About one in eight adults in the United States has tried or currently uses a GLP-1 medication, and a quarter of those users cite weight loss as their main goal. But weight loss doesn’t discriminate between fat and muscle. Patients using GLP-1 drugs can experience rapid and substantial muscle loss, accounting for as much as 40% of their total weight loss. So how can we lose weight without also losing critical muscle?
A new study from the Salk Institute has revealed that a protein called BCL6 is key to maintaining healthy muscle mass. The experiments showed that mice with lower levels of BCL6 had significantly reduced muscle mass and strength, but increasing BCL6 successfully reversed those losses. The results suggest that pairing GLP-1 medications with a BCL6-boosting drug may help counteract unwanted muscle loss. Similar therapies could also be used to treat other populations prone to muscle loss, such as older adults and patients with systemic diseases like sepsis or cancer.
The findings were published in Proceedings of the National Academy of Sciences on January 22, 2025.
“Muscle is the most abundant tissue in the human body, so its maintenance is critical to our health and quality of life,” says Ronald Evans, professor and director of the Gene Expression Laboratory at Salk. “Our study reveals how our bodies coordinate the upkeep of all this muscle with our nutrition and energy levels, and with this new insight, we can develop therapeutic interventions for patients losing muscle as a side effect of weight loss, age, or illness.”
Going too long without eating puts your body in a fasted state. When this happens, your empty stomach sends a hormone called ghrelin to your brain to say, “I’m hungry!”The brain responds by releasing growth hormone into the rest of your body, where it regulates growth and metabolism in your many cells, tissues, and organs. As it travels through your body, growth hormone latches on to cells and directs them to make another protein called insulin-like growth factor 1 (IGF1), which then does the important work of controlling muscle growth.
In the time between growth hormone’s arrival and IGF1 synthesis, there is a complex web of proteins that determine how much IGF1 is made. One such protein is SOCS2, which slows down IGF1 production. Without SOCS2, IFG1 production runs out of control and causes gigantism. On the other hand, too much SOCS2 means not enough IFG1, leading to losses in body size and strength.
Still, SOCS2 is only one player in the path between growth hormone and IGF1. To protect people from rapid muscle loss, Salk scientists needed to get a clearer picture of the mechanisms underlying muscle maintenance. In search of other potential players, the researchers scoured a national database of human tissue samples and noticed an abundance of BCL6 in muscle cells — a clue that it may play an important role in this process.
To determine whether BCL6 was involved in muscle maintenance, the team compared mice with and without functional BCL6 proteins. Mice lacking BCL6 had 40% less muscle mass than their healthy counterparts, and the muscle they did have was compromised both in structure and function. However, when the researchers increased the expression of BCL6 in the animals’ muscles, this successfully reversed the losses in muscle mass and strength. And when they compared normal mice and those that had fasted overnight, they found fasting mice had less BCL6 in their muscles.
Clearly, BCL6 was controlling muscle maintenance — but how?
Through a series of subsequent experiments, the steps along the path became clear. Fasting promotes the secretion of growth hormone, which reduces BCL6 levels in muscle cells. BCL6 is a regulator of SOCS2, so less BCL6 leads to less SOCS2. At normal levels, this allows BCL6 to control how much SOCS2 is expressed and therefore how much IGF1 is made. In animals without BCL6, the lack of control over SOCS2 slowed IGF1 production so much that muscles became weaker and smaller.
“We are excited to reveal BCL6’s important role in maintaining muscle mass,” says first author of the study Hunter Wang, a postdoctoral researcher in Evans’ lab. “These were very surprising and special findings that open the door for a lot of new discoveries and potential therapeutic innovations.”
For GLP-1 patients hoping to lose weight while retaining muscle mass, it’s possible that a BCL6-boosting injectable could hit the market one day. In the meantime, the researchers plan to investigate what effects longer-term fasting has on BCL6 and muscle maintenance. Wang also notes that hormones tend to operate in cycles and that BCL6 naturally rises and falls with a strong circadian rhythm. A better understanding of this pattern may help further elucidate BCL6’s relationship with growth hormone and muscle growth.
Other authors include Hui Wang, Weiwei Fan, Sihao Liu, Kyeongkyu Kim, Satoshi Ogawa, Hyun Gyu Kang, Jonathan Zhu, Gabreila Estepa, Mingxiao He, Lillian Crossley, Morgan Truitt, Ruth Yu, Annette Atkins, and Michael Downes of Salk; Ayami Matsushima of Kyushu University; Christopher Liddle of University of Sydney; and Minseok Kim of Daegu Gyeongbuk Institute of Science and Technology.
The work was supported by the National Institutes of Health (P01 HL147835, DK057978, DK120515, CCSG P30 CA23100, CCSG P30 CA014195, CCSG P30 CA014195, P30 AG068635), Department of the Navy Office of Naval Research (N00014-16-1-3159), Larry Hillblom Foundation (2021-D-001-NET), Wu Tsai Human Performance Alliance, American Heart Association (916787), Salk GT3 (RRID:SCR_014847) and Waitt Advanced Biophotonics (RRID:SCR_014838) Core Facilities, San Diego Nathan Shock Center, Henry L. Guenther Foundation, and Waitt Foundation.
But, of course, not everyone will be feeling quite so jubilant.
With only a handful of slots to fill, some of the biggest and most-celebrated performances of the past 12 months have gone unchecked by the Academy, with cinephiles on social media already going off about this year’s most notable “snubs”.
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Here are 11 of them…
Daniel Craig
Daniel Craig in Queer
Timothée Chalamet, Adrien Brody, Colman Domingo and Ralph Fiennes’ spots in the Best Actor category were pretty much dead certs by the time the Oscar nominations rolled around, leaving a few big names competing for the one remaining spot.
In the end, it’s gone to Sebastian Stan for his performance as Donald Trump in The Apprentice, but there are sure to be a few disappointed Daniel Craig fans.
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The former James Bond actor couldn’t have been further from the roles that have made him most famous in Luca Guadagnino’s Queer, in which he plays William Lee (a fictionalised version of the author William S Burroughs), an American writer who embarks on a journey of sexual and substance exploration.
Danielle Deadwyler and Ray Fisher in The Piano Lesson
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American performer Danielle Deadwyler received a wave of acclaim for her performance in the August Wilson adaptation The Piano Lesson.
While the film itself failed to score much awards season buzz, fans had hoped Danielle might scrape through in the Best Supporting Actress category for her role as Berniece, a woman determined to hold onto her late father’s piano when the rest of her family are hoping to sell it.
Considering the original Gladiator was a Best Picture recipient, it might come as a surprise to some to see the sequel pick up just one nomination in 2025, in the Best Costume Design category.
Lead actor Paul Mescal was among those to be singled out for praise when the action-packed epic hit cinemas last year, but it’s Denzel Washington who was really being tipped for awards buzz.
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After scoring a nomination at the Golden Globes last month, however, both the Baftas (who, interestingly, have never nominated Denzel in his entire 40-year screen career) and Oscars have paid him dust, making him one of this year’s most noticeable snubs.
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As their pasts and presents collide, and tensions run high, Tashi must ask herself, what will it cost to win.\n \nFOLLOW SONY SOUNDTRACKS: \n► Facebook: https://www.facebook.com/SonyMusicSoundtracks/\n► Instagram: https://www.instagram.com/sonymusicsoundtracks/ \n► Twitter: https://twitter.com/sonysoundtracks/\n► Discord: https://discord.com/invite/DCKp3RYRK3 \n► TikTok: https://www.tiktok.com/@sonysoundtracks \n► Newsletter: https://soundtracks.lnk.to/newsletter \n \nFOLLOW MILAN RECORDS: \n► Facebook: https://www.facebook.com/milanrecords\n► Instagram: https://www.instagram.com/milanrecords/\n► Twitter: https://twitter.com/MilanRecLabel\n \nFOLLOW CHALLENGERS:\n► Facebook: https://www.facebook.com/challengersmovie\n► Instagram: https://www.instagram.com/challengersmovie/\n► Twitter: https://twitter.com/challengersmov\n► TikTok: https://www.tiktok.com/@challengersmovie\n \nSUBSCRIBE to our channels for more: \n► https://soundtracks.lnk.to/sonysoundtracksvevoID\n► https://milanrecords.lnk.to/youtube \n \nCHALLENGERS (ORIGINAL SCORE)\n \nTRACKLISTING – \n1. 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It’s rare that you’ll find outcry over a snub in the Best Score category – but then again, it’s rare a score will capture people’s attention in the way that Challengers’ did.
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The Nine Inch Nails musicians delivered one of last year’s most iconic contributions to the world of cinema when they scored Luca Guadagnino’s tennis-themed romance drama Challengers, perfectly amping up the tension between its central trio with their musical output.
We’re sure we’re not the only ones confused to see the score – which won a Golden Globe just a matter of weeks ago – not even nominated for an Oscar when it felt like such a shoo-in.
Margaret Qualley
Margaret Qualley in The Substance
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The Substance has been the surprise hit of 2025’s awards season, and we’re over the moon to see not just Demi Moore landing an acting nomination, but Coralie Fargeat’s name popping up on the Best Director shortlist.
However, there’s no denying that The Substance was a two-header, and while we’re over the moon for Demi scoring her first Oscar nomination at this stage of her career, we’re still a little sad there wasn’t space for Margaret Qualley in the Best Supporting Actress category.
The Maid star has made no secret of what she put herself through to help bring the character of Sue (and, perhaps more impressively, Monstro Elisasue) to life, and she was the perfect foil to her Golden Globe-winning co-star’s character in the graphic body horror.
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Marianne Jean-Baptiste
Marianne Jean-Baptiste in Hard Truths
She may not have had the fanfare and loud push behind her that the likes of Wicked’s Cynthia Erivo or even Demi Moore have had over the last few months, but Marianne Jean-Baptiste had quietly been climbing up the ranks as a contender for a Best Actress nomination thanks to her role in Mike Leigh’s Hard Truths.
When Hard Truths premiered at Toronto Film Festival towards the end of last year, Marianne’s performance as a pessimistic woman struggling to connect with those closest to her saw her being met with a wave of praise, which has translated into recognition from the Baftas and Critics’ Choice Awards.
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The British performer was nominated for an Oscar once before for her role in another of Mike Leigh’s projects, Secrets & Lies.
Pamela Anderson
Pamela Anderson in The Last Showgirl
Alright, we know this one was always going to be a long shot, but “Oscar nominee Pamela Anderson” had such a ring to it that we couldn’t help crossing our fingers that this could be her year.
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Oscar nomination or not, we’ll still be seeing The Last Showgirl the second it hits UK cinemas, and we’re certain this is the beginning of a new era of the former Baywatch star’s career.
For the past few months, Stanley Tucci has been hovering around the middle of the list of favourites to score a Best Supporting Actor nod (which would have marked his second ever nomination, after 2009’s The Lovely Bones) but sadly, it wasn’t to be.
He’ll just have to make do with being the entire internet’s imaginary husband instead, we suppose…
","type":"video","meta":{"author":"Warner Bros. Pictures","author_url":"https://www.youtube.com/channel/UCjmJDM5pRKbUlVIzDYYWb6g","cache_age":86400,"description":"Long Live the Fighters. #DunePartTwo only in theaters March 15.\n\n—————–\nhttps://www.instagram.com/dunemovie/\nhttps://www.facebook.com/dune\nhttps://twitter.com/dunemovie \nhttps://www.tiktok.com/@dunemovie \n—————–\nThe saga continues as award-winning filmmaker Denis Villeneuve embarks on “Dune: Part Two,” the next chapter of Frank Herbert’s celebrated novel Dune, with an expanded all-star international ensemble cast. The film, from Warner Bros. Pictures and Legendary Pictures, is the highly anticipated follow-up to 2021’s six-time Academy Award-winning “Dune.”\nThe big-screen epic continues the adaptation of Frank Herbert’s acclaimed bestseller Dune with returning and new stars, including Oscar nominee Timothée Chalamet (“Wonka,” “Call Me by Your Name”), Zendaya (“Spider-Man: No Way Home,” “Malcolm & Marie,” “Euphoria”), Rebecca Ferguson (“Mission: Impossible – Dead Reckoning”), Oscar nominee Josh Brolin (“Avengers: End Game,” “Milk”), Oscar nominee Austin Butler (“Elvis,” “Once Upon A Time…In Hollywood”), Oscar nominee Florence Pugh (“Black Widow,” “Little Women”), Dave Bautista (the “Guardians of the Galaxy” films, “Thor: Love and Thunder”), Oscar winner Christopher Walken (“The Deer Hunter,” “Hairspray”), Stephen McKinley Henderson (“Fences,” “Lady Bird”), Léa Seydoux (the “James Bond” franchise and “Crimes of the Future”), with Stellan Skarsgård (the “Mamma Mia!” films, “Avengers: Age of Ultron”), with Oscar nominee Charlotte Rampling (“45 Years,” “Assassin’s Creed”), and Oscar winner Javier Bardem (“No Country for Old Men,” “Being the Ricardos”).\n“Dune: Part Two” will explore the mythic journey of Paul Atreides as he unites with Chani and the Fremen while on a warpath of revenge against the conspirators who destroyed his family. Facing a choice between the love of his life and the fate of the known universe, he endeavors to prevent a terrible future only he can foresee. \nVilleneuve directed from a screenplay he co-wrote with Jon Spaihts based on Herbert’s novel. The film is produced by Mary Parent, Cale Boyter, Villeneuve, Tanya Lapointe and Patrick McCormick. The executive producers are Josh Grode, Herbert W. Gains, Jon Spaihts, Thomas Tull, Brian Herbert, Byron Merritt, Kim Herbert, with Kevin J. Anderson serving as creative consultant.\nVilleneuve is again collaborating with his “Dune” creatives: Oscar-winning director of photography Greig Fraser; Oscar-winning production designer Patrice Vermette; Oscar-winning editor Joe Walker; Oscar-winning visual effects supervisor Paul Lambert; Oscar-nominated costume designer Jacqueline West. Oscar-winning composer Hans Zimmer is again on hand to create the score.\n“Dune: Part Two” was filmed on location in Budapest, Abu Dhabi, Jordan and Italy. The film is slated for a March 15, 2024 worldwide release from Warner Bros. 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With 10 slots in the Best Picture category and only five in Best Director, there’s always going to be someone who winds up disappointed.
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But considering everything that Denis Villeneuve had to contend with to make Dune: Part Two the epic that it was (it’s one of the year’s most-nominated films thanks to recognition in more technical categories, which is no mean feat for a sequel), a Best Director nomination would have been fitting.
Angelina Jolie
Angelina Jolie in character as Maria Callas
The Best Actress category was absolutely heaving with competition this year, and we understand there can’t be room for everyone, but Angelina Jolie’s major comeback to the cinema world after a few years away felt so triumphant that an Oscar nomination would have been more fitting – especially given the performance she delivers in Maria.
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While this may not be the year the former Best Supporting Actress wins over the Academy yet again, there’s no denying that it’s great to have Angelina back, and we can’t wait to see what this unusual thinker chooses for her next project.
Selena Gomez
Selena Gomez in Emilia Pérez
Emilia Pérez may not have been to everyone’s tastes, but do a quick search on social media for Selena Gomez’s name, and you’ll see it for yourself, there are a lot of people seriously pissed off that she didn’t make the cut.
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The divisive Netflix musical is, of course, this year’s most-nominated film at the Oscars, with 13 nods in total. Had Selena been recognised, that number would have matched Emilia Pérez with Titanic, All About Eve and La La Land as the joint most-nominated films in history.
Still, some better news… Yesterday, Variety shared a happy fact about the future of the show.
A preview of The White Lotus season 3
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The publication said that season four has been given the go-ahead by HBO, and producers hope it’ll come out in 2026.
The news comes after the show’s creator Mike White announced last November that he’d pitched his ideas for a further season.
“Mike, obviously — if he wants to move forward and do the four seasons — he will do the fourth season,” HBO and Max executive Casey Bloys said at the time.
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Season four has been confirmed before season three, which is set to hit our screens on February 13, comes out.
A director’s clapboard for The White Lotus
Fabio Lovino /HBO
We don’t know much about season 4 ― neither writers nor execs have shared where the show, which has previously been shot in Hawaii and Sicily, will be filmed.
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But let’s be real ― so long as the Emmy-winning show sticks to its “rich people’s opulent nuttiness” theme, we reckon fans are bound to be satisfied.
Ed Sheeran has denied reports that he recently attended an event thrown by JK Rowling.
Journalist India Willoughby shared a screenshot earlier this week of an opinion piece claiming that Ed had “brought joy to wounded IDF [Israel Defense Forces] soldiers”. She then alleged he’d also attended a New Year’s Eve party at the home of the Harry Potter author, based on recent reports in the press.
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Ed later responded to both of the claims in India’s post on his Instagram story, insisting: “Respectfully, India Willoughby, and any other journalist who has reported both these stories, neither are true.”
JK Rowling in 2019
via Associated Press
“I spent New Year with my family and friends,” he wrote. “The story about wounded soldiers at my show, was a charity that sourced tickets to my show in Cyprus last year, which was a large scale public concert.”
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The Lego House singer added: “This sort of reporting is [divisive] and damaging, please research before you post things.”
The former Celebrity Big Brother housemate then responded: “This is great to hear. I used the word ‘reportedly’ about JK Rowling’s NYE party, because it was widely reported by UK and international media at the time.
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“I also reached out directly to you in the first [week of January] via Twitter to ask if the story was correct – but no reply. Delighted to hear you didn’t go!”
“Delighted I can still be an Ed Sheeran fan,” she added in a follow-up post.
Here’s my original tweet asking directly. I note the Daily Express has now removed their made-up story. Delighted I can still be an @edsheeran fan 😊✌️❤️🏳️⚧️ pic.twitter.com/oMN9KhxrTC
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Delighted I can still be an @edsheeran fan 😊✌️❤️🏳️⚧️ pic.twitter.com/oMN9KhxrTC— India Willoughby (@IndiaWilloughby) January 21, 2025\n\n\n","options":{"_hide_media":{"label":"Hide photos, videos, and cards","value":false},"_hide_thread":{"label":"Hide previous Tweet in conversation thread","value":true},"_maxwidth":{"label":"Adjust width","placeholder":"220-550, in px","value":""},"_theme":{"value":"","values":{"dark":"Use dark theme"}}},"provider_name":"Twitter","thumbnail_height":814,"thumbnail_url":"https://pbs.twimg.com/media/Gh1lDRjWwAAlzPA.jpg:large","thumbnail_width":1170,"title":"India Willoughby on Twitter / X","type":"rich","url":"https://twitter.com/IndiaWilloughby/status/1881771331764810094","version":"1.0"},"flags":[],"enhancements":{},"fullBleed":false,"options":{"theme":"news","device":"desktop","editionInfo":{"id":"uk","name":"U.K.","link":"https://www.huffingtonpost.co.uk","locale":"en_GB"},"originalEdition":"uk","isMapi":false,"isAmp":false,"isVideoEntry":false,"isEntry":true,"isMt":false,"entryId":"67920532e4b06448cdc87e63","entryPermalink":"https://www.huffingtonpost.co.uk/entry/ed-sheeran-addresses-jk-rowling-party-reports_uk_67920532e4b06448cdc87e63","entryTagsList":"ed-sheeran,jk-rowling,india-willoughby","sectionSlug":"entertainment","deptSlug":null,"sectionRedirectUrl":null,"subcategories":"","isWide":false,"headerOverride":null,"noVideoAds":false,"disableFloat":false,"isNative":false,"commercialVideo":{"provider":"custom","site_and_category":"uk.entertainment","package":null},"isHighline":false,"vidibleConfigValues":{"cid":"60afc140cf94592c45d7390c","disabledWithMapiEntries":false,"overrides":{"all":"60b8e525cdd90620331baaf4"},"whitelisted":["56c5f12ee4b03a39c93c9439","56c6056ee4b01f2b7e1b5f35","59bfee7f9e451049f87f550b","5acccbaac269d609ef44c529","570278d2e4b070ff77b98217","57027b4be4b070ff77b98d5c","56fe95c4e4b0041c4242016b","570279cfe4b06d08e3629954","5ba9e8821c2e65639162ccf1","5bcd9904821576674bc55ced","5d076ca127f25f504327c72e","5b35266b158f855373e28256","5ebac2e8abddfb04f877dff2","60b8e525cdd90620331baaf4","60b64354b171b7444beaff4d","60d0d8e09340d7032ad0fb1a","60d0d90f9340d7032ad0fbeb","60d0d9949340d7032ad0fed3","60d0d9f99340d7032ad10113","60d0daa69340d7032ad104cf","60d0de02b627221e9d819408"],"playlists":{"default":"57bc306888d2ff1a7f6b5579","news":"56c6dbcee4b04edee8beb49c","politics":"56c6dbcee4b04edee8beb49c","entertainment":"56c6e7f2e4b0983aa64c60fc","tech":"56c6f70ae4b043c5bdcaebf9","parents":"56cc65c2e4b0239099455b42","lifestyle":"56cc66a9e4b01f81ef94e98c"},"playerUpdates":{"56c6056ee4b01f2b7e1b5f35":"60b8e525cdd90620331baaf4","56c5f12ee4b03a39c93c9439":"60d0d8e09340d7032ad0fb1a","59bfee7f9e451049f87f550b":"60d0d90f9340d7032ad0fbeb","5acccbaac269d609ef44c529":"60d0d9949340d7032ad0fed3","5bcd9904821576674bc55ced":"60d0d9f99340d7032ad10113","5d076ca127f25f504327c72e":"60d0daa69340d7032ad104cf","5ebac2e8abddfb04f877dff2":"60d0de02b627221e9d819408"}},"connatixConfigValues":{"defaultPlayer":"8b034f64-513c-4987-b16f-42d6008f7feb","clickToPlayPlayer":"5a777b9b-81fe-41a6-8302-59e9953ee8a2","videoPagePlayer":"19654b65-409c-4b38-90db-80cbdea02cf4"},"topConnatixThumnbailSrc":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAEAAAABCAQAAAC1HAwCAAAAC0lEQVR42mNkYAAAAAYAAjCB0C8AAAAASUVORK5CYII=","customAmpComponents":[],"ampAssetsUrl":"https://amp.assets.huffpost.com","videoTraits":null,"positionInUnitCounts":{"buzz_head":{"count":0},"buzz_body":{"count":0},"buzz_bottom":{"count":0}},"positionInSubUnitCounts":{"article_body":{"count":11},"blog_summary":{"count":0},"before_you_go_content":{"count":0}},"connatixCountsHelper":{"count":0},"buzzfeedTracking":{"context_page_id":"67920532e4b06448cdc87e63","context_page_type":"buzz","destination":"huffpost","mode":"desktop","page_edition":"en-uk"},"tags":[{"name":"Ed Sheeran","slug":"ed-sheeran","links":{"relativeLink":"news/ed-sheeran","permalink":"https://www.huffingtonpost.co.uk/news/ed-sheeran","mobileWebLink":"https://www.huffingtonpost.co.uk/news/ed-sheeran"},"relegenceId":6019493,"url":"https://www.huffingtonpost.co.uk/news/ed-sheeran/"},{"name":"JK Rowling","slug":"jk-rowling","links":{"relativeLink":"news/jk-rowling","permalink":"https://www.huffingtonpost.co.uk/news/jk-rowling","mobileWebLink":"https://www.huffingtonpost.co.uk/news/jk-rowling"},"relegenceId":3687670,"url":"https://www.huffingtonpost.co.uk/news/jk-rowling/"},{"name":"india willoughby","slug":"india-willoughby","links":{"relativeLink":"news/india-willoughby","permalink":"https://www.huffingtonpost.co.uk/news/india-willoughby","mobileWebLink":"https://www.huffingtonpost.co.uk/news/india-willoughby"},"url":"https://www.huffingtonpost.co.uk/news/india-willoughby/"}],"isLiveblogLive":null,"isLiveblog":false,"cetUnit":"buzz_body","bodyAds":["
Here’s my original tweet asking directly. I note the Daily Express has now removed their made-up story. Delighted I can still be an @edsheeran fan 😊✌️❤️🏳️⚧️ pic.twitter.com/oMN9KhxrTC
The tabloid’s article on Rowling’s party is still live, but makes no reference to Ed Sheeran, having been updated five days after it was originally published on New Year’s Day.
David Schwimmer has claimed he couldn’t let Friends’ recent milestone anniversary go past without commemorating it.
Towards the end of last year, the beloved sitcom celebrated 30 years since it first aired on US television and became a global phenomenon, winning a string of Emmys and running for 10 years in total.
Speaking to the Australian radio station Nova, David – who played Ross Geller in all 10 seasons – was asked by host Smallzy: “Do you reflect when you hit a milestone like 30 years? Do you think ‘wow what a great run’? Or do you go, ‘god, I feel really old, don’t say that’?”
“All of the above,” the Emmy nominee admitted with a big laugh, before revealing he “happened to be back in Los Angeles around the day that marked the 30th year of when we aired”.
“I took [Matt] LeBlanc out to dinner, actually,” he shared. “We reminisced and toasted to the 30 years.”
Reflecting on Friends’ continued success, David added: “It’s amazing to me that people are still watching and finding it funny and comforting, and I feel nothing but gratitude.”
In 2021, the entire cast came together for a star-studded reunion special looking back at what made the show such a success.
Your gut is a battleground. The cells that line your small intestine have to balance two seemingly contradictory jobs: absorbing nutrients from food, while keeping a wary eye out for pathogens trying to invade your body.
“This is a surface where pathogens can sneak in,” says La Jolla Institute for Immunology (LJI) Assistant Professor Miguel Reina-Campos, Ph.D. “That’s a massive challenge for the immune system.”
So how do immune cells keep the gut safe? New research led by scientists at LJI, UC San Diego, and the Allen Institute for Immunology shows that pathogen-fighting immune cells called tissue-resident memory CD8 T cells (TRM cells) go through a surprising transformation — and relocation — as they fight infections in the small intestine.
In fact, these cells literally rise up higher in the tissue to fight infections before pathogens can spread to deeper, more vulnerable areas.
“The tissue in the gut has evolved to provide signals to immune cell infiltrates — to put immune cells in specific places so they have a better ability to stop pathogens,” says Reina-Campos, who served as first author of the new Nature study alongside co-first author Alexander Monell of UC San Diego and co-senior authors Maximilian Heeg, M.D., and Ananda W. Goldrath, Ph.D., of the Allen Institute for Immunology and UC San Diego.
The new findings add to the growing body of evidence that immune cells adapt to protect specific tissues. Reina-Campos thinks these “tissue-resident” immune cells may be key players in future cancer immunotherapies that target tumors in specific organs.
T cells on the move
Reina-Campos and his colleagues investigated the formation of TRM cells in the small intestine. The team harnessed a cutting-edge technology called spatial transcriptomics to track these cells in both human and mouse tissue samples.
Their work showed that the small intestine holds two types of TRM cells. These cells are split between the tiny, finger-like “villi” structures that line the small intestine or the “crypts” between the protruding villi.
The researchers found that progenitor-like TRM cells live closer to the crypts between the villi. On the other hand, differentiated TRM occupy more exposed regions at the top of the villi. “Differentiated immune cells are more exposed at the top of the villi, and that’s where they have a better ability to protect you from infections,” says Reina-Campos.
Meanwhile, a reserve population of progenitor-like TRM cells continues to lie low in the crypts. “These cells can replenish the pool of effector T cells, so the immune system keeps them as back-ups in the deeper parts of the tissue,” adds Reina-Campos.
What keeps these populations organized and in check?
To spy on these important immune cells within their natural habitat, Reina-Campos and colleagues used a new technology — called spatial transcriptomics — to observe millions of messenger RNA molecules simultaneously at subcellular resolution.
“For the first time, we were able to capture the formation of immunological memory in space and time,” says Reina-Campos.
Looking at small intestines after a viral infection, the scientists found that the gut releases chemical signals to instruct immune cells where to go and what to do. “This study offers a new resource for finding signals that position immune residents to strengthen our gut immunity,” says Reina-Campos.
Checkmate for disease?
Reina-Campos credits his mentor, Goldrath, as well as Heeg’s and Monell’s expertise for making this study possible. As Reina-Campos explains, Heeg and Monell developed new computational approaches to make sense of the massive amounts of data captured through spatial transcriptomics.
“It’s led to a breakthrough in our ability to look at hundreds to thousands of genes simultaneously in intact tissues,” says Reina-Campos. “With this study, we’ve opened up a new path for discovery.”
Reina-Campos compares the battle between immune cells and pathogens to a chess match.
“To be a chess grandmaster, you need to know not only about the pieces: the bishops, pawns, rooks, etc, but also how they move in concert on the chessboard,” he says.
For a long time, scientists have studied the chess pieces — by analyzing cells extracted from tissue — but they haven’t gotten a good look at the chess match itself. “We don’t know as much about how the chessboard works — and we know even less about the rules that apply to our chess pieces as they move across the board,” says Reina-Campos.
The new study gives researchers a detailed look at how immune cells interact with each other and their cellular gameboard.
Reina-Campos says the new finding should guide future research into how immune cells develop and move through other organs with different tissue structures, such as the kidneys and lungs — and how immune cells might fight tumors in these organs.
Maternal stress hormone levels during early pregnancy can have a lasting effect on the stress system of the offspring. The results of a long-term study on wild Assamese macaques in Thailand indicate that maternal stress in the first half of pregnancy is particularly relevant. Elevated stress hormones later during pregnancy or after birth did not have the same effects. The long-term study conducted by the University of Göttingen and the German Primate Center — Leibniz Institute for Primate Research provides important insights into the influence of early life stages on the development of the stress system under natural environmental conditions.
Influence of very early life stages
The research team investigated how maternal stress affects the stress hormone system of the offspring. They found that the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a central role in coping with stress, can be significantly influenced by exposure to maternal glucocorticoids during development. The early phase of organ differentiation in the first half of pregnancy proved to be a particularly critical period. “Our results show that the HPA-axis activity of offspring was enhanced, the more adversity the other had experienced during early pregnancy — which could be food shortages or social conflicts for example,” says Simone Anzá, former doctoral student at the University of Göttingen and the German Primate Center and first author of the study.
Investigation in the wild
In contrast to studies in the laboratory, the monkeys were observed in their natural habitat. Over a period of nine years, the researchers repeatedly collected fecal samples from pregnant females and measured the concentration of glucocorticoid metabolites in them in order to determine the animals’ exposure to environmental factors such as food scarcity, temperature fluctuations and social interactions. These values were compared with the stress hormone levels of the offspring at different ages. The effects on the stress axis of the offspring were evident from infancy through the juvenile period and into adulthood at nine to ten years of age. Previous analyses from the same study had already shown that early prenatal stress was also associated with altered growth, negative changes in the gut microbiome and impaired immune function, underlining the comprehensive influence of the environment in the early prenatal period on various physiological systems. In contrast, maternal glucocorticoid levels in late pregnancy or during lactation had no or different influences.
Relevance for health research
“Our research results indicate that the timing of maternal stress hormone exposure during and after pregnancy crucially affects the consequences for the development and health of the offspring. It is also important to note that these effects do not require catastrophic events, but that even moderate changes in environmental conditions are sufficient,” says Oliver Schülke, scientist at the University of Göttingen and the German Primate Center and head of the study. Stress in early pregnancy can also have a long-term effect on health in humans and increase the risk of stress disorders and immune problems. “Our findings may help to identify the timing and mechanisms that preventive measures should address in order to reduce long-term health risks,” says Oliver Schülke.
Around 45 million years ago, a 4.6 feet-tall (1.40 metres) flightless bird called Diatryma roamed the Geiseltal region in southern Saxony-Anhalt. An international team of researchers led by the Martin Luther University Halle-Wittenberg (MLU) and the Senckenberg Research Institute and Natural History Museum in Frankfurt report on the bird’s fully preserved skull in the scientific journal Palaeontologia Electronica. The fossil was unearthed in the 1950s in a former lignite mining area in the Geiseltal in Germany. It was initially misclassified and thus led a shadowy existence until its rediscovery. The only other place that a similar skull fossil has been found is the USA.
The Geiseltal Saxony-Anhalt is located south-west of Halle and was a lignite mining area until 1993. Numerous exceptionally well-preserved animal fossils have been unearthed here. The Geiseltal Collection at MLU comprises 50,000 fossils and is considered a national heritage asset. These fossils offer unique insights into the evolution of animals and the Eocene Epoch around 45 million years ago. At that time, the Geiseltal was a warm, tropical swamp. Ancient horses, early tapirs, large land crocodiles as well as giant tortoises, lizards and numerous birds lived here. Some of the latter were flightless and the largest of these was Diatryma, a herbivore with a gigantic beak which stood around 4.6 feet high.
For many years no one knew that an almost completely preserved skull of Diatryma was part of the collection. “The find was initially misidentified as a crocodile skull,” says Michael Stache, a geological preparator at MLU’s Central Repository of Natural Science Collections. Stache came across the fossil again by chance several years ago. He realised the mistake and got down to work, restoring and then analysing the piece of skull. He combined the fossil with another object from the collection, reconstructing an almost entire skull. Dr Gerald Mayr, a researcher at the Senckenberg Institute, examined the find more closely and realised its importance: the skull clearly belonged to a Diatryma. Only one other fully preserved skull is known to exist in the world and is housed in the American Museum of Natural History in the USA.
“This shows once again that many of the most interesting discoveries in palaeontology occur in museum collections. Just a few years ago, nobody would have thought that the Geiseltal Collection would contain such surprises,” says Gerald Mayr. Michael Stache also reports that there is great scientific interest in the fossils. Researchers from Germany and abroad come to MLU on a regular basis to investigate the objects. “This research expands our understanding of the Eocene Epoch in the Geiseltal even though the excavations were completed long ago,” says Michael Stache. Up until ten years ago, for example, it was assumed that Diatryma hunted prehistoric horses in the Geiseltal. More recent investigations have found that the bird was, in fact, a herbivore.
There are around 40 specimens of the bird in the Geiseltal Collection. “Diatryma was probably a rare guest in the Geisetal. Otherwise, there would probably be more fossils,” concludes Stache.
