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Optimizing boosters: How COVID mRNA vaccines reshape immune memory after each dose

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mRNA vaccines developed against the spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2), displayed remarkable efficiency in combating coronavirus 19 (COVID-19). These vaccines work by triggering both cellular and humoral immune responses against the spike protein of the virus. Cellular immunity may play a more protective role than humoral immunity to variants of concerns (VOC) against SARS-CoV-2, as it targets the conserved regions of spike protein and possibly cross-reacts with other variants.

Since a single spike epitope is recognized by multiple T-cell clones, the mRNA vaccination-induced T-cell response may consist of multiple spike-reactive clones. Thus, it is important to understand the mechanism of mRNA vaccination-induced cellular immune response. However, to address this clonal-resolution analysis on T-cell responses to mRNA vaccination has not been performed yet.

To bridge this gap, a team of researchers, led by Associate Professor Satoshi Ueha, including Professor Kouji Matsushima from the Tokyo University of Science (TUS), Japan, Mr. Hiroyasu Aoki from the University of Tokyo, and Professor Toshihiro Ito from Nara Medical University, aimed to develop a kinetic profile of spike-reactive T-cell clones during repetitive mRNA vaccination. For this, they performed a longitudinal TCR sequencing on peripheral T cells of 38 participants who had received the Pfizer vaccine from before the vaccine to after the third vaccination and then analyzed the single-cell gene expression and epitope specificity of the clonotypes.

Their findings, published in Cell Reports on March 7, 2024, revealed that while the primary T-cell response of naïve T cells generally peaked 10-18 days after the first shot, expansion of “early responders” was detected on day 7 after the first shot, suggesting that these early responders contain memory T cells against common cold coronaviruses. They also found a “main responder” that expanded after the second shot and did not expand early after the first shot and a “third responder” that appeared and expanded only after the third shot.

By longitudinally tracking the total frequency of each response pattern, it was observed that, after the second shot, a shift among the clonotypes occurred, wherein the major population changed from early responders to main responders, suggestive of a shift in clonal dominance. A similar shift of responding clones was also observed in CD4+ T cells.

Expanding upon the research process, Prof. Ueha says, “We next analyzed the phenotype of main responders after the second and the third vaccination. The results showed that the main responders after the second and third shots mostly consist of effector-memory T cells (TEM), with more terminally differentiated effector memory-like phenotype after the third shot.”

The researchers then examined the repertoire changes of main responders, revealing that the expansion of main responders, which occurred after the second shot, diminished following the third shot, and the clonal diversity decreased and was partially replaced by the third responders. This may potentially mean that the third vaccination selected better-responding clones.

Due to the vaccination-induced shift in immunodominance of spike epitopes, the study supports the inter-epitope shift model. In addition, there were intra-epitope shifts of vaccine-responding clonotypes within spike epitopes.

Prof. Ueha explains the significance of these results, “Our analysis suggests that T cells can “re-write” themselves and reshape their memory populations after successive vaccinations. This re-writability not only maintains the number of memory T cells but also maintains diversity that can respond to different variants of pathogens. Moreover, by tuning the replacement of memory cells, more effective vaccines can be developed that can also be tailored to an individual’s unique immune response.”

Overall, this study provides important insights into mRNA vaccine-induced T-cell responses, which will be crucial for developing next-generation vaccines for more effective and broad protection against viruses.

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Pushing the boundary on ultralow frequency gravitational waves

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A team of physicists has developed a method to detect gravity waves with such low frequencies that they could unlock the secrets behind the early phases of mergers between supermassive black holes, the heaviest objects in the universe.

The method can detect gravitational waves that oscillate just once every thousand years, 100 times slower than any previously measured gravitational waves.

“These are waves reaching us from the farthest corners of the universe, capable of affecting how light travels,” said Jeff Dror, Ph.D., an assistant professor of physics at the University of Florida and co-author of the new study. “Studying these waves from the early universe will help us build a complete picture of our cosmic history, analogous to previous discoveries of the cosmic microwave background.”

Dror and his co-author, University of California, Santa Cruz postdoctoral researcher William DeRocco, published their findings Feb. 26 in Physical Review Letters.

Gravitational waves are akin to ripples in space. Like sound waves or waves on the ocean, gravitational waves vary in both frequency and amplitude, information that offers insights into their origin and age. Gravitational waves that reach us can be oscillating at extremely low frequencies, much lower than those of sound waves detectable with the human ear. Some of the lowest frequencies detected in the past were as low as one nanohertz.

“For reference,” Dror explained, “the frequency of sound waves created by an alligator roar are about 100 billion times higher than this frequency — these are very low-pitched waves.”

Their new method of detection is based on analyzing pulsars, neutron stars that emit radio waves at highly regular intervals. Dror hypothesized that searching for gradual slowdown in the arrivals of these pulses could reveal new gravitational waves. By studying existing pulsar data, Dror was able to search for gravitational waves with lower frequencies than ever before, increasing our “hearing range” to frequencies as low as 10 picohertz, 100 times lower than previous efforts that detected nanohertz-level waves.

While gravitational waves with frequencies around a nanohertz have been detected before, not much is known about their origin. There are two theories. The leading idea is that these waves are the result of a merger between two supermassive black holes, which, if true, would give researchers a new way to study the behavior of these giant objects that lie at the heart of every galaxy.

The other main theory is that these waves were created by some sort of cataclysmic event early in the universe’s history. By studying gravitational waves at even lower frequencies, they may be able to differentiate these possibilities.

“Looking ahead, the next step is to analyze newer data sets,” Dror said. “The datasets we used were primarily from 2014 and 2015, and a huge number of pulsar observations have been undertaken since that time.”

Dror also plans to run simulations on mock data using UF’s HiPerGator supercomputer to further unravel cosmic history. The supercomputer can efficiently run large, complex simulations, significantly reducing the time required to analyze data.

This study was supported in part by the National Science Foundation and the Department of Energy.

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The Ups and Downs of World Politics

The Ups and Downs of World Politics

The Current Political Landscape

The Current Political Landscape

Politics has always been a hot button topic, especially for those who are passionate about social justice, governance and human rights. The year 2021 has been no exception, with controversial and unprecedented events unfolding on the global political stage.

The rise of far-right extremism has been particularly alarming, with many countries witnessing an increase in hate crimes against minority groups. The global pandemic also had a profound impact on politics, exposing the flaws in healthcare systems, government response mechanisms and economic structures. Governments all around the world were forced to take a hard look at their failings and address the urgent need for reform.

The Role of Political Leadership

The Role of Political Leadership

The actions of political leaders can have far-reaching consequences, both positive and negative. Leaders who prioritize the well-being of their citizens, respect human rights and work towards a fairer and more equitable society are essential for the betterment of humanity. Conversely, leaders who spread hatred, disregard democratic institutions and manipulate the masses for personal gain can lead to disastrous consequences.

The recent election in the United States brought forth a glimmer of hope, with the election of Joe Biden as President. Biden has promised to prioritize the fight against climate change, tackle systemic racism and put an end to the COVID-19 pandemic. His administration has also signaled a shift towards multilateralism and a commitment to working with international organizations to tackle global issues.

The Power of Mass Movements

The Power of Mass Movements

Beyond political leadership, mass movements have a crucial role to play in shaping the political landscape. The Black Lives Matter movement, for instance, brought the issue of systemic racism to the forefront of public consciousness and led to widespread protests and demonstrations. The #MeToo movement similarly shed light on the pervasive issue of sexual harassment and assault.

Mass movements have the power to hold political leaders accountable, increase public pressure for change and mobilize communities towards a common cause. It is their collective action that can bring about real change and drive progress towards a more just and equitable society.

The Road Ahead

The Road Ahead

The road ahead is fraught with challenges, but there is also reason for hope. There is growing awareness and action towards important issues like climate change, racial and social justice, gender equality and healthcare reform. Political leaders, activists and everyday citizens all have a role to play in creating a better future for all.

It is up to us to use our collective voices and demand more from our leaders, hold them accountable and push for reforms that can bring about lasting change. Only then can we hope to build a more just, equitable and peaceful world.

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The Role of Politics in Shaping Society

The Role of Politics in Shaping Society

Introduction

Politics plays an integral role in shaping society as we know it today. It is the driving force behind every decision made by our governments, influencing not just our daily lives but also the future of our nations.

The Purpose of Politics

The Purpose of Politics

The purpose of politics is to establish and maintain order within a society. This includes creating and enforcing laws, distributing resources, and providing public services. It also involves the representation of citizens at various levels of government and ensuring their voices are heard.

The Impact of Politics on Society

The Impact of Politics on Society

Politics has a profound impact on every aspect of society, from economics and education to healthcare and the environment. The policies and laws implemented by governments significantly influence the lives of their citizens, determining access to vital resources and shaping the overall quality of life.

The Importance of Political Engagement

The Importance of Political Engagement

Political engagement is essential for a healthy and functioning democracy. Voting, attending town halls and participating in peaceful protests are ways citizens can help shape the policies and decisions being made by their elected officials. A lack of political engagement not only leads to a disengaged and uninformed electorate, but it leaves decisions to be made by a small group with their own interests in mind.

The Future of Politics in Society

The Future of Politics in Society

As the world continues to change and evolve, so too will politics. Technological advancements and the growing importance of global issues such as climate change will undoubtedly shape the political landscape of the future. It is up to our leaders and citizens to adapt and respond in an effective and responsible manner.

Conclusion

In conclusion, the role of politics in shaping society cannot be overstated. It is the cornerstone of our governments and the driving force behind our collective futures. As active and informed citizens, we must engage in the political process to ensure our voices are heard and our communities are represented appropriately.

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Politics

The Art of Politics: Understanding the Game of Power

The Art of Politics: Understanding the Game of Power

The Essence of Politics

The Essence of Politics

Politics is the art of influencing and making decisions that affect the world we live in. It is a complex and multifaceted field that encompasses a range of activities, from election campaigns and policymaking to diplomacy and conflict resolution. At its core, politics is about bringing people together, building consensus, and creating a better future for all.

The Players of the Game

The Players of the Game

Politics is a game of power, and as such, it has its own set of players. These include politicians, activists, lobbyists, interest groups, and the media. Each of these players has a role to play in shaping public opinion and policy outcomes. Politicians are the most visible and influential players in the game, but they are often influenced by others who seek to advance their own interests.

The Art of Persuasion

The Art of Persuasion

At the heart of politics lies the art of persuasion. This involves convincing people to see things from our perspective or to support our policies or candidates. Persuasion is not just about making a logical argument; it also involves emotional appeals, personal connections, and the use of symbols and imagery. The most successful politicians are those who can connect with people on a personal level and inspire them to take action.

The Ethics of Politics

The Ethics of Politics

Politics is not always a noble pursuit, and it can be tainted by corruption, greed, and self-interest. However, there are many politicians and activists who strive to do good in the world and to make a positive impact. Ethics play a crucial role in the world of politics, and it is important for those who engage in political activity to act with integrity, honesty, and transparency.

The Future of Politics

The Future of Politics

The world of politics is constantly evolving, and new challenges and opportunities are emerging all the time. The rise of new technologies, changing demographics, and global uncertainty are just some of the factors that will shape the future of politics. As we look to the future, it is important to remember that politics is ultimately about people and the relationships we build with one another.

Conclusion

The art of politics is a complex game of power and influence, where ideas clash and decisions shape the world we live in. It is a field that requires skill, dedication, and a passion for making a difference. As we navigate the challenges of our time, may we never forget the importance of building bridges and working together to create a better world.

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Politics

The Power of Politics: Understanding its Impact on Society

The Power of Politics: Understanding its Impact on Society

Introduction

Politics is a vital aspect of any society. It is the force that drives change, both good and bad. It is the means by which individuals and groups in a society gain and exercise power, often at the expense of others. Therefore, it’s important for people to understand how politics can impact society.

The Political Landscape

The Political Landscape

Political Parties

Political Parties

Political parties are an essential element of any political system. They are groups of people who share similar views and work together to gain power and influence. Political parties represent different ideologies and interests and compete against each other in elections.

Government Institutions

Government Institutions

The government is the institution that has the power to make and enforce laws. It consists of three branches: the executive, legislative, and judicial. Each branch has its own responsibilities and is designed to check and balance the power of the other branches.

The Impact of Politics on Society

The Impact of Politics on Society

Politics can have a significant impact on society in many ways. It can influence policies that affect people’s lives and affect economic stability. It can also impact social issues such as immigration, education, and healthcare. Politics plays a critical role in shaping the future of society.

Furthermore, politics can lead to conflict and instability. When individuals or groups with different political views clash, tension and violence can arise. Therefore, it’s essential to have open and respectful discourse that allows individuals to advocate for their beliefs while respecting the views of others.

Conclusion

Politics is the mechanism for change in society. It can create a better future or lead to chaos and disorder. Understanding the political landscape, the impact of politics on society, and the need for civil discourse are crucial to ensure the stability and prosperity of society.

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Politics

The Power of Politics: Understanding How it Shapes Our Lives

The Power of Politics: Understanding How it Shapes Our Lives

Introduction

Politics is a topic that is always relevant and important in our lives. It affects every single one of us, whether we realize it or not. From the taxes we pay to the laws we must abide by, politics is deeply ingrained in our society.

The Basics

The Basics

Politics is the process by which groups of people make decisions and take action to achieve common goals. At its core, politics is about power – who has it, how they got it, and how they use it. Political systems vary widely from country to country, but they all share some basic characteristics.

  • Political systems are hierarchical
  • They involve the use of force or the threat of force
  • They have rules and procedures for decision-making
  • They involve competition between different groups or individuals

Why Politics Matters

Why Politics Matters

Politics plays a crucial role in shaping our lives, from the laws we must obey to the services we rely on. Here are just a few examples of why politics matters:

  1. Politics determines how much we pay in taxes and what services we receive in return
  2. Politics determines who has access to healthcare and education
  3. Politics determines how we respond to emergencies and disasters
  4. Politics determines who can enter or leave a country, and under what conditions
  5. Politics determines how we protect our environment and natural resources

The Power of Political Participation

The Power of Political Participation

One of the most important ways we can shape politics is by becoming involved in the political process ourselves. There are many ways to do this, such as:

  • Registering to vote and actually voting in elections
  • Contacting your elected representatives to voice your concerns and opinions
  • Joining a political party or interest group that shares your values and beliefs
  • Participating in peaceful protests and demonstrations to raise awareness of important issues
  • Running for political office yourself

Conclusion

Politics is a complex and often frustrating topic, but it is also incredibly important. By understanding the basics of political systems and participating in the political process, we can help shape the world around us and create a better future for ourselves and our communities.

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Politics

Techrooted Groups Seek To Shake Up San Francisco Politics

Techrooted Groups Seek To Shake Up San Francisco Politics

SAN FRANCISCO — Tech entrepreneurs who came to San Francisco two decades ago, bringing jobs and wealth along with rising house prices and gentrification, are becoming a growing political force in a city they see as completely out of place.

They are building advocacy organizations including TogetherSF Action, Abundant SF and Grow SF to pressure officials to address rising housing costs, community drug trafficking and other issues exacerbated by the COVID-19 pandemic.

While the organizations differ in their priorities, they all say that a small group of powerful individuals, many of whom are progressive, are holding the city back from addressing some of its most pressing problems. The groups highlight divisions among Democrats in this liberal bastion that is struggling to recover from the pandemic.

“There are a lot of political ideologies in San Francisco that prevent people from working together on things they actually agree on,” said Kanishk Cheng, who founded the company in 2020 with billionaire venture capitalist Michael Moritz, a former journalist. He also launched the San Francisco Standard News website and was an early investor in Google.

This year's TogetherSF action is raising awareness of the city's drug problem and pushing for a stronger police presence to hold drug dealers accountable and provide treatment options to keep drug addicts off the streets. Like many other cities, San Francisco is experiencing a fentanyl crisis and is reporting almost two overdose deaths a day.

Another tech entrepreneur looking to influence change is Jack Rosen, co-founder and CEO of internet platform Pantheon, who helped launch YIMBY California, a development advocacy group fighting for statewide zoning reform.

Rosen said he was motivated by his and his wife's desire to start their family in San Francisco. He is frustrated by the lack of affordable housing as the workers at the bike shop he owns are leaving their jobs, and he wants to get rid of the red tape and red tape that hinders new construction.

Now Rosen, his wife and other tech couples are the driving force behind Abundant SF, which plans to spend millions on ballots and candidates that will create safe, affordable public spaces and increase housing stock for all income levels.

“There are a lot of complaints and little action,” Rosen said. "We want to be part of the solution."

Technology has had a strong presence in San Francisco since the early 2000s, when major companies including Google, Twitter, and Uber began renting office space as Silicon Valley expanded northward.

But lately, industry leaders have been openly trying to influence politics and elections. Some of them grew bolder last year when their moderate campaign led to the defeat of several progressive candidates in the elections: the school principal, three members of the school board and district attorney Chesa Budin.

They range from seasoned activists influencing city and state politics to high-profile figures like Elon Musk who use social media to criticize officials.

Earlier this month, Musk joined the protest on Twitter, which he bought last year for $44 billion, pointing to the murder of cash app founder Bob Lee, who was repeatedly stabbed on the road, as an example of the emerging situation. check. The decline of San Francisco.

In fact, according to the FBI, San Francisco has the lowest violent crime rate of the 23 largest cities in the country. And the acquaintance was eventually arrested after Li's death, and authorities say the attack was not random street violence, but the result of an altercation between the men.

However, many residents feel unsafe due to an increase in property crime, including theft of catalytic converters from shops and grocery stores, and home burglaries. Many people are put off by the sight of drug dealers peddling in public places and suffering mental anguish or littering downtown sidewalks.

In an April city poll, only a third of San Francisco residents said they felt safe going out at night, up from 53 percent in 2019 when officials last polled. When asked to rate the government and the police department, residents gave them a C and a C, respectively.

With these issues in mind, GrowSF, an advocacy group founded in 2020 by two software engineers who quit their jobs in tech to start one, focuses on public safety and helps elected officials tackle issues like property crime and the market. drugs.

“People have been frustrated with this for years,” said co-founder Sachin Agarwal, who worked at Twitter and later at Lyft.

With over 15,000 Twitter followers, GrowSF also publishes voter guides in support of smart candidates and supports efforts to defeat progressive incumbent Dean Preston, who is running for re-election next year. It is also fueling opposition to plans to turn the iconic 100-year-old Castro Theatre, located in the heart of the historically gay Castro neighborhood, into an event venue.

“There is a very small minority of people who do not like change and want the city to remain stagnant and leave it in the past,” Agarwal said. "But the vast majority of people here want to see growth and progress."

Preston, who won her seat in 2019 after running as a Democratic Socialist, dismissed such talk, saying she wants progress too, but needs to include the working class and the poor.

The executive said he has been targeted by many groups created by tech entrepreneurs because of his support for things like tenant rights, affordable housing for low-income residents, anti-displacement initiatives and taxes on the rich. In 2020, she supported a voter-approved $10 million measure in real estate sales tax.

Preston looks vaguely at the new political engines in the tech world, saying he doesn't see them as true advocates for ordinary San Francisco residents.

“I don't think they are interested in solving the problem together. "They're more likely to fight in public and try to use these wedge issues to win the election."

Emily Lee, co-director of the nonprofit San Francisco Rising, is also skeptical of technology advocacy groups, saying they don't work with the people most affected by homelessness and addiction to understand their root causes. He said the city's inability to make any real progress was due to the inconsistency of elected officials.

“There is a chronic inability for mayors and leaders to work together,” Li said. “We need all these politicians to stop being condescending and arguing with each other, and really do something to solve the problems of society.”

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Michigan Matters Talk Of USFL Football, Freep Film Festival & Politics

Michigan Matters  Talk Of USFL Football, Freep Film Festival & Politics

(CBS DETROIT) — As the Michigan Panthers prepare to head to Ford Field for the Fripp Film Festival on April 30, talk of a return to the United States Football League (USFL) has been in the air, and there has been a bit of politics involved . in an interview during recording.CBS Detroit. Michigan affairs.

In the second season of the Spring Football League, newly appointed USFL President Daryl Johnston will look back 40 years after the Panthers won the USFL's inaugural season in the early 1980s. The league was discontinued after two seasons.

Johnston spoke to executive producer/host Carol Cain about how he believes the league will thrive this time around with a new game plan under new ownership.

Kathy Keliszewski, news director of the Detroit Free Press and artistic director of the Freep Film Festival, spoke about the festival, which opens next week and celebrates its 10th anniversary. He spoke about how the Spring Film Festival has become an iconic event in Metro Detroit, supporting films and documentaries, many of which have ties to the region.

It was from April 26th to 30th. Award-winning actor Laurence Fishburne will also be in Detroit for the festival and will star in two films.

And at a panel discussion, Brian Barnett, Mayor of Rochester Hills, Denise Ilitch, CEO of Ilitch Enterprises, and Susie Avery, former Chairwoman of the Michigan Republican Party, discussed the Lansing news. Among the issues discussed were efforts to change the law to allow Michigan colleges to sell alcohol at football, basketball and hockey games.

Speaking of football, Ilyich shares an interesting story about his late father, Mike Ilyich, who invested in the Arena Football League in the late 1980s and ended up getting a $200,000 jacket.

The panel discussed Donald Trump, who owned the New Jersey USFL Generals in the early 1980s, and his chances if he ran for president in 2024.

They also talk about Joe Biden and his re-election bid.

Watch Michigan Affairs Sundays at 8:00 am on CBS Detroit.

Interview with QB Ben Holmes (NJ General) | USFL interview

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No 10 Says SunakBiden Meetings Not ‘lowkey After White House Scales Back Bilateral Event To Coffee Meeting UK Politics Live

No 10 Says SunakBiden Meetings Not ‘lowkey After White House Scales Back Bilateral Event To Coffee Meeting  UK Politics Live

an important phenomenon

Some of the poll results were upbeat for Labour, showing the highest support in almost five months for people who believe the party will do enough to tackle the housing crisis.

In a poll by Redfield & Wilton Strategy, 42% said they believed the party would "take appropriate steps to address the housing crisis" if it were in government.

He has a six-point lead over those who think they won't have fun.

However, other polls paint a mixed picture: most believe the government is doing the right thing – 59% – and opinion polls show Labor's narrow lead over business after Rishi Suna became prime minister: Keir Starmers' party is just 14 points ahead of him on 44%.

A New Statesman [Paywall] article by Rachel Wearmouth about Labour's advertising campaign contains several anonymous quotes.

It informs two schools of thought about intra-party advertising, which fuels criticism and opposition within the party.

A source said: "Mission accomplished. We've seized the news agenda and are starting a serious conversation about the Tories' horrific crime."

The New Statesman article says that for members of the "shadow cabinet" disaffected with propaganda, the campaign team led by Morgan McSweeney, who first worked with Labor before the 1997 election, was relatively powerless when fighting against more cautious political advisers.

However, some of the differences are summed up in this quote: "[Labor strategists] will be happy for him to start a fight and look like Linton Crosby," said one aide.

"But that's not going to work because we can't beat the gridlock, our biggest problem is not attacking Rishi, not having a positive alternative approach and looking at previous records because it's not going to end well. . For Keir, the Tories are going to town on the DPP register.

Meanwhile, Stephen Bush of the Financial Times [Paywall] shares with Michael Dugher (see 11:21) that hype over ad campaigns often precedes a successful party in an election.

In an Inside Politics article this morning, he said: "A pattern has emerged when covering elections: a political party or referendum campaign unveils a new line of attack, poster or criticism. Westminster continues to talk about excess.". that is, then that party wins".

“I suspect there will be a similar pattern in terms of Labour's attack on Rishi Sunak in the local elections this week and next month. More thoughts on this, political campaigning and some of the weaknesses of the Labor Party in today's story.'

He drew parallels between Suna and Labor ads attacking the Conservatives, which put Gordon Brown at the center of their ads, and the 2016 announcement of the NHS and Turkey's EU membership vote, which sparked outrage.

Bush added: "The Labor Sun's attempts to make a personal connection with the convictions of criminals tried 'under the Tories' created a lot of internal fear and loathing in Keir Starmer's party. However, the most positive Daily Mail tabloid and an op-ed I can recall. Starmer's paper This , basically hits every beat Labor leaders want to play: Labor is tough on crime and the Conservatives are weak, Suna (elected to parliament in 2015) has been personally culpable for the past 13 years, etc.

President Biden commented on the AUKUS partnership