World in brief: Ukraine and nuclear proliferation to dominate G7 The World Today mhiggins.drupal 28 March 2023

Following Russia’s ongoing intimidation, Japan will use its presidency of the G7 – and its history – to prioritize the dangers of nuclear threats, writes James Orr.

Two issues are expected to dominate the agenda as Japan hosts the G7 summit in Hiroshima from May 19-21. Central to talks will be the conflict in Ukraine, with member states eager to highlight a message of unity and resolve in the face of Russia’s continuing aggression.

Fumio Kishida, Japan’s prime minister, made an unannounced visit to Kyiv on March 21, meeting the Ukrainian president Volodymyr Zelenskyy.  This coincided with a visit to Moscow by China’s leader Xi Jinping, who described Russian president Vladimir Putin as a friend and partner.

‘Absolutely unacceptable’

Hosting the G7 summit in Hiroshima is significant, too, with Kishida expected to emphasize the ‘absolutely unacceptable’ threat of nuclear proliferation. Ongoing tensions between China and Taiwan, together with recent North Korean ballistic missile tests, have heightened fears of a breakdown in security in the region.

Meanwhile, President Vladimir Putin’s menacing references to the use of nuclear weapons in Ukraine has raised the prospect of a potentially devastating conflict with NATO. ‘Kishida’s principal goal for the presidency of the G7 is to try to draw the world away from the path of destruction that is another nuclear conflict,’ said Duncan Bartlett, a research associate at SOAS, the School of Oriental and African Studies, in London.

‘Early last year, Putin warned of terrible consequences if NATO and the West interfered in the Ukraine conflict, and that was widely seen as being a nuclear threat. North Korea is also pursuing its nuclear weapons programme, and in February an intercontinental ballistic missile went into the sea just near the northern Japanese island of Hokkaido,’ said Bartlett.

After Russia invaded Ukraine in February 2022, Kishida has taken a firm position on Putin, in line with his G7 peers. President Zelenskyy has addressed the Japanese parliament via video link and Dmytro Kuleba, Ukraine’s minister of foreign affairs, was invited by his Japanese counterpart to a G7 meeting held during the Munich Security Conference earlier this year.

Kishida committed $600 million in financial support to Ukraine and his government may well announce the provision of further non-lethal assistance to Zelenskyy at the summit. The country’s constitution effectively outlaws the export of deadly weapons to foreign forces. On his visit to Kyiv, Kishida promised a further $30 million to Ukraine.

‘Kishida has revised key defence documents and is pursuing a radical and controversial expansion of Japan’s defence budget and capabilities,’ said Hugo Dobson, Professor of Japan’s International Relations at the University of Sheffield.

‘He and his G7 partners have signed historic defence agreements, pledged to strengthen ties or declared the inseparability of their security in light of actual conflict in Ukraine and potential conflict in East Asia. Kishida has linked the two by emphasizing that Ukraine today may be East Asia tomorrow,’ said Dobson.

Aside from security matters, Kishida will at the summit address issues on clean energy, climate change, global health and boosting multilateral cooperation to drive post-pandemic economic recovery.

Invitation to Nagasaki

He is understood to have invited President Joe Biden to visit Nagasaki, where the second of America’s two atomic bombs is estimated to have killed 60,000 people in August 1945. No sitting US president has ever visited the city, and Kishida, who grew up in Hiroshima, may see the visit as an opportunity to boost his flagging domestic approval ratings. It may also serve as a timely reminder to Russia and others that the G7 opposes any future nuclear weapon use.

China’s renewed influence in the Gulf Interview LJefferson 14 April 2023

By disseminating narratives of its own supremacy, China deepened relations with the Gulf during the COVID-19 pandemic.

China has used the COVID-19 pandemic as an opportunity to rebrand its international role as a ‘responsible’ and ‘great’ power by voicing narratives of its own supremacy to regions like the Gulf.

In this interview, Julia Gurol-Haller draws on her International Affairs article to trace how the UAE, Saudi Arabia, Qatar and Iran have responded to China’s narratives, with key implications for Sino-US competition and regional autonomy for the Gulf. This illustrates how words and narratives help bolster authoritarian power.

What have the China-Gulf relations looked like in context of the COVID-19 pandemic?

Bilateral relations between China and the Gulf countries have grown in importance over the past decade, particularly since 2013 with the Belt and Road Initiative. The Gulf plays a crucial role in China’s Belt and Road Initiative and its westward expansion, owing to its favourable geographic position and proximity to the Red Sea. 

In the beginning, transregional relations were mainly economic partnerships since China has a growing appetite for oil and gas and the Gulf monarchies fulfil these needs. China is one of the most important markets for Saudi Arabia, the UAE, and Qatar to export these goods.

Over time, we’ve seen the Sino-Gulf relations expand beyond just economic ties and towards policy fields like security and cultural relations. While these processes were already in place, they were boosted during the COVID-19 pandemic, not only in material terms but also in respect of Chinese attempts to advance its soft power, leverage, and influence in the Gulf region.

When COVID-19 began to ravage the globe, China took that window of opportunity to rebrand its international role. Through efforts such as mask diplomacy, vaccine diplomacy and the strategic diffusion of narratives, China tried to project its image as a ‘global saviour’ and a responsible and great power.

The Gulf monarchies and Iran were among the main target audiences for this public diplomacy campaign. So, the COVID-19 pandemic has been a catalysing factor for deepening relations between China and the Gulf region.

What exactly are narratives and why are they important in China’s approach to the Gulf states during the COVID-19 pandemic?

Through diplomatic statements, news outlets and social media, China has engaged in, what I call, a ‘narrative power-play’. To understand what that is, we need to understand the political importance of narratives.

Narratives are deliberately constructed by (political) actors to influence a certain target audience. In authoritarian contexts, narratives are a useful resource for political actors to bind audiences to their rule and to appeal to people’s emotions by strategically projecting certain images. 

Ultimately, this creates linkages via attraction or persuasion that enhance the actors’ legitimacy and consolidate their power. So, in the narrative power-play, authoritarian leaders function as ‘storytellers-in-chief’, shaping reality in their favour.

What kinds of narratives has China disseminated to the Gulf region in backdrop of the COVID-19 pandemic?

There are two sets of narratives that China disseminated to the Gulf: narratives of supremacy and narratives of a new world order.

China disseminates narratives of systemic supremacy which include praising the overall efficiency of its governance structures. For instance, the Chinese political system is presented as highly efficient and centralized. It has high amounts of ‘state capacity’ for mobilization and the ability to ‘quickly adapt’ to changing situations.

Narratives of performative supremacy refer to the tangible performance of the Chinese Communist Party or China as a whole, such as economic performance, performance in governance, provision of public goods or pandemic response. The performance narratives also highlight the ‘incredible logistical efficacy’, the highly professionalized medical sector and the innovative scientific sector. 

Narratives of normative supremacy are often informed by nationalist notions such as the reclaiming of China’s rightful position in the world and negative feelings towards Western imperial powers who are depicted as having inflicted great pains on China during the ‘century of humiliation’. Overall, these narratives serve to depict China as a responsible, caring and loyal world power that helps other states. The whole idea of mask diplomacy was also carved into that notion of China’s normative supremacy.

Together, China has used these narratives to construct the idea of a new world order in which China is believed to play a much bigger role. The world order narratives are closely linked to stories about the failure of the Western system and show the intertwinement of practices of othering and self-glorification that can also be observed in Chinese official media narratives in other contexts such as diplomatic stand-offs with the United States.

What do these narratives tell us about how China understands the world order?

The narratives China disseminated to the Gulf region show that in the Chinese understanding of politics, the world order is in flux and undergoing major power reconfigurations. For China, this implies a window of opportunity to position itself as a responsible and great power and move from the side-lines to the centre stage of international politics.

This is a trend that has been long in the making in Chinese foreign policy. For instance, the launch of the Chinese Global Security Initiative or the recent brokering of the Iran-Saudi rapprochement agreement show clearly that China is becoming much more than an economic powerhouse and is adopting a more proactive foreign policy.

During the recent state visit of Xi Jinping to Moscow, he said at one point that China stands ready to ‘safeguard (…) the international order underpinned by international law ’. These examples are quite telling regarding the role China ascribes itself on the international stage.

How have the Gulf countries responded to China’s power narratives during the COVID-19 pandemic?

Saudi Arabia, the UAE, Qatar and Iran all picked up the narrative of China’s superior performance during the global crisis. That was a unified response, but they did that to different degrees and by highlighting different aspects.

The strongest reproduction of Chinese narratives can be found in the Emirati media. They buy into the story of the COVID-19 pandemic as evoking a global power shift, which includes a decline of US hegemony and a corresponding rise of China. The explicit wording of Chinese narratives such as ‘community of shared future of humankind’ has been picked up word-for-word by some Emirati media outlets.

Iranian newspapers have also reproduced Chinese narratives. However, the difference is that they also praise China’s unconditional solidarity during the COVID-19 pandemic, which is believed to be superior and more ‘responsible’ than the ostensible individualism of the West. This tells us a lot about Iran’s relationship with the West and how China is believed to be a lifeline or anchor for stability.

Saudi Arabia has been more cautious in reproducing the Chinese narratives. While it does not contest China’s role in containing the COVID-19 pandemic, Saudi Arabia has adopted a more inward-looking perspective, stressing its own role as a responsible regional player during the pandemic.

This might be explained by the kingdom’s own regional leadership claims and the attempt to use the crisis as an opportunity to strengthen this role. The most pressing questions seem to be whether the post-COVID world will be a multipolar order, and what Saudi Arabia’s own position within it might be. 

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Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

This article is by Toni Šušnjar.

Warfare and military are an integral part of much of ancient and medieval fantasy. This is no surprise: warfare was a key element in development of society and of history, and much of mythology is also about it. As such, it is difficult for fantasy writers and readers alike to avoid war and military matters in general. And if you are going to do something, try to do it well. Army does not spring from the ground like the spartoi of Jason.

Environment and Geography

Environmental conditions include terrain, climate and resources. All three influence how an army will fight and which weapons it will use.

Terrain can be highly varied, but I will divide it into three categories: mountainous, rolling hills and flat. Mountains and forests – and especially forested mountains – are conductive to infantry warfare. Depending on other conditions (such as society, climate etc.), this can mean either light infantry with focus on ambushes, raiding and guerilla warfare; or heavy infantry, with focus on direct confrontation. Both of these were, at different points, in evidence in Spain and Greece.

Continue reading Building a Fantasy Army — Environment & Society at Mythic Scribes.