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Discovery And Receptor Profile — Hands-On Walkthrough

By Editorial Desk · published 2026-05-16 · last reviewed 2026-05-31 · Faq

glucagon receptor comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.

Updated 2026-05-31. Numbers and descriptions here follow the published literature rather than marketing material.

Discovery and Receptor Profile

Pharmacologically, retatrutide acts as a triple agonist at the glucagon-like peptide-1 receptor, the glucose-dependent insulinotropic polypeptide receptor, and the glucagon receptor. Activation of the first two receptors is associated with improved insulin secretion and reduced appetite. The glucagon receptor component is thought to increase energy expenditure, a mechanism that distinguishes this molecule from dual-agonist compounds. Researchers continue to investigate how the three activities interact and whether the combined profile offers advantages that justify additional clinical testing.

Several questions about the compound remain unresolved. The durability of weight reduction after treatment stops, the frequency of gastrointestinal side effects, and the long-term cardiovascular profile are topics of ongoing study. Regulatory submissions and phase 3 trial outcomes have not been fully reported in the public literature. Because most available data come from controlled trials rather than general-population use, conclusions about effectiveness outside study settings are provisional. The distinction between established findings and open questions matters when interpreting early coverage of the drug.

Retatrutide is an investigational peptide developed by a pharmaceutical company as a multi-receptor agonist for treating obesity and type 2 diabetes. The compound emerged from research into gut-hormone analogues that act on several receptors simultaneously rather than on a single target. Early preclinical work examined how combined activity at three distinct receptors might produce greater metabolic effects than single-receptor compounds. Published phase 2 results have described substantial reductions in body weight among participants, although the compound remains unapproved in most jurisdictions as of the mid-2020s.

Retatrutide Background and Receptor Activity

Human evidence remains limited to controlled studies. A phase 2 trial in adults with obesity reported large, dose-dependent reductions in body weight over 48 weeks, with gastrointestinal events as the most frequently recorded adverse effect. Phase 3 programs designated TRIUMPH, for obesity, and TRANSCEND, for type 2 diabetes, are intended to confirm efficacy and to characterize safety in larger populations. Related studies are examining conditions such as knee osteoarthritis in people with obesity and metabolic liver disease. Open questions include long-term tolerability, effects on lean mass, and what happens after treatment is stopped.

Retatrutide is an investigational synthetic peptide that acts on three receptor targets at once: glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon. It is developed by Eli Lilly and appears in the literature and in trial registries under the code LY3437943. The molecule belongs to a class of engineered peptides designed to resist rapid breakdown and permit infrequent subcutaneous administration. No regulatory agency has approved it for clinical use, and all available human data come from controlled trials rather than from routine practice.

Retatrutide at a glance

PropertyValueNotes
Molecular classSynthetic peptideContains non-natural residues
Receptor targetsGLP-1, GIP, glucagonTriple agonist profile
Route of administrationSubcutaneous injectionIn clinical trial settings
Development statusInvestigationalNot approved in major markets
Approximate molecular massAbout 4.7 kDaPeptide-scale molecule

Analytical Methods, Stability, and Storage

Peptides in this class degrade mainly through hydrolysis, oxidation, and aggregation. The lipid modification improves plasma residence time but can also promote self-association in aqueous solution at higher concentrations. Oxidation of methionine and deamidation of asparagine residues are common chemical liabilities that accumulate during storage. Stability studies therefore track purity loss, aggregate formation, and changes in receptor-binding potency over time under defined temperature and humidity conditions.

Solid peptide is generally held as a lyophilised powder at low temperature to slow degradation, with desiccant to limit moisture uptake. Reconstituted solutions are less stable and are usually kept refrigerated and protected from light for short periods. Repeated freeze-thaw cycles are avoided because they encourage aggregation. Laboratory handling includes work in a fume hood or laminar flow cabinet to limit inhalation and contamination. Weighing and transfer steps are performed with antistatic tools to reduce static-driven loss of fine powder.

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瑞他鲁肽开发背景

与仅靶向单一受体的同类药物相比,瑞他鲁肽增加胰高血糖素受体成分,理论上可提高能量消耗并改变脂肪分布。临床中观察到的体重变化是否主要来自该额外机制,目前尚无定论。胃肠道反应是该类药物常见不良事件,试验中通过剂量递增和监测进行管理。停药后体重反弹、个体差异和长期耐受性仍需更多数据。

瑞他鲁肽是一种在研合成肽,同时作用于胰高血糖素样肽-1、葡萄糖依赖性促胰岛素多肽和胰高血糖素受体。该分子属于多受体激动剂类别,尚未获得任何监管机构的上市批准。当前临床开发主要针对肥胖和2型糖尿病,研究代号为LY3437943。已确立的信息包括受体靶点和部分中期试验结果;最终疗效、长期安全性和适用人群仍属开放问题。

Peptide Identity and Receptor Targets

Pharmacologically the compound activates three receptors: GLP-1, GIP, and glucagon. GLP-1 and GIP signaling contribute to glucose-dependent insulin release, delayed gastric emptying, and reduced appetite, while glucagon receptor activation is associated with increased energy expenditure and hepatic fat oxidation. The single-molecule design is intended to keep these activities in one peptide rather than combining separate agents. Relative activity at each receptor differs, and the balance between them is a central question in interpretation. The glucagon component is partly offset by incretin-mediated insulin secretion, an interaction that remains incompletely characterized.

Development has progressed from single- and multiple-ascending-dose studies in healthy volunteers into larger randomized trials in adults with obesity, type 2 diabetes, and fatty liver disease. Early reports describe dose-dependent reductions in body weight and improvements in glycemic markers over treatment periods of several months. Whether the glucagon arm adds tolerability cost without added benefit is still debated. Long-term cardiovascular outcomes, effects after treatment stops, and performance in older or comorbid populations are open questions rather than settled findings. Approval status may change, so the current investigational label should be confirmed against regulatory sources.

Background and Receptor Pharmacology

Clinical studies have reported notable reductions in body weight among participants. Early trials measured safety and explored several dose levels, and later studies tracked body-weight change over months of treatment. Investigators also monitor effects on glycemic markers, liver fat, and blood lipids. Because the compound is still in development, questions about long-term safety, cardiovascular outcomes, and durability after treatment ends remain open.

The three-receptor design places retatrutide in a distinct category relative to older incretin-based therapies. Single agonists target one receptor, and dual agonists target two. Adding a third target broadens the pharmacological footprint and introduces new trade-offs among efficacy, tolerability, and glucose control. How these trade-offs resolve in large trials is a central focus of current research.

Reference notes

=== Pharmacodynamics === Alazocine shows stereoselectivity in its pharmacodynamics. The (−)-enantiomer is a non-selective and high-affinity ligand of the μ-, κ-, and δ-opioid receptors (Ki = 3.0, 4.7, and 15 nM in guinea pig brain membranes) with very low affinity for the sigma σ1 receptor (Ki = 1,800–4,657 nM in guinea pig brain membranes). It acts as a moderate-efficacy partial agonist of the κ-opioid receptor (Ki = 0.4 nM, EC50 = 24 nM, and Emax = 66% for (±)-alazocine against the mouse receptor transfected in HEK293 cells) and as an antagonist of the μ-opioid receptor (Ki = 1.15 nM for (±)-alazocine against the mouse receptor transfected in HEK293 cells). It is also an agonist of the δ-opioid receptor with far lower potency (Ki = not reported, IC50 = 184 nM, and Imax = 68% for (±)-alazocine against the mouse receptor transfected in HEK293 cells). Conversely, the (+)-stereoisomer has little affinity for the opioid receptors (Ki for 1,900 nM, 1,600 nM, and 19,000 nM for the μ-, κ-, δ-opioid receptors in guinea pig brain membranes) and instead is a selective and high-affinity agonist of the σ1 receptor (Ki = 48–66 nM in guinea pig brain membranes). However, the (+)-enantiomer also shows moderate affinity for the dizocilpine (MK-801) or phencyclidine (PCP) site of the NMDA receptor (Ki = 587 nM in rat brain membranes relative to 45 nM for the σ1 receptor) and, hence, is an uncompetitive NMDA receptor antagonist as well at higher concentrations. As such, (+)-alazocine is only modestly selective as a ligand of the σ1 receptor.

Carrey's first stand-up comedy experience took place in 1977 at the age of 15 with his father trying to help him put together a stage act, driving him to downtown Toronto to debut at the recently opened Yuk Yuk's comedy club operating one-night-a-week out of community center The 519's basement on Church Street. For the performance, Carrey had his attire—a polyester leisure suit—chosen by his mother who reasoned "that's how they dress on The Dean Martin Celebrity Roast". Pubescent Carrey's conventional impersonations bombed, proving ill-suited for a club with a raunchy comedic sensibility and giving him doubts about his potential as a professional entertainer. Decades later, recalling Carrey's stand-up debut, Yuk Yuk's owner Mark Breslin described it as "bad Rich Little". His family's financial struggles made it difficult for them to support Carrey's show business ambitions. Eventually, the family's financial situation improved and they moved into a new home in Jackson's Point. With more domestic stability, Carrey returned to the stage in 1979 with a more polished act that led to his first paid gig: a 20-minute spot at the Hay Loft club on Highway 48 in Scarborough for a reported $20 compensation on a bill with the Mother of Pearl performer from The Pig and Whistle. He soon faced his fears and went back downtown to the site of his debacle from two years earlier—Yuk Yuk's that had in the meantime moved into a permanent location on Bay Street in the fashionable Yorkville district.

Scabies (, SKAY-beez; also sometimes known as the seven-year itch) is a contagious human skin infestation by the tiny (0.2–0.45 mm) mite Sarcoptes scabiei, variety hominis. The word is from Latin: scabere, lit. 'to scratch'. It is a particular public health problem in crowded settings such as care homes, schools, refugee camps, prisons, and hospitals. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin from eggs that are about to hatch. In a first-ever infection, the infected person usually develops symptoms within three weeks. During a second infection, symptoms may begin within 24 hours. These symptoms can be present across most of the body or just in certain areas such as the wrists, between fingers, or along the waistline. The head may be affected, but this is typically only in young children. The itch is often worse at night. Scratching may cause skin breakdown and an additional bacterial infection in the skin. Various names have been given to this condition and the name "seven year itch" has been recorded in many documents from the 1800s. Although the 1952 play The Seven Year Itch and modern treatment methods have generally changed this name to refer to human relationships, the condition was historically very difficult to treat. Scabies is caused by infection with the female mite Sarcoptes scabiei var. hominis, an ectoparasite. The mites burrow into the skin to live and deposit eggs. The symptoms of scabies are due to an allergic reaction to the mites.

=== Synthesis of other elements === 210Po can be manufactured by bombarding 209Bi with neutrons in a nuclear reactor and around 100 grams of 210Po are produced each year. 209Po and 208Po can be made through the proton bombardment of 209Bi in a cyclotron. Astatine can also be produced by bombarding 209Bi with alpha particles. Traces of 209Bi have also been used to create gold in nuclear reactors. 209Bi has been used as a target for the creation of several isotopes of superheavy elements such as dubnium, bohrium, meitnerium, roentgenium, and nihonium.

UK and international clinical practice guidelines do not recommend metformin as a first-line treatment or do not recommend it at all, except for people with glucose intolerance. The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from medical treatment. Metformin treatment decreases the risk of developing type 2 diabetes in people with PMOS who exhibited impaired glucose tolerance at baseline. In Poland, metformin is listed as an approved and reimbursed treatment for PMOS.

Sources: en.wikipedia.org

Reference notes

Anshel Pfeffer(Hebrew: אנשיל פפר, born 22 June 1973); British -Israeli journalist; a senior correspondent and columnist for Haaretz, covering military, Jewish and international affairs, and Israel correspondent for The Economist.; has also written for The Guardian, The New York Times, The Washington Post and The Times; received the B'nai B'rith award for "Recognizing Excellence in Diaspora Reportage" Melanie Phillips,(born 4 June 1951) Neoconservative, and right wing hawkish pro Zionist journalist; began her career writing for The Guardian and New Statesman; during the 1990s, she came to identify with ideas more associated with the right and currently writes for The Times, The Jerusalem Post, and The Jewish Chronicle, covering political and social issues from a social conservative perspective.Irving Kristol, defines her as a liberal who has "been mugged by reality";was panellist on BBC Radio 4 programme The Moral Maze and BBC One's Question Time; was awarded the Orwell Prize for Journalism Hella Pick CBE (24 April 1929 – 4 April 2024); in 1960, was UN correspondent of The Guardian newspaper, tutored by chief US correspondent Alistair Cooke; awarded CBE in 2000; was Arts & Culture Programme Director at Institute for Strategic Dialogue, an independent think-tank based in London; author ofSimon Wiesenthal: A Life in Search of Justice, Weidenfeld & Nicolson, 1996; Guilty Victim – Austria from the Holocaust to Haider, I B Tauris & Co Ltd, 2000 and Invisible Walls, Weidenfeld & Nicolson, 2021 Gabriel Pogrund (born 1993 or 1994) is a journalist who has worked for the New Statesman, Shortlist, Ha'aretz and Jewish News and is currently Whitehall editor at The Sunday Times; won 2017 Young Journalist of the Year at the British Press Awards and in 2018 was a Stern Fellow at The Washington Post. In 2020 Pogrund and Patrick Maguire published Left Out: The Inside Story of Labour Under Corbyn, which in part, addresses charges of, and assumptions about 'the new anti-Semitism' in the Labour Party. Eve Pollard Evelyn, Lady Lloyd, (née Pollard, formerly Winkleman, born 25 December 1943); has been the editor of several tabloid newspapers; was fashion editor at Honey magazine; also worked for Daily Mirror; was launch editor-in-chief of Elle magazine in the US and edited Sunday magazine for the News of the World and You magazine for the Mail on Sunday; also worked in television as features editor of TV-am (1982–1983) and devised Frocks on the Box for ITV contractor TVS.; often appeared on radio and TV; was regular participant in Through the Keyhole; was a guest panellist on the talk show Loose Women; in 2016, was appointed the first Chair of Reporters without Borders in the UK. In June 2019, was awarded the prestigious Journalist Laureate prize by the London Press Club. She has been a member, appointed in 1999, of the Competition Commission's Newspaper Takeover Panel. Pollard was appointed Officer of the Order of the British Empire (OBE) in the 2008 Birthday Honours List for services to journalism. Stephen Pollard (born 18 December 1964); was editor of The Jewish Chronicle; was researcher for Labour MP Peter Shore; worked for the Fabian Society; joined the Social Market Foundation; Senior Fellow at Civitas; was president for the Centre for the New Europe and in 2007, first chair of the European Institute for the Study of Contemporary Antisemitism;signatory founder of the Henry Jackson Society, a neoconservative British foreign policy think tank. Karen Pollock journalist, writer, activist chief executive of Holocaust Educational Trust (HET); was Director of the All-Party Parliamentary Group against Antisemitism; later joined Holocaust Educational Trust (HET); is involved with the anti-fascist organisation Searchlight and London Jewish Forum, as well as the Holocaust Memorial Day Trust. She has written for The Guardian, Jewish News, The Jewish Chronicle, and The Huffington Post; gave TED talk entitled 'The search for humanity in the Holocaust' for TEDxDurhamUniversity 2016. She represented British Jews at United Nations World Conference against Racism. She is a vice-president of the Jewish Leadership Council. She was appointed Member of the Order of the British Empire (MBE) in the 2012 New Year Honours for services to education, specifically about the Holocaust, and Commander of the Order of the British Empire (CBE) in the 2020 Birthday Honours for services to Holocaust education. Marjorie Proops, agony aunt Richard Quest(born 9 March 1962) journalist and barrister working as news anchor for CNN International; also an editor-at-large of CNN Business; anchors Quest Means Business, the five-times-weekly business program and fronts the CNN shows Business Traveller, The Express and Quest's World of Wonder; Quest wrote the book, The Vanishing of Flight MH370: The True Story of the Hunt for the Missing Malaysian Plane, published by Penguin Random House on 8 March 2016. Kimberly Quinn (formerly Fortier; née Solomon; born 1961); journalist, commentator and magazine publisher and writer; publisher of British conservative news magazine The Spectator; has written for The Wall Street Journal, Vogue and UK newspapers The Daily Telegraph, The Times, Evening Standard, and The Independent; was the Communications and marketing director for Condé Nast Publications in the UK. Gideon Rachman (born 1963) is a British journalist of Jewish South African ancestry; adherent of Neoconservatism and right wing hawkish pro Zionism; was chief foreign affairs commentator of the Financial Times in July 2006. In 2016, won the Orwell Prize for political journalism and was awarded the Commentator Award at the European Press Prize awards; also worked with BBC World Service in 1984 and from 1988 to 1990, was a reporter for The Sunday Correspondent newspaper, Washington, D.C.; spent 15 years at The Economist newspaper. Barnaby Raine is an anti fascist, anti Zionist, pro-Palestinian author, journalist, intellectual and broadcaster, writing for New Internationalist, n+1, Salvage, Red Pepper, Novara Media, Jacobin, Counterfire and others. Claire Rayner, agony aunt Jay Rayner (born 14 September 1966) food critic for The Guardian, The Mail on Sunday, GQ, Esquire, Cosmopolitan, New Statesman and Granta; first novel, The Marble Kiss, published in 1994, shortlisted for Author's Club First Novel Award; second novel, Day of Atonement (1998) shortlisted for the Jewish Quarterly Prize for Fiction Hugo Rifkind(born 30 March 1977); columnist for The Times; presenter on Times Radio; regular guest on The News Quiz, on BBC Radio 4; contributes to GQ; son of Conservative Party politician Sir Malcolm Rifkind; Columnist of the Year in the 2011 Editorial Intelligence Comment Awards, and Media Commentator of the Year in the same awards in 2012; highly commended in the Best of Humour category at the Society of Editors' Press Awards; was Stonewall's Journalist of the Year; also named Best Grooming Journalist in the P&G Beauty Awards; In 2015, at the Comment Awards, he was named Arts, Culture and Entertainment Commentator of The Year. in 2017, he won both Best of Humour and Critic of the Year at the Society of Editors' Press Awards. Robert Rinder (born 31 May 1978), barrister, television personality and columnist for The Sun, Daily Mail, Evening Standard; host for TalkTV. In 2014, began hosting reality courtroom series Judge Rinder. In 2019, began hosting Channel 4 series The Rob Rinder Verdict. In 2022, Rinder became a regular host on ITV's Good Morning Britain. Nick Robinson (journalist), BBC broadcaster of German Jewish ancestry; was president of the Oxford University Conservative Association; president of the Conservative Party youth group; was deputy editor of Panorama; worked for ITV News as political editor; presented Westminster Live, Weekend Breakfast and Late Night Live on BBC Radio 5 Live, and Newsnight on BBC Two; covered general election for BBC Radio; co-hosted BBC Two's Icons: The Greatest Person of the 20th Century alongside Claudia Winkleman; hosted final debate between Boris Johnson and Jeremy Corbyn prior to 2019 general election; author of two books. Barney Ronay, chief sports writer for The Guardian, of Austrian Jewish descent; was educated at the University of Oxford; was included in list of most respected journalists working in Britain as published by the National Council for the Training of Journalists; nominated in the 'writer of the year' category at the 2018 Football Supporters Federation Awards. Jon Ronson, journalist, author, documentary filmmaker and radio presenter David Rose (journalist) (born 21 July 1959); author and investigative journalist; contributing editor with Vanity Fair; special investigations writer for The Mail on Sunday. His interests include human rights, miscarriages of justice, the death penalty, racism, the war on terror, politics, and climate change denial; author of six non-fiction books and a novel, Taking Morgan, a thriller set in Washington, Oxford, Tel Aviv and Gaza; named News Reporter of the Year in the Society of Editors British Press Awards for 2015; brother of Bernard Rose (director), filmmaker and screenwriter, considered pioneer of digital filmmaking. Phil Rosenberg (Jewish leader) (b. 1986) writes for Jewish Chronicle, Jewish News, Times of Israel, regularly appears on British television as social commentator; current President of the Board of Deputies of British Jews; served as a Labour councillor ; served as Director of the Faiths Forum for London managing relationships between various religious denominations; at University, was co-director of Muslim-Jewish dialogue group; ran Arab-Jewish dialogue group at Hebrew University in Jerusalem; works as consultant in government relations, media, faith, and diplomacy; Vice President at the World Jewish Congress, extending influence and involvement in global Jewish affairs; Vice President of the Jewish Leadership Council and a Trustee of the Holocaust Memorial Day Trust. Steve Rosenberg (born 5 April 1968); was part of CBS News crew covering first war in Chechnya; journalist for BBC News and has been the BBC's Moscow correspondent since 2003, except for stint as Berlin correspondent between 2006 and 2010; in 2022, was appointed BBC's Russia editor. Jonathan Rosenhead (born 21 September 1938), mathematician, operational researcher and Labour Party activist; author of a number of scholarly monographs and works of political analysis, including The Technology of Political Control, published by Penguin Books; op-ed journalist for The Guardian, New Scientist, Haaretz, Times Higher Education (THE), openDemocracy, and anti-Zionist website Mondoweiss; active in the British Society for Social Responsibility in Science over a 20-year period; is chairman of the British Committee for the Universities of Palestine (BRICUP) and information officer for Jewish Voice for Labour. Joshua Rozenberg KC (hon) (born 1950), British solicitor, legal affairs commentator, journalist; husband of Melanie Phillips, began career in journalism in 1975 at the BBC where he launched Law in Action on BBC Radio 4 in 1984. At BBC he worked as producer, reporter and legal correspondent; in 2000 left to join The Daily Telegraph as legal affairs editor, where he remained until 2008. After leaving the Telegraph wrote for Evening Standard ; writes for Law Society Gazette and The Critic; wrote for The Guardian's online law page from 2010 to 2016; returned to the BBC to present Law in Action, nearly 25 years after leaving the radio programme. He continues to be seen on BBC Television News as a legal affairs analyst. In January 2016, was made an honorary QC. Dan Sabbagh, Defence and Security Editor and Journalist for The Guardian Jonathan Sacerdoti, writer, campaigner, broadcaster, journalist and TV producer; covers stories relating to the UK and Europe, as well as terrorism and extremism stories, race relations, Middle East analysis and the British royal family. He is also a campaigner against antisemitism. James Schneider (born 17 June 1987) political organiser, journalist; co-founded the left-wing grassroots movement Momentum; was PR advisor to Jeremy Corbyn as Director of Strategic Communications; joined Think Africa Press in 2010, a role he held until he became the senior correspondent at New African; has written articles for publications such as The Independent, the New Statesman, Novara Media, and LabourList. L. J. K. Setright, motoring journalist Rachel Shabi; British journalist and author; contributing writer to The Guardian and the author of Not the Enemy, Israel's Jews from Arab Lands, which argued that Israel has discriminated against and culturally stripped its population of Jews from Arab and Muslim countries. The book received a National Jewish Book Award.Born in Israel to Iraqi Jewish parents in Ramat Gan, Shabi grew up in the UK. Jonathan Shalit (born 17 April 1962), journalist writing for Jewish Chronicle, The Sun, The Telegraph, Daily Express, Royal Television; talent manager and chairman of the InterTalent Rights Group; advises government on the UK's entertainment and creative industries; has guided and managed Charlotte Church, Mel B, Baroness Brady, Kelly Brook, Cher, Dame Joan Collins, Rebecca Ferguson, Katherine Jenkins, Sir Elton John, Vinnie Jones, Kelly Hoppen, Lorraine Kelly, Myleene Klass, N-Dubz, Arlene Phillips, Sir George Martin (the Beatles' producer), Pixie Lott, Sting, Tulisa, Gregg Wallace, Simon Cowell, and the winners of the ITV television talent show Britain's Got Talent. Shalit is chair of trustees and Chief Barker of Variety, the Children's Charity and a leading figure behind the return to London of the Variety Club Showbusiness Awards in 2022. He is also Chairman of the MOBO Charity Foundation (Music of Black Origin), a Trustee of both ChickenShed (Theatre Changing Lives), Patron of the Royal Television Society and co-chairman of the Classic BRITS, and a supporter of Norwood. He gave evidence to Leveson Inquiry into practices and ethics of British Press and was awarded the OBE in 2014 for services to entertainment industry. He also holds an honorary professorship, awarded in 2012, and honorary doctorate at Henley Business School of Reading University in recognition of his contribution to the arts, music and broadcasting. Miriam Shaviv (born 24 August 1976), columnist for "The Jewish Chronicle", "Haaretz", "The Times of Israel", "The Forward"; former literary editor of The Jerusalem Post; Features Editor of the "Times Higher Education" magazine. David Shukman (born 30 May 1958) journalist, and the former science editor of BBC News. Alexandra Shulman (born 13 November 1957); daughter of the critic Milton Shulman and the writer Drusilla Beyfus; previously worked at Arista Records; columnist for The Daily Telegraph and Daily Mail; first novel, Can We Still Be Friends?, published in 2012; was assessed as one of the 100 most powerful women in the United Kingdom by Woman's Hour on BBC Radio 4. Shulman was appointed Officer of the Order of the British Empire in the 2005 New Year Honours for services to the magazine industry. She was later promoted to Commander of the Order of the British Empire in the 2018 New Year Honours for services to fashion journalism; was formerly a trustee of the National Portrait Gallery. Brother Jason Shulman worked as graphic designer for The Sunday Telegraph and art director for Harpers & Queen and Harvey Nichols' magazines. Jake Wallis Simons; Editor of the Jewish Chronicle, writer for The Jerusalem Post, The Times of Israel, Haaretz, the Spectator, the Telegraph, a commentator for Sky News and a broadcaster for BBC Radio 4 and the World Service; was Associate Global Editor for the Daily Mail Online, and features writer for the Sunday Telegraph; also worked for the Times, The Guardian, CNN, POLITICO, Newsweek and La Repubblica; author of Israelophobia: The Newest Version of the Oldest Hatred and What To Do About It, published by Little, Brown and Company Samantha Simmonds (born 1972 or 1973); newsreader, television presenter and journalist; was a news anchor for Sky News until July 2016; returned to presenting for BBC News in March 2017; has also written for Jewish News, MSN (US), Daily Mail, Daily Mirror, The Sun, The Telegraph, Yahoo News Australia, Evening Standard, Times of Israel, Good Housekeeping (UK), HuffPost UK, Women's Health, Women's Health (UK), TV Times, Glamour (UK), Celebs Now, The Jewish Chronicle, Woman Magazine. Ruth Smeeth (née Anderson; born 29 June 1979);Labour Party politician;became director of public affairs and campaigns at the Britain Israel Communications and Research Centre (BICOM) in November 2005; writes for Index on Censorship, The Guardian, Daily Mail, The Independent, The Telegraph, Daily Express, The Sunday Times, The Times, Times of Israel, HuffPost UK, New Statesman;was a deputy director of anti-racist organisation, Hope not Hate. She has also been employed by the Community Security Trust and has worked for the Board of Deputies of British Jews and she is a member of Labour Friends of Israel.; became chief executive of Index on Censorship, an organisation which campaigns for freedom of speech. Jon Sopel, journalist; presents The Politics Show on BBC One; one of the lead presenters on News 24; voted 'Political Journalist of the Year' by Public Affairs Industry; shortlisted for 'National Presenter of the Year' at the Royal Television Society television journalism awards 2011/2012. Hedi Stadlen (6 January 1916 – 21 January 2004), British, of Austrian Jewish ancestry, journalist, pamphleteer, Communist, Musicologist, better known in Sri Lanka as Hedi Keuneman, was an Austrian Jewish philosopher, political activist, and musicologist. She was one of the handful of European Radicals in Sri Lanka. Matthew Stadlen is her grandson. Matthew Stadlen (b.1979); presenter on LBC, BBC Radio 5 Live; grandson of concert pianist Peter Stadlen and Hedi Stadlen, activist and musicologist; worked on Newsnight, The New Statesman, The Spectator and for Radio Times, and has worked as a consultant on ITV political programmes Bob Stanley (born Robert Andrew Shukman; 25 December 1964); musician, journalist, author, film producer; member of indie pop group Saint Etienne and music journalist for NME, Melody Maker, Mojo, The Guardian and The Times, as well as writing three books on music and football; also has a career as a DJ and as a producer of record labels, and has collaborated on a series of films about London. His second publication, Yeah! Yeah! Yeah!: The Story of Modern Pop, published by Faber & Faber; third publication Let's Do It: The Birth of Pop Music: A History, published by Pegasus. Mark Steyn (born 8 December 1959) is a British-Canadian author and a radio and television presenter. He has written several books. He is Anglican, but has Jewish maternal ancestry. Steyn's great-aunt was artist Stella Steyn. His mother's family was Belgian. Zoe Strimpel(born 8 July 1982); journalist, author, and commentator on gender and relationships. She is a columnist for The Sunday Telegraph where she writes a weekly column, commenting on gender, feminism, dating, relationships and identity politics;has also written on relations between men and women for Elle, the Sunday Times Style magazine, and HuffPost. She has also contributed to The Jewish Chronicle, The Spectator, and UnHerd. John Suchet, newsreader, journalist and brother of actor David Suchet, son of Jack Suchet, of Russian Jewish ancestry. He is the father of Russia Today RT journalist and presenter Rory Suchet. Helen Szamuely (25 June 1950 – 5 April 2017), historian and Eurosceptic, researcher for the Bruges Group (United Kingdom); daughter of Lenin Boys leader, Tibor Szamuely, wrote for the BBC Russian Service, History Today, Standpoint, New Statesman, Guardian, Salisbury Review, EUobserver and Social Affairs Unit; sister of George Szamuely. Christopher Tugendhat, Baron Tugendhat (born 23 February 1937),; Conservative Party politician, businessman, journalist and author; Member of Parliament until 1977, then Member of the European Commission, Lord Tugendhat entered the House of Lords in 1993; sits as Life Peer; was features editor and leader writer for the Financial Times; served as Vice-President of European Commission; author of Oil: The Biggest Business (1968); Multinationals (1971); Making Sense of Europe (1986); Options for British Foreign Policy in the 1990s (Nov 1988) Tom Tugendhat (born 27 June 1973) journalist; has written for Daily Mail, Financial Times, Jewish News, Jewish Chronicle; is also Minister of State for Security; member of Conservative Party, Member of Parliament; was chairman of the House of Commons Foreign Affairs Committee; has served as public relations consultant in the Middle East and was officer in the British Army reserves, the Territorial Army; Tugendhat served in the Iraq War and the Afghanistan War. Ed Vaizey (born June 1968) Baron Vaizey of Didcot; of Polish Jewish ancestry; commentator for Conservative Party in broadcast and news media; wrote for The Guardian, The Sunday Times, The Times and The Daily Telegraph; briefly wrote editorials for the Evening Standard; also a regular broadcaster, having appeared on Fi Glover's and Edwina Currie's shows on BBC Radio 5 Live, as regular panelist on Channel 5's The Wright Stuff, BBC Radio 4's Despatch Box and Westminster Hour, and occasionally presented People and Politics on the BBC World Service; in 2010, was named tenth in the 2010 Guardian Film Power 100 list. He played a cameo role as an Oxfordshire MP in the 2012 film Tortoise in Love. Adam Wagner; journalist and op-ed writer for The Jewish Chronicle, Times of Israel, Haaretz, The Guardian, Forbes, Daily Mirror, HuffPostUK, New Statesman; barrister, a member of the Equality and Human Rights Commission's panel of counsel. In 2019 he represented Campaign Against Antisemitism (CAA) in its case a formal investigation under section 20 of the Equality Act 2006 into whether Labour Party had "unlawfully discriminated against, harassed or victimised people because they are Jewish"; specialist in human rights and public law, including COVID-19 lockdown rules. George Weidenfeld, Baron Weidenfeld, (13 September 1919 – 20 January 2016) was a British publisher, philanthropist, and newspaper columnist. He was also a lifelong Zionist and renowned as a master networker. He was on good terms with popes, prime ministers and presidents and put his connections to good use for diplomatic and philanthropic ends; founder of Institute for Strategic Dialogue Victor Weisz, Vicky, cartoonist Claudia Winkleman (born 15 January 1972); television presenter, radio personality, film critic and journalist; has written for The Sunday Times, The Independent, London paper Metro and has written opinion-led lifestyle journalism for Cosmopolitan, Tatler and The Independent; has also written for BBC, Daily Mail, The Mirror UK, The Sun, The Telegraph, Daily Express, The Times, and Radio Times Jonathan Wittenberg (born 17 September 1957 in Glasgow, Scotland); Masorti rabbi, the Senior Rabbi of Masorti Judaism UK; leading writer and thinker on Judaism; has written for The Guardian, Daily Mirror, HuffPost, Times of Israel, Haaretz, and The Jewish Chronicle. He is Rabbi of the New North London Synagogue,; member of the Elijah Interfaith Institute Board of World Religious Leaders.; has featured on Thought for the Day on the BBC Radio Four Today programme. Martin Wolf (born 16 August 1946 in London) journalist; chief economics commentator at the Financial Times; widely regarded as one of the most influential economics journalists in the world. Lawrence H. Summers called him "the world's preeminent financial journalist." Mohamed A. El-Erian, former CEO of the PIMCO, said Wolf is "by far, the most influential economic columnist out there".Prospect magazine described him as "the Anglosphere's most influential finance journalist",; Kenneth Rogoff said, "He really is the premier financial and economics writer in the world". In 2012, he received the Ischia International Journalism Award.In 2019, Wolf received the Gerald Loeb Lifetime Achievement Award from the UCLA Anderson School of Management. Donald Zec (12 March 1919 – 6 September 2021); author of over ten books, newspaper journalist and biographer; worked for the Daily Mirror for 40 years.

=== Differentiation === CAFs can also be derived from differentiation of other cell types such as mesenchymal stem cells, which was proved in murine models with cancers such as glioma, breast, pancreatic and gastric cancers. Another suggested origin is differentiation of endothelial or epithelial cells via trans-differentiation or epithelial to mesenchymal transition, respectively. Less common origin of CAFs is by differentiation of other tumor adjacent cells such as epithelial or endothelial cells, adipocytes, pericytes and smooth muscle cells. Adipocytes, especially white adipocytes transdifferentiate into CAFs upon activation with TGF-β1. Through TGF-β1 can be transformed also peritoneal mesothelial cells. It has been suggested that CAFs are better conceptualised as a “cell state” Research has found that CAF trans-differentiation can be caused by epigenetic factors.

The legislative bill is aimed at strengthening capabilities in the area of technology, such as quantum computing and AI specifically to face the competitive threat from China perceived as urgent. Senator Chuck Schumer, the leader of the Senate majority and one of the sponsors of the industrial policy bill invoked the threat of authoritarian regimes that want “grab the mantle of global economic leadership and own the innovations”. In 2022, U.S. Innovation and Competition Act was amended and turned into the Chips and Science Act with planned spending of 280 billion US dollars, 53 billion thereof are allocated directly to subsidies for semiconductors manufacturing. Commentators identified possible positive effects on innovation from the US attempts to compete with China in a perceived rivalry. Among the main beneficiaries of the US CHIPS Act are the semiconductor producers Intel, TSMC and Micron Technology.

Human trafficking for the purpose of sexual exploitation is a major cause of contemporary sexual slavery and is primarily for prostituting women and children into sex industries. Sexual slavery encompasses most, if not all, forms of forced prostitution. The terms "forced prostitution" or "enforced prostitution" appear in international and humanitarian conventions but have been insufficiently understood and inconsistently applied. "Forced prostitution" generally refers to conditions of control over a person who is coerced by another to engage in sexual activity. Official numbers of individuals in sexual slavery worldwide vary. In 2001 International Organization for Migration estimated 400,000, the Federal Bureau of Investigation estimated 700,000 and UNICEF estimated 1.75 million. The most common destinations for victims of human trafficking are Thailand, Japan, Israel, Belgium, the Netherlands, Germany, Italy, Turkey and the United States, according to a report by UNODC.

Sources: en.wikipedia.org

Reference notes

From then on, the two teams interacted regularly and Watt coined the term ionosphere to describe the multiple atmospheric layers they discovered. In 1927 the two radio labs, at the Met Office and NPL, were combined to form the Radio Research Station (with the same acronym, RRS), run by the NPL with Watt as the Superintendent. This provided Watt with direct contact to the research community, as well as the chief signals officers of the British Army, Royal Navy and Royal Air Force. Watt became a well-known expert in the field of radio technology. This began a long period where Watt agitated for the NPL to take a more active role in technology development, as opposed to its pure research role. Watt was particularly interested in the use of radio for long-range aircraft navigation, but the NPL management at Teddington was not receptive and these proposals went nowhere.

The ease with which our potatoes lend themselves to all sorts of stews gave me the idea of composing a meal of them, to which I invited several amateurs; and at the risk of being thought to be afflicted with potato mania, I will end this review by describing it: it was a dinner. We were first served two soups, one of mashed potatoes from our roots, the other of a fatty broth, in which the potato bread simmered quite well without crumbling; then came a matelote followed by a dish in white sauce, then another in maitre d'hôtel, and finally a fifth in roux. The second service consisted of five other dishes not less good than the first; first a pâté, a frying, a salad, fritters, and the economic cake of which I gave the recipe; the remainder of the meal was not very extensive, but delicate and good; a cheese, a pot of jam, a plate of cookie, another of tarts, and finally a brioche also of potatoes, made up the dessert; after that we had the coffee, also described above. There were two kinds of bread; the one mixed with potato pulp and wheat flour, fairly represented soft bread; the second, made of potato pulp, with their starch, bore the name of firm dough bread; I would have wished that fermentation had put me in a position to make a drink of our roots, to fully satisfy my guests, and to say with foundation: "Do you like potatoes, we have put them everywhere." Every one was cheerful; and if potatoes are drowsy, they produce on us a very opposite effect.

Schumer did an episode (#154) of WTF with Marc Maron podcast on March 3, 2011, in which she discusses her early life in more detail. Schumer has appeared in roles on the NBC comedy series 30 Rock, the Adult Swim mockumentary series Delocated, and the two HBO series, Curb Your Enthusiasm and Girls. She was also a frequent guest on The Howard Stern Show and the Opie and Anthony radio show. Schumer released a stand-up comedy album, Cutting, in 2011. Her stand-up comedy special Mostly Sex Stuff premiered on Comedy Central on August 18, 2012, to positive reviews. Schumer said in February 2012, "I don't like the observational stuff. I like tackling the stuff nobody else talks about, like the darkest, most serious thing about yourself. I talk about life and sex and personal stories and stuff everybody can relate to, and some can't." She acted in three films in 2012: the independent comedy Price Check, the comedy-drama Seeking a Friend for the End of the World, and the independent comedy Sleepwalk with Me. Schumer also appeared on The Comedy Central Roast of Charlie Sheen in September 2011, and The Comedy Central Roast of Roseanne Barr in August 2012. In June 2012, Schumer began work on a sketch comedy series for Comedy Central. The show included single-camera vignettes of Schumer playing "heightened versions" of herself. The vignettes are linked together with footage of Schumer's stand-up.

=== Gas exchange === The major function of the lungs is gas exchange between the lungs and the blood. The alveolar and pulmonary capillary gases equilibrate across the thin blood–air barrier. This thin membrane (about 0.5 –2 μm thick) is folded into about 300 million alveoli, providing an extremely large surface area (estimates varying between 70 and 145 m2) for gas exchange to occur.

Alternatives to the above closed-channel continuous-flow systems include novel open structures, where discrete, independently controllable droplets are manipulated on a substrate using electrowetting. Following the analogy of digital microelectronics, this approach is referred to as digital microfluidics. Le Pesant et al. pioneered the use of electrocapillary forces to move droplets on a digital track. The "fluid transistor" pioneered by Cytonix also played a role. The technology was subsequently commercialised by Duke University. By using discrete unit-volume droplets, a microfluidic function can be reduced to a set of repeated basic operations, i.e., moving one unit of fluid over one unit of distance. This "digitisation" method facilitates the use of a hierarchical and cell-based approach for microfluidic biochip design. Therefore, digital microfluidics offers a flexible and scalable system architecture as well as high fault-tolerance capability. Moreover, because each droplet can be controlled independently, these systems also have dynamic reconfigurability, whereby groups of unit cells in a microfluidic array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. Although droplets are manipulated in confined microfluidic channels, since the control on droplets is not independent, it should not be confused as "digital microfluidics". One common actuation method for digital microfluidics is electrowetting-on-dielectric (EWOD).

Sources: en.wikipedia.org

Frequently asked questions

What receptors does retatrutide target?

It is designed as a triple agonist acting on the GLP-1, GIP, and glucagon receptors. This combination is intended to influence appetite, insulin secretion, and energy expenditure. Single-receptor and dual-receptor compounds act on a narrower set of targets.

Has retatrutide been approved for use?

No. It remains investigational, and phase 3 results have not been fully published or reviewed by regulators. Official approval status should be confirmed through regulatory agencies rather than secondary sources.

How does it differ from dual-agonist compounds?

The added glucagon receptor activity is the main difference in its mechanism. Whether that addition produces meaningful benefits in clinical outcomes is still being studied. Comparisons between compounds rest largely on indirect rather than head-to-head trial data.

What is retatrutide?

It is an investigational peptide that activates three hormone receptors: GIP, GLP-1 and glucagon. It is being studied mainly for obesity and type 2 diabetes, and it is not approved for any clinical use. Published information comes from controlled trials rather than from general practice.

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