We all know that *one* guy who acts like he's doing the world a favor just by showing up.

The post Demonic & Damned to Ridiculously Redeemed! (Eph.2:1-10) appeared first on Clash Daily.

Just because you’re paranoid, it doesn’t mean you’re wrong. And for any supporters of President-elect Donald Trump who feel that they’ve been unfairly targeted by the government, but were summarily […]

The post Fired FEMA Worker Reveals Discrimination Against Trump Supporters Was Even Worse Than First Reported appeared first on The Western Journal.

CNN reportedly will be making more cuts in the near future, including to its highly paid on-air personalities, following poor election ratings. The New York Post reported that Fox News […]

The post On-Air Talent Will Not Be Spared as CNN Prepares Mass Layoffs in Wake of Election: Report appeared first on The Western Journal.

President-elect Donald Trump has chosen the next director of the CIA. Trump tapped former Texas congressman and director of national intelligence John Ratcliffe for the job. According to a statement […]

The post 'Warrior for Truth': Trump Has Chosen His Next CIA Director, Crediting Pick for 'Exposing Russian Collusion' Hoax appeared first on The Western Journal.

China Needs to Make the Belt and Road Initiative More Transparent and Predictable Expert comment sysadmin 29 April 2019

The global infrastructure project must move beyond mish-mash of opaque bilateral deals

As China welcomes dozens of world leaders to Beijing for its second Belt and Road forum, it has one simple aim: relaunching President Xi Jinping’s controversial global infrastructure drive.

Since it began five years ago, the Belt and Road Initiative (BRI) has sunk hundreds of billions into port, railway and power projects stretching from south-east Asia to central Europe. But its path has been bumpy, drawing sharp criticism over the ruinous debts that some countries have racked up amid Chinese largesse.

Xi will stress sustainable financing and transparency this week, amid the usual talk of ‘win win’ cooperation. Yet BRI’s problems are structural, not presentational. For any pledges to be meaningful, China must move beyond its present mish-mash of opaque, bilateral deals.

After bad headlines last year, BRI has in fact enjoyed a good run in recent weeks. Malaysia announced it would resume a previously cancelled high-speed rail project, while Italy’s decision to join up last month marked a further European incursion. Indeed, if attendance is any guide to success, BRI looks in fine fettle. The first forum in 2017 attracted 29 world leaders. China says 37 will turn up this week. Phillip Hammond, UK chancellor, arrives hunting deals too, just a day after news that Chinese technology group Huawei will be allowed to help build 5G networks in Britain.

Even so, three interlinked problems remain at the heart of President Xi’s pet project, all of which must be addressed if BRI is to move beyond the pitfalls that have damaged its reputation.

The first and most obvious is debt. Critics allege that China ‘traps’ its BRI partners financially, often pointing to a debt-for-equity deal that handed China control of a port in Sri Lanka. These claims are exaggerated — few other projects have ended up this way. Yet poorer nations from Laos to Tajikistan are still signing up to vastly expensive Chinese schemes that offer poor value for money while straining their public finances.

The second problem is transparency. Despite its grand scale there is still no reliable list of BRI projects, no disclosure of the lending standards China follows, nor even the amount China has invested. Beijing claims more than $1 trillion; independent estimates suggest perhaps a few hundred billion. Either way, it will be hard for China to convince doubters on debts until it is open about the criteria it uses in deciding who to lend to and why.

BRI’s third and most important challenge is its muddled organization. Despite BRI’s image as a centrally run mega-project, China has allowed many deals to be struck locally, via a mix of state-backed companies, public sector banks and freewheeling regional governments. And it is here that the problems began.

Infrastructure deals are notoriously complex, especially for transnational projects like high-speed rail. Renegotiations are common, even for experienced bodies like the World Bank. Yet BRI has repeatedly seen terms negotiated behind closed doors, in countries such as Malaysia and Pakistan, come unstuck in the face of public outcry.

Rather than seeking to trap others with debt, China’s central government more often has to step in to fix dubious projects agreed by underlings lower down the chain.

These negotiations go one of two ways. Either China’s partners complain and win terms, as was true in Malaysia and in Myanmar over a multibillion-dollar deep-sea port. Or, as in the case of Sri Lanka, the renegotiations go in China’s favour, but at the cost of accusations of debt trickery. In both cases China looks bad.

Speaking last year, Xi responded to criticism of BRI by describing it as ‘an open platform for cooperation’. Yet, so far, he has proved resistant to the step that would deliver on that vision — namely turning BRI into an institution with open standards and international partners.

The reasons for his reluctance are obvious. Ending BRI’s reliance on loose bilateral deals would limit Beijing’s room for geopolitical manoeuvre. Yet what might be lost in political flexibility could easily be gained in economic credibility, while avoiding some of the painful renegotiations that have dogged many BRI projects.

At a time when China’s economy is slowing and its current account surplus is shrinking, formalising and institutionalising, BRI could also help avoid wasting scarce public resources on white elephant projects. China even has an easy template in the form of the Asian Infrastructure Investment Bank, the Beijing-based institution that has won plaudits for its project quality and openness since it started in 2016.

Whichever model is chosen, a dose of Chinese-style central planning is called for, along with more openness. Without it, the oddly chaotic and decentralised model pioneered in BRI’s first five years is unlikely to help the project thrive over the next five.

This article was originally published in the Financial Times.

Europe's response to the US Inflation Reduction Act 27 March 2023 — 2:00PM TO 3:15PM Anonymous (not verified) 9 March 2023 Chatham House and Online

This event explores the implications of the US Inflation Reduction Act, how Europe can respond and what options the UK has.

While the US Inflation Reduction Act (IRA) has led to an outcry in the EU, member states have different concerns and preferences for how to respond. The European Commission’s proposed ‘Green Deal Industrial Plan’ includes the relaxation of state aid rules to drive funding. But will this lead to a ‘subsidies race’ between the US and EU and is a ‘green trade war’ brewing?  
 
The UK’s response to the IRA has been much more muted than the EU’s. But caught between US subsidies and EU subsidies, can the UK compete and create an independent response to the IRA? And what steps can be taken to facilitate global cooperation and to make trade work for the green transition?

Dr Martin Porter, Executive Chair at the Cambridge Institute for Sustainability Leadership, will kick off the discussion with short remarks followed by an interactive discussion among all participants

This discussion is part of the Chatham House Global Trade Policy Forum. We would like to take this opportunity to thank our founding partner and supporting partners for their generous support of the forum.  

Yu Xue
Sep 1, 2008; 7:1598-1608
Research

Redefine the Commonwealth now to safeguard its future Expert comment NCapeling 6 October 2022

Although seen as one of the Queen’s greatest legacies, the Commonwealth must provide tangible benefits to its citizens in an era of geopolitical competition.

The Commonwealth’s breadth allows a wide diversity of countries of different sizes, geographies, cultures, and values to be members – it is both rich and poor, north and south, and ethnically diverse. This makes it more interesting than many other multilateral institutions such as the G7, NATO, and the European Union (EU).

But it suffers from an unclear purpose. Since its inception, successive UK governments have grappled with its role – whether it is a preferential trading bloc or merely a source of most of Britain’s post-war immigration.

This lack of purpose – and structure – has left the Commonwealth impotent in dealing with a host of bilateral difficulties between the UK, its overseas territories, and Commonwealth partners in recent years.

Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand – while development aid, one of the most tangible ways the UK worked with many Commonwealth countries, has been cut and the UK’s defence focus has pivoted towards the Indo-Pacific and Europe’s Eastern front.

The UK also suffered embarrassing and overwhelming defeats in both the UN General Assembly (UNGA) and the International Court of Justice (ICJ) on the legality of its continued occupation of the Chagos Islands and has avoided directly challenging India’s tacit support for Russia’s invasion of Ukraine in the hope of securing a trade deal.

At the recent Commonwealth Heads of Government Meeting (CHOGM), Boris Johnson reportedly attempted to depose Baroness Scotland, the Commonwealth’s Secretary General, but suffered a humiliating defeat in a vote of Commonwealth members.

These challenges are likely to continue, especially in the wake of the death of HM The Queen which could be seen by republican movements as an opportune time to rally support. Australia and New Zealand’s leaders, both republicans, downplayed the idea of a poll on the monarchy immediately after the Queen’s death, but it would be a mistake to assume this has gone quiet forever. Antigua and Barbuda’s prime minister has already said there will be a referendum on becoming a republic within three years.

Defining a new vision for the future

A concrete vision for the Commonwealth is long overdue and there is no better time to cast one than now. HM The Queen was more than just a figurehead for the Commonwealth and it remains unknown exactly what role King Charles III will see for himself.

But, unlike his mother who was a young, modern Queen heralding a post-imperial future, Charles takes the throne at a later age and at a time when important questions need to be addressed in an increasingly fractured world.

Most importantly the UK should avoid the temptation to define the Commonwealth in terms of shared principles and values. India, Pakistan, and Bangladesh all abstained on the United Nations (UN) motion condemning Russia’s invasion of Ukraine, and Commonwealth members are likely to be similarly divided over China’s territorial claims, the US-China conflict, the net-zero agenda, and nuclear non-proliferation.

The Commonwealth’s breadth – its greatest strength – means consensus is often impossible, and so should not be the goal. Instead the Commonwealth should focus on tangible areas of cooperation where there is mutual interest such as trade, aid, and migration.

The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns, from post-COVID vaccine provision to climate financing. Boosting the aid budget and opening borders may prove more important in engaging developing country partners than traditional diplomatic avenues.

Liz Truss’s British International Investment project could be a valuable vehicle for financing, especially if it leverages private sector funding, but many Commonwealth countries are feeling the more immediate impact of the UK’s aid cuts. In these circumstances many have already turned to Chinese infrastructure financing.

This is where the Commonwealth could be valuable. In the Pacific, it links certain island nations to the UK, Australia, and New Zealand at a time of renewed geopolitical competition with China in the Pacific. The fact the Commonwealth is not explicitly about promoting a particular ideology or countering China is helpful.

Commonwealth should be less UK-centric

There is also no reason why all the Commonwealth operations need to be based in London, which is not only expensive but also reinforces an approach to governance that assumes everything must be decided by civil servants in London. As the world’s largest democracy, India is an obvious alternative candidate although its reluctance to condemn Russia’s invasion and its domestic political tensions may count against it.

It is also important the Commonwealth’s wealthier members – the UK, Canada, and Australia – provide financing for countries such as India to take on extra responsibilities. The Commonwealth Games is a good place to start – despite having 72 competing nations and territories, the games have only been held three times outside the UK, Canada, Australia, and New Zealand.

The Commonwealth also needs to be forward-looking and one of its most exciting assets is its demographic youthfulness. Europe, China, and the US have ageing populations whereas Nigeria, India, and Bangladesh have some of the world’s largest young populations.

How modular renewables can reduce the costs of relying on carbon capture Expert comment LToremark 10 October 2024

COP29 must raise countries’ ambitions to deploy vastly more low-cost modular renewable technologies to help meet the tripling of renewables target set at COP28 and reduce our reliance on expensive carbon capture systems.

The most important international climate conference is around the corner. COP29 in Baku, Azerbaijan will be especially important because next year countries will submit their five-yearly national climate plans – or Nationally Determined Contributions (NDCs) – as set out under the Paris Agreement.

At COP28 in Dubai last year, the final text was heralded as a last-minute success as – somewhat surprisingly – it was the first ever COP to commit to ‘transition away from fossil fuels in energy systems in a just, orderly and equitable manner’. To support this, over 200 countries also committed to triple renewable capacity by 2030.

Under current NDCs, even if all countries achieve their most ambitious decarbonization plans, the world would still fall 30 per cent short of tripling renewable capacity by 2030. 

At COP29 in November, hosted by a petrostate, additional agreement is needed to operationalize the removal of fossil fuels from the global energy system and set the ambition for those crucial NDCs in 2025. Failing to do so means the opportunity to triple renewables by 2030 will slip away. But the actions of oil producing nations, international oil companies, their associated supply chains and networks of lobbyists have in recent years done their best to disrupt and slow down the energy transition and water down key negotiations during COPs and elsewhere. 

During the final days of COP28, the Organization of the Petroleum Exporting Countries (OPEC) sent private letters to its 13 members – including COP28 host the United Arab Emirates (UAE) – urging them to ‘proactively reject any text or formula that targets energy, i.e. fossil fuels, rather than emissions’. OPEC members own 80 per cent of global oil reserves.

Due to the startling decline in the cost of renewables and electric vehicles, fossil fuel producers are increasingly concerned. To fight back they are turning to carbon capture and storage (CCS) technologies and carbon removal options, which would enable the continued burning of fossil fuels – and protect their assets and business models.

A key battle ground for oil and gas producers is the difference between abated and unabated fossil fuels.

Abatement is the process of capturing CO₂ as fossil fuels are burnt to prevent a proportion of those CO₂ emissions from entering the atmosphere, either by using that CO₂ in products or storing it in geological formations deep underground in near perpetuity, commonly referred to as CCS.

After COP28 there was optimism that the final agreement was significant and covered all fossil fuels without ambiguity around whether they are unabated or abated. 

But the definition of unabated has not actually been agreed within the COP process. During the 2021 COP26 summit, the Glasgow Climate Pact mentioned unabated in reference to coal. Could a gas power station capturing 51 per cent of the emitted CO₂ be considered abated?

And what about the so-called downstream emissions? Downstream emissions from cars, planes, tanker ships and diesel generators etc make up 50–80 per cent of the total emissions from oil – and there are no plans to attach mini-CCS systems to cars.

CCS and engineered carbon removals are also likely to be expensive. Analysis by the Oxford Smith School of Enterprise and the Environment has shown that high CCS pathways to net zero emissions in 2050 would cost at least $30 trillion more than a low CCS pathway with more renewables – roughly $1 trillion more per year.

The costs of CCS have also remained the same for the past 40 years, while the costs of renewables like solar, wind and lithium-ion batteries have dropped radically. Solar costs have declined by 90 per cent in the last decade. 

The rapid cost reductions of solar, wind and batteries are due to their modular nature. Around 70 billion solar cells will be manufactured this year, the majority in China. It is the repetitive modular manufacturing process that has led to rapid efficiency improvements and cost reductions. Each Tesla has around 7,000 lithium-ion battery cells, and the price of these modular batteries fell 14 per cent between 2022 and 2023 alone. 

The modular criteria can help define the technology winners of the future, technologies we should selectively support and accelerate over the coming years. 

While huge industrial power stations, oil rigs and refineries have their benefits, they are not modular in the same way. Their economy of scale is in the large size of each asset. CCS is bolted on to fossil fuel infrastructure but there are less than 50,000 fossil fuel producing assets globally. By contrast, there were 1.5 billion solar panels produced in 2022. The cost of deploying CCS is therefore unlikely to benefit from the rapid cost reductions of modular renewables. Nuclear even less so. There are 440 nuclear power stations in operation today, they take many years to build and remain hugely expensive. 

Harris and Trump's shared goal masks a fundamental AI policy divide Expert comment rgold.drupal 3 November 2024

Both presidential candidates will pursue US tech dominance but differ on the means to achieve it.

There remain some differences between the US presidential candidates’ positions on the governance of artificial intelligence and other emerging technology, notably around competition. 

But under either future administration, US decision-making looks set to be heavily influenced by growing securitization, the aims of the US technology industry and broader competition with China. 

‘Safe’ AI development 

Vice President Kamala Harris attended the inaugural Global AI Safety summit in the UK in 2023, where she announced President Joe Biden’s Executive Order on AI. This significant move by the federal government sought to define national and cyber security guidelines for AI developers and outline privacy and transparency guarantees. It also committed the federal government to a review of the National Security implications of this emerging technology, which was published last week.

In her remarks at the summit, Harris was clear that her definitions of safety extended beyond catastrophic risk mitigation to societal and personal harm. She noted the corrosive effects of some algorithmic decision-making and disinformation on democracy, appealing for AI that is developed ‘in the service of the public interest’.

A number of initiatives developed during the Biden administration have attempted to steer emerging technology as it takes root in society. This includes the establishment of the US AI Safety Institute, various schemes on global AI governance and investment in Public AI projects like the National AI Research Resource (NAIRR).

The US public is largely supportive: polling by the AI Policy Institute (AIPI) points to a majority preference for safety standards governing the US effort to lead in AI, rather than pedal-to-the-metal development. Investment in public options on AI and the infrastructure required to develop and sustain it is a bold direction that the incoming administration should consider expanding.

Biden’s Executive Order on AI has come under fire by the Trump campaign. At a rally in Iowa, Trump explained that he would cancel the order ‘on day one’, echoing a Republican platform that described it as imposing ‘Radical Leftwing ideas’ . 

Trump does, however, have his own track record in technology policy. During his first presidency, his administration passed an Executive Order on AI, stressing that ‘continued American leadership in Artificial Intelligence is of paramount importance to maintaining the economic and national security of the United States’. The tools and institutions announced as part of the order – including AI research investment, national AI research institutes and AI regulatory guidance including on federal use of AI – echo those of the current administration. 

Four years is a long time in AI, however. As the power of this technology is revealed, talk of safety may give way to talk of security. While the candidates may disagree on the role of the federal government in setting standards, there will be close alignment on the central need for US supremacy in national security. Neither administration seems likely to erect barriers to securitization of AI should it emerge as a critical strategic asset.

AI regulation at home 

American industry will remain the pivotal force shaping the US AI ecosystem, particularly as America jostles for position as the maker of the global rules governing AI. A notable aspect of Biden’s AI Executive Order was where it staked responsibility. Reports by AI and Cloud companies on the safety of their tools and infrastructure are sent to the Department of Commerce.

Under Secretary Gina Raimondo, whose star continues to rise, the department has become significantly more engaged with technology companies. In the absence of any other legal authority, AI governance has therefore sat under the purview of a secretary who herself has noted that they are ‘not a regulator’. 

The trend of industry leaders driving the government agenda on AI is replicated in other departments. There was an outcry over the composition of the new Department of Homeland Security advisory panel, the Artificial Intelligence and Security Board, with civil society groups concerned about the preponderance of industry voices: the 22-member panel includes the CEOs of OpenAI, Anthropic, NVIDIA, IBM, AWS, Adobe, Microsoft and Alphabet.

Under a Harris presidency, these trends seem likely to continue. Plus with deadlock in Congress probable, establishing new legal authorities for emerging technology will be difficult. That will likely mean emerging tech governance remains heavily influenced by the Department for Commerce. 

Like Harris, Trump has his allies in industry. While the Biden administration has courted the CEOs of AI companies who have historically spoken out in favour of regulation, Trump’s allies tend towards a more deregulatory agenda. 

Silicon Valley billionaires Elon Musk and Marc Andreessen have backed Trump’s plans to minimize AI regulation, lauding his support for ‘little tech’. They have also backed reported plans for so-called ‘Manhattan Projects’ to develop military technology, stewarded by ‘industry-led’ agencies. Trump’s aversion to strong regulatory institutions may mean an end to Biden’s anti-trust efforts, benefitting the biggest voices in the room, though his VP pick may disagree. JD Vance has somewhat surprisingly come out strongly in defence of the current chair of the Federal Trade Commission, Lina Khan, and her anti-trust efforts targeting US big tech.

Regardless, business interests will likely shape either a Harris or Trump administration’s approach as the US grapples with balancing the ambitions of its industry with an increasingly protectionist stance towards its biggest import market, China.

Competition abroad

China looms large in the imaginations of both campaigns. 

The US has signalled to its allies that American AI standards should replace Chinese standards. Export controls on semiconductors were expanded in September this year, with key voices in the industry – notably the Netherlands, Japan and South Korea – describing the restrictions as ‘economically motivated’ despite nominally being tied to national security by the US. 

Following its snap election, Japanese politics has entered uncharted waters Expert comment LToremark 5 November 2024

Prime Minister Ishiba’s election gamble has failed. Japan now faces another period of political uncertainty, which could affect its international standing.

In Japan’s snap election on 27 October, the ruling coalition of the Liberal Democratic Party (LDP) and New Komeito lost the overwhelming majority it had held since the 2012 general election. The ruling coalition now has 215 seats, leaving it 18 seats short of a majority. 

The largest opposition party is the Constitutional Democratic Party of Japan (CDP), which gained 50 seats to 148. The second largest opposition party is the Japan Innovation Party (Ishin), which lost six seats to 38, and the third largest opposition party is the National Democratic Party (NDP), which gained 21 seats to 28.

But the opposition is divided and there is no real appetite to form a coalition government. This will likely result in a hung parliament, which will further destabilize Japan’s government.

The election results reveal three key things  about the state of Japanese politics and what comes next.

First, that Prime Minister Ishiba’s snap election gamble has failed. The aim was for Ishiba, a non-mainstream member of the LDP, to strengthen the party base and stabilize his administration. But with the ruling coalition losing its majority, the party base has been further weakened and the Ishiba administration is now more likely to be short-lived. LDP voters as well as the public in general  had hoped that Ishiba, as the ‘opposition within the party’, would change the LDP’s structure and government policies, eliminate the uncertainty surrounding party funding and increase transparency on how MPs use public funds to finance political activities.

However, when Ishiba became LDP leader and prime minister, he abandoned his previously more critical stance and prioritized carrying on the policies of the mainstream LDP, leaving his supporters feeling betrayed.

Second, while the ruling coalition has been punished, the people of Japan still did not vote for a change of government. The opposition is divided and, despite its gains in this election, the CDP is not fully committed to take the lead and consolidate the opposition to form a coalition. The CDP also suffers from internal division. The left wing of the party would prefer a coalition with the Communist Party, while the right wing of the party does not want to form a coalition with the LDP or the Communist Party, preferring a partner such as the NDP.

Third, the NDP has become the key to future Japanese politics. By becoming the minority ruling party, the NDP is in a position to control the fate of Ishiba administration. While the CDP has no intention of cooperating with the LDP, the NDP is more willing to do so in order to implement its own policies. As the budget cannot be passed without the NDP’s cooperation, the ruling coalition will have no choice but to accept the NDP’s policy of substantial tax cuts through the expansion of tax credits. It will also likely have to accept an option for married couples to decide their family names, which requires a change of civil codes and is something it has been reluctant to do so far. 

If the NDP’s demands are rejected, a no-confidence motion will likely be submitted and passed, leaving the Ishiba cabinet with no choice but to resign or dissolve the House of Representatives (the lower house of Japan’s parliament).

But the NDP has chosen to not form a coalition with the ruling party and enter government. Why? From the NDP’s point of view, forming a coalition with the LDP, would mean getting involved in the LDP’s internal turmoil – something it wishes to avoid. In addition, elections to the House of Councillors (upper house of parliament) will be held in the summer of 2025. The NDP may have judged that it will have a better chance of implementing its policies by cooperating with the government on a case-by-case basis, rather than forming a coalition with a party that is losing public support and risk following suit.

The minority ruling system that has emerged after the election is extremely rare in Japan’s political history and is likely to make its politics even more unstable in the years ahead. The Ishiba administration will probably be able to survive until the budget is passed in March next year by cooperating with the NDP, but beyond that its prospects are unclear.

As the House of Councillors elections get closer, some in the LDP may say that they cannot fight the election with Ishiba as prime minister. If so, they may choose the option of a same-day election for the lower and the upper house. The cost of an election campaign is significant, and the LDP’s financial strength gives it an advantage in the case of a same-day election. There is also a strong possibility that the public will choose the LDP to regain stability in government. However, this election has shown that public distrust of the LDP is high, and if Ishiba continues to be pushed around by the NDP, his party’s chances of winning would be reduced.

Japanese politics has entered uncharted waters, where the patterns and customs of the past do not apply. There are now doubts both at home and abroad as to whether Ishiba, who has a weak party base, will be able to stay on and steer the government. Over the past decade, the Abe and Kishida administrations have provided Japan with political stability, which has in turn enhanced its international presence. An unstable political system, with frequent changes of government, will likely lead to a decline in Japan’s international influence.

There is also a risk that US–Japan relations  could become unstable. Although the NDP does not have a strong agenda to change the course of this relationship, Ishiba may struggle to keep the promise made by his predecessors to increase defence spending. Ishiba’s nationalist posture could also create a confrontational relationship with the United States, while his weak leadership means he may not seek to invest in strengthening the US–Japan alliance. 

Donald Trump’s win in the US presidential election could pose a further risk. Although Trump might be open to Ishiba’s demand for parity with the US, he could become irritated with Ishiba’s weak domestic position. Ishiba may not be able to make decisions – or a deal with Trump – unless the NDP agrees to it.

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles

MS Brown
Jul 1, 1980; 21:505-517
Reviews

W Gamble
Nov 1, 1978; 19:1068-1070
Articles

JL Dixon
Feb 1, 1993; 34:167-179
Reviews

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

Expert

Expert

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

Plant-based 'Meat' and Cultured Meat: Revolutionizing the Livestock Sector 10 April 2019 — 4:00PM TO 5:30PM Anonymous (not verified) 14 March 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Consensus is building across the scientific, environmental and public health communities that a radical shift away from excessive meat-eating patterns is urgently needed to tackle the unsustainability of the livestock sector. Recognizing the scale of the challenge ahead, public policymakers, civil society and innovators have increasingly sought to prompt shifts in consumer food choices – away from the most resource-intensive meat products and towards more sustainable alternatives.

Meat analogues – plant-based ‘meat’ and cultured meat also known as ‘lab-grown’ meat – mark a departure from traditional meat alternatives. Both are intended to be indistinguishable from – and in the case of cultured meat biologically equivalent to – animal-derived meat and are marketed principally at meat-eaters. Innovation and investment in meat analogues have increased significantly, but the direction and pace of growth in the meat analogue industry will depend upon a multitude of factors, including public acceptance, civil society support and incumbent industry responses.

This event will explore the challenges of scaling up production and generating demand for meat alternatives. It will also look at the ways policymakers in the UK and EU can impact the direction of the industry while examining what factors will influence consumer acceptance of plant-based ‘meat’ and cultured meat as substitutes for animal-derived meat.

Root Causes of Rohingya Crisis Must Not be Ignored Expert comment sysadmin 28 September 2017

The focus on Aung San Suu Kyi masks the complete lack of an adequate response to the crisis in Myanmar, whether at the global or regional level.

Aung San Suu Kyi’s recent speech on the Rohingya crisis was - at best - light on details on how the current situation could be remedied and - at worst - full of easily disproven assertions.

While she does not directly control the military, it is her government that is blocking humanitarian access to the areas affected by the violence. And the Rohingya have faced systemic persecution and discrimination for decades.

Some may argue this is simply realpolitik and that any public support for the Rohingya could mean facing a backlash from the military and a large part of her support base. But arguably, she does have moral authority (which helped her in the past to stand up to the military generals) that is now being eroded by her ambivalence in speaking out.

However, the focus on Aung San Suu Kyi masks the complete lack of an adequate response to the crisis – whether at the global or regional level.

Undertaking dangerous and perilous journeys

Since the attacks on border and military posts by the armed group Arakan Rohingya Salvation Army (ARSA) in August 2017, there has been a strong military crackdown against the Rohingya in Rakhine state: a substantial number of Rohingya villages destroyed; close to half a million people Rohingya fleeing into Bangladesh and tens of thousands internally displaced within Myanmar.

Prince bin Ra’ad , UN High Commissioner for Human Rights, has called the crisis a “textbook example of ethnic cleansing” and tens of thousands of Rohingya are still undertaking dangerous and perilous journeys seeking sanctuary. In response, the UN and EU have focused on addressing the immediate humanitarian crisis in Bangladesh, which is already home to many formerly displaced Rohingya communities.

Within the region, Sheikh Hasina’s secular Awami League government in Bangladesh initially proposed joint military operations with Myanmar against the ARSA - in part because of concerns about the long standing relationship between Rohingya political or armed groups and the Jamaat-e-Islami, an ally of the main opposition Bangladesh Nationalist Party (BNP).

However, faced with massive refugee flows, Bangladesh turned its focus to the humanitarian crisis while stressing that Myanmar must allow the return of refugees. Bangladesh’s concern is partly motivated by internal security concerns. If the current situation becomes protracted, with no clear resolution in sight, frustration could create the conditions for further radicalisation within Rohingya communities.

The Association of South East Asian Nations (ASEAN) has yet to come to grips with the situation. Despite its mandate to ensure peace and stability within the region, its policy of non-interference and consensus trumps the need to secure and maintain stability. Instead countries have responded bilaterally - for example, Indonesia sent its foreign minister to both Myanmar and Bangladesh while Malaysia has been consistently vocal about its concerns.

So this raises broader questions on the effectiveness of ASEAN. Currently celebrating its 50th anniversary, ASEAN needs to decide how to mediate and resolve issues with regional implications as its principle of non-intervention effectively blocks any constructive discussion on the Rohingyas ongoing statelessness and impact of this on the region.

However, there is also an opportunity here for ASEAN to consider how mediation and negotiation could potentially manage such crises. And there is a historical precedent: the 1989 Comprehensive Plan of Action on Indo-Chinese refugees saw cooperation between recipient countries in the region and the international community on how to resettle Vietnamese refugees (although Cold War considerations did play a part in that specific crisis).

India and China have both backed Myanmar, reflecting their economic and security interests in the country but also motivated by each wanting to contain the influence of the other within Myanmar. Rakhine is important with its natural resources and coastal location and, as China is not directly affected by the refugee crisis, it has less to lose than others in standing by Aung San Suu Kyi and her government.

India is nearing completion of the Kaladan Multi-modal Transit Transport Project, connecting the Bay of Bengal with the northeast Indian state of Mizoram, and sees Myanmar as an important market for its regional ambitions. For parts of the Indian administration, the crisis plays to a domestic narrative that some of the Rohingya already settled in Jammu and Kashmir have links to armed groups in Pakistan and are an internal security concern.

So while India is providing humanitarian aid to Bangladesh, it is also threatening to deport almost 40,000 Rohingya. The case is currently being heard at the Indian Supreme Court, but given that the Rohingya lack citizenship in Myanmar, it is not clear to where they would be deported.

Myanmar, ASEAN and other affected countries need to show political will to find a solution to the Rohingya’s long-standing issue of statelessness - discrimination was legally formalised in a 1982 Burma Citizenship Law, which recognised 135 ethnicities for citizenship but excluded the Rohingya.

The root causes of this crisis – long standing discrimination, persecution and lack of citizenship – cannot be ignored. There is a need for a comprehensive peace process, which recognises the ethnic and religious diversity within Myanmar.

And incentives, such as improving infrastructure, access to services and livelihoods, may also be needed to ensure there is a lasting solution that allows the Rohingya return and thrive as part of Myanmar society.

Without such a response, it is difficult to see an end to the current impasse.

Sangsan Warakkagun
Conform. Geom. Dyn. 28 (), 115-130.
Abstract, references and article information

Otto Overkamp
Trans. Amer. Math. Soc. 377 (), 5863-5903.
Abstract, references and article information

Anne-Miek Bibbe posted a photo:

JOEPIE: I'm almost there! I wish Uncle Jeroen was here, I'm a little, really just a little bit afraid of the dark.
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JOEPIE: Ik ben bijna bij Peter! Ik wou dat oom Jeroen hier was, ik ben een beetje, echt maar een héél klein beetje bang in het donker.

Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'...

Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection.

Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity.

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Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure.

3 July 2020