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.

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

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

Sudan’s gold boom: Connections to conflict and transnational impacts 7 December 2022 — 2:00PM TO 3:30PM Anonymous (not verified) 24 November 2022 Online

At this event, experts will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts. 

At this webinar panellists will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts.

Sudan is one of the largest gold producers on the continent, with the industry constituting Sudan’s foremost source of hard currency since the secession of South Sudan in 2011 and resulting loss of oilfields.

The gold rush that has ensued has had important implications for domestic and transnational conflict dynamics. Military actors and armed groups have sought control of gold-producing areas in the peripheries and to capitalize on the flow of labour migrants, against a wider backdrop of conflict partly stemming from contestation for control between central and local actors.

International interests are prominent, including increased Russian involvement in the sector, while gold smuggling has also interlaced with mercenary activity in neighbouring CAR, Chad and Libya.
 
At this event, panellists will discuss Sudan’s gold trade, its connections to conflict, and transnational impacts, including the international politics of Sudan’s gold extraction and role of armed groups. It will also explore the environmental and socio-economic dimensions of gold in Sudan’s border areas. 
 
This roundtable is an output of the Cross-Border Conflict: Evidence, Policy and Trends (XCEPT) research programme, funded by UK Aid from the UK government.
 

Independent Thinking: China in Africa, conflicts in 2023 Audio NCapeling 13 January 2023

Episode ten discusses Africa and the complex role China plays on the continent, and how the world should be responding to the major conflicts of 2023.

The first episode of 2023 examines Africa and the complex role China plays on the continent as a new Chatham House report highlights 22 African countries suffering from debt distress with Beijing a key creditor to many of them.

China’s new foreign minister Qin Gang is also touring several African states this week and next, with visits planned to Ethiopia, Angola, Gabon, and the headquarters of the African Union (AU).

This week Chatham House also hosted Dr Comfort Ero, president of the International Crisis Group, to discuss ten conflicts to watch in 2023. The panel examines some of the key conflicts mentioned and how the world is responding to them.

Joining Bronwen Maddox on the podcast this week from Chatham House are Dr Alex Vines, director of the Africa programme, Creon Butler, director of the Global Economy and Finance programme, Dr Yu Jie, senior fellow on the Asia-Pacific programme, and Armida van Rij, research fellow with the International Security programme.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

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

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

Stephanie E. Hood
Dec 1, 2020; 61:1720-1732
Research Articles

Akemi Kakino
Nov 3, 2020; 0:jlr.RA120000767v1-jlr.RA120000767
Research Articles

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.

Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (Lipin^NLS), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult Lipin^NLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in Lipin^NLS flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring.

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.

Small admixtures in water, e.g. of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppress cell growth and induce oxidative stress in mitochondria. We thus hypothesize that deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. Because growth acceleration is reduced approximately by half by addition to water a minute amount (0.15%) of ¹⁸O isotope, at least part of the deuterium effect on cell growth can be explained by the isotopic resonance phenomenon. A slight (2-fold) enrichment of deuterium in water accelerates human cell growth. Quantitative MS based proteomics determined changes in protein abundances and redox states and found that deuterium-enriched water acts mainly through decreasing ROS production in mitochondria. This action is opposite to that of deuterium depletion that suppresses cell growth by inducing oxidative stress. Thus deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. The role of isotopic resonance in this effect was validated by further experiments on bacteria.

MS-based proteome profiling has become increasingly comprehensive and quantitative, yet a persistent shortcoming has been the relatively large samples required to achieve an in-depth measurement. Such bulk samples, typically comprising thousands of cells or more, provide a population average and obscure important cellular heterogeneity. Single-cell proteomics capabilities have the potential to transform biomedical research and enable understanding of biological systems with a new level of granularity. Recent advances in sample processing, separations and MS instrumentation now make it possible to quantify >1000 proteins from individual mammalian cells, a level of coverage that required an input of thousands of cells just a few years ago. This review discusses important factors and parameters that should be optimized across the workflow for single-cell and other low-input measurements. It also highlights recent developments that have advanced the field and opportunities for further development.

Thermal proteome profiling (TPP) allows for the unbiased detection of drug – target protein engagements in vivo. Traditionally, one cell type is used for TPP studies, with the risk of missing important differentially expressed target proteins. The use of whole organisms would circumvent this problem. Zebrafish embryos are amenable to such an approach. Here, we used TPP on whole zebrafish embryo lysate to identify protein targets of napabucasin, a compound that may affect Signal transducer and activator of transcription 3 (Stat3) signaling through an ill-understood mechanism. In zebrafish embryos, napabucasin induced developmental defects consistent with inhibition of Stat3 signaling. TPP profiling showed no distinct shift in Stat3 upon napabucasin treatment, but effects were detected on the oxidoreductase, Pora, which might explain effects on Stat3 signaling. Interestingly, thermal stability of several aldehyde dehydrogenases (Aldhs) was affected. Moreover, napabucasin activated ALDH enzymatic activity in vitro. Aldhs have crucial roles in retinoic acid metabolism and functionally we validated napabucasin-mediated activation of the retinoic acid pathway in zebrafish in vivo. We conclude that TPP profiling in whole zebrafish embryo lysate is feasible and facilitates direct correlation of in vivo effects of small molecule drugs with their protein targets.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

Prices, Products and Priorities: Meeting Refugees’ Energy Needs in Burkina Faso and Kenya Other resource sysadmin 24 January 2018

As the number of displaced people increases, and aid budgets come under further pressure, the imperative to identify cost-effective and sustainable solutions for delivering energy to refugees is more pressing than ever.

This paper examines the issue of energy and displacement in detail, using insights from refugees in camps in Burkina Faso and Kenya. It seeks to promote a better understanding of their energy needs, priorities and preferences, and explores how increased access to energy might help to achieve lasting impact in the two camps surveyed. The paper is based on primary research from the Goudoubo camp in Burkina Faso and the Kakuma I camp in Kenya, but the analysis and conclusions are pertinent in the wider context of camps for forcibly displaced people.

Summary points

• There is a low level of energy access in the refugee camps of Kakuma I and Goudoubo, which contributes to poverty and hampers relief and development efforts. Trying to meet basic cooking, lighting and phone-charging needs is costly for refugees, consuming a significant share of stretched monthly budgets.
• The predominant cooking solution consists of basic improved cookstoves burning wood and charcoal. The ‘three-stone fire’ method also remains commonplace. Three out of five families in Kakuma I report health problems due to smoke from cookstoves.
• Street lighting is a high priority for residents, due to concerns about security and safety in camps. In Goudoubo, 86 per cent of survey respondents said that more household members would go out after dark if there were better public lighting.
• A significant proportion of refugees would pay for cleaner and more efficient energy technologies, but many lack the financial resources required, and the development of markets for such products remains partially contingent on sustained financial support.
• There is a need for a diversity of energy technologies that give varying levels and qualities of service; a ‘one size fits all’ approach is inappropriate if universal access to sustainable energy is to be achieved.
• Clean cookstoves and fuels (LPG, ethanol, biogas, etc.) are in high demand, but require much greater investment if they are to be introduced at scale. Solid biomass and improved cookstoves will continue to be important cooking solutions in Kakuma I and Goudoubo, as well as in other refugee camps. A shift to more efficient cooking can be achieved at little or no extra cost for the significant proportion of people who still cook on three-stone fires.
• Users of quality-verified household solar products spend dramatically less on light and power than do people using inferior technologies. Strong brand recognition and a high willingness to pay indicate a large market and a significant opportunity for the solar private sector.
• Centralized electricity supply solutions – mini-grids or grid connections – are more economic than multiple standalone diesel generators. The current piecemeal and ad hoc approach, with each facility managing its own power supply, is inherently wasteful. Greater coordination among humanitarian clusters is required so that centralized solutions can be assessed, designed, financed and implemented.
• Collecting data on energy expenditure and use, as well as quantification of the wide ranging impacts of improved technologies, is necessary to build a compelling case for investment in electricity infrastructure. In addition, engaging refugees on their needs, preferences and willingness to pay can improve the sustainability and impact of energy interventions.
• Private-sector and market development approaches offer long-term, cost-effective solutions for refugees and can also benefit host communities. As the number of displaced people in the world increases, and as aid budgets come under further pressure, the imperative to identify cost-effective and sustainable solutions is more pressing than ever.

Chatham House is a part of the Moving Energy Initiative, a consortium working towards clean energy for refugees. For more information visit movingenergy.earth

Drones and the European Union: Prospects for a Common Future Research paper sysadmin 30 January 2018

The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.

Summary

• The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.
• Countries would benefit from working together to identify accountability gaps arising from fundamental elements of military cooperation, including the role of intelligence transfers in joint operations, and the distribution of responsibility for lethal actions in the context of coalition operations.
• Transparency in investigation procedures, as well as devoting sufficient resources towards ensuring that mistakes are identified, will improve the perception of drone use among domestic audiences.
• Identifying and communicating common standards and practices of mitigating complicity should be a priority for countries to ensure that they do not unwittingly become complicit in unlawful lethal operations.
• Although operational safety may hinder the ability of states to be completely transparent, understanding among the general public could be improved through the communication of policies and procedures regarding non-lethal assistance to partner states conducting lethal operations, both inside and outside the context of an armed conflict.

Infrastructure Management Contracts: Improving Energy Asset Management in Displacement Settings Research paper sysadmin 17 April 2019

This paper highlights a number of options for managing electricity infrastructure in refugee camps and outlines the challenges, opportunities and operational implications associated with them. It takes the Kalobeyei settlement in Kenya as a case study.

• Building and maintaining electricity infrastructure to power offices, businesses, households and other operations in displacement settings is difficult. It is especially challenging for the Office of the United Nations High Commissioner for Refugees (UNHCR) and its partner agencies, because supplying electricity is not their core business.
• Private-sector companies exist that are willing and able to develop infrastructure management contracts to provide energy as a service in displacement settings. However, institutional barriers within humanitarian agencies persist, with short budgeting cycles in particular preventing humanitarian agencies from entering into the sorts of long-term service agreements required by the private sector.
• A number of options exist to leverage the expertise of the private sector through ‘public–private partnership’ (P3) structures. Such mechanisms can promote more efficient management of infrastructure by drawing on private-sector experience and expertise, incentivizing appropriate risk-sharing and providing options to leverage private capital in project development.
• Field work from the Kalobeyei settlement in Kenya suggests that a solar/diesel hybrid mini-grid solution was the most economical option to power camp services and infrastructure there. Compared to distributed diesel generation, the annual savings in operating costs were estimated at $49,880, with the additional investment paid back within 3.6 years.
• Humanitarian agencies need to be willing to change their policies to enable long-term service agreements. Alternatively (or, more likely, in conjunction with this option), financial mechanisms such as partial risk guarantees need to be developed to offset some of the risks. This change will need high-level support from donors and humanitarian agencies.
• Once the first infrastructure management contracts can be signed and tested in displacement locations (through the use of donor funding or otherwise) and associated data collected, it will ease the way for future investments in these types of projects.

The 30 prospects below all are getting very long looks this spring with an eye toward breaking camp with the parent club. Even if they start the year in the Minors, they all should get the chance to contribute at some point in the very near future.

Who do the Phillies have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for Philly's Top 30 Prospects on MLBPipeline.com's Prospect Watch.

The Phillies list isn't quite as strong as it once was because of the Realmuto deal, but there's still some very good talent at the top and some exciting players on the rise.

The 30 prospects below all are getting very long looks this spring with an eye toward breaking camp with the parent club. Even if they start the year in the Minors, they all should get the chance to contribute at some point in the very near future.

Who do the Angels have in the pipeline? Get scouting reports, video, stats, projected ETAs and more for the Halos' Top 30 Prospects on MLB Pipeline's Prospect Watch.

Afonso Dhlakama’s Death Changes the Calculation for Peace Prospects in Mozambique Expert comment sysadmin 4 May 2018

If politicians continue to act in good faith, the death of the opposition leader may be a significant opportunity to finally draw a line under Mozambique’s long war.

The unexpected death of opposition and ex-rebel leader Afonso Dhlakama on 3 May is a game changer for Mozambique’s politics and an almost-completed peace process. The 65-year old Dhlakama, who died of a heart attack, had led Renamo for 38 years and had totally dominated his party. Dhlakama regularly boasted that he was Mozambique’s ‘father of democracy’, despite not allowing competition within his own party, and he leaves a legacy of more than 30 years of struggle, through both armed action and peaceful politics.

A long war

Originally Renamo had been a tool for the white minority regimes of Rhodesia and apartheid South Africa to challenge the socialist Frelimo political party that took power in Mozambique in 1975. But under Dhlakama’s command, by the late 1980s Renamo had become increasingly independent and rooted in Mozambique. After Renamo’s long war with Frelimo ground to a hurting stalemate, a transition led to Mozambique’s first multiparty elections in 1994, and the creation of a new joint army. A ‘pay and scatter’ programme successfully dispersed and reintegrated many thousands of ex-combatants.

But early post-election gains did not translate to lasting peace. Disarmament was a time-limited, technical process, and devoted declining resources and attention to clusters of ex-combatants that failed to disperse. In addition, Dhlakama was allowed to maintain an armed militia under the guise of a presidential guard.

Mounting economic inequality, notably in opposition strongholds such as central Mozambique, saw Renamo made political gains and Dhlakama nearly won the 1999 presidential elections. (Some believe he did.) The result focused Frelimo’s attention on the threat that Renamo posed and, ultimately, a strategy of pursuing total Frelimo domination across the country, culminating in a crushing Frelimo victory at the 2009 elections.

This humiliated and marginalized former Renamo rebels, resulting in Dhlakama ordering their return to targeted armed violence in 2013. Frelimo’s new leader, President Filipe Nyusi, took power in 2015 and sought direct dialogue with Dhlakama. Five rounds of internationally mediated peace talks took place from July to December. Finally, in late December 2016, Dhlakama announced a unilateral truce, which was extended twice and subsequently made indefinite.

New peace talks also started and, in August 2017 and February 2018, President Nyusi and Dhlakama showed the courage to meet in person, near Renamo’s base in central Mozambique, to build up mutual trust and discuss the details of the emerging peace deal – including the demobilization or integration into government security forces for Renamo’s now mostly middle-aged gunmen.

Dhlakama the ‘Big Man’

Dhlakama’s sudden death has fundamentally changed the negotiation dynamics. He never allowed for any serious succession planning, and ensured all key decisions were his and his alone. Renamo had already decided that he would be its presidential candidate for the 2019 national elections.

His party is significantly weakened by his death and unlikely able to fully recover – but needs to try and reach consensus quickly on a successor, as it will also compete in municipal elections in October and was expecting significant gains. There will be a number of contenders to succeed him including from the parliamentary wing, led by his niece Ivone Soares, its secretary general, Manuel Bissopo, and a few others.

But Renamo’s key leverage for now remains some 1,000 middle-aged gunmen in central Mozambique who have been stoically loyal to Dhlakama since the 1980s and who have little respect for the younger generation of professional politicians based in Maputo. Some may be bought off by government offers, others integrated into localised organized crime groups and others into internal Renamo sectarianism. The risk of fragmentation is real.

Renamo’s weakness could also embolden Frelimo hardliners to seek a return to unilateral domination of Mozambique’s political landscape, and to undermine the peace process. That would be a serious tactical mistake by Frelimo, as a lasting deal is close and the death of Dhlakama could actually assist in making this settlement lasting. Dhlakama was quixotic and prone to changing his mind, often influenced by the last person he spoke to – his death potentially introduces greater predictability in negotiations and in any post-deal implementation.

President Nyusi is clearly aware of this as he hailed on state television TVM that Dhlakama was ‘a citizen who has always worked for Mozambique’ and said he was distraught at the news of his death. He stated, ‘I hope that we as Mozambicans can continue to do everything so things do not go down.’ He also addressed Renamo’s support base by saying that ‘[Dhlakama] did everything so that there would be peace. The last time he spoke to me, he said he was not going to miss out anything in peace negotiations.’

Renamo’s gunmen are fatigued and want to retire with dignity but are vulnerable to manipulation and political miscalculation by Mozambican’s positioning politicians. International partners and investors can engage, by emphasizing that sustainable peace is the only pathway to poverty reduction and inclusive economic development.

This includes assisting development and reconciliation projects in areas impacted by the renewed conflict since 2013. Long-term investment for development in Renamo’s key constituencies could help avoid fragmentation at a critical time – faith groups and NGOs may also have a key role to play.

If Mozambique’s politicians continue to act in good faith, the death of Dhlakama may constitute a significant opportunity to finally draw a line under Mozambique’s long war.

South Africa’s 2019 Election: Polling Data and Party Prospects 13 March 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 7 March 2019 Chatham House, London

On 8 May 2019, South Africans will vote in their sixth national election. Incumbent President Cyril Ramaphosa is leading his ANC party campaign, which promises inclusive economic growth and social transformation, including through a sustainable land reform programme. However, public frustrations with the party’s record of service delivery and government corruption after 25 years in power could threaten the ANC’s electoral dominance especially in urban areas.

At this meeting, Professor David Everatt, head of the Wits School of Governance and political pollster, will present polling data and discuss the prospects and strategies of the main parties and their leaders ahead of the May election.

Attendance at this event is by invitation only.

South Africa’s ANC party policy conference 2022: Outcomes and prospects 10 August 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 4 August 2022 Online

Paul Mashatile, Treasurer-General of the African National Congress (ANC), discusses the outcomes of the 6th ANC Policy Conference 2022.

The African National Congress (ANC) recently concluded its 6th National Policy Conference in Johannesburg, in the year that the ANC has declared ‘The Year of Unity and Renewal to Defend and Advance South Africa’s Democratic Gains’. The conference was a precursor to the party’s 55th National Elective Conference to be held in December.

The conference has come less than a year after municipal polls in which the ANC garnered less than 50 per cent of votes, its lowest since 1994. Many believe internal factionalism is impeding party reform and hampering its ability to address unemployment and entrenched inequality.

At this webinar, Paul Mashatile, Treasurer-General of the ANC, will discuss the outcomes of the ANC Policy Conference 2022, including measures to accelerate inclusive growth, job creation and a just energy transition.

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

Angola forum 2022: Prospects for Angola's social and economic future 15 December 2022 — 1:00PM TO 4:30PM Anonymous (not verified) 28 November 2022 Online

At this online Angola forum, experts will discuss Angola’s social and economic future, and what to expect from 2023.

At this virtual Angola Forum, speakers will discuss Angola’s social and economic future and what to expect from 2023.

Angola experienced positive economic momentum in 2022 allowing it to exit its six-year recession, with the economy taking centre stage in the August national multiparty elections. Increased oil prices and high levels of production have driven Angola’s economic growth and improved macroeconomic conditions, as well as helping the country to reduce its public debt to 56.5 per cent of Gross Domestic Product (down from 79.7 per cent in 2021).

However, a global economic downturn in 2023, with increased inflation, means Angola’s re-elected MPLA government will need to focus on job creation, greater economic inclusivity and diversifying away from an oil-led economy. It will also require Angola to navigate its international partnerships more effectively in this era of heightened geopolitical rivalries.  

At this online Angola forum, experts will discuss Angola’s social and economic future and what to expect from 2023. Speakers will reflect on the social and economic trends seen in 2021-22 and explore election trends, human rights and international relations.

This Angola Forum is supported by the Konrad-Adenauer-Stiftung.

Ten conflicts to watch in 2023 11 January 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 8 December 2022 Chatham House and Online

This event examines the most dangerous wars and crises through the lens of the International Crisis Group’s flagship annual report ‘10 Conflicts to watch in 2023’.

Each year, International Crisis Group compiles a list of the ten conflicts to watch that examines key conflicts across the globe. Please join us for this event at which Dr Comfort Ero, International Crisis Group president and CEO, discusses today’s and tomorrow’s most impactful wars and crises.

Key questions to consider include:

• What far-reaching repercussions and knock-on effects of Russia’s war on Ukraine will have for Europe and the rest of the world?

• Which crises beyond Ukraine warrant collective attention in the year ahead?

• How do rising tensions among major powers impact multilateral efforts to resolve these conflicts, impede progress on global challenges and impact institutions working on crisis prevention?

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

How Russia’s war affects politics in southeast Europe 4 April 2023 — 11:00AM TO 12:00PM Anonymous (not verified) 24 March 2023 Online

This event will discuss how the war on Ukraine has affected southeastern Europe.

This event will discuss how the war on Ukraine has affected southeastern Europe. How have the governments and publics responded to the war?

The panel will discuss Russia’s goals and leverage in the region, including the impact of its disinformation campaigns. Are the governments reassessing their foreign policy options?

The granting of EU candidate status to Ukraine and Moldova has brought attention to the stalled accession process in the Western Balkans. What lessons from the Western Balkans can be applied in Ukraine and Moldova? Have new linkages emerged between the two regions?

EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit 12 December 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 26 November 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey and the EU have been in a customs union since 1995. Both sides recognize that the current agreement is in need of modernization and have agreed to open negotiations to expand its scope to include services, public procurement, agriculture and other elements that would help bring it into the 21st century.

At the same time, the UK Parliament is debating whether to approve the agreement on the UK’s withdrawal from the EU. It includes a backstop which – if triggered – would keep the UK and the EU in a single customs territory which would limit the disruption of withdrawal but hamper Britain’s ability to pursue an independent trade policy. The political declaration proposes building on this customs arrangement as the basis for the future relationship.

In this context, the speaker will discuss the current EU-Turkey customs union arrangement and its shortcomings, examine the prospects for its modernization and share his insights on the lessons for the UK’s future trading relationship with the EU.

The event will launch the briefing paper ‘EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit’.

Attendance at this event is by invitation only.

The National Toy Hall of Fame in Rochester, N.Y., announced this year's inductees: My Little Pony, Transformers and Phase 10.

WASHINGTON, Oct. 30, 2024 — The U.S. Department of the Treasury (Treasury) today issued a final rule (Final Rule) to implement Executive Order 14105 of August 9, 2023, “Addressing United […]

The post US Treasury Issues Final Rule Addressing Investments in Certain National Security Technologies and Products appeared first on HPCwire.

The U.S. Navy conducted a two-missile test flight of unarmed life-extended Trident II-D5LE missiles from the USS Wyoming in the Eastern Test Range off the coast of Cape Canaveral, Fla, the Navy announced.

RUTHERFORD, N.J., Dec. 5, 2023 — Intelligent Light has announced it has been selected by AFWERX for a Direct-to-Phase II contract in the amount of $1.15 Million focused on IntelliTwin […]

The post AFWERX Selects IntelliTwin as the Realizable Digital Thread for HPC-scale CFD appeared first on HPCwire.

Nov. 8. 2024 — High-performance computing (HPC) has been an indispensable research tool for accessing physical realms difficult, or impossible, to achieve with experiment alone. For several decades, the Department […]

The post ECP: ‘Forward’ Projects Boost US Leadership in Advanced Computing and AI appeared first on HPCwire.

President-elect Donald Trump has chosen former Republican Rep. Lee Zeldin of New York to run the Environmental Protection Agency.

Your intelligence could influence how much alcohol you consume.

Did you grow up in a world void of social media platforms? Then, you’re probably the last ‘lucky’ generation. A part of Generation Y and most of Generation Z have been raised alongside the internet and social media. Individuals belonging to the latter have practically been raised by such platforms, as they interact with strangers […]

The post Sacrificing the Human Psyche at the Altar of Social Media? 4 Concerning Ill-Effects to Know first appeared on What is Psychology?.

The justices ruled 5-4 that a Montana state constitutional provision barring aid to religion discriminated against religious schools and families seeking to benefit from a tax credit for donations for scholarships.

The 5-4 decision involving a dispute in Montana appears to cast doubt on as many as 30 state constitutions that bar aid to religious schools.

Facing big transportation costs due to the COVID-19 pandemic, some school districts will pay parents or caregivers to get their kids to school, or charge them for the bus ride.

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.

Two rural North Dakota school districts will switch to a four-day school week to save costs and improve student and teacher morale.

Facing big transportation costs due to the COVID-19 pandemic, some school districts will pay parents or caregivers to get their kids to school, or charge them for the bus ride.

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.

Pandemic-inflicted budget cuts have cost thousands of educators their jobs. Here’s how that’s playing out in five districts around the country.