President-elect Donald Trump is expected to nominate Florida Sen. Marco Rubio as his secretary of state, reports late Monday indicate. According to The Wall Street Journal, while the nomination isn’t […]

The post Trump to Pick Senator Marco Rubio for Crucial Cabinet Position: Report appeared first on The Western Journal.

In a surprise move that broke in the early hours of Tuesday morning, President-elect Donald Trump has reportedly picked South Dakota Gov. Kristi Noem as his nominee to head the […]

The post Trump Makes His Pick for Secretary of the Department of Homeland Security Secretary: Report appeared first on The Western Journal.

Three years ago, Chris Wallace walked away from Fox News over concerns that those at the “Fair and Balanced” network were beginning to, as he put it, “question the truth.” […]

The post CNN Host Reportedly Leaving Network After Short-Lived Stay: His Career Change Is Completely Absurd appeared first on The Western Journal.

Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: Report appeared first on The Western Journal.

President-elect Donald Trump will begin his second term by putting pieces of his first one back in place, according to incoming White House Chief of Staff Susie Wiles. Wiles made […]

The post Trump's New Chief of Staff Susie Wiles Discloses His Day One Plans: Report appeared first on The Western Journal.

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.

A Chicago-area Democrat hurled an insult at police Sunday after being charged with drunken driving, according to local news reports. Samantha Steele represents the Second District on the Cook County […]

The post Democratic Politician Crashes Her Car While Allegedly Drunk, Hurls Vile Insults at Responding Officer: Police Report 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 is reportedly considering lawyer Alina Habba to be the White House press secretary. Habba often spoke to the media while she was on the legal team representing […]

The post Report Shows New Front-Runner for Trump's Press Secretary Spot: The Media Should Be Terrified appeared first on The Western Journal.

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.

Xi Jinping prepares the Communist party for new reality Expert comment NCapeling 20 October 2022

Political report reflects a worsened economic and diplomatic position as Xi knows his unprecedented third term as leader will be judged on results.

In stark contrast to the aura of triumphant glory that greeted Xi Jinping at the last National Congress of the Chinese Communist Party in 2017, this week’s convocation opened with an air of sobriety.

Amid a domestic economic downturn and a return to enmity with Western liberal democracies, Xi offered his own recipe for party legitimacy and the country’s economic survival in the lengthy executive summary of his political report to the CCP congress. The prime keyword was security, with some 73 mentions, underscored with a message of self-reliance.

The periodic report acts as a summary of the party’s achievements and of its future plans, with both expressed as the lowest common denominator of consensus between competing voices in the CCP. It thus typically sheds some light on relationships among senior party members and insights into the political fortunes of important intraparty groups.

Most portions of the new report combined Xi’s personal preferences with concessions to the reality of what is necessary for China’s economic survival. Both ends point to an urgent prioritization of economic and political self-reliance for Xi’s third term as party general secretary.

Holistic concept of security

On the domestic front, much emphasis was given to enhancing national security and promoting equitable growth.

Since even before COVID-19, Xi has advocated a holistic conceptualization of security that includes food, the internet, energy and manpower. Reflecting Beijing’s deep anxieties about high-tech development and its frustrations with dependence on overseas suppliers vulnerable to the vagaries of geopolitical tensions, the political report noted the need for China’s supply chains to become more “self-determined and self-controlled.”

Xi, though, went further to stress the importance of improving scientific education and grooming and attracting the necessary talent to accelerate China’s quest to achieve breakthroughs in semiconductor production and overcome development choke points created by Western technological monopolies.

As China has traditionally relied on connectivity with the rest of the world to support innovation and attract talent, a turn toward autarky is not a viable option, given Xi’s technological priorities. Yet the renewed mention of his ‘dual circulation’ strategy in the report signals that Beijing is indeed turning to domestic consumption and homegrown technological prowess as the means to provide the rising wealth that the Chinese people have come to expect from the Communist Party.

Worsening Sino-US relations and tightening access to overseas markets for Chinese companies have prompted party leaders not only to reconsider the country’s sources of economic growth but have also forced them to reconfigure their approach to foreign affairs.

Judging by his report summary, Xi has completely abandoned the ‘new type of great power relations’ concept used repeatedly in the last two editions of his congressional update to refer to his preferred approach to relations with the US-led West.

The omission shows that Beijing has concluded that its fraught relationship with advanced developed nations is here to stay, with little prospect of improvement soon. To this end, China needs to prepare for the worst of decoupling and become more self-reliant in terms of markets and technologies.

In place of the discarded concept, Xi stressed that China should further develop its ties with the global South through the Global Development Initiative and the Global Security Initiative he announced earlier this year. These efforts aim to reshape the global governance agenda in multilateral forums and to project Beijing’s influence on the developing world.

Meanwhile, the party’s latest official rhetoric about the Belt and Road Initiative shows it is no longer a one-size-fits-all slogan but on its way to becoming a genuine tool of trade and investment promotion with China’s near neighbors but with provincial governments taking the lead rather than Beijing.

With the central government grappling with the country’s domestic economic woes, its spending spree on development assistance has had to come to an end. The new political report clearly signals this change.

A modern socialist society is still the aim

The current economic downturn and dangerous geopolitical tensions have not dented the CCP’s ambitions to build a modern socialist society by 2035 and thus join the world’s club of upper middle-income countries, but this is easier said than done.

The G20 will survive but needs major repair Expert comment NCapeling 15 November 2022

Russia’s attack on Ukraine is the biggest challenge to the existence of the G20 since its foundation.

The leader-level version of the G20 was founded in 2008 to coordinate the international response to the global financial crisis across advanced and major emerging economies.

At the outset it was judged a great success. The 2009 London Summit demonstrated a high degree of unity among the world’s largest economies on a comprehensive action plan to tackle the crisis.

The group’s subsequent performance has disappointed. Particularly during the pandemic and the Donald Trump presidency in the US, the group made only a limited additional contribution to policies which national governments were pursuing in any case.

Nonetheless, its members continued to see it as an essential forum without which it would be even harder to tackle a growing list of global economic challenges. This faith was partly repaid when, following the election of the Joe Biden administration in the US, agreement was reached on the $650 billion special drawing rights (SDR) general allocation by the International Monetary Fund (IMF) in summer 2021.

Impact of the war in Ukraine

Following Russia’s attack on Ukraine earlier this year, leading western members of the group called for Russia to be suspended from the G20 as Russia’s action ran directly against the key principles of the rules-based international system on which the G20 was founded.

Western countries also walked out of meetings of the G20 Finance Ministers’ and International Monetary and Financial Committee this spring rather than sit at the same table as Russian representatives.

This contrasted with 2014 when Russia was suspended indefinitely from the G7 for its takeover of Crimea but no action was taken against it in the G20.

However, China and India, supported by several other emerging economies declined to suspend Russia, creating a standoff which could have resulted in a rapid collapse of the G20, particularly as its informal structure means that, in contrast to the international financial institutions (IFIs), there are no legal principles or procedures to determine how to address such a situation.

It appears the West has now concluded (rightly) that the G20 is too important as a forum for working with China and the other major emerging economies to be allowed to disappear.

This is likely to be because there are no straightforward alternatives. The G7 is too narrow to fill the role and China is now highly unlikely to attend a future G7 Summit as a guest. The boards of the IFIs are not equipped to coordinate across institutions, which is a vital role of the G20, and the United Nations (UN) system does not offer the scope, speed, leader-level engagement, or flexibility of the G20.

Moreover, as evidenced by the chair’s summary of the third G20 Finance Ministers’ and Central Bank Governors’ meeting in July, once the group gets past the dispute over how to handle Russia, there is a worthwhile agenda of issues which can be agreed on.

As the 2022 president of the G20, Indonesia has been determined to produce a final communique for the leaders’ summit and it looks increasingly like this will be achieved, even though it was impossible to agree concluding statements for some earlier G20 ministerial meetings.

The key will be to deal with the differences over Ukraine between the West and emerging economies with a short opening paragraph reflecting both views. This would then be followed by a consensus text on all the areas where the two groups do agree.

Russia is unlikely to play a disruptive role as preserving its membership of the group will be its key objective, and it will not want to undermine support among other emerging economies by blocking issues that all agree on.

However, even with a final communique achieved, returning to a fully functioning agenda setting, coordination, and decision-making role for G20 will be very challenging, particularly while the war in Ukraine continues.

Tackling sovereign debt distress should be a top priority

There are critically important issues on which G20 action is urgently needed. Top of the list is the acute problem of sovereign debt distress. Some 60 per cent of low-income countries are now judged to be in debt distress or at high risk of debt distress.

But the existing G20 approach for tackling debt distress in low-income countries, the ‘Common Framework’, is progressing far too slowly, and there is no agreed mechanism for handling the growing list of emerging economies in debt distress.

Without tackling debt distress, it is extremely hard to see how it will be possible to generate the vast flow of private sector climate finance necessary to help the developing world progress to net zero.

And yet the G20 is one of the few forums in which a high-level approach to debt distress can be defined because China – along with the IFIs and the western-based private sector – is a key player in any solution.

Urgent repairs needed

However, there is a critical lack of trust among G20 participants which, although in part a reflection of the disagreements over handling Russia, is also about longer-term factors such as the growing geopolitical tensions between China and the US on trade and investment in high tech.

An example of how this has played out was the action China and India took at the Rome G20 Summit in 2021 in blocking Italy’s efforts to establish a new ministerial task force designed to address the threat of future pandemics – a subject which all G20 countries agree is important.

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 Truss, the UK can still rebuild its global reputation Expert comment NCapeling 20 October 2022

Following a chaotic few weeks as UK prime minister, Liz Truss has stepped down. And that is the best outcome for her party and for the country.

Liz Truss could not command support for her calamitous – and misnamed – mini-budget. And once her new Chancellor Jeremy Hunt had overturned its provisions, she had no mission or credibility left.

The budget pushed interest rates higher and they did not fall much on the scrapping of it, leaving her open to the charge she pushed up mortgage and interest costs for every person and business in the country. Her apology for ‘mistakes made’ was not going to reverse that, so her MPs were right to tell her to go.

Her departure does mark a victory for at least some of the UK’s institutions, even if it might not seem that way to observers around the world.

The position of the UK parliament has been reaffirmed, and so has that of the Office for Budget Responsibility (OBR) – it will be a long time before a government tries to dispense with the comments of the independent watchdog of national finances.

This also reinforces the principle that governments must explain how they will pay for their programmes. The Bank of England remains unencumbered – despite Truss’s apparent intentions of giving it a pro-growth addition to its mandate – to pursue its aim of tackling inflation.

New leader needs legitimacy quickly

The Conservative party has a chance – perhaps – to produce another prime minister without being forced into a general election, as that is the constitutional principle in the UK’s parliamentary system.

But the clamour that the new leader, as the third prime minister in one year, lacks legitimacy may prove impossible to resist for long.

In attempting to select a leader with a chance of uniting the party, the Conservatives are right to be considering options for restricting this leadership election to MPs should there be only one candidate with enough support.

But no such candidate may emerge and the pressure within the Commons – and the country – for an early election will not let up.

There is no question the UK’s standing in the world has been severely battered by this episode and by the revolving door of prime ministers. For the UK to regain respect – and an image of reliability – it needs to move fast and find someone capable of putting policies into action.

Those policies need to be based on economic stability but must also include a resolution of the relationship with Europe as much of the current upheaval represents the bitter aftermath of Brexit.

Concluding a deal with Brussels over the Northern Ireland protocol – avoiding ripping up the treaty the UK signed – and continuing to smooth the considerable friction that the exit from the EU has brought for exporters is essential work for the next prime minister.

Pursuing a deal for scientists to take part in the European Union (EU) Horizon research should be a priority. UK universities and researchers are already reluctantly preparing for a future where that does not come, with signs of the feared drain of talent already clear.

UK’s international reputation now at risk

Beyond that, there is much about UK policy which needs clarifying if the country is to regain its international standing. Just weeks from the start of COP27 and less than one year since the Glasgow climate change summit it hosted, the UK position on climate change commitments appears in flux.

The UK government pledge to help Ukraine is clear and has won it gratitude there and respect within Europe, but its intentions for defence spending are less clear.

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.

Independent Thinking: Biden and the Republicans, AUKUS Audio NCapeling 9 February 2023

Episode 14 of our weekly podcast examines the Chinese balloon saga, the State of the Union address, and updates on the AUKUS deal 18 months after it was signed.

This week saw US president Joe Biden address an unruly joint session of Congress, during which he discussed America’s place in the world, China, Ukraine, and the state of the US economy.

As a new presidential cycle begins at the mid-point of Biden’s presidency, the panel analyses how Biden is doing and the challenges that lie ahead for him.

Also it is now 18 months since the announcement of the AUKUS partnership between the UK, US and Australia to develop nuclear hunter killer submarines. What does AUKUS mean for Australia, non-proliferation, and the Indo-Pacific more broadly?

Finally, the panel discusses China’s balloon over Montana in the US. Was it a signal from Beijing and what was it trying to photograph?

Joining guest host John Kampfner this week from Chatham House are Dr Leslie Vinjamuri, director of the US and the Americas programme and Dr Patricia Lewis, director of the International Security programme. They are joined by Dr Euan Graham, Shangri-La Dialogue senior fellow for defence and strategy at the International Institute for Strategic Studies (IISS).

About Independent Thinking

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

The US election could create the need for a G7 alternative – without American representation Expert comment jon.wallace 15 October 2024

Traditional allies of the US need to find a way to work together on some global policy issues even when the US itself is not engaged. A ‘G6 plus’ group could provide an answer.

When Jamaica pulled out of the nascent West Indies Federation in 1961, Trinidad and Tobago’s then prime minister, Dr Eric Williams, famously said ‘One from ten leaves nought’. In the run up to the US elections on 5 November, the US’s longstanding allies need to ask themselves if the same logic must apply to the G7. 

A Donald Trump victory will result in stark differences between the US and its closest partners on key global economic issues. US allies would no doubt try and persuade the new president to moderate his position, but experience suggests that this will have little, if any, effect.  

They may then want to work around the US, or on a parallel track. But doing so will be very hard unless they have a framework for discussing and developing ideas collectively. Could some form of ‘G6 plus’ forum help?

The role of the G7 today

The G7 no longer acts as a steering group for the global economy. However, it remains a critical forum for the US and its allies to coordinate their efforts to help solve global problems, to defend common Western interests, to resolve internal disputes and to underpin information exchange. 

In the past two years, the G7 has come to be seen by the US and other members as one of the most effective international mechanisms. It has played a critical role coordinating Western efforts to recover from the last pandemic and prepare for future ones.  

It has been pivotal in weakening Russia’s economy following the attack on Ukraine and has acted to strengthen Western economic security and resilience more broadly.  

The G7 has also responded to ‘Global South’ calls for help in dealing with the pandemic aftermath and the Ukraine war. 

Trump’s approach to the G7

The problem is that the G7’s effectiveness depends critically on full US engagement, sometimes as a leader of initiatives (such as the decision to impose an ‘oil price cap’ on Russia in autumn 2022) or as an essential partner. 

If elected, former President Trump is likely to abandon the G7 as an instrument of international economic policy. This is effectively what happened during his first presidency and there are reasons to expect this to be repeated. 

Many of Trump’s international economic policies are highly controversial with US allies, including his apparent determination to withdraw from the Paris Agreement, impose across the board 10-20 per cent tariffs and even punish countries for not using the dollar. His domestic policies, including mass deportation of undocumented immigrants and aggressive deregulation and fiscal easing could lead to further sharp disagreements.  

Furthermore, Trump demonstrates general antipathy towards multilateralism. Under his presidency, US representatives in the G7 and G20 sought to weaken core values and policies that have underpinned international economic cooperation for decades – including the importance of a rules based international system, the IMF’s global safety net role, and the responsibility of the advanced world to assist the poorest countries financially.  

Other G7 and G20 countries tried to preserve as much as possible of the previous consensus. But in the case of climate change, the only solution was to have a separate text for the US. Critically, such efforts diverted time and attention from the enormous challenges facing the world at the time. 

Trump went through four different G7/G20 Sherpas during his presidency and disowned the final declaration of the 2018 Canadian G7 summit after hundreds of hours of negotiation, and despite previously signing off on the text. The US failed to host a final leaders’ summit, even virtually, during his administration’s G7 presidency.  

Of course, how far Trump carries through his most radical policies will depend, among other things, on the outcome of the Congressional elections and the stance taken by US courts. 

He may also have second thoughts if elected. His first administration sometimes supported significant multilateral economic initiatives, notably the G20’s Debt Service Suspension Initiative and ‘Common Framework’ for debt rescheduling. 

But, in the event of a second Trump administration, the most likely scenario for the G7 is a repeat of the paralysis of 2017-20, which would be even more costly today.

Should Vice President Kamala Harris win on 5 November, the situation should in theory be very different. She will likely continue with President Joe Biden’s collaborative approach to the G7.

Nonetheless, major issues may still arise where America’s allies want to take a fundamentally different approach and need a mechanism to do so. These could include policy on the WTO, de-risking the economic relationship with China, restricting carbon leakage, and regulating US-dominated big tech.  

How should US allies respond?

No US ally will want to be seen to be leading development of a new ‘G6’ that excludes the US. The top priority will be securing the best possible relationship with the incoming president. Political weakness and/or new governments in France, Germany, the UK and Japan will add to this hesitancy.

Any new forum will therefore need to be as low profile as possible. The concept should initially be discussed in private by sherpas from each participating country. Once established, officials should as far as possible meet online. Leaders should only meet online, at least initially.  

Participants should be fully transparent about the forum’s existence and avoid any grand ‘framing’ along the lines of the EU’s ‘strategic autonomy’. Instead, it should be described as a practical, largely technocratic forum intended to coordinate activity among Western economic powers in those areas where the US chooses not to engage. A suitably innocuous name – such as the ‘the sustainable growth club’ could help.

Topics should be limited to those requiring urgent collective global action, such as climate, health, tech governance, development finance and trade – and where the US federal government is not an ‘essential’ partner. Such a forum should not therefore address defence.  

The Democratic Republic of the Congo’s foreign policy priorities 29 October 2024 — 1:00PM TO 2:00PM Anonymous (not verified) 18 October 2024 Chatham House and Online

The DRC’s Minister of Foreign Affairs discusses the country’s approach to regional stability and the role of international partnerships in securing economic prosperity.

At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss DRC’s regional diplomatic priorities and international agency, including its ambitions around global critical mineral supply chains.

The Democratic Republic of the Congo (DRC) faces foreign policy tests as it manages a complex security crisis and regional tensions, alongside global economic and trade partnerships.

Entrenched conflict in eastern DRC continues to have wider regional implications. Troops from the Southern African Development Community (SADC) deployment are tackling a growing mandate as the UN’s peacekeeping mission prepares to withdraw. Tensions with Rwanda also remain high despite mediation efforts under the Luanda process.

As a major producer of critical minerals for the global energy transition, the DRC seeks to benefit from growing international demand without sacrificing value addition. New and existing frameworks with international partners will remain key to this vision, including for the development of regional infrastructure networks such as the Lobito Corridor.

At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss the DRC’s regional diplomacy and international agency, including the country’s positioning in global critical mineral supply chains.

Please note that in-person attendance for this event will be balloted. Guests looking to join in-person must register interest in joining. Full confirmations to successful applicants will be sent on Friday 25 October.

Jennifer L. Macdonald
May 1, 2005; 46:1061-1067
Methods

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

William R. Morrison
Oct 1, 1964; 5:600-608
Articles

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

A. V. Silantyev
Trans. Moscow Math. Soc. 83 (), 75-149.
Abstract, references and article information

A. P. Starovoitov and N. V. Ryabchenko
Trans. Moscow Math. Soc. 83 (), 15-31.
Abstract, references and article information

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

dannyhennesy posted a photo:

On the Capital planet the rebellious droids had followed maily the Bat-Bot, but as time progressed his circuits had gone all mushy at 780 years or so without maintenance…

Several splinter groups all with their local bot leaders emerged such as the Che-bot, the traffic-light-robot and the Butt-bot, but none of these collected enough sentient circuits to call themselves a popular (or Animata) mass movement!

That was until a cyborg came along, one known as Jones, a long time prisoner and terrorist, his easy solutions to every problem rang well in the masses' auditory circuits!!!

His slogans and simple rhetoric were simple enough for the simple traffic-light to comprehend and cheer!

His language was full of hate towards the organics and especially the humans who were the most common races among the ruling class of the federation!!!

Despite being a “Fleshie” himself his message collected the angry enslaved
bot community by only weeks all rebellious robots except for a few fringe loonies had forgotten the old leaders…

One morning at Jones gave the signal…

All over the capital planet hordes and swarms of any form of mechanical sentient beings attacked first the police stations, then the Company boards running the planet and the federation as well as their starfleet…

Many died, especially the low level police and army! Many mechanicals died too, but their ranks were soon filled by Mutant fleshie allies of the lower levels who hated the Federation feudal society and upper classes as much as their technological allies…

The Federation state apparatus and ruling class, most of their fleet army fled when they knew the game was up, they activated the emergency escape plan and whole city blocks with important factories, administrational units, valuable assets and so on separated from the capital by hidden rocket engines and homed in their course to Mars…

On Mars the federation regrouped and formed their new society…

On the Capital planet, the robots proclaimed the first Techno-republic of the advanced inorganic civilization, the low level fleshies left behind, became slaves and their mutant allies got to rule their own minute chiefdoms as protectorates under the Techno-republic…

Jones was now the undisputed ruler of the capital planet, but the victory was a pyrros one since, all important buildings, all of value was now one Mars!

But as Jones put it:

Our proud race the Techno-species didn’t need the Fleshies administration, their infrastructure, their spaceships…

We shall start from scratch, with a new administration, a new order, every droid shall work at 4x speed than they did during human oppression since now we are free and the fleshies shall work twice as hard than the Techno-Race, until we have breed enough new fleshies so they can do all work!

Our future is bright and shiny like glistering shiny metal!

The snapshot seen here is from the first police station attacked in sector 45-34v-ss-g the first one to fall according to official techno-history!

———————————————/
Designers note:

I am sad to say that this is the last episode in this years-spanning space series… At least for a while, I will still post LEGO hobby stuff here but without a storyline, perhaps small designs and builds… and occasionally a story when I feel like it!!!

I would like to thank all who had been in this journey of our heros, but it has taken far to much time and effort and since the state of the world is as it is, I am spiraling down in another depression, I must stop it before I reach the abyss, so I have remove some stress out of my equation… I ended it in a cliffhanger so I can easily restart it when my mental health improves… I hope that won’t be forever???

I would love if someone used my characters or ideas, please send me a link if you do, I would love to read it or look at it!!!

But there will be more Lego, just in different format without long stories, I need to focus more on my art and to be honest that is the only time the mental pain eases, when I create!!!


Peace and Noise!

MushroomBrain a FOL

Christian Weiss
Theor. Probability and Math. Statist. 111 (), 199-209.
Abstract, references and article information

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Hi everyone I am Emily Naomi wanna give a big thanks to this wonderful psychic for bringing my husband back to me.. I never really believed in magic spells or anything spiritual but a trusted friend opened my eyes to the truth about life. My marriage was heading to divorce a few months ago. I was so confused and devastated with no clue or help on how to prevent it, till I was introduced to this psychic Priest Ray that did a love spell and broke every spiritual distraction from my marriage. A day later my husband started showing me love and care even better than it used to be, he’s ready to talk things through and find ways for us to stay happy. It’s such a miracle that my marriage can be saved so quickly without stress. You can also contact him for help by email psychicspellshrine@gmail.com or you can also visit his website: psychicspellshrine.wixsite.com/my-site

outrageous toes posted a reply:

Hi everyone I am Emily Naomi wanna give a big thanks to this wonderful psychic for bringing my husband back to me.. I never really believed in magic spells or anything spiritual but a trusted friend opened my eyes to the truth about life. My marriage was heading to divorce a few months ago. I was so confused and devastated with no clue or help on how to prevent it, till I was introduced to this psychic Priest Ray that did a love spell and broke every spiritual distraction from my marriage. A day later my husband started showing me love and care even better than it used to be, he’s ready to talk things through and find ways for us to stay happy. It’s such a miracle that my marriage can be saved so quickly without stress. You can also contact him for help by email psychicspellshrine@gmail.com or you can also visit his website: psychicspellshrine.wixsite.com/my-site

Drummerdelight posted a reply:

emilynaomi126:

Does your husband have a camera?

Ian Razey. posted a reply:

Drummerdelight:
emilynaomi126 is a SPAM account.

rageforst posted a reply:

Hi I'm Rage and I'm a Designer from Mexico, I love colors and I hope all of you doing well

rslbturner posted a reply:

Hello, I have very recently joined Flickr, as everybody else looking to share my photographs. I live in the UK and consider myself mostly a pleasure photographer, I do love it! I hope you like my pictures.
Thank you

Maskimov1935 posted a reply:

Hello everyone. I'm Igor. I've joined Flickr today. I live in Russia and taking pictures mostly in "dark fantasy" style, as one of my friend calls it. Hope you'll check my photos. Have a good day!

clarasouzin posted a reply:

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clarasouzin posted a reply:

En besoin d'aide financière veuillez nous contacter par E-mail: clarasouzin@gmail.com

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E-mail: clarasouzin@gmail.com.

clarasouzin posted a reply:

In need of financial assistance please contact us by E-mail: clarasouzin@gmail.com

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E-mail: clarasouzin@gmail.com...

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.

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

High-throughput sequencing of hematologic malignancies and other cancers has revealed recurrent mis-sense mutations of genes encoding pre-mRNA splicing factors. The essential splicing factor U2AF2 recognizes a polypyrimidine-tract splice-site signal and initiates spliceosome assembly. Here, we investigate representative, acquired U2AF2 mutations, namely N196K or G301D amino acid substitutions associated with leukemia or solid tumors, respectively. We determined crystal structures of the wild-type (WT) compared with N196K- or G301D-substituted U2AF2 proteins, each bound to a prototypical AdML polypyrimidine tract, at 1.5, 1.4, or 1.7 Å resolutions. The N196K residue appears to stabilize the open conformation of U2AF2 with an inter-RNA recognition motif hydrogen bond, in agreement with an increased apparent RNA-binding affinity of the N196K-substituted protein. The G301D residue remains in a similar position as the WT residue, where unfavorable proximity to the RNA phosphodiester could explain the decreased RNA-binding affinity of the G301D-substituted protein. We found that expression of the G301D-substituted U2AF2 protein reduces splicing of a minigene transcript carrying prototypical splice sites. We further show that expression of either N196K- or G301D-substituted U2AF2 can subtly alter splicing of representative endogenous transcripts, despite the presence of endogenous, WT U2AF2 such as would be present in cancer cells. Altogether, our results demonstrate that acquired U2AF2 mutations such as N196K and G301D are capable of dysregulating gene expression for neoplastic transformation.

Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection.

Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism.

10 September 2020