialogue Commission – whose 11 commissioners were appointed in February 2022 – has begun a four-phased process of preparations for a dialogue, with its initial stage focused on stakeholder engagement and local knowledge mobilization.

There are major challenges, however, in ensuring inclusivity amidst ongoing conflict and questions on how a country-wide process will sit alongside local dialogue initiatives and wider mediation and peacebuilding efforts. Linking the process to constitutional bodies will also be an important priority to ensure dialogue outcomes are effectively implemented.

At this public event, panellists will exchange perspectives on how to shape an effective national dialogue in Ethiopia, including priorities for building a credible National Dialogue Commission and the roles and responsibilities of other national, regional and local-level actors. They will also discuss key implementation mechanisms and long-term priorities for trust-building and cultivating a conducive environment for inclusive dialogue.

This webinar is part of a series of events and outputs on Ethiopia’s political transition.

This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page.

What challenges does the new president of Somalia face? Explainer Video aboudiaf.drupal 28 June 2022

Ahmed Soliman examines the challenges the new president Hassan Sheikh Mohamud faces in his first 100 days as president.

Key issues for the new administration are a deteriorating situation with regards to drought as close to half the population are facing food insecurity due to a fourth failed rainy season.

Combined with an inflation rate above ten per cent, many Somalis are at risk of famine and starvation. Many areas of the country are affected from the pastoralist regions to those which house IDP camps around the capital city and other towns, all being exacerbated by the war in Ukraine as Somalia was importing much of its wheat imports from Ukraine and Russia.

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

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

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

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

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

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

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

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

Europe’s changing focus in Africa 

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

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

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

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

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

The future of energy exports and COP27

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

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

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

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

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

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

A natural climate change priority for Africa Expert comment LJefferson 28 September 2022

Nature-based solutions can protect African nations’ shared natural endowment and meet the needs of their people.

Africa’s principal climate change negotiators have long understood the important contribution of ‘nature-based solutions’ (NBS) in delivering land (and sea) based options as part of the goals of the Paris Agreement. Limiting temperature rises to only 1.5°C by 2050 will demand finding innovative ways to protect Africa’s vast natural endowment that also meets the equally acute needs of its people. Nature-based solutions may do both.

The urgency for Africa cannot be overstated. At a Chatham House conference in Libreville, the Gabonese minister for the environment highlighted that if global warming surges by 2.5° or 3°C the impact would be at least 6°C for Africa. Decision-makers on the continent and across the world need to understand that ‘business as usual’ cannot be an option given the potential for loss of life, conflict and chaos.

Adaption, mitigation, or both?

Although adaptation to climate change has hitherto tended to be the continent’s main concern, there has also been growing recognition of the ways that Africa’s natural environments, from forests and grasslands, to peatlands and coastal and marine ecosystems, all also mitigate its impacts by sequestering carbon. The Congo Basin alone is said to store upwards of 4 per cent of global emissions annually.

These environments are under increasing pressure. Deforestation is a sad reality, caused mostly by unsustainable and extensive agricultural practices focused on cash crops for export more than food production to feed local populations. And arguing that African states and peoples should slow the development of their economies and infrastructure in response to a crisis born of the already-industrialized world does not find a responsive audience in a continent hungry for jobs and opportunity.

Nature-based solutions offer an answer to this conundrum. There is growing evidence that natural habitats both help avoid losses from climate change-related disasters and can drive economic growth. There is thus potential for NBS to tackle both adaptation and mitigation challenges at relatively low cost.

NBS – the rocky road from commitment to policy

It was logical therefore for Africa and like-minded countries to work to integrate NBS more strongly into the climate change agenda at COP26. The final Glasgow Climate Pact duly emphasized the importance of protecting ecosystems. The Global Forest Finance Pledge signed in the margins was also significant. African focus, with COP 27 in Egypt soon to take place, is now on domestic implementation and delivery of these pledges. The new African Union Climate Change and Resilient Development strategy (2022-2032) sets out many of the challenges and opportunities.

Choosing the right development pathway is tough, requiring political will and inclusive governance. Besides the challenge of securing alternative national revenue if a country moves away from fossil-intensive fuels – particularly acute for Africa’s resource-producing states – there is a dizzying array of policy decisions to be taken. African governments need to choose the most appropriate renewable energy sources, secure alternative livelihoods and continue to meet basic needs of the most vulnerable in the context of radical restructuring.  

Towards African solutions

There can be no one-size-fits-all answer to these questions – it is sadly still necessary to underline the enormous geographic, cultural and political diversity of the continent – but African experts have begun to draw together some emerging common themes from work already underway.  

Maintaining the ‘status quo’ in agricultural practices is no longer an option. Emphasis on sustainable agriculture is urgently needed andthat includes the elaboration of a ‘new deal’ between nature and people.  

Conservation also needs to be reframed as an economic opportunity, particularly in the elaboration and development of ecosystem services that deliver the true value of Africa’s forests, and that involve, value and reward local communities, respecting their rights and livelihoods.

Regional cooperation is likewise key, including on the management of forest, wildlife and water resources – Africa’s ecosystems do not respect arbitrary political boundaries, and accomplishing the dual feat of protecting cross-border systems at the same time as realizing their economic potential will demand effective collaboration, as well as training, education and communication at all levels.

The imperative of finance

A further imperative will be securing sufficient developed country financing – whether that be to secure value for net sequestration and effective forest management or for models of context-appropriate ‘smarter’ sustainable rural conservation and ecosystem resilience.

Africa’s strategic priorities and global role 27 January 2023 — 1:00PM TO 2:00PM Anonymous (not verified) 18 January 2023 Chatham House and Online

At this hybrid event, HE John Dramani Mahama, former president of the Republic of Ghana, will discuss his ideas on the key economic and governance reforms required for economic stability and prosperity across Africa.

Ghana recently became the fourth country, after Chad, Ethiopia and Zambia, to seek debt treatment under the G20 Common Framework in January 2023 – reflecting the culmination of a series of internal and external shocks affecting the wider region, including extreme weather events, the COVID-19 pandemic and the Russia-Ukraine crisis.

Prospects for economic recovery and growth, nevertheless, remain positive in many parts of the continent, with the African Development Bank (AfDB), for example, reforecasting economic growth of 5.5 per cent in East Africa in 2023. Coordinated reforms can help to deepen regional integration and promote long-term economic prosperity, particularly in light of Africa’s evolving regional economic governance structures, notably the fledgling African Continental Free Trade Area (AfCFTA) headquartered in Accra.

At this hybrid event, HE John Dramani Mahama, former president of the Republic of Ghana, will discuss his ideas on the key economic and governance reforms required for economic stability and prosperity across Africa. He will also discuss priorities for regional integration and Africa’s role and responsibilities in global economic governance.

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.

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

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

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

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

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

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

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

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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.

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Tricia Rowlison
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Toma Keser
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Ji Eun Kim
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Alison M. Kurimchak
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