The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.

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.

Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of > 90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, while diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear co-localization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of "royal jelly bees" (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior.

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon- induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon- protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

The EGFR tyrosine kinase inhibitor gefitinib is commonly used for lung cancer patients. However, some patients eventually become resistant to gefitinib and develop progressive disease. Here, we indicate that ecto-ATP synthase, which ectopically translocated from mitochondrial inner membrane to plasma membrane, is considered as a potential therapeutic target for drug-resistant cells. Quantitative multi-omics profiling reveals that ecto-ATP synthase inhibitor mediates CK2-dependent phosphorylation of DNA topoisomerase IIα (topo IIα) at serine 1106 and subsequently increases the expression of long noncoding RNA, GAS5. Additionally, we also determine that downstream of GAS5, p53 pathway, is activated by ecto-ATP synthase inhibitor for regulation of programed cell death. Interestingly, GAS5-proteins interactomic profiling elucidates that GAS5 associates with topo IIα and subsequently enhancing the phosphorylation level of topo IIα. Taken together, our findings suggest that ecto-ATP synthase blockade is an effective therapeutic strategy via regulation of CK2/phospho-topo IIα/GAS5 network in gefitinib-resistant lung cancer cells.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

The absence of the dystrophin protein in Duchenne muscular dystrophy (DMD) results in myofiber fragility and a plethora of downstream secondary pathologies. Although a variety of experimental therapies are in development, achieving effective treatments for DMD remains exceptionally challenging, not least because the pathological consequences of dystrophin loss are incompletely understood. Here we have performed proteome profiling in tibialis anterior muscles from two murine DMD models (mdx and mdx52) at three ages (8, 16, and 80 weeks of age), all n = 3. High-resolution isoelectric focusing liquid chromatography-tandem MS (HiRIEF-LC–MS/MS) was used to quantify the expression of 4974 proteins across all 27 samples. The two dystrophic models were found to be highly similar, whereas multiple proteins were differentially expressed relative to WT (C57BL/6) controls at each age. Furthermore, 1795 proteins were differentially expressed when samples were pooled across ages and dystrophic strains. These included numerous proteins associated with the extracellular matrix and muscle function that have not been reported previously. Pathway analysis revealed multiple perturbed pathways and predicted upstream regulators, which together are indicative of cross-talk between inflammatory, metabolic, and muscle growth pathways (e.g. TNF, INF, NF-B, SIRT1, AMPK, PGC-1α, PPARs, ILK, and AKT/PI3K). Upregulation of CAV3, MVP and PAK1 protein expression was validated in dystrophic muscle by Western blot. Furthermore, MVP was upregulated during, but not required for, the differentiation of C2C12 myoblasts suggesting that this protein may affect muscle regeneration. This study provides novel insights into mutation-independent proteomic signatures characteristic of the dystrophic phenotype and its progression with aging.

Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

O-GlcNAcylation, the addition of a single N-acetylglucosamine residue to serine and threonine residues of cytoplasmic, nuclear, or mitochondrial proteins, is a widespread regulatory post-translational modification. It is involved in response to nutritional status and stress and its dysregulation is associated with diseases ranging from Alzheimer’s to diabetes.  While the modification was first detected over thirty-five years ago, research into the function of O-GlcNAcylation has accelerated dramatically in the last ten years due to the development of new enrichment and mass spectrometry techniques that facilitate its analysis.  This article summarizes methods for O-GlcNAc enrichment, key mass spectrometry instrumentation advancements, particularly those that allow modification site localization, and software tools that allow analysis of data from O-GlcNAc modified peptides.

The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.

The Rhizobium-legume symbiosis is a beneficial interaction in which the bacterium converts atmospheric nitrogen into ammonia and delivers it to the plant in exchange for carbon compounds. This symbiosis implies the adaptation of bacteria to live inside host plant cells. In this work we apply RP-LC-MS/MS and  iTRAQ techniques to study the proteomic profile of endosymbiotic cells (bacteroids) induced by Rhizobium leguminosarum bv viciae strain UPM791 in legume nodules. Nitrogenase subunits, tricarboxylic acid cycle enzymes, and stress response proteins are amongst the most abundant from over one thousand rhizobial proteins identified in pea (Pisum sativum) bacteroids. Comparative analysis of bacteroids induced in pea and in lentil (Lens culinaris)nodules revealed the existence of a significant host-specific differential response affecting dozens of bacterial proteins, including stress-related proteins, transcriptional regulators, and proteins involved in the carbon and nitrogen metabolisms. A mutant affected in one of these proteins, homologous to a GntR-like transcriptional regulator, showed a symbiotic performance significantly  impaired in symbiosis with pea, but not with lentil plants. Analysis of the proteomes of bacteroids isolated from both hosts also revealed the presence of different sets of plant-derived nodule-specific cysteine rich (NCR) peptides, indicating that the endosymbiotic bacteria find a host-specific cocktail of chemical stressors inside the nodule. By studying variations of the bacterial response to different plant cell environments we will be able to identify specific limitations imposed by the host that might give us clues for the improvement of rhizobial performance.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.

We have previously shown that multimers of plasma pentraxin-3 (PTX3) were predictive of survival in patients with sepsis. To characterize the release kinetics and cellular source of plasma protein changes in sepsis, serial samples were obtained from healthy volunteers (n=10, 3 time-points) injected with low-dose endotoxin (LPS) and analyzed using data-independent acquisition (DIA) MS. The human plasma proteome response was compared to an LPS-induced endotoxemia model in mice. Proteomic analysis of human plasma revealed a rapid neutrophil degranulation signature, followed by a rise in acute phase proteins. Changes in circulating PTX3 correlated with increases in neutrophil-derived proteins following LPS injection. Time course analysis of the plasma proteome in mice showed a time-dependent increase in multimeric PTX3, alongside increases in neutrophil-derived myeloperoxidase (MPO) upon LPS treatment. The mechanisms of oxidation-induced multimerisation of PTX3 were explored in two genetic mouse models: MPO global knock-out mice and LysM CreNox2KO mice, in which NADPH oxidase 2 (Nox2) is only deficient in myeloid cells. Nox2 is the enzyme responsible for the oxidative burst in neutrophils. Increases in plasma multimeric PTX3 were not significantly different between wildtype and MPO or LysM CreNox2KO knock-out mice. Thus, PTX3 may already be stored and released in a multimeric form. Through in vivo neutrophil depletion and multiplexed vascular proteomics, PTX3 multimer deposition within the aorta was confirmed to be neutrophil-dependent. Proteomic analysis of aortas from LPS-injected mice returned PTX3 as the most upregulated protein, where multimeric PTX3 was deposited as early as 2 h post-LPS along with other neutrophil-derived proteins. In conclusion, the rise in multimeric PTX3 upon LPS injection correlates with neutrophil-related protein changes in plasma and in aortas. MPO and myeloid Nox2 are not required for the multimerisation of PTX3; instead, neutrophil extravasation is responsible for the LPS-induced deposition of multimeric PTX3 in the aorta.

Maikel Franco followed the endless and often mind-numbing speculation the past few months from the Dominican Republic. Franco knows that Manny Machado could show up at Spectrum Field at any moment. The Phillies entertained him at Citizens Bank Park just before Christmas. They have made him at least one contract offer. If the Phillies sign him, Franco also knows he could be traded.

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.

What is Labour’s foreign policy? 24 January 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 3 January 2023 Chatham House and Online

In conversation with David Lammy, the UK shadow foreign secretary.

David Lammy MP, shadow secretary of state for foreign, commonwealth and development affairs, outlines Labour’s plan for UK foreign policy if elected to government.

He addresses the UK’s strengths and opportunities in a world that has become more divided, more dangerous, and more unpredictable. He also offers a critique of the current UK government’s approach to foreign policy, particularly at strained relationships with allies and Britain’s economic woes.

The shadow foreign secretary explores the following key questions:

• What would a future Labour government do to modernize Britain’s diplomacy and rebuild alliances to improve Britain’s global influence?

• In a new age of warfare in Europe, how would Labour pursue security cooperation with allies?

• How would Labour address high energy costs, energy security, and the climate crisis?

• As Britain’s economy falters, how can foreign policy drive prosperity at home?

• What is Labour’s plan for international development, following the UK government’s abandonment of the 0.7% commitment?

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

Read a transcript

The state of the union? US foreign policy and a new US Congress 30 January 2023 — 5:30PM TO 6:30PM Anonymous (not verified) 11 January 2023 Chatham House and Online

As a new Congress takes shape, what is the impact for US foreign policy?  

The recent US 2022 midterm elections have led to a split with Republicans in command of the US House of Representatives and Democrats retaining a slim majority in the Senate.

Following a gruelling selection process for the new Speaker of the House, the new Congress took its seats in January 2023, but President Joe Biden no longer enjoys single-party control of Congress.

• What will be the implications of this for US leadership and US foreign policy?
• How will domestic politics constrain foreign policy objectives?
• Can policymakers across government set aside political differences to tackle global challenges?

This panel also unpacks insights into the following questions:

• What will this Congress view as foreign policy priorities?
• Will policies that are tough on China ramp up?
• Can the US continue its support for Ukraine with a split Congress?
• Will the next two years lead to any considerable foreign policy pivots with a general election on the horizon?

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

Read the transcript.

Disruptive technologies by nation states and malign cyber actors – the US response 16 February 2023 — 1:00PM TO 2:00PM Anonymous (not verified) 2 February 2023 Chatham House and Online

Lisa Monaco, the US deputy attorney general, discusses how autocratic governments and malign cyber actors use disruptive technologies to project power and engage in illicit activity.

Weaponizing data, ransomware attacks and other illicit cyber activity represent significant threats to national security. 

Governments and malicious cyber actors around the world exploit disruptive technology to engage in criminal activity, track citizens and coerce other countries thereby weakening the rules-based order and fundamental principles of democracy. 

Lisa Monaco discusses how the world is at an inflection point when it comes to meeting this challenge and describes how the US and partner nations are responding to protect their citizens and the broader international community.

Key questions to discuss include:

• What steps does the US government need to take to properly address this threat?
• How are countries coordinating policies to confront the problem?
• To what extent does this challenge go beyond US-China competition?

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

Read the transcript.

Director’s breakfast briefing: Shifts in European foreign policy since 9/11 14 October 2021 — 8:00AM TO 9:15AM Anonymous (not verified) 4 October 2021 Chatham House

Former MI6 chief, Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

Former MI6 chief Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

The dramatic events surrounding the withdrawal from Afghanistan demonstrates a profound shift in European security priorities since the beginning of the ‘war on terror’. Against the backdrop of the 20th anniversary of 9/11, former MI6 chief, Sir Alex Younger, discusses recent shifts in European foreign policy.

How has the focus on counterterrorism changed over the last two decades particularly in light of new and evolving strategic challenges? Why were many long-term objectives in Afghanistan left unachieved? Has the threat of terrorism changed across Europe? How has cooperation between security and intelligence services across the world changed particularly across the Atlantic? And, 20 years on, is the ‘war on terror’ really over?

This event is only open to Chatham House Partners and Major Corporate Members as well as selected giving circles of Chatham House. If you would like to attend, please RSVP to Linda Bedford at RSVP@chathamhouse.org.

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.

Turkey's Foreign Policy in the Middle East 14 May 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 29 April 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey is cooperating closely with Russia to secure its border with Syria and to encourage a long-term political resolution to the Syrian conflict. Its efforts have staved off a humanitarian catastrophe in the northern Syrian province of Idlib and initiated the trilateral ‘Astana Process’ with Russia and Iran as the primary framework to settle the future of Syria.

By contrast, Turkey and the US disagree on a range of important issues including Turkey’s purchase of the Russian-made S-400 air missile defence systems and American support for the PKK-affiliated Peoples’ Protection Units (YPG) in Syria.

In this session, the speaker will outline Turkey’s foreign policy priorities in the Middle East and share his country’s perspectives on the US and Russian policies in that region.

Attendance at this event is by invitation only.

Turkey's Foreign Policy: The Perspective of the Main Opposition Party 5 November 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 14 October 2020 Online

The Republican People’s Party (CHP), the main Turkish opposition party, is becoming a serious contender for a leading role in the country’s politics.

This is an online only event.

CHP’s mayoral candidates defeated the Justice and Development Party (AKP) incumbents in the 2019 local elections in Ankara and Istanbul, which held both cities for a quarter of a century. Its ascendency in Turkish politics is improving prospects for a CHP-led government after the next general election in 2023.

In this webinar, the speaker will share CHP’s stance on the country’s foreign policy towards key regional allies in Europe, as well as its take on relations with Russia, the US and Turkey’s position and role in the Middle East. Finally, the speaker will share how CHP’s external policy might differ from the ruling AKP. 

Turkey's foreign policy: The perspective of the İYİ Parti 25 January 2021 — 12:00PM TO 1:00PM Anonymous (not verified) 14 January 2021 Online

The centre-right İYİ Parti, the second largest opposition party in Turkey, is attracting voters from the governing alliance between the Justice and Development Party (AKP) and the pro-Turkish National Movement Party (MHP).

Please complete your registration on Zoom:

The İYİ Parti, which was set up in 2017, formed the Nation Alliance (Millet İttifakı) with the left-of-centre Republican People’s Party (CHP) and the pro-Islam Felicity Party (Saadet Partisi) in the 2018 parliamentary elections winning 43 seats in the Grand National Assembly.

In the 2019 municipal elections, the İYİ Parti’s alliance alliance with the CHP played an important role in enabling the latter’s candidates to become the mayors of Istanbul and Ankara after a quarter-century dominance by the ruling Justice and Development Party (AKP).

Its popularity has been rising steadily, according to recent polls. In this webinar, the speaker will outline the party’s viewpoint on the country’s foreign policy towards the European Union, as well as its perspectives on relations with Russia, the US, Iran and the Arab world. Finally, he will share the ways in which the İYİ Parti’s approach to external policy might differ from the ruling AKP.

Turkey’s foreign and domestic policy: A story of mutual creation? 1 November 2022 — 2:00PM TO 3:00PM Anonymous (not verified) 12 October 2022 Online

Panellists discuss the link between Turkey’s domestic and foreign policies under President Erdoğan.

From Turkey’s ongoing rapprochement with its erstwhile Middle Eastern antagonists to its Syria policy and earlier approach towards the West, there has been extensive discussion on the domestic drivers behind Ankara’s foreign policy.

Less discussed but no less important is how Turkish foreign affairs have shaped its internal politics. Under the rule of the Justice and Development Party (AKP) government and President Recep Tayyip Erdoğan, Turkey’s foreign and domestic policies have mutually reshaped each other.

In this webinar, launching Gönül Tol’s new book Erdoğan’s War: A Strongman’s Struggle at Home and in Syria, panellists will take stock of how Turkey’s domestic and foreign policies under the leadership of President Erdoğan have influenced and shaped each other. Speakers will also discuss the internal drivers behind Turkey’s current reset in relations with the Middle East, and examine how Ankara’s foreign affairs play into the country’s political and identity fault lines.

The event will be held on the record and will be live-streamed on the MENA Programme’s Facebook page.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

The Carolina Panthers signed running back Chuba Hubbard to a four-year contract extension worth $33.2 million, a league source told UPI on Thursday.

U.S. Defense Secretary Lloyd Austin signed a new security agreement with Georgia Monday, seeking to buttress relations with the Black Sea nation as it continues to face Russian troops in two of its regions.

Nov. 6, 2024 — Harnessing the power artificial intelligence (AI) and the world’s fastest supercomputers, a research team led by the U.S. Department of Energy’s (DOE) Argonne National Laboratory has developed […]

The post Argonne Team Breaks New Ground in AI-driven Protein Design appeared first on HPCwire.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

PITTSBURGH, June 19, 2024 — Ansys today announced that it is adopting NVIDIA Omniverse application programming interfaces (APIs) to offer 3D-IC designers valuable insights from Ansys’ physics solver results through […]

The post Ansys Enables 3D Multiphysics Visualization of Next-Gen 3D-IC Designs with NVIDIA Omniverse appeared first on HPCwire.

The Mediterranean island nation of Cyprus signed the U.S.-led Artemis Accords on Wednesday, becoming the 46th signatory to the agreement that establishes principles for the safe exploration of space.

It could be possible to increase your IQ.

Levels are typically lower in the body through the winter months in northern latitudes.

The most common ADHD symptoms in adults are often different to those in children.

High IQ brains have greater functional connectivity and higher synchronisation, but this has an unexpected real-world effect.

The study found that 68% were vitamin D deficient.

Children brought up like this tend to be happier as adults.

This sign is not normally linked to being smart.

What if solving poverty, caring for nature and fostering well-being were the ultimate goals of the economy, instead of growth for its own sake? Environmentalist and economist Gaya Herrington proposes a shift in thinking from "never enough" to "enough for each," asking us to contemplate whether the end of exponential growth on a finite planet will come by design — or disaster.

The student newspaper at duPont Manual High School in Louisville, Ky., first reported on the state's problematic police training material.

State Superintendent Steve Canavero resigned just two weeks before the state's legislative session was to begin, with more than 80 education-related proposals, including a new funding formula, is on the agenda.

With David Hespe's resignation, announced Friday, New Jersey has had five education commissioners in the last seven years.