As captain, Aiden Markram is allowed a long rope from a wonky form perspective, but how long can that rope be as the run river continues to shrivel, asks Khanyiso Tshwaku.

Proteas all-rounder Marco Jansen, while acknowledging that spin has been a challenge for them in the ongoing T20 series against India, reckons things could be a bit different for Wednesday's third T20 in Centurion.

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season.

The Springboks will continue to evolve their attack, but they must do so within the framework of what has made them so successful, says attack coach Tony Brown.

Jannik Sinner hit the accelerator at the end of each set as he cruised past Taylor Fritz 6-4, 6-4 on Tuesday to close in on a semi-final spot at the ATP Finals in Turin.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

The first battle cry has sounded ahead of the showdown at Twickenham on Saturday, with English winger Tommy Freeman reckoning that the Springboks are 'still human' and 'still playing the same game'.

Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium.

Wednesday's third T20 between South Africa and India at SuperSport Park in Centurion is shaping up to be a run-drenched one, especially if the weather holds and SA's bowling centre doesn't.

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.

Late injection Johan Grobbelaar may find himself more than simply an “extra” on the Bok tour, writes Rob Houwing.

Springbok team doctor Jerome Mampane says that injured utility back Sacha Feinberg-Mngomezulu is recovering well.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.

Divided US support shows time is not on Ukraine’s side Expert comment LJefferson 17 February 2023

Growing public opinion evidence and uncertainty about the future of the war suggests that continued American support for aiding Ukraine should not be assumed.

One year into Russia’s war on Ukraine, fears that American support for Kyiv would rapidly wane have proven demonstrably wrong. Western financial and military backing has been robust thanks to allied unity and an unexpectedly mild winter. But, as financial analysts constantly remind us, past performance is no guarantee of future results.

People like to back winners. If the anticipated Russian spring offensive looks successful or the counterpart Ukrainian offensive is uninspiring, expect louder US voices calling for a negotiated settlement. The warning signs are already here.

American officials privately express growing apprehension that there will be an early resolution of the conflict. As one White House official recently observed to me, by the end of the year the war could well be about where it is today. And a plurality of Americans intuitively grasp this: 46 per cent believe neither Russia nor Ukraine currently has the advantage in the conflict.

Momentum matters  

In public opinion, perception of momentum matters. Americans’ support for the Vietnam War waned as the conflict persisted, falling from six-in-ten Americans in 1965 to four-in-ten in 1973.

Similarly, backing for the Iraq war fell from more than seven-in-ten in 2003 to barely four-in-ten in 2008. And with Afghanistan, as the war dragged on, support for US involvement fell from more than nine-in-ten in 2002 to less than five-in-ten in 2021. Notably, once the American public turned on these wars, support never returned.

Of course, Americans were fighting and dying in those wars, which is not the case in the Ukraine conflict. But initially the Vietnam, Iraq, and Afghanistan war support was buoyed by the belief that continued US engagement was justified, otherwise American sons and daughters had died in vain. With no American lives at stake in Ukraine, only financial and military resources, there is a growing wariness of throwing good money after bad.

In the last year, the share of Americans who say the United States is doing too much for Ukraine has nearly quadrupled, from seven to 26 per cent. And the portion that believe Washington has not done enough has halved, from 49 per cent to 17 per cent.

Sentiment about Ukraine support has become increasingly partisan. In March 2022, nine per cent of Republicans and five per cent of Democrats said the US was doing too much for Ukraine. By January 2023, 40 per cent of Republicans but just 15 per cent of Democrats complained Washington was doing too much.

This erosion of Americans’ support for Ukraine does not bode well for the future. Less than half (48 per cent) of the public in November, compared to 58 per cent in July, believed Washington should support Ukraine for as long as it takes, even if it means American households have to pay higher gas and food prices as a consequence.

A similar share, 47 per cent – up from 38 per cent in July – said the United States should urge Ukraine to settle for peace as soon as possible so the costs aren’t so great for American households, even if that means Ukraine will lose some territory.

A partisan divide

The partisan divide over Ukraine is largely driven by Republican political rhetoric during and after the 2022 midterm elections. Current Republican Speaker of the House Kevin McCarthy observed last October: ‘I think people are going to be sitting in a recession and they’re not going to write a blank cheque to Ukraine.’

More recently, in the wake of Ukrainian president Zelenskyy’s December speech to Congress, Florida Republican Representative Matt Gaetz, whose vote was pivotal in making McCarthy Speaker, tweeted: ‘Hemorrhaging billions in taxpayer dollars for Ukraine while our country is in crisis is the definition of America last.’

In January, newly-elected Ohio Republican Senator J.D. Vance told a Cleveland radio station that it was ‘ultimately not in our national security interest’ to send M1 Abrams tanks to Ukraine, despite the fact that they will be built by his constituents in Ohio.

In addition, ten Republican members of the House of Representatives have introduced legislation asserting ‘that the United States must end its military and financial aid to Ukraine, and urges all combatants to reach a peace agreement.’ 

And this month former President Donald Trump said: ‘That war has to stop, and it has to stop now, and it’s easy to do’ and it ‘can be negotiated within 24 hours’. Why worry about continued support for the war if it’s about to be over?

The road to 2024

With the 2024 US presidential election already revving up, Americans’ appetite for continued backing for Ukraine may hinge on how voters judge the Biden administration’s handling of the conflict.

Democrats are more than twice as likely as Republicans (61 per cent versus 27 per cent) to approve of the Biden administration’s response to the Russia invasion, suggesting Ukraine will be yet another partisan talking point as the campaign heats up. Notably, men are much more likely than women to approve of Biden’s efforts, as are older Americans compared with younger Americans.

It sounds like an oxymoron: “How to keep blood-sports interesting?” You’ve got blood and you’ve got sports, the term does its own advertising! And yet, fighting promotions rise and fall, where Pride and Strikeforce once reigned, now stand One and Bellator, but one promotion stands above all its competitors. The world of MMA knows one promotion which has clawed its way to the international top and established itself as the gold standard upon whose hallowed surface skulls are crushed and blood is poured. I’m talking about none other than the UFC.

Having established itself over the years as a beacon of both quality matches and consistent drama, the UFC attracts the lion’s share of international talent in the MMA world, and with it the eyes and ears of MMA fans everywhere. Having well and truly stroked the ego of the promotion, you might be wondering what on earth any of this has to do with writing or fantasy?

Well, does your world happen to feature prizefighting, ritual combat, or the eternally popular fantasy fixture called the gladiatorial arena? If so, there are a lot of writing and worldbuilding lessons you can learn from observing the biggest promotion in the biggest modern blood-sport of the world.

Continue reading Lessons from the UFC: How to Keep Blood-Sports Interesting at Mythic Scribes.

Independent Thinking: Reporting Putin’s wars Audio NCapeling 8 December 2022

Episode eight of our new weekly podcast reflects on almost one year of war in Ukraine, and 12 years of war in Syria.

In the studio with Bronwen Maddox is special guest Oz Katerji, a war correspondent and freelance journalist who in the early stages of the Syrian uprising reported on the brutality of the regime of Bashar al-Assad and its impact on neighbouring Lebanon and Turkey.

Having written extensively on Syria and the Middle East, in January 2022 he journeyed to Ukraine and was in Kyiv on 24 February as Russia began its invasion. He has reported extensively on the battle for Ukraine’s capital, and later the Donbas, in Foreign Policy magazine, the New Statesman and Rolling Stone.

Joining Bronwen and Oz to discuss the conflicts in Ukraine and Syria from Chatham House are James Nixey, director of the Russia and Eurasia programme, and Lina Khatib, director of the Middle East and North Africa programme.

What is COP29 and why is it important? Explainer jon.wallace 17 October 2024

The COP29 summit will see negotiators try to agree how to finance the climate action the world urgently needs.

COP29, the 29th UN annual conference on climate change, takes place in Baku, Azerbaijan from 11–22 November 2024.

Every COP conference is an important opportunity for international collaboration on climate change. COP29 will have a particular focus on how to make finance available to developing countries for climate action.

COP29 is already contentious, because Azerbaijan’s economy is highly dependent on fossil fuels, the main cause of climate change. That means that Azerbaijan’s government, which will preside over the summit, has a strong incentive to avoid rapid multilateral progress towards phasing out fossil fuels. 

It’s urgent that progress is made at COP29. Climate action lags far behind both what has been promised by countries, and what scientists agree is needed. The impacts of climate change are also rapidly escalating, while backlash against government policies to reduce fossil fuel use is being seen in many places around the world. 

What is a ‘COP’?

The ‘Conference of the Parties’ or ‘COP’ is an annual event that brings together the governments which have signed up to environmental action under the United Nations (UN). 

Governments or ‘parties’ attend the climate change COP if they are part of the United Nations Framework Convention on Climate Change, or the international environmental treaties the Kyoto Protocol (1997) or the landmark and legally binding Paris Agreement (2015).

World leaders, ministers, and negotiators convene at the COP to negotiate and rubber stamp plans to jointly address climate change and its impacts. 

Civil society, businesses, international organizations and the media normally ‘observe’ proceedings to bring transparency, accountability and wider perspectives to the process.

‘Mission 1.5°C’ 

COP28, the 2023 climate conference held in Dubai, was the first of three consecutive COP summits intended to ‘reset’ global climate action – what the UN calls the ‘Roadmap to Mission 1.5°C’ – the ambition to keep global temperatures from rising more than 1.5°C above pre-industrial levels. 

To support continuity and progress across the three COPs, the UAE (COP28), Azerbaijan (COP29) and Brazil (COP30) have formed a COP presidential ‘Troika’ or group of three.

In 2023 the first ‘global stocktake’ of international action to address climate change indicated that the world was far off track for targets set by the Paris Agreement. The ‘UAE Consensus’ agreement, which formed the main output of COP28, set out how parties should respond. 

COP29, the second of the three COPs, is intended to get the finance in place to enable this response. COP30, to be held in Brazil in 2025, will then try to agree how a new round of nationally determined climate plans or ‘contributions’ to global climate efforts (NDCs) should be put into action.

COP29 will be the third consecutive COP held in an authoritarian state, and the second consecutive COP hosted by a petro-state. Taken together, the ‘Troika’ hosts make up the world’s 4th largest oil producer, after the United States, Russia and Saudi Arabia. 

This presents both an opportunity and a risk: the countries are well placed to understand and tackle the core issue of fossil fuel extraction and use. But they also have strong incentives to stall, distract and deflect the negotiations away from phasing out fossil fuels.

Key issues at COP29

Finance – money on the table, and a New Collective Quantified Goal

COP29 has a remit to secure funding for a ‘course correction’ on global climate action. Countries’ revised climate plans (NDCs) are due in February 2025. For developing countries to deliver new ambitious NDCs, however, COP29 must first make clear what finance will be available to help them.

Climate finance is one of the thorniest issues in the negotiations. The previous climate finance goal, of $100 billion per year from developed to developing countries between 2020-25, was symbolic (being a fraction of the sum actually needed) and contentious (developed countries did not meet the target until 2022, and then only with accusations of double-counting). 

A New Collective Quantified Goal (NCQGs), to be agreed at COP29, will need to reflect developing countries’ needs and priorities. Estimates vary, but it is accepted that the scale will be trillions, not billions. To bridge this enormous gap, private finance will need to be mobilized and broader reforms made to global financial architecture. Issues such as subsidies, fossil fuel profits and ‘solidarity levies’ will also need to be on the table. 

Little progress has been made in the run-up to COP29. Parties disagree on who should pay, how much should be paid, what forms the funding should take (loans or grants) and how the funds should be accessed. 

Also up for debate is how funds should be directed – towards mitigating the impacts of climate change (preventing climate change becoming worse), adapting to its effects, or supporting countries to manage loss and damage (climate impacts that have already happened or cannot be avoided).  

In discussions of the NCQG to date, developed countries have consistently called for higher income developing countries, such as China and India, to contribute. 

Such countries have pushed back forcefully against this. For a new goal to be agreed, such divisions will need to be resolved.

Enhanced transparency?

COPs act as showcases for international agreement, but many processes rumble on behind the scenes. COP29 will be an important moment for transparency under the Paris Agreement, as the Parties’ first Biennial Enhanced Transparency Reports (BTRs) are due in December 2024. 

BTRs are an important tool in the Paris Agreement, requiring countries to provide a snapshot of their progress in cutting emissions, setting climate policies, and providing resources for national and international climate action. 

BTRs are meant to build the evidence base for strong NDCs, build trust and promote ambitious climate action. They are also meant to help developing countries showcase achievements and attract climate finance. 

The COP29 presidency has launched the Baku Global Climate Transparency Platform to encourage participation, and support countries in finalising their BTRs. The Platform is meant to provide space for collaboration between government, NGO and private sector stakeholders. 

This is one of the areas in which COP29 host, Azerbaijan, runs into criticism. The country ranks highly on indexes of corruption, and has repeatedly restricted space for NGOs and wider civil society actors through a series of escalating government crackdowns, including imprisonment of environmental activists, in the run-up to the conference.

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

Linda J. Pike
Jul 1, 2006; 47:1597-1598
Report

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Supporting Next Generation of Leaders in Sustainability News Release NCapeling 28 January 2021

A new programme offering paid internships for young people who are passionate about social, economic, and environmental sustainability has been launched.

Supporting Civic Space: The Role and Impact of the Private Sector 23 September 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online

The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism.

A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.

However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.

This roundtable brings together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space.

The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.

This meeting is the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. 

Supporting Civic Space: The Role and Impact of the Tech Sector 13 October 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online

This event brings together a diverse and international group of stakeholders to exchange perspectives and experiences on the role that tech actors can play in supporting civic space.

In a deteriorating environment for civic freedoms, tech sector actors are increasingly engaging, publicly or otherwise, on issues of civic space.

In the US, for example, a number of tech companies have cancelled contracts with the Pentagon and stopped censoring search results in China as a result of protests by employees. The Asia Internet Coalition recently wrote to Pakistan’s Prime Minister expressing human rights concerns about new rules regulating social media.

While we have recently seen technology companies show support for the social movements, including through substantial pledges, in some cases these have elicited criticism of hypocrisy, and the interventions of social media platforms on freedom of expression and privacy issues have been closely linked to the preservation of their own business models.

The COVID-19 crisis has also posed new dilemmas for the tech sector with the pervasiveness of disinformation, as well as new tools for tracking individuals which raise privacy issues.

This roundtable provides an opportunity to explore the drivers of (and barriers to) corporate activism, develop a better understanding of existing initiatives, identify good practice and routes to effective collaboration with other actors, and discuss practical strategies that could be adopted by the tech community.

It is the second of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space.

Expert

Expert

The functional mechanisms of multidomain proteins often exploit interdomain interactions, or “cross-talk.” An example is human Pin1, an essential mitotic regulator consisting of a Trp–Trp (WW) domain flexibly tethered to a peptidyl-prolyl isomerase (PPIase) domain, resulting in interdomain interactions important for Pin1 function. Substrate binding to the WW domain alters its transient contacts with the PPIase domain via means that are only partially understood. Accordingly, we have investigated Pin1 interdomain interactions using NMR paramagnetic relaxation enhancement (PRE) and molecular dynamics (MD) simulations. The PREs show that apo-Pin1 samples interdomain contacts beyond the range suggested by previous structural studies. They further show that substrate binding to the WW domain simultaneously alters interdomain separation and the internal conformation of the WW domain. A 4.5-μs all-atom MD simulation of apo-Pin1 suggests that the fluctuations of interdomain distances are correlated with fluctuations of WW domain interresidue contacts involved in substrate binding. Thus, the interdomain/WW domain conformations sampled by apo-Pin1 may already include a range of conformations appropriate for binding Pin1's numerous substrates. The proposed coupling between intra-/interdomain conformational fluctuations is a consequence of the dynamic modular architecture of Pin1. Such modular architecture is common among cell-cycle proteins; thus, the WW–PPIase domain cross-talk mechanisms of Pin1 may be relevant for their mechanisms as well.

Korea's New Energy Policy and Implications for LNG Imports 3 October 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 17 September 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The new energy policy of Moon Jae-In’s administration aims to swing radically from coal and nuclear towards renewables and LNG for power generation. During the last 12 months the priority given to the expansion of renewable energy has been overwhelming and the support for the expansion of gas not as strong as many observers had expected. The 13th gas supply and demand plan announced in Spring 2018 confirmed the trend. Based on this projection, Professor K. Paik will discuss how this new energy policy will affect Korea’s LNG imports strategy and what are the implications of Korea’s northern policy towards this LNG supply strategy and pipeline gas imports to the Korean Peninsula.

Attendance at this event is by invitation only.

Mining, Minerals and Metals Expert Roundtable: Forest-Smart Mining Report Launch 10 May 2019 — 5:30PM TO 6:30PM Anonymous (not verified) 12 April 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states 17 February 2021 — 3:00PM TO 4:00PM Anonymous (not verified) 8 February 2021 Online

 This event explores lessons and opportunities from conflict-affected states.

In the field of peacebuilding, scholars and policymakers increasingly recognize the importance of environmental restoration, afforestation and infrastructural renewal for creating the sustainable livelihoods necessary for successful peacebuilding efforts.

Featuring academics writing for International Affairs on environmental peacebuilding in Colombia, Yemen and the Sahel, this webinar discusses the policy implications of the turn to environmental peacebuilding.

This event is part of the Chatham House’s Environment and Society Discussion Series in which the Energy Environment and Resources Programme brings together leading academics and policymakers to discuss key issues in environmental policy.

In particular, this event focuses on the role of environmental peacebuilding in creating sustainable livelihoods. From the impact the destruction of infrastructure can have on poverty as a driver of conflict, to the role environmental peacebuilding can play in bringing communities together by creating sustainable shared spaces of employment, the importance of the environmental livelihood creation is difficult to overstate.

Panellists focus on how policymakers can best encourage inclusive and sustainable livelihood creation and on addressing the key challenges such approaches face in the context of environmental peacebuilding efforts.

The Migration-Deportation-Return Nexus 6 June 2018 — 1:00PM TO 5:30PM Anonymous (not verified) 23 May 2018 Chatham House, London

In 2015, the unprecedented numbers of migrants crossing borders subjected the EU to extraordinary moral and political pressure, as the number of asylum-seekers soared 122 per cent to 1.3 million people.

In response, the EU has sought to accelerate the deportation of failed asylum-seekers and migrants who arrive without proper documentation. The European Commission has recommended that “all leverage and incentives” be used to “ensure that third countries fulfil their international obligation to take back their own nationals residing irregularly in Europe.”

The Valletta Action Plan, the EU-Turkey deal, the Brussels Agreement with Afghanistan, the EU deal with Nigeria and the new “results-oriented Partnership Framework” signal more restrictive approaches and an outsourcing of the securitization of migration.

However, the EU’s attempt to reconcile its legal and humanitarian obligations with stronger measures has encountered some serious challenges.

This roundtable stimulates dialogue on the circumstances surrounding migrant youth both in Afghanistan and the Edo state in Nigeria, and identifies key questions for further research on the ground.

Contextualising young people’s experiences within a “migration-deportation-return” nexus provides an entry point for the identification of both the commonalities and specifics of the challenges and risks that migrant youth face.

In line with UNICEF’s policy priorities related to children on the move, and initiating global debates in child rights and development, this collaboration forms part of the efforts that seek to inform global research and policy agenda for this most vulnerable of groups under the radar.

The intended outcome of this collaboration is to begin developing a set of core objectives and indicators to help guide the EU, Afghanistan and Nigeria in their treatment of youth, and to facilitate improved donor and host government understanding of the issues.

Participants include experts, researchers, academics, representatives of civil society and governmental institutions.

Attendance is by invitation-only.

The event is co-hosted with UNICEF Office of Research – Innocenti and the University of Cambridge.

Stacey Finley from University of Southern California discusses how mathematical models support the research of cancer biology. Cancer research is a crucial job, but a difficult one. Tumors growing inside the human body are affected by all kinds of factors. These conditions are difficult (if not impossible) to recreate in the lab, and using real patients as subjects can be painful and invasive. Mathematical models give cancer researchers the ability to run experiments virtually, testing the effects of any number of factors on tumor growth and other processes — all with far less money and time than an experiment on human subjects or in the lab would use.

Dr. Outi Tervo of Greenland Institute for Natural Resources, shares how mathematics helps recommend speed limits for marine vessels, which benefits narwhals and Inuit culture. Narwhals "can only be found in the Arctic," said Outi Tervo, a senior scientist at GINR. "These species are going to be threatened by climate change more than other species that can live in a bigger geographical area." The collaboration has already lobbied on behalf of the narwhals to reduce the level of sea traffic in their habitat, after using mathematical analysis to identify how noise from passing boats changes the narwhals' foraging behavior.

PORT-AU-PRINCE, Haiti (AP) — Haiti's main airport remained closed on Tuesday, a day after violence erupted as the country swore in its new prime minister in a politically tumultuous transition.

When using the distinct count function in SAS Visual Analytics reports, you might find that a negative value is displayed instead of the actual distinct count: imgalt="distinct_count" src="{fusion_66562_1_disti

TNF is a highly pro-inflammatory cytokine that contributes not only to the regulation of immune responses but also to the development of severe inflammatory diseases. TNF is synthesized as a transmembrane protein, which is further matured via proteolytic cleavage by metalloproteases such as ADAM17, a process known as shedding. At present, TNF is mainly detected by measuring the precursor or the mature cytokine of bulk cell populations by techniques such as ELISA or immunoblotting. However, these methods do not provide information on the exact timing and extent of TNF cleavage at single-cell resolution and they do not allow the live visualization of shedding events. Here, we generated C-tag TNF as a genetically encoded reporter to study TNF shedding at the single-cell level. The functionality of the C-tag TNF reporter is based on the exposure of a cryptic epitope on the C terminus of the transmembrane portion of pro-TNF on cleavage. In both denatured and nondenatured samples, this epitope can be detected by a nanobody in a highly sensitive and specific manner only upon TNF shedding. As such, C-tag TNF can successfully be used for the detection of TNF cleavage in flow cytometry and live-cell imaging applications. We furthermore demonstrate its applicability in a forward genetic screen geared toward the identification of genetic regulators of TNF maturation. In summary, the C-tag TNF reporter can be employed to gain novel insights into the complex regulation of ADAM-dependent TNF shedding.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.

12th International Forum on Illegal, Unreported and Unregulated Fishing 18 May 2020 TO 22 May 2020 — 2:00PM TO 3:30PM Anonymous (not verified) 27 September 2019

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in both health and disease.

Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset.

Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations.

18 August 2020