In Alzheimer's disease (AD), tau, a microtubule-associated protein (MAP), becomes hyperphosphorylated, aggregates, and accumulates in the somato-dendritic compartment of neurons. In parallel to its intracellular accumulation in AD, tau is also released in the extracellular space, as revealed by its increased presence in cerebrospinal fluid (CSF). Consistent with this, recent studies, including ours, have reported that neurons secrete tau, and several therapeutic strategies aim to prevent the intracellular tau accumulation. Previously, we reported that late endosomes were implicated in tau secretion. Here, we explore the possibility of preventing intracellular tau accumulation by increasing tau secretion. Using neuronal models, we investigated whether overexpression of the vesicle-associated membrane protein 8 (VAMP8), an R-SNARE found on late endosomes, could increase tau secretion. The overexpression of VAMP8 significantly increased tau secretion, decreasing its intracellular levels in the neuroblastoma (N2a) cell line. Increased tau secretion by VAMP8 was also observed in murine hippocampal slices. The intracellular reduction of tau by VAMP8 overexpression correlated to a decrease of acetylated tubulin induced by tau overexpression in N2a cells. VAMP8 staining was preferentially found on late endosomes in N2a cells. Using total internal reflection fluorescence (TIRF) microscopy, the fusion of VAMP8-positive vesicles with the plasma membrane was correlated to the depletion of tau in the cytoplasm. Finally, overexpression of VAMP8 reduced the intracellular accumulation of tau mutants linked to frontotemporal dementia with parkinsonism and α-synuclein by increasing their secretion. Collectively, the present data indicate that VAMP8 could be used to increase tau and α-synuclein clearance to prevent their intracellular accumulation.

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves  are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as  prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using -3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2) that releases the incorporated DHA from phospholipids and enhances the synthesis of docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer  RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A).  RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.

Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr^–/– mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr^–/–/Bco1^–/– mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.

Ion mobility separates molecules in the gas-phase based on their physico-chemical properties, providing information about their size as collisional cross-sections. The timsTOF Pro combines trapped ion mobility with a quadrupole, collision cell and a TOF mass analyzer, to probe ions at high speeds with on-the-fly fragmentation. Here, we show that on this platform ion mobility is beneficial for cross-linking MS (XL-MS). Cross-linking reagents covalently link amino acids in proximity, resulting in peptide pairs after proteolytic digestion. These cross-linked peptides are typically present at low abundance in the background of normal peptides, which can partially be resolved by using enrichable cross-linking reagents. Even with a very efficient enrichable cross-linking reagent, like PhoX, the analysis of cross-linked peptides is still hampered by the co-enrichment of peptides connected to a partially hydrolyzed reagent – termed mono-linked peptides. For experiments aiming to uncover protein-protein interactions these are unwanted byproducts. Here, we demonstrate that gas-phase separation by ion mobility enables the separation of mono-linked peptides from cross-linked peptide pairs. A clear partition between these two classes is observed at a CCS of 500 Ų and a monoisotopic mass of 2 kDa, which can be used for targeted precursor selection. A total of 50-70% of the mono-linked peptides are prevented from sequencing, allowing the analysis to focus on sequencing the relevant cross-linked peptide pairs. In applications to both simple proteins and protein mixtures and a complete highly complex lysate this approach provides a substantial increase in detected cross-linked peptides.

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Plasmodium, the malaria parasite, undergoes a complex life cycle alternating between a vertebrate host and a mosquito vector of the genus Anopheles. In red blood cells of the vertebrate host, Plasmodium multiplies asexually or differentiates into gamete precursors, the male and female gametocytes, responsible for parasite transmission. Sexual stage maturation occurs in the midgut of the mosquito vector, where male and female gametes egress from the host erythrocytes to fuse and form a zygote. Gamete egress entails the successive rupture of two membranes surrounding the parasite, the parasitophorous vacuole membrane and the erythrocyte plasma membrane. In this study, we used the rodent model parasite Plasmodium berghei to design a label-free quantitative proteomic approach aimed at identifying gender-related proteins differentially released/secreted by purified mature gametocytes when activated to form gametes. We compared the abundance of molecules secreted by wild type gametocytes of both genders with that of a transgenic line defective in male gamete maturation and egress. This enabled us to provide a comprehensive data set of egress-related molecules and their gender specificity. Using specific antibodies, we validated eleven candidate molecules, predicted as either gender-specific or common to both male and female gametocytes. All of them localize to punctuate, vesicle-like structures that relocate to cell periphery upon activation, but only three of them localize to the gametocyte-specific secretory vesicles named osmiophilic bodies. Our results confirm that the egress process involves a tightly coordinated secretory apparatus that includes different types of vesicles and may put the basis for functional studies aimed at designing novel transmission-blocking molecules.

Les médicaments utilisés pour le traitement des troubles mentaux peuvent avoir des effets secondaires plus ou moins graves sur la santé des patients. C’est le cas de seroplex, un médicament largement utilisé comme traitement dans le domaine de la santé mentale. Mais en réalité, quelle est la composition de ce médicament et quels sont ses […]

L’article Quels sont les effets secondaires de seroplex ? est apparu en premier sur Ortho Doc France.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.

The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector Research paper sysadmin 27 November 2018

Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The corporate sector has traditionally engaged governments at national rather than international level in lobbying for action related to climate change. Where it has engaged at an international level, this has often been to restrain regulation and ambition, such as in air transport. Over time, many businesses have increasingly understood that there is more commercial opportunity in a strong, consistent approach to tackling climate mitigation and adaptation, and an increasing number are willing to speak up on the issue. The Paris Climate Conference in 2015 demonstrated this positive engagement.
• Businesses are more powerful when engaging directly with national governments on detailed policies – by demonstrating what is possible and indirectly influencing national governments’ international pledges. Traditional trade/industry sector associations and groups have tended to suffer from the ‘lowest common denominator’ effect of their least progressive members. Progressive business groups coalescing around climate ambition can help to counter this.
• Unlike at the Copenhagen climate talks in 2009, the business community provided a positive, supportive backdrop to the 2015 Paris talks, mindful of the public relations opportunities in taking a progressive stance and of the benefits of targets that reflected the science. The carbon market was a particular focus for corporates, which succeeded in getting emissions trading options and market mechanisms included in Article 6 of the Paris Agreement.
• Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. With increasing awareness of resource scarcity, businesses are pursuing ever more creative solutions.
• Wide recognition that the avoidance of future emissions is increasingly dependent on developing and emerging economies means that business voices from these countries will potentially be more influential in the next few years.

Cooking in Displacement Settings: Engaging the Private Sector in Non-wood-based Fuel Supply Research paper sysadmin 22 January 2019

In displacement settings, providing cooking solutions that reduce negative impacts on the environment and health remains a challenge for local governments, humanitarian agencies, businesses and refugees.

Summary

• Providing adequate cooking fuel and clean-burning, fuel-efficient stoves in displacement settings has long been a major challenge for local authorities, humanitarian agencies, non-governmental organizations, local communities and refugees themselves. Refugees generally have limited access to modern cooking solutions. Most either depend on insufficient humanitarian agency handouts of ‘in-kind’ firewood or have to travel long distances to collect firewood.
• There is significant potential for private-sector engagement in this context – which, though largely overlooked to date, could result in win-win scenarios for all stakeholders. Refugee camps and other displacement settings present opportunities for private-sector cooking fuel companies to expand their customer bases, with the added advantage for vendors of offering concentrated demand and scope for economies of scale.
• For the Kakuma refugee camp complex in Kenya, the Moving Energy Initiative (MEI) decided to engage with the private sector directly. The MEI requested expressions of interest from local private-sector companies for expanding sales and distribution of fuels in the complex through the concession. The winning company – National Oil Corporation of Kenya – is to receive a prize of $50,000 for its proposed concession to supply liquefied petroleum gas both to refugees in the Kakuma complex and to the surrounding host community.
• The MEI also conducted interviews with various stakeholders in other contexts and countries who are engaged in efforts to develop market-based approaches to providing clean, fuel-efficient cooking solutions to refugees.
• Based on the interviews and the concession process, the MEI recommends greater donor investment and longer-term guaranteed funding for cooking interventions. This is needed to allow sufficient time to build sustainable markets and secure the requisite engagement and investments from the private sector.
• Larger, longer-term investments by the private sector – supported through partnerships with donors and humanitarian agencies – in infrastructure and demand creation (both in and outside the refugee community) can reduce the price of alternative solutions and support a gradual transition away from subsidies.

Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden Book sysadmin 15 January 2020

How can democratic governments hold intelligence and security agencies to account when what they do is largely secret? Jamie Gaskarth explores how intelligence professionals view accountability in the context of 21st century politics.

Using the UK as a case study, this book provides the first systematic exploration of how accountability is understood inside the secret world. It is based on new interviews with current and former UK intelligence practitioners, as well as extensive research into the performance and scrutiny of the UK intelligence machinery.

The result is the first detailed analysis of how intelligence professionals view their role, what they feel keeps them honest, and how far external overseers impact on their work.

The UK gathers material that helps inform global decisions on such issues as nuclear proliferation, terrorism, transnational crime, and breaches of international humanitarian law. On the flip side, the UK was a major contributor to the intelligence failures leading to the Iraq war in 2003, and its agencies were complicit in the widely discredited U.S. practices of torture and ‘rendition’ of terrorism suspects. UK agencies have come under greater scrutiny since those actions, but it is clear that problems remain.

Secrets and Spies is the result of a British Academy funded project (SG151249) on intelligence accountability. The book is published as part of the Insights series.

Praise for Secrets and Spies

About the author

Jamie Gaskarth is Professor of Foreign Policy and International Relations at The Open University. He was previously senior lecturer at the University of Birmingham where he taught strategy and decision-making. His research focused on the ethical dilemmas of leadership and accountability in intelligence, foreign policy, and defence. He is author/editor or co-editor of six books and served on the Academic Advisory panel for the 2015 UK National Security Strategy and Strategic Defence and Security Review.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

Phillies manager Gabe Kapler believes the two most important spots in a lineup are the Nos. 2 and 4 holes. Rhys Hoskins and Carlos Santana hit there most of last season. But with J.T. Realmuto, Andrew McCutchen and Jean Segura joining the Phillies in the offseason, Kapler has more options.

POSTPONED: Zimbabwe Futures 2025: Financial Sector Expansion and Policy Priorities 15 November 2017 — 9:00AM TO 11:30AM Anonymous (not verified) 6 November 2017 Harare, Zimbabwe 

This roundtable will draw on current best practice and senior level expertise to identify policy options for financial stability and sector growth. A depoliticized analysis of the development agenda will highlight requisite conditions and prospective policies for a business-driven roadmap to the economic recovery of Zimbabwe, with a specific focus on the financial sector.

Participants will discuss macro-economic policy and stability, retail banking products and services, fintech, mobilizing domestic finance for national infrastructure and balancing consumer price index and inflation.

This event is being held in partnership with the Zimbabwe Business Club.

PLEASE NOTE, THIS EVENT HAS BEEN POSTPONED UNTIL FURTHER NOTICE.

Zimbabwe Futures 2030: Sector Priorities for Policy Implementation 4 June 2019 — 9:00AM TO 5:15PM Anonymous (not verified) 21 June 2019 Harare, Zimbabwe

Webinar: Finding Solutions to Insecurity in Cabo Delgado 16 June 2020 — 3:00PM TO 4:30PM Anonymous (not verified) 9 June 2020

South Africa’s foreign policy: Reflections on the United Nations Security Council and the African Union 20 January 2021 — 2:00PM TO 3:00PM Anonymous (not verified) 8 January 2021 Online

HE Dr Naledi Pandor, South Africa’s Minister of International Relations and Cooperation, discusses South Africa’s role in pursuing its regional and global goals.

To receive joining instructions, please finalise your registration by clicking the link below. Once you have registered you will receive a confirmation email from Zoom, which will include the unique joining link you will need to attend.

In 2019-2020, South Africa served its third term as a non-permanent member of the UN Security Council, seeking to strengthen its role as a bridge-builder and further justify a more permanent role for the country and continent on the body.

In February 2021, South Africa will also conclude its time as Chair of the African Union, having used its tenure to promote peace and security issues, including closer cooperation with the UNSC, and advance regional economic integration.

South Africa took up these roles at a time of global and regional upheaval. As COVID-19 tested countries’ commitment to cooperation over isolation, South Africa coordinated regional responses to address the challenges of stressed public health systems, vaccine strategies, and economic stimulus and debt support across Africa.

Its leadership has been further tested by ongoing and emerging insecurity in the Sahel, and in Cabo Delgado in neighbouring Mozambique. The crux of its regional strategy remains squaring the circle between promoting regional economic cooperation while protecting its own domestic economic priorities.

At this event, HE Dr Naledi Pandor, Minister of International Relations and Cooperation of the Republic of South Africa, reflects on the country’s two years on the UNSC and one year of chairing the AU, and discuss South Africa’s role in pursuing regional and global goals.

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

Read event transcript. 

Nigeria's 2023 elections: Security, economic and foreign policy imperatives 5 December 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 23 November 2022 Chatham House and Online

Bola Ahmed Tinubu, presidential candidate for the All-Progressives Congress, discusses his vision and recently-unveiled manifesto for ‘renewing hope’ in Nigeria.

Nigeria is scheduled to hold presidential and national assembly elections on 25 February 2023 as well as governorship and other subnational elections on 11 March 2023.

The elections will end President Muhammadu Buhari’s two terms in office since his election in 2015 and will mark the first time that he is not engaging in a presidential poll since Nigeria’s transition to civilian rule in 1999 – an important marker in Nigeria’s trajectory of democratic consolidation.

Nigeria’s recently enacted Electoral Act has contributed to improved hope around the election process, reflected in the addition of 12.29 million new voters in Nigeria’s voter registration exercise across the federation’s 36 states and 1,491 constituencies.

Yet Nigeria stands at a critical juncture, having suffered from two recessions in the past six years, unprecedented levels of food insecurity, persistent fuel scarcity and high levels of crude oil theft.

Civic fatigue also remains an important challenge and President Muhammadu Buhari’s three main policy pillars of security, economy and corruption continue to be defining issues for citizens.

At this event, Bola Ahmed Tinubu, presidential candidate for the All-Progressives Congress, discusses his vision and recently unveiled manifesto for ‘renewing hope’ in Nigeria including his policy proposals for economic reform and revival and how to deliver secure and inclusive job opportunities for Nigerian citizens.

Download a transcript

This event is a members and Africa programme event and is part of a series of events and outputs examining Nigeria’s 2023 elections and political developments.

As with all Chatham House member events, questions from members drive the conversation.

The security gap 7 March 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 24 February 2023 Chatham House and Online

With the increasingly significant role that women play in national defence, will perceptions change or are current attitudes towards women in uniform here to stay? 

Women have been part of armed conflicts for all of human history, serving alongside men, as well as in their own distinctive units.

More recently, scores of women are involving themselves in Kurdish resistance fighting, being deployed in Syria as fighter pilots for Israel’s Armed Forces and serving on Ukrainian frontlines.

Women have been integrated into militaries around the world including in the Canadian, Swedish and Norwegian armies to name a few.

This discussion aims to tackle some of the following questions:

• What are some of the challenges that more inclusive militaries bring and can these challenges be overcome?
• Can more inclusive militaries help solve the human resources problems that many modern militaries face?
• Are attitudes changing as more women serve in combat? 
• What are the opportunities for women in militaries and in wider defence efforts?

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

Belarus-EU border crisis reveals wider security threat Expert comment NCapeling 8 December 2021

By engineering a crisis at the Belarus border, Lukashenka is attempting to exacerbate vulnerabilities within the EU. Securitizing migration is not the answer.

When thousands of migrants began freezing to death in the forests on the Belarus border with Poland, Belarusian leader Aliaksandr Lukashenka was forcing the European Union (EU) into a tough choice – either give in to blackmail and welcome migrants whose attempts to trespass the EU border were a result of his policy of luring them to Belarus to put pressure on the EU, or keep the borders closed and declare solidarity with Poland despite its known mistreatment and illegal pushbacks of potential asylum-seekers.

Lukashenka’s action was aptly exploiting three key pressure points of the EU – as a normative power where the human dignity of migrants is overlooked while the European border and coastguard agency Frontex stands by, as a geopolitical actor seeking to externalize its migration problem by signing readmission agreements with transit countries, and as a community of values with the EU-Poland dispute over rule of law.

His approach is typical ‘dictaplomacy’ and democracies which have confronted such a ‘continuation of war by other means’ in their past dealings with dictatorships know that blackmail mostly serves to divert attention away from a rogue leader’s misdemeanours towards his own population. But if this had been game of chess the EU would have been in check.

Thankfully checkmate was avoided – so far – as a compromise was found following weeks of heightened diplomatic efforts. Lukashenka was forced to back-pedal and take care of the migrants, and no humanitarian corridor was needed as the EU sent funds and took measures to support organizations providing shelter for the migrants in Belarus, while airlines and governments in the source countries were pressured to restrict flights to Minsk and started repatriating part of the migrants.

Causing a nuisance

‘Operation Gateway’ – the outline of which was allegedly drawn several years ago and tested by Russia in 2016 at its own borders with Norway and Finland – certainly caused a nuisance, but it ultimately backfired as Lukashenka now has to manage the remaining 2,000-5,000 migrants who refused to be flown back, as well as facing increased international sanctions. However, the fact that Angela Merkel had to personally call him made it look as if Lukashenka did not back down for nothing.

The EU and NATO, including the UK, only reacted collectively to this crisis once it was already out of hand, leaving questions over whether this experience of Lukashenka’s dictaplomacy is a wake-up call to boost resilience against rogue warfare, and to upgrade strategic assessments of the ‘Lukashenka problem’ too.

Back in June, the Belarus ministry of foreign affairs (MFA) announced its withdrawal from the Eastern Partnership and the visa facilitation and readmission agreement with the EU, while Lithuania sent early warnings about a ‘hybrid attack’ at its own border with Belarus. In August, Der Spiegel reported details of an alleged smuggling scheme whereby Tsentr Kurort – a company closely linked to the Administration of the President of Belarus with offices in the Middle East – was handling the shipping, accommodation, and relocation of migrants.

The smuggling of migrants was entirely predictable as Lukashenka has hinted many times Belarus could stop ‘protecting the EU from armed migrants’ seeking to enter it illegally. He has upped his rhetoric beyond notions of hybrid warfare by saying he needs Russian nuclear-capable bombers to ‘help him navigate the migrant crisis’, even hinting Belarus could station both Russian nuclear weapons and S-400 anti-aircraft missile systems. This shows Lukashenka is feeling increasingly cornered – which could lead to more unpredictable security crises.

Russia and Belarus are deepening relations

Although there is no smoking gun pointing to direct Russian involvement in orchestrating the hybrid attack at the EU’s borders, a new step in the military rapprochement between the two countries came when Putin and Lukashenka approved a new Military Doctrine of the Union-State of Russia and Belarus – a non-public document including a joint concept of migration policy. Lukashenka has also come off the fence over Crimea by openly accepting the legality of the peninsula’s integration with Russia.

Given Russia is also sabre-rattling over Ukraine, the risk of an accidental escalation into armed conflict is increasing in what feels like a return to classic Cold War logic, with the difference that the East is now offensively using the South for confronting the West. In recognition of the threat, the UK has joined the US, Canada, and the EU in the fresh sanctions on Belarus.

How European security is changing Expert comment LJefferson 10 January 2022

Although migration, economic, health, tech and climate policy are increasingly thought of in terms of security, different issues are taking place in each of these policy areas.

Since the end of the Cold War, debates about security among both academics and policymakers have shifted away from traditional military or state security towards a broader conception of what security is – including, for example, ideas such as ‘human security’.

More recently, there has been a widespread perception of a ‘return of great power competition’ and even renewed fears about great power war – in other words, a resurgence of traditional security debates that many hoped and believed were a thing of the past. At the same time, and especially since the COVID-19 pandemic began in 2020, the concept of ‘security’ has also been increasingly applied to other areas like economic and health policies.

These complex and parallel developments raise a number of difficult questions. First, does the changing way in which the concept of ‘security’ is used – and in particular the way people now increasingly speak of ‘economic security’ and ‘health security’ – reflect a changing reality or rather simply a changing perception of reality? Second, are these changes in the way we think about security helpful or not? In other words, is the redefinition of security that seems to be taking place leading to good policy responses and making citizens more secure, or is it rather unhelpfully ‘securitizing’ policy areas and possibly undermining democracy in the process?

Part of the reason that these questions are difficult to answer is that there are different developments taking place in different policy areas. This article briefly analyses developments in five policy areas: migration policy, economic and trade policy, health policy, technology policy, and climate policy.

The authors argue there are at least three separate developments taking place, though it is often quite difficult to disentangle them – and more than one development may be taking place in each policy area. The analysis focuses on developments in Europe – defined broadly as including countries such as the UK which are outside the European Union (EU) – which may be different from those taking place elsewhere.

Five policy areas, three trends

In migration policy, the clearest development that is taking place, in particular since the so-called ‘refugee crisis’ of 2015, is the militarization of borders in Europe – in particular, the militarization of the EU’s external border.

The removal of borders within Europe was once seen by some as a step towards a borderless world, but since 2015 the EU seems to have concluded that the internal removal of borders requires a much harder external border than was previously the case.

In particular, since the ‘refugee crisis’, the EU has massively invested in Frontex, its border agency, which describes itself as ‘Europe’s first uniformed service’ that ‘helps guarantee free movement without internal borders checks that many of us take for granted’. In short, we are seeing an application to migration policy of military tools, including armed border guards.

Something different seems to be taking place in economic policy. For the last three or four decades since the end of the Cold War, economic policy has been dominated by (neo-)liberal assumptions. But these are now increasingly being challenged and a shift may be taking place away from this macroeconomic paradigm.

The reasons for this are complex – in part, a domestic backlash against this paradigm, particularly from the ‘losers’ or ‘left behind’ (in other words those who have suffered from the distributional consequences of the economic and especially trade policies of the last 30-40 years going back to the ‘neoliberal turn’), and in part a sense among analysts and policymakers that a different set of more protectionist policies are required in order to compete with China as a ‘systemic rival’.

These two different drivers of an economic paradigm shift have become even more tightly connected since the COVID-19 pandemic began in 2020. The pandemic led to both an increased demand for a new economic paradigm and a sense of intensified competition with China and, in the EU, to a lesser extent with the United States.

However, because the set of rules governing economic and in particular trade policy was set during the earlier period of (neo-)liberal hegemony, they restricted the ability of states to pursue what were seen as protectionist policies in order to redistribute and created exceptions only for security reasons. This has created a structural pressure on nation states to present economic policies in terms of security.

Here, however, the EU may be an outlier. During the last few decades, the EU has gone even further than the rest of the world has in creating rules around economic policy – at least internally. In particular, the EU’s fiscal rules may prevent its member states from borrowing to invest and its state aid rules may prevent them from experimenting with new kinds of industrial policy.

Therefore, the EU may be structurally constrained from making the kind of paradigm shift in economic policy that many now think is necessary. In particular, despite the rhetoric about a more ‘geopolitical’ EU, it may be limited in the extent to which it can think of economic policy in terms of security – sometimes to the regret of security establishments, as is the case for debates around 5G, for example.

In health policy, something similar may be happening as in economic policy. During the last three or four decades, health policy has been approached in a rather liberal way. Across Europe, though to different degrees and in different ways, market principles have been introduced into health systems.

In many cases such as the UK, this has involved privatizing what were previously state functions in healthcare. But since the pandemic, there has been a renewed focus on renationalizing or, in the case of the EU, ‘re-regionalizing’ supply chains, in particular for personal protective equipment (PPE) and vaccines, which is presented in terms of ‘health security’. COVID-19 has also reinforced the need to better include pandemic preparedness in national security planning.

A similar trend seems to be taking place in technology policy, which as with health policy is now increasingly viewed in a defensive, protectionist way rather than the liberal way it was previously seen. For example, the production of semiconductors was previously viewed in economic liberal terms – in other words, they should be produced wherever they can be produced most efficiently.

But analysts and policymakers increasingly see technology as central to the competition between China and the United States – or even more broadly between authoritarian states and democracies. As in health policy, there is an increasing focus on a shared approach among allies and on the ‘resilience’ of supply chains for technology. A similar shift is taking place on the management of data flows and the need to think harder – and maybe, be less naive – about the security impact of our online life.

Finally, in climate policy, something different seems to be taking place. Here, there is neither an attempt to apply military tools (notwithstanding the fact some national European militaries as well as NATO are increasingly interested in climate security, for instance regarding the ability to train and fight in altered weather conditions, notably extreme heat) nor a paradigm shift away from liberalism – although some, especially on the left, do question whether it is possible to prevent catastrophic climate change unless we abandon economic liberalism and much of the debate about green investment is closely connected to debates about an economic paradigm shift.

Rather, what is striking is the increasing talk of a ‘climate emergency’ – with its implication of the need to suspend normal democratic decision-making – and of the need to take extraordinary measures to prevent catastrophic climate change. However, for the time being, such rhetoric on climate change is not matched by relevant extraordinary emergency measures.

Across these five policy areas, in other words, there seem to be at least three developments taking place that are reshaping how we think about security in Europe. The difficult question is whether each of these developments is a ‘good’ thing or not, i.e. whether they actually make European citizens more secure in an appropriate way.

In other words, is it a good idea to militarize the EU’s borders, to shift away from the earlier liberal paradigm in economic, health and technology policy and frame the shift in terms of ‘security’, or to invoke an emergency in order to be able to take more drastic measures to prevent climate change?

The limits of securitization theory

One way of thinking about these issues is what academics call ‘securitization’ – the situation when something is identified in rhetoric as an existential threat to some object, specifying a point of no return, that legitimizes the use of extraordinary measures and pushes the issue higher on the political and policy agenda.

The response to COVID-19 can be seen as an example of securitization – the existential threat to human beings but also healthcare systems was used to legitimize lockdowns and social distancing requirements.

Ukraine response reveals Europe’s security is changing Expert comment NCapeling 8 February 2022

Recent events regarding Ukraine show an active UK responding quickly while EU powers deliberate. But pulling ahead of the pack is not the same as leadership.

Britain’s relationship with Ukraine appears to be thriving, with Ukrainian defence journalist Illia Ponomarenko recently tweeting the ‘British are just unstoppable these days’ and that the UK finds itself ‘on the right side of history’ while one Ukrainian wine bar has started offering free drinks to British nationals.

Ponomarenko’s remarks and the wine bar offer – certainly one post-Brexit benefit of having a British passport – are down to the UK decision to send anti-tank weapons to support Ukraine’s forces against a potential Russian attack.

The UK’s quick response was praised by Ponomarenko as being ‘wise enough not to be lured into going the easiest way, which is always the fastest lane straight to hell’ and strikes a clear contrast with that of Germany, whose typically moderated approach to geopolitical tensions went down badly in Kyiv.

The chief of Germany’s navy was forced to resign after saying Russian president Vladimir Putin ‘deserved respect’ and that Ukraine will never win back annexed Crimea. The German government also sought an energy exception to proposed US sanctions, so that gas can continue to flow into Europe.

France’s response was somewhat stronger but rather confusing as Emmanuel Macron initially called for European Union (EU) member states to ‘conduct their own dialogue’ with Russia, seemingly as an alternative to supporting the US-led NATO response.

Risks of a ‘bullying’ Russia

Although positioning himself as the convener of a transatlantic response to the Ukraine crisis brings welcome respite for UK prime minister Boris Johnson from his domestic ‘partygate’ fiasco, he is also reported as saying some world leaders ‘may not appreciate the deteriorating picture on the Ukrainian border, or fully comprehend the risks posed by a bullying Russia’.

One particular image sums up the difference in approach between the UK and the EU, as a flight path shows a British RAF plane flying around Germany before taking a detour over Denmark on route to Ukraine.

Given that Germany later blocked the export of NATO ally Estonia’s weapons to Ukraine, this image gives ‘Global Britain’ advocates a strong symbol of apparent British reliability and resourcefulness in the face of supposed European deliberation and disunity.

But although the UK’s response to the Ukraine crisis has rightly been credited as swift and substantial, it also reveals deeper developments in the current European security landscape as EU countries had worried Britain might choose to become absent post-Brexit.

Losing one of its two main military powers would certainly have been a blow to Europe, particularly as Russia’s threat has grown in recent years, so there will be relief that the Ukraine crisis shows Britain is undoubtedly committed to the region. Now the question for leaders in Paris, Berlin, and Brussels is how to deal with an active Britain committed to Europe but under no obligation to work within EU processes.

The UK already has an interesting network of bilateral and mini-lateral relationships with European allies. Its Joint Expeditionary Force brings together ten European countries – including Scandinavian and Baltic states – and is well-placed to support NATO activities while also remaining flexible and independent. In the past year, the UK worked with Norway in the Arctic region, provided military engineers support to Poland, and worked directly with France and Germany through the E3 grouping – once again bypassing EU institutions.

The UK also brings a unique diplomatic, technology, and intelligence-sharing relationship with the US which is unavoidably important in dealing with the threat from Russia. As the US sees European security through a NATO lens – rather than an EU one – this makes Britain a leading player as one of the few countries meeting its NATO spending commitments.

UK must do more to win trust

But despite such creative partnerships transcending the constraints of Brexit, the UK must do more to win the trust of the EU’s biggest players France and Germany to be a permanent power in the region. And relations with France have deteriorated following disputes over fishing, a lack of cooperation on migrants, and the AUKUS defence technology agreement between the UK, US, and Australia.

When it comes to Germany, the UK must not use the Ukraine crisis as an opportunity for geopolitical point-scoring. There are good historical reasons for Germany’s cautious approach to military engagement, even if these do constrain the country’s response to this challenge.

In dealing with Russia, some members of Germany’s ruling SPD sincerely believe their party’s less confrontational posture was central to de-escalating conflict during the Cold War. And although some historians may dispute that belief, it is still a distinct and more noble motivation for ‘dovishness’ than pure economic self-interest.

Cooperation always requires some compromise on all sides. Germany must accept some level of economic risk if sanctions against Russia are to be meaningful and France has to accept the necessity of the UK and US’s involvement and that the most effective dialogue is unlikely to be achieved through EU institutions.

Meanwhile, the UK must accept some role for the two biggest EU players, particularly as the Normandy Format which includes Russia, Ukraine, France, and Germany has proved productive in the past. And the UK needs to clamp down on its own economic ties with Russia.

Why the UK must deliver on Nordic-Baltic security Expert comment NCapeling 16 December 2022

Hard choices are needed but it is crucial the UK provides security and leadership to its European partners given the wider context of the war in Ukraine.

The UK’s role in Nordic-Baltic security has been growing over the past decade. The region is key to core British strategic interest and engagement, and UK threat assessment closely aligns with long-held regional perspectives – the 2021 Integrated Review defines Russia as ‘the most acute threat to our security’.

Since Russia’s invasion of Ukraine, the UK’s strong stance towards Moscow and the concrete steps taken to assist Ukraine and strengthen defence and deterrence on NATO’s eastern flank have been widely appreciated in the Nordic-Baltic region.

The UK is seen as a reliable partner but, for it to continue to deliver in the region, difficult choices must be made with regards to UK defence spending and military capabilities, and London’s more global ambitions.

The UK is a major contributor to NATO’s deterrence posture on the eastern flank, serving as a framework nation for NATO’s Enhanced Forward Presence (EFP) battlegroup in Estonia, and contributing to another battlegroup in Poland.

UK remains crucial to regional security

Coupled with its contribution to NATO’s Baltic Air Policing mission and maritime forces in the area, the UK is a crucial security partner both in the region and in a broader arch across Europe.

Over the past decade and a half, the UK has been developing a dense network of bilateral and minilateral relations in the region which are major assets in the current security environment.

It leads the Joint Expeditionary Force (JEF) which is a military cooperation format highly valued for its flexibility in responding to the needs of the participating nations – including non-NATO Sweden and Finland – and is increasingly focused on the North Atlantic, High North and wider Baltic areas. The UK has also seen increased bilateral defence cooperation with Norway, Denmark, Estonia, and other regional allies and partners.

There are reasonable expectations that Germany or France may at some point assume a greater role in this part of Europe, building on France’s participation in the EFP in Estonia, and Germany’s lead of the EFP in Lithuania.

However, while Paris remains more focused on NATO’s southern (and south-eastern) flank and building the European Union’s defence role, Berlin often underperforms as a leading or an organizing power of collaborative efforts across Europe.

Both also have a credibility problem in the Nordic-Baltic region due to their past policies towards Russia that occasionally reappear when discussing military support to Ukraine or how to treat Russia in the post-war European security order.

By contrast, the UK offers military capability, strong political will, a long-standing tradition of engagement in the Nordic-Baltic area, and fast decision-making.

The latter is exemplified by the bilateral security guarantees provided to Sweden and Finland during their accession to NATO, and the surge of assets sent to the region in the wake of Russia’s full-scale invasion of Ukraine such as an additional battlegroup and Chinook helicopters to Estonia, as well as forward-deployed elements of the Standing Joint Force Headquarters to Latvia and Lithuania as part of the JEF.

Such pragmatic and resolute engagement help substantiate the UK’s post-Brexit claim that although it left the EU, it did not leave Europe. London also understands and facilitates the pivotal role that the US plays in European security – a shared perspective with the Nordic-Baltic partners.

Only the US – which has just recently decided to step up its military presence in the Baltics – has a greater appeal than the UK as a major ally. But Washington’s truly global responsibilities make it more difficult for it to play a regional leadership role.

With the context of the war in Ukraine, the centre of gravity of European security is moving east. The Nordic-Baltic region is likely to feature more prominently in the upcoming refresh of the UK’s Integrated Review, as the war in Ukraine and NATO’s new forward defence approach will focus UK attention and military capabilities on Europe for the foreseeable future.

But the UK still has limited resources and, despite the worsening security environment, there is currently no commitment by the Rishi Sunak government to increase defence spending beyond two per cent of GDP, as set out in the recently-published Autumn Statement.

This difficult fiscal reality contrasts UK ambition to also increase its footprint and engagement in the Indo-Pacific, a region highlighted by Rishi Sunak in his first foreign policy speech. London is already confronted with increasing expectations from its Nordic and Baltic partners, which are rattled by Russia’s aggression and seek more engagement and commitments from larger and more resourceful allies, and are insisting on prompt implementation of NATO’s new defence and deterrence plans.

This all comes on top of the resources that further assistance to Ukraine will require in the coming months and years. Balancing competing priorities and demands from partners is routine for a major power with global ambition but, in the current context, if the UK government fails to prioritize and increase resources, over-extension is in sight for its armed forces.

The war in Ukraine confirms that, beyond the rhetoric around the ‘Indo-Pacific tilt’, the Euro-Atlantic is – and will remain – the priority theatre of engagement for the UK. To keep delivering in the Nordic-Baltic region and remain a reliable partner, UK ambitions should be set clearly, and expectations managed with regional partners.

A good example is the recent UK-Estonia joint statement and defence roadmap, which is an attempt to reconcile London’s vision of modern deterrence with Tallinn’s preference for ‘more boots on the ground’.

The joint statement also clarifies initial misunderstandings regarding the upcoming withdrawal of the second UK battlegroup deployed to Estonia in the wake of Russia’s invasion of Ukraine – support Tallinn expected to continue ‘as long as necessary’ but London saw as temporary. It offsets the poor political ‘optics’ of the withdrawal while providing solid ground for deepening the common agenda in the near future.

By the 2023 NATO summit in Vilnius, progress on implementing the roadmap will be a crucial measure of success for the bilateral relationship, and for the UK’s broader regional role. It should serve as an opportunity for the UK to reflect on its force development priorities and balance, with Baltic partners arguing in favour of the UK rebuilding some mass in its armed forces and providing more resources to the land component.

Much to gain for the UK

The UK gains many benefits from deepening and widening its engagement in the Nordic-Baltic region, and not only by showcasing its regional leadership at a time of dire need or having more weight in Europe and across the Atlantic in strategic debates about future security architecture.

Africa and Europe: Climate security for the future 20 April 2023 TO 21 April 2023 — 7:30AM TO 12:00PM Anonymous (not verified) 31 March 2023 Slovenia and Online

The 12th Africa Day International Conference hosted in Slovenia offers a platform for interregional exchange and policy cooperation between African and European countries on climate security.

The 12th Africa Day International Conference offers a platform for inter-regional exchange and cooperation to further contribute to progress on climate security.

The 12th Africa Day International Conference is hosted by the Ministry of Foreign and European Affairs of the Republic of Slovenia, in collaboration with the European Commission and the Chatham House Africa Programme. This high-level annual event seeks to improve policy outcomes for citizens in Europe and Africa on the basis of mutual understanding and cooperation between the two regions, while strengthening bilateral relations between Slovenia and African countries.

Climate change poses one of the most serious threats to global security. No individual country or region can face it alone; strong regional and international partnerships are crucial. Analysing risk and taking action can help towards achieving a number of SDGs and a more secure and sustainable future. Addressing climate security is essential for the well-being and future stability of nations and societies around the world, and for the global community as a whole.

This conference will offer a platform for interregional exchange and cooperation on the topic of climate security policy. It will bring together decision-makers and experts from Europe, Africa and across the globe to identify the key challenges and policy priorities in addressing climate security.

The conference will be broadcast live on the Slovenian Ministry of Foreign Affairs webpage, and on the Africa Programme Facebook page.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

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