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PeptideMHCtargeted engineered viruslike particles enable selective priming and gene editing of tumorspecific T cells

As well as T cells bearing an engineered TCR55-A50E, which forms catch-bonds with both HIVpol/B∗35 pMHC and Pep20/B∗35 pMHC. We treated TCR55 and TCR55-A50E cells with pMHC-eVLPs pseudotyped with either HIV/B∗35 or Pep20/B∗35 and subsequently assessed T cell activation by CD69 upregulation and eVLP transduction. Consistent with previous reports, we observed increased CD69 upregulation in TCR55 cells by Pep20/B∗35 eVLPs compared to HIV/B∗35 eVLPs, whereas TCR55-A50E cells were similarly activated by both pMHC-eVLPs (Figure S4G). Notably, pMHC-eVLPs presenting HIV/B∗35 were still able to induce CD69 upregulation on TCR55 cells despite reported slip-bond formation (Figure S4G). Interestingly, both HIV/B∗35 and Pep20/B∗35 pMHC-eVLPs were able to efficiently transduce both TCR55 and TCR55-A50E cells (Figure S4H), suggesting that antigen specificity and physiological TCR·pMHC affinity, rather than catch-bond formation, are the primary determinants of pMHC-eVLP-mediated T cell activation and transduction.

Collectively, these findings demonstrate that the pMHC-eVLP platform can be programmed with different antigens and HLA allotypes to enable selective and efficient targeting of tumor-specific T cells via natural TCRs with physiological antigen affinities, and that pMHC-eVLPs induce antigen-specific T cell activation during TCR-mediated entry.

Sleep could help identify people at risk of developing Alzheimer’s disease at an earlier stage

What if certain signs of the disease were to manifest subtly during sleep, long before the first memory problems appear? This is the line of inquiry being explored by a team of researchers at ULiège.

A team of scientists from the University of Liège (GIGA Neurosciences), supported by the Stop Alzheimer’s Foundation, has analyzed the sleep patterns of more than 500 healthy people. Among middle-aged participants, a higher frequency of nocturnal micro-awakenings was found to be associated with a greater genetic risk of developing Alzheimer’s disease, whereas this link was not observed in young adults. This research, published in the journal Sleep, suggests that the study of sleep could, in the long term, contribute to the early identification of vulnerable individuals.

NASA astronaut Mike Fincke leaves agency months after medical emergency in space

Longtime NASA astronaut Mike Fincke is stepping away from his role at the space agency. The news comes months after he experienced a medical emergency aboard the International Space Station, which forced a premature end to the journey for him and three crewmates.

Fincke’s last day at the space agency is Wednesday, NASA said in a news release.

Although he is leaving NASA, Fincke said he remains “deeply committed to the work of exploration.”

Have we already found the fountain of youth? — The Global Story, BBC World Service

Scientists are optimistic that existing drugs that could one day slow or reverse our ageing.

For centuries, people have pursued the dream of eternal youth. It might seem like the stuff of myth or science fiction, but researchers have been making fascinating progress in understanding what happens in our bodies as we age. There’s optimism that we might soon be able to use drugs to slow down or even reverse how we age, extending the number of years we live healthy, productive lives. What’s more, some of us might be taking these drugs already.

On today’s episode, Lucy Hockings speaks to Dr Andrew Steele, author of Ageless: The New Science of Getting Older Without Getting Old to find out whether we might drink from the fountain of youth in our lifetime.

00:00 Intro.
01:07 Questions about anti-ageing.
02:05 Cosmetic and cellular anti-ageing.
03:48 What is biological age?
05:51 What is ageing?
07:55 Is it a humanitarian crisis?
09:23 Lifespan and healthspan.
10:53 Can we slow down our ageing?
12:29 Is there a drug?
14:10 Therapies for ageing.
16:01 When could this happen?
17:10 Anti-ageing advice.
18:45 Outro.

Watch more episodes of The Global Story here 👉🏽 • The Global Story.

You can listen to more episodes of The Global Story here. Making sense of the news with our experts around the world. Insights you can trust, Monday to Friday, from the BBC 👉🏽 https://www.bbc.co.uk/programmes/w13x… credit: Getty —————- This is the official BBC World Service YouTube channel. If you like what we do, you can also find us here: Instagram 👉🏽 / bbcworldservice Twitter 👉🏽 / bbcworldservice Facebook 👉🏽 / bbcworldservice BBC World Service website 👉🏽 https://www.bbc.co.uk/worldserviceradio Thanks for watching and subscribing! #BBCWorldService #WorldService #ageing #youth.

Continue reading “Have we already found the fountain of youth? — The Global Story, BBC World Service” | >

Discovering a new layer of control for a decades-old leukemia drug

For more than 70 years, the drug 6-thioguanine (6-TG) has been used to treat leukemia. Although its clinical effects have been studied extensively, scientists are still uncovering the molecular mechanisms that determine whether cells succumb to the drug or survive its attack.

Now, researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, together with collaborators at the University of Oxford, the Weizmann Institute of Science and the University of Dundee, have identified an unexpected player in this process: the protein NUDT5. Their paper is published in the journal Nature Communications.

The discovery builds directly on a recent breakthrough from the Kubicek and Huber laboratories. In that work, researchers showed that NUDT5 performs a critical cellular function independently of its enzymatic activity. Instead of acting primarily as a catalyst, NUDT5 was found to serve as a molecular scaffold that helps organize cellular metabolism. This unusual behavior has direct consequences for the action of the important cancer drug.

Prostate cancer: evading immunity, inspiring therapy

Mereu et al. present ESPACE, a single-cell multi-omic atlas of the human pancreas spanning fetal development, adulthood, and type 2 diabetes. Combining transcriptomics, chromatin accessibility, and spatial imaging, they uncover a rare population of plastic centroacinar cells and hidden diversity among hormone-producing islet cells, informing pancreas regeneration and disease.

Stellar stream beyond Milky Way offers new tool to map dark matter

In the image above, a faint trail of stars can be seen stretching across the galaxy. These structures, known as globular cluster stellar streams, are coherent stellar structures that retain a record of their dynamical history and can provide unique insights into the evolution of galaxies and the nature of dark matter.

Globular cluster stellar streams offer astronomers a unique opportunity to map otherwise invisible dark matter and study how it behaves. For many years, they have been difficult to observe because they are extremely faint. However, advances in large astronomical data sets and sophisticated analysis techniques have recently made stellar streams one of the most promising tools in galactic astronomy.

Now, Ph.D. student Julie Kiel Holm from the Niels Bohr Institute and associate professor Sarah Pearson from DTU Space, together with an international team of researchers, have made a discovery that has never been seen before. Their findings have just been published in Nature.

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