Independent Thinking: Consequences of the Iraq war Audio NCapeling 23 March 2023

Episode 20 of our weekly podcast marks 20 years since the invasion of Iraq, with special guest Clare Short who resigned from the UK government over the issue.

Launched amid fears that Saddam Hussein was acquiring weapons of mass destruction, the Iraq war changed the Middle East and inflicted huge damage with effects that persist today.

This week’s panel examines the war from the perspective of those in power in London when the decision was made to commit UK forces to the invasion, and with those in Iraq who lived with the consequences.   

Joining Bronwen Maddox is special guest Clare Short, former Secretary of State for International Development, who served in the UK cabinet and resigned after the invasion began, becoming one of the best-known critics of prime minister Tony Blair’s approach to the war.

On the panel from Chatham House is Dr Patricia Lewis, director of the International Security programme, and three members of the Middle East and North Africa programme; the director Dr Lina Khatib, senior research fellow Dr Renad Mansour who is also project director of the Iraq Initiative, and research associate Hayder Al-Shakeri.

About Independent Thinking

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

Independent Thinking: How can France survive its budget crisis? Audio john.pollock 17 October 2024

Sophie Pedder and Shahin Vallée join the podcast to discuss France’s contentious budget and political drama, and the potential impact on Europe and beyond.

On this episode

France is facing political turmoil. The survival of Michel Barnier’s new government rests on whether he can pass a controversial budget intended to rescue the country from its huge fiscal deficit. Bronwen Maddox is joined by Sophie Pedder, the Paris bureau chief of The Economist, Shahin Vallée, a former adviser to Emmanuel Macron and Armida van Rij, the head of our Europe Programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

Independent Thinking: Will debt constrain Western foreign policy? Audio john.pollock 24 October 2024

Patrick Wintour and Ranil Dissanayake join the podcast ahead of the UK Budget to discuss the high debt facing G7 economies and its impact on foreign, defence and development policies.

On this episode

Ahead of a crucial Budget by Chancellor Rachel Reeves, UK national debt is at almost 100 per cent of GDP – and it’s not alone. Many G7 economies face massive debt levels, restricting ambitions when it comes to foreign policy and global engagement. 

Bronwen Maddox is joined by Patrick Wintour, the Guardian’s diplomatic editor and Ranil Dissanayake, a senior research fellow at the Centre for Global Development. With them are Olivia O’Sullivan and David Lubin from Chatham House.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

Independent Thinking: Why is North Korea sending troops to Russia? Audio john.pollock 31 October 2024

Orysia Lutsevych, Edward Howell and Yossi Mekelberg discuss North Korean troops fighting with Russian forces against Ukraine, as well as the issue of military conscription.

On this episode

North Korea is sending troops to Russia, but what is Kim Jong-Un hoping to get from Vladmir Putin for this military assistance against Ukraine? The panel also discuss the role military conscription plays in Israel, South Korea and Ukraine’s defence.

Bronwen Maddox is joined by Edward Howell, the Korea Foundation fellow at Chatham House, Orysia Lutsevych, the head of our Ukraine Forum and Yossi Mekelberg, a senior consulting fellow with our Middle East and North Africa Programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

Independent Thinking: What does Donald Trump’s re-election mean for the world? Audio john.pollock 8 November 2024

Edward Luce, Leslie Vinjamuri and Gerald Seib join the podcast this week to discuss Donald Trump’s victory over Kamala Harris in the US presidential election.

On this episode

Donald Trump has decisively defeated Kamala Harris in the US presidential election. What does his return to the White House mean for America and the world? 

Bronwen Maddox is joined by Edward Luce, the FT’s North America editor, Gerald Seib, the former Washington bureau chief of The Wall Street Journal and Leslie Vinjamuri, the head of our US and Americas programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

Independent Thinking: War in Tigray, Zaporizhzhia under fire Audio NCapeling 24 November 2022

Episode six of our new weekly podcast examines the ongoing conflict in Ethiopia and the international response to further attacks on Europe’s largest nuclear plant in Ukraine.

In Tigray, the world’s largest armed conflict rages between Ethiopian federal government troops and the Tigray Defence Forces. With estimates placing those killed in the fighting at 600,000, how did Ethiopia, one of Africa’s great success stories, descend into civil war, and what hopes are there for recent peace initiatives?

Meanwhile in Ukraine, all eyes are on Zaporizhzhia, as Europe’s largest nuclear plant continues to be occupied by Russian forces. With fresh reports of explosions near the reactors, how is the international community responding?

Finally, what role does Turkey, a middle power country with great power ambitions, play in both conflicts?

Joining guest host John Kampfner on the podcast this week are Dr Patricia Lewis, director of the International Security programme at Chatham House, Ahmed Soliman, senior research fellow with our Africa programme, and Galip Dalay, associate fellow with our Middle East and North Africa programme.

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

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

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

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

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

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

About Independent Thinking

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

Zilu Ye
Dec 28, 2020; 0:R120.002204v1-mcp.R120.002204
Review

Tirsa L. E. van Westering
Dec 1, 2020; 19:2047-2067
Research

Neutrophils are primary host innate immune cells defending against pathogens. One proposed mechanism by which neutrophils prevent the spread of pathogens is NETosis, the extrusion of cellular DNA resulting in neutrophil extracellular traps (NETs). The protease neutrophil elastase (NE) has been implicated in the formation of NETs through proteolysis of nuclear proteins leading to chromatin decondensation. In addition to NE, neutrophils contain three other serine proteases that could compensate if the activity of NE was neutralized. However, whether they do play such a role is unknown. Thus, we deployed recently described specific inhibitors against all four of the neutrophil serine proteases (NSPs). Using specific antibodies to the NSPs along with our labeled inhibitors, we show that catalytic activity of these enzymes is not required for the formation of NETs. Moreover, the NSPs that decorate NETs are in an inactive conformation and thus cannot participate in further catalytic events. These results indicate that NSPs play no role in either NETosis or arming NETs with proteolytic activity.

The acyltransferase LCAT mediates FA esterification of plasma cholesterol. In vitro studies have shown that LCAT also FA-esterifies several oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of sterols in 206 healthy volunteers and 8 individuals with genetic LCAT deficiency, including familial LCAT deficiency (FLD) and fish-eye disease (FED). In the healthy volunteers, the mean values of the ester-to-total molar ratios of the following sterols varied: 4β-hydroxycholesterol (4βHC), 0.38; 5,6α-epoxycholesterol (5,6αEC), 0.46; 5,6β-epoxycholesterol (5,6βEC), 0.51; cholesterol, 0.70; cholestane-3β,5α,6β-triol (CT), 0.70; 7-ketocholesterol (7KC), 0.75; 24S-hydroxycholesterol (24SHC), 0.80; 25-hydroxycholesterol (25HC), 0.81; 27-hydroxycholesterol (27HC), 0.86; and 7α-hydroxycholesterol (7αHC), 0.89. In the individuals with LCAT deficiency, the plasma levels of the FA-esterified forms of cholesterol, 5,6αEC, 5,6βEC, CT, 7αHC, 7KC, 24SHC, 25HC, and 27HC, were significantly lower than those in the healthy volunteers. The individuals with FLD had significantly lower FA-esterified forms of 7αHC, 24SHC, and 27HC than those with FED. It is of note that, even in the three FLD individuals with negligible plasma cholesteryl ester, substantial amounts of the FA-esterified forms of 4βHC, 5,6αEC, 7αHC, 7KC, and 27HC were present. We conclude that LCAT has a major role in the FA esterification of many plasma oxysterols but contributes little to the FA esterification of 4βHC. Substantial FA esterification of 4βHC, 5,6αEC, 7αHC, 7KC, and 27HC is independent of LCAT.

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.

This article has been withdrawn by the authors. This article did not comply with the editorial guidelines of MCP. Specifically, single peptide based protein identifications of 9-19% were included in the analysis and discussed in the results and conclusions. We wish to withdraw this article and resubmit a clarified, corrected manuscript for review.

Sparkling wine is an alcoholic beverage enjoyed around the world. The sensory properties of sparkling wine depend on a complex interplay between the chemical and biochemical components in the final product. Glycoproteins have been linked to positive and negative qualities in sparkling wine, but the glycosylation profiles of sparkling wine have not been previously investigated in detail. We analysed the glyco/proteome of sparkling wines using protein- and glycopeptide-centric approaches. We developed an automated workflow that created ion libraries to analyse Sequential Window Acquisition of all THeoretical mass spectra (SWATH) Data Independent Acquisition (DIA) mass spectrometry data based on glycopeptides identified by Byonic. We applied our workflow to three pairs of experimental sparkling wines to assess the effects of aging on lees and of different yeast strains used in the Liqueur de Tirage for secondary fermentation. We found that aging a cuvée on lees for 24 months compared to 8 months led to a dramatic decrease in overall protein abundance and an enrichment in large glycans at specific sites in some proteins. Secondary fermentation of a Riesling wine with Saccharomyces cerevisiae yeast strain Siha4 produced more yeast proteins and glycoproteins than with S. cerevisiae yeast strain DV10. The abundance and glycosylation profiles of grape glycoproteins were also different between grape varieties. This work represents the first in-depth study into protein- and peptide-specific glycosylation in sparkling wines and describes a quantitative glycoproteomic SWATH/DIA workflow that is broadly applicable to other sample types.

Data independent acquisition (DIA) is now an emerging method in bottom-up proteomics and capable of achieving deep proteome coverage and accurate label-free quantification. However, for post-translational modifications (PTM), such as glycosylation, DIA methodology is still in the early stage of development. The full characterization of glycoproteins requires site specific glycan identification as well as subsequent quantification of glycan structures at each site. The tremendous complexity of glycosylation represents a significant analytical challenge in glycoproteomics. This review focuses on the development and perspectives of DIA methodology for N- and O- glycoproteomics and posits that DIA-based glycoproteomics could be a method of choice to address some of the challenging aspects of glycoproteomics. First, the current challenges in glycoproteomics and the basic principles of DIA is briefly introduced. DIA based glycoproteomics is then summarized and described into four aspects based on the actual samples. Lastly, we discussed the important challenges and future perspectives in the field. We believe that DIA can significantly facilitate glycoproteomic studies and contribute to the development of future advanced tools and approaches in the field of glycoproteomics.

Independent Thinking: Sweden, Finland, and NATO Audio NCapeling 31 March 2023

Episode 21 of our weekly podcast examines the latest developments relating to Sweden and Finland’s proposed accession to NATO.

The Hungarian parliament has finally ratified Finland’s membership to the NATO alliance, two weeks after President Erdogan in Turkey gave his seal of approval following a meeting with the Finnish president.

Sweden however remains trapped in limbo, with both Turkey and Hungary delaying Stockholm’s membership and Erdogan in particular asking for more concessions.

The panel discusses why Turkey and Hungary took issue with Sweden and Finland, what the strategic situation in the Baltic looks like now with only Finland joining NATO, and the challenges facing Sweden amid its fraught ties with President Erdogan.

We also look ahead to Turkey’s presidential election in May as recent opinion polls point to a neck-and-neck race, with some polls even showing President Erdogan falling behind the opposition. The panel examines what the sentiment is like in Turkey ahead of the election, and how the world would respond if there was a change in power in Ankara for the first time in 20 years.

Joining Bronwen Maddox on the podcast this week is Henri Vanhanen, research fellow with the Finnish Institute of International Affairs, and Galip Dalay, associate fellow with our Middle East and North Africa programme.

About Independent Thinking

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

Donna M. Wilcock
May 1, 2003; 23:3745-3751
Development Plasticity Repair

It is well established that holding information in working memory (WM) elicits sustained stimulus-specific patterns of neural activity. Nevertheless, here we provide evidence for a distinct class of neural activity that tracks the number of individuated items in working memory, independent of the type of visual features stored. We present two EEG studies of young adults of both sexes that provide robust evidence for a signal tracking the number of individuated representations in working memory, regardless of the specific feature values stored. In Study 1, subjects maintained either colors or orientations across separate blocks in a single session. We found near-perfect generalization of the load signal between these two conditions, despite being able to simultaneously decode which feature had been voluntarily stored. In Study 2, participants attended to two features with very distinct cortical representations: color and motion coherence. We again found evidence for a neural load signal that robustly generalized across these distinct visual features, even though cortically disparate regions process color and motion coherence. Moreover, representational similarity analysis provided converging evidence for a content-independent load signal, while simultaneously showing that unique variance in EEG activity tracked the specific features that were stored. We posit that this load signal reflects a content-independent "pointer" operation that binds objects to the current context while parallel but distinct neural signals represent the features that are stored for each item in memory.

Independent Elizabeth Smith-McCrossin is back on the campaign trail in Cumberland North, but opponents say the riding would be better represented by an MLA from an official party. 

Females perform better than males • Malta’s computer literacy score is within international average for computer literacy and substantially below average in computational thinking

Remarks by Masatsugu Asakawa, President, Asian Development Bank, at the 21st Annual Meeting of the Independent Accountability Mechanisms of Multilateral Banks and International Financial Institutions, 1 October 2024, ADB headquarters, Manila, Philippines

Wooden tablets containing a language of glyphs called Rongorongo may be evidence that the people of Rapa Nui, also known as Easter Island, created their own writing system without the influence of European language

Title: Stay Independent of Asthma, Allergies This July 4th
Category: Health News
Created: 7/1/2022 12:00:00 AM
Last Editorial Review: 7/1/2022 12:00:00 AM

The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα_i/o or Gα_q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα_i/o and Gα_q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

Should the BBC pass the torch to a seasoned veteran or opt for a fresh voice when Lineker steps down?

Dr Aluvihare

The newly launched asthma drug by the London-based drug maker, GlaxoSmithKline (GSK) is not cost-effective, reports an independent nonprofit organization.

Yahoo, otherwise known as the company that pays my salary (full disclosure: Yahoo owns TC), today announced that it’s spinning off Vespa, the big data serving engine, into an independent venture. Jon Bratseth, previously a VP architect in the big data and AI group at Yahoo and one of the main contributors to Vespa, has […]

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Former BJP MP Gopal Shetty withdraws nomination from Borivali, Mumbai, after being denied ticket for upcoming elections

Traders submit a memorandum to the Lieutenant Governor, Chief Minister and Director General of Police seeking stern action against Ramu, a resident of Thilaspet

International Monetary Fund

National Library of Australia

Chennai-based Annie Titus Mammen, who does embroidery for Chanel, Balenciaga and Louis Vuitton, has launched Tambour’s first Independent product line of embellished pashmina stoles in Delhi

How does an independent CRM play with an existing marketing stack? What's the role of an independent CRM? Daina Middleton of Ansira has answers

Jan 19 - In an interview with Reuters Global Editor-at-Large Chrystia Freeland, GE CEO Jeffrey Immelt touts the conglomerate's success with joint ventures in China, but says GE has succeeded on its own.

Get your style locked down, and support independent British brands

Sweden should establish an independent committee of experts to oversee its National Pension Funds and set a clear, measurable financial objective for investments to ensure their long-term viability, according to a new OECD report.

OECD analyses have begun to understand the relationship between digitalisation, jobs and skills, the magnitude of potential job substitution due to technological change, the relationship between globalisation and wage polarisation, as well as the changes to the organisation of work.

Georgia has achieved significant progress in reducing corruption over the past decade. To build on this progress, the Government should focus on strengthening its professional civil service and ensure independence of the judiciary, according to a new OECD report.

Earth's north magnetic pole is heading for Russia  The Independent Barents Observer

Current software tools for the automated building of models for macro­molecular X-ray crystal structures are capable of assembling high-quality models for ordered macromolecule and small-molecule scattering components with minimal or no user supervision. Many of these tools also incorporate robust functionality for modelling the ordered water molecules that are found in nearly all macromolecular crystal structures. However, no current tools focus on differentiating these ubiquitous water molecules from other frequently occurring multi-atom solvent species, such as sulfate, or the automated building of models for such species. PeakProbe has been developed specifically to address the need for such a tool. PeakProbe predicts likely solvent models for a given point (termed a `peak') in a structure based on analysis (`probing') of its local electron density and chemical environment. PeakProbe maps a total of 19 resolution-dependent features associated with electron density and two associated with the local chemical environment to a two-dimensional score space that is independent of resolution. Peaks are classified based on the relative frequencies with which four different classes of solvent (including water) are observed within a given region of this score space as determined by large-scale sampling of solvent models in the Protein Data Bank. Designed to classify peaks generated from difference density maxima, PeakProbe also incorporates functionality for identifying peaks associated with model errors or clusters of peaks likely to correspond to multi-atom solvent, and for the validation of existing solvent models using solvent-omit electron-density maps. When tasked with classifying peaks into one of four distinct solvent classes, PeakProbe achieves greater than 99% accuracy for both peaks derived directly from the atomic coordinates of existing solvent models and those based on difference density maxima. While the program is still under development, a fully functional version is publicly available. PeakProbe makes extensive use of cctbx libraries, and requires a PHENIX licence and an up-to-date phenix.python environment for execution.