In a September 1 Instagram post, Dr Saurabh Sethi, a gastroenterologist trained at Harvard, AIIMS and Stanford Universities, shared eight signs of colon cancer, or colorectal cancer, that one should never ignore.
According to the gastroenterologist, most colon cancers start silently, which is why if the signs appear, you should consult your doctor.(Shutterstock)
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The gastroenterologist stressed that cancer of the colon or rectum usually starts silently. Therefore, most people tend to overlook the symptoms. Here are some signs that should alert you and push you or your loved ones to visit an expert.
8 colon cancer warning signs you should never ignore
In the post, the gastroenterologist pointed out that subtle signs like changes in your bowel movement, unexplained weight loss, pain in the abdomen, fatigue, or even the feeling of incomplete bowel movement can all point towards colon cancer. Therefore, at the first sign, one should visit their physician. Here are the 8 signs you shouldn’t ignore:
1. Blood in stool
Bright red or dark, tarry stool can signal bleeding in the colon. Dr Sethi stressed that you shouldn’t assume it’s just haemorrhoids.
2. Persistent bowel changes
“Constipation, diarrhoea, or narrowing of stools lasting more than a few days is a red flag,” the gastroenterologist warned.
3. Abdominal pain or cramping
Frequent bloating, cramps, or abdominal pain that’s new or unexplained deserves a check-up.
4. Unexplained weight loss
Dr Sethi said, “Losing weight without dieting or lifestyle changes could mean your gut isn’t absorbing nutrients properly.”
5. Ongoing fatigue
Chronic tiredness, weakness, or dizziness may result from slow blood loss and anaemia, and could be a sign of colon cancer.
6. Unexplained iron-deficiency anaemia
“If labs show low iron, especially in men or post-menopausal women, it can be an early hidden sign of colon cancer,” Dr Sethi highlighted.
7. Feeling of incomplete emptying
“If it feels like you ‘can’t finish’ after a bowel movement, it may point to blockage or tumour growth,” the gastroenterologist said.
8. Family history
Lastly, if you have close relatives with colon cancer, it increases your risk. Therefore, don’t delay screening if symptoms appear.
All you need to know about colon cancer
According to the gastroenterologist, most colon cancers start silently, which is why if the signs appear, you should consult your doctor. If caught early, there’s a 5-year survival rate of 90 percent. “Don’t wait if you notice symptoms. Get screened – colonoscopy saves lives,” the expert stressed.
Note to readers: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.
A tsunami of excitement sweeps the fashion system as new creative directors take the reins across luxury’s top brands, driving shoppers back to stores. At least that’s what brands are betting on.
Going into a month packed with designer debuts — 10 of fashion’s biggest names including Chanel, Gucci and Dior are set to unveil revamped creative visions between now and early October — many industry insiders are more measured in their outlook, noting that success is far from guaranteed as a hyper-competitive season plays out against a difficult macroeconomic backdrop for luxury.
Even the most successful designer refreshes will face the same pressures that stymied predecessors: the challenge of creating products and imagery that read as “new” without alienating a diverse, global mix of existing customers; steep price inflation that has narrowed the audience for luxury fashion; and a saturated, ultra-fast-paced media environment that is making it harder for novel propositions to cut through the noise and stick.
“If you define creativity as expressing a strong personal ideology, being fearless, being willing to experiment, then it’s harder and harder to operate creatively in today’s landscape. The bigger the house, the more complicated it is,” art director and Self Service magazine co-founder Ezra Petronio said. “The potential cost of risk taking is so high. And when you’re addressing such a big, global audience things often need to be flattened out and simplified for the mass market.”
Still, the wide-reaching creative reset is seen as fashion’s best hope for reigniting demand after two years of falling sales.
“It’s harder to question the system, to propose new ideas when everything’s working — so this moment is a big opportunity,” said Lucien Pagès, founder of the eponymous Paris PR firm.
While the consumer economy is less buoyant than during its heady post-Covid rebound, experts see stagnant creativity (along with inflated prices) as having exacerbated the slowdown.
“There had been a sort of collective tiredness: tired of the fashion cycle, tired of iterative design. It became hard to find the headspace to appreciate and untangle the creativity that is out there due to this tiresome rhythm,” said Judd Crane, executive director for buying and brand at Selfridges. “We’re feeling this mood of excitement for newness, and anticipating renewed desirability at several key brands.”
Mega-Brand Refresh
Over the next month, three of luxury’s five biggest brands are embarking on designer reboots,setting the scene for a new fashion era.
Gucci — which stagnated, then slipped in its final years under designer Alessandro Michele and CEO Marco Bizzarri — has been in free-fall since the duo’s exit. Sales fell 16 percent in the first half of 2025, on top of a 23 percent decline last year. Following two years under creative director Sabato De Sarno — whose effort at restoring sensual, sartorial glamour to the brand failed to catch fire — star designer Demna has been brought over from Kering stablemate Balenciaga to revamp the brand.
Demna brings a native understanding of how internet culture changed fashion along with both a savvy touch for accessible products like sneakers and merch and a devoted following for his high-end ready-to-wear. Gucci will provide a first glimpse at his efforts during Milan Fashion Week on September 23 — though it’s holding fire on a full-fledged runway show until next spring.
Dior, LVMH’s second-biggest brand, has also seen sales decline sharply as clients pull back. Under former creative directors Maria Grazia Chiuri and Kim Jones and CEO Pietro Bizzarri, revenues nearly quadrupled from €2.7 billion ($3.2 billion) in 2018 to more than €9 billion in 2023. But over the past two years, customers have balked at steep price hikes as well as storytelling and design that was seen as too repetitive. Current CEO Delphine Arnault is now counting on Jonathan Anderson, fresh off a transformative tenure at the group’s smaller Loewe brand, to rejuvenate Dior with his prolific creativity, curatorial sensibility and cast of of-the-moment collaborators in art and cinema.
Anderson’s well-received debut menswear show in June teased a cool, neo-preppy silhouette. His Oct. 1 womenswear debut will be the next test of how his off-kilter, often niche sensibility can continue to impress while being adapted for a commercial juggernaut.
Alba Rohrwacher wore Dior at the Venice Film Biennale—a first glimpse of Anderson’s womenswear for the French brand. (Getty Images)
Even blue-chip couture-and-beauty giant Chanel — previously seen as unassailable — has come under pressure from a slow-burning grassroots assault on its runway creativity, styling and the quality of its manufacturing: called out by customers and content creators on social media as not up to par with its top-of-the-line pricing. Revenues fell 4 percent last year.
Matthieu Blazy, a poised and approachable spokesperson known for his exacting behind-the-scenes leadership on design, product development, materials innovation and art direction, has taken over the brand’s creative direction and is set to debut his vision at its Oct. 1 ready-to-wear show.
For financial analyst Luca Solca, the creative shakeups were a business necessity. “This was required. Prices have gone up a lot — especially in soft luxury. If consumers need to spend more, it has to be at least for something new and exciting,” he said. “The industry is built on making heritage current. Not innovation at all costs, but innovation that puts the brand equity at the centre of attention and at the centre of the social debate today.”
Reboot or Slipstream?
Anderson and Blazy have left red-hot brands and businesses in their wake at LVMH’s Loewe and Kering’s Bottega Veneta, respectively.
Both brands will nonetheless need to commit to their new creative directors’ visions if they want to maintain their reputations for cutting-edge creativity. Louise Trotter, formerly of Carven and Lacoste, will stage her debut for Bottega Veneta Sept. 27. Jack McCollough and Lazaro Hernandez, the co-founders of New York’s Proenza Schouler, will follow with their first show for Loewe in Paris Oct. 3.
At the same time, both brands — among the few to have continued growing as the wider industry slumped — will likely be careful not to disrupt their relatively resilient commercial performance. Head-to-toe overhauls of merchandising and communications, as seen at Valentino under Alessandro Michele since 2024, are unlikely.
At Kering’s Balenciaga, excitement for Demna’s more accessible merch has cooled in recent seasons. But the brand’s sculptural, subversive couture collections and savvy celebrity partnerships have left it with a powerful platform that may better be retooled than fully rebooted under new creative director Pierpaolo Piccioli, formerly Valentino’s longtime creative chief.
Futuristic, norm-core, goth — key themes that fuelled the brand under Demna — may no longer be the fastest-growing buzzwords in fashion. But they evoke enduring customer archetypes who can be reactivated through new creative. “Our intention is to evolve. It’s not to lose the business and the segment that Balenciaga already had, but to build on this with the aesthetic that Pierpaolo will bring to the brand,” Kering’s deputy CEO Francesca Bellettini said in a July call with investors.
Other brands getting in on fashion’s creative reset this season include OTB’s Jil Sander (which tapped Simone Bellotti, former creative director of Bally), L’Oréal’s Mugler (where former Sportmax designer Miguel Castro Freitas is taking the reins) and Puig’s Jean Paul Gaultier (relaunching ready-to-wear under Duran Lantink).
Capri-owned Versace is also in the midst of a creative transition, emerging as a notable wild card in the season. Expectations were high for new creative director Dario Vitale, who recently played a key role turning Miu Miu into fashion’s hottest brand. But his Milan debut has been postponed — replaced by a low-key presentation — after Versace turned loss-making, while a deal to sell the brand to Prada Group has yet to close. A first peek at Vitale’s vision did little to reassure the market: Julia Roberts — a megawatt star, albeit with no aesthetic or creative connection to Versace — wore a sharp but generic jeans and blazer by the brand to the Venice Film Festival, followed by an archive-inspired black harlequin gown.
Marketing Rollout
In today’s celebrity-driven internet culture, establishing a credible, coherent and ideally surprising programme of red-carpet partnerships can be as powerful as the runway for fuelling interest in a brand.
That explains why Versace isn’t the only brand to have capitalised on Venice this year as a platform for providing sneak peaks at their new creative directors’ visions ahead of a busy fashion month, or to keep up momentum for recent debuts: Dior teased its upcoming womenswear debut by Anderson, dressing actresses Alba Rohrwacher (in a bustled crepe gown) and Mia Goth; Bottega Veneta’s Trotter dressed Jacob Elordi and new ambassador Vicky Krieps.
Tom Ford, which staged a well-received womenswear debut by designer Haider Ackermann in March, threw a star-studded party, dressing Tilda Swinton and Kate Moss.
Tilda Swinton and Haider Ackermann attend the Tom Ford “Black Orchid Reserve” Private Event at Palazzo Contarini Polignac. (Getty Images)
Maison Margiela, which staged its first haute couture show by Glenn Martens in July, has fought to hold onto its renewed spotlight: the brand eschewed its longstanding codes of anonymity — tapping Miley Cyrus for its first-ever celebrity campaign, days before dressing Kim Kardashian and Cate Blanchett at the Venice gathering.
But creating runway and red carpet moments are just the tip of the iceberg for designers at global brands that require their input on more touchpoints than ever. From mainline collections, carry-over products and one-off VIP ensembles to collaborations, ad campaigns, store concepts and commercial capsules for beach, Lunar New Year and more, “everything has to be aligned,” Pagès said.
“Being a creative director is no longer just about creating a silhouette — it’s also about shaping a point of view. You’re a cultural interpreter, working across product, image, values and community,” said Julian Klausner, who staged his first womenswear show as creative director of Dries Van Noten in March, followed by a menswear debut in June that was a highlight of the Paris season. “It demands that you listen more, delegate well, and keep the vision elastic — but still anchored.”
Brand Halo
Fully transitioning a brand’s output to a new aesthetic can take years. Still, the biggest luxury brands can begin to reap the benefits of a creative director change almost immediately after broadcasting a new vision: many customers buy into luxury without much attention to who designed the products, and can be influenced by an uptick in buzz months before refreshed collections arrive in stores.
Dior’s June menswear debut owned the fashion conversation for days, fuelling a steady drip of content about archival references, celebrity attendees, a watch party and potential “it” bags. Some of that attention translates to store traffic.
“There were so many layers to unpeel at Dior; it gave people a lot to get excited about. For brands that took those kind of steps, we see some really positive business coming through thanks to the halo on the brand,” Selfridges’ Crane said. “At the same time, we’re still anticipating a lot of people will hold back for new products to arrive.”
Smaller, more fashion-driven brands have to make tough choices about when and where to allocate their creative focus and budget.
Givenchy, which staged its womenswear debut by Sarah Burton in March has been less focused on driving social media chatter than with restoring the brand’s prestige: renewing ties with stylists and fashion magazines in an effort to have a stronger editorial presence by the time the collection arrived in stores. A single-brand shoot in Vogue starring Anne Hathaway was a big win, followed by a campaign starring Adut Akech, Kaia Gerber and more. Venice may have to wait for next year.
New Products
While runway creativity, red carpet, social media content and campaigns often drive the conversation surrounding an aesthetic refresh — novel products are what brands may need most. “Eighty percent of what this industry is about is product. Everything else has to support,” Solca said.
What will those products look like? Brands that rely less on seasonal fashion — like Hermès, Brunello Cucinelli, Loro Piana and Zegna — have proven more resilient during the industry’s recent downturn. But seeking to emulate their understated aesthetics could backfire. “Timeless designs are great. But the problem is consumers may already have them in their wardrobe. I have a feeling that ‘quiet luxury’ is past its peak,” Solca said.
Selfridges’ Crane sees fashion demand in two camps — with continued momentum for “archetypal” products like a Birkin bag or the perfect cashmere sweater coexisting alongside renewed interest in bold, seasonal looks.
“Recently there’s been a lot of stuff that’s sort of in-between, which doesn’t respond to the growing sense of discernment in the market. I see it moving to the extremities: a mix of core, comforting, understandable pieces and ones that can really excite the imagination,” Crane said.
The Next Big Bang?
Fashion is hoping this year’s creative reset could ignite a new era of excitement and demand: much like in 1997, when Galliano’s theatrical take on Dior, McQueen’s Givenchy, Nicolas Ghesquière’s Balenciaga and Martin Margiela’s Hermès were all nascent concepts accelerating the fusion of fashion creativity, pop culture and French couture (as documented in a recent exhibition at Paris’ Palais Galliera fashion museum). The same year in Milan, Tom Ford’s Gucci was hitting its sleazy stride and Prada was making waves with its subversive, “ugly pretty” twists on Milanese glamour.
1997’s fashion “big bang” also coincided with a business that needed rethinking: sales in Japan (previously luxury’s biggest export market) were slowing, and fresh ideas were needed to make European heritage relevant for a burgeoning US market. This time, it’s an over-dependence on China that needs weaning, while the US has become more volatile and polarised across brands. Despite buoyant pockets like the Gulf, its unclear which markets the industry can turn to next in order to capitalise on its creative refresh.
With many luxury stocks already depressed, however, financial markets are likely to focus on the upside. “The stock market will be fast to react to any subtle sign of inflection. The feedback on the upcoming fashion shows will be very important,” Solca said. “Then, most often, self-help stories tend to work like yo-yos, rising on expectations and sometimes falling back on disappointing updates. Prada, Burberry, Ferragamo, Kering have all been following this pattern multiple times.”
“All the hiring and firing puts brands’ names in the media spotlight — but the hiring is simply the beginning of a new chapter,” System magazine co-founder Elizabeth von Guttman said. “Desirability requires time and is incredibly tough to maintain — winners and losers will inevitably emerge.”
The industry will need to be patient while designers and brands find their footing, both creatively and commercially.
“Not everything can work right away. It takes time to put something in place and to refine it, and for it to find its audience. But you do need some strong early signals to make people believe,” Pagès said.
In addition to seeing nearly eight percent sales growth in 2024, the Urban Outfitters-owned retailer has been expanding its retail footprint in the US, including a return to a key brick-and-mortar location in New York’s Soho. It has also spun its Maeve subbrand into its own freestanding label, a launch which includes a new store set to open in Raleigh, North Carolina in October.
As the brand continues to grow, it is also flexing its marketing muscle. Best known for its feminine, bohemian take on apparel, this week, the retailer is rolling out its most high-profile celebrity campaign to date, which will be shared across its social media channels, on email and in out-of-home ads — as well as further amplified by a cast of influencers.
Starring the actress Camila Mendes, who rose to fame on “Riverdale” and is set to appear in Mattel’s “Masters of the Universe” film next year, the campaign shows her in several scenes throughout London, from dancing in her bedroom in a sequinned dress to hailing a cab in a fluffy faux fur jacket. According to Barbra Sainsurin, the retailer’s new chief marketing officer, it’s designed to reflect the many “characters” a woman can play throughout the day, whether she is running errands or attending a glitzy event.
Mendes felt like the right fit for the campaign given her “subtly playful sense of style,” she said. “As an actor, I can be somewhat of a chameleon when it comes to how I dress,” she told BoF in an email. “I like trying on different personalities.”
Mendes in Anthropologie’s autumn 2025 campaign. (Anthropologie)
It’s also Sainsurin’s first major marketing moment as Anthropologie’s CMO, a position she was promoted to from global executive director of brand and digital marketing in May 2025. The Mendes campaign, she said, is a sign of where she plans to take the brand’s marketing going forward; telling more immersive, longer-form stories to build out the world of Anthropologie.
“The campaign takes kind of a cinematic rom-com approach, where we’re essentially narrating what a day in the life of a modern fashion customer would look like,” said Sainsurin.
While the brand rolled out its first celebrity campaign in 2023, starring “Vampire Diaries” actress Phoebe Tonkin, the Mendes campaign not only features a star with a bigger presence in today’s zeitgeist, but also marks a step in incorporating more famous faces throughout the brand’s channels, including less splashy marketing efforts. The first-ever interview featured in Maeve’s Substack newsletter “& one more thing,” launched in July, for instance, was a sit-down with “Saturday Night Live” comedian Chloe Fineman.
“What we’ve learned is that when we partner with culturally relevant voices, it helps to amplify both our reach and engagement,” said Sainsurin. “Camila was the perfect partner because she reflects who we are as a brand, but more importantly, where we want to go. She has this amazing appeal with Gen-Z and Millennial women.”
Longer-Form Storytelling
As Anthropologie shakes up its marketing approach to broaden its reach, it is also experimenting with new channels to enhance its long-form storytelling abilities. For instance, it plans to test additional formats like print and linear TV, in addition to new media channels like Maeve’s Substack.
“We’re going big on storytelling platforms like YouTube and Substack,” said Sainsurin. “Immersive, rich content that builds these deeper connections have risen in importance for the customer … so we’ve prioritised these platforms.”
It’s all a part of getting people to think about Anthropologie as a true fashion destination that can dress them from day to night, she added. To that end, the campaign is highlighting product categories Anthropologie sees the most potential for growth in, including jackets, denim in new silhouettes and shoes.
“We’re not only the brand that you can come to when you have a specific occasion, but we offer such a wide range that you could come to us for, yes, those occasions, but also just for living every day and running those everyday errands,” said Sainsurin.
Microsoft is testing a shared clipboard between Windows 11 and Android via Link to Windows.
Sync is near-instant and keyboard-agnostic (works with Gboard and Samsung’s offerings), making it handy for managing passwords and contacts.
The feature is now available in the Windows 11 Dev build; a general release will follow later, after any necessary bug fixes have been implemented.
When I got both a Samsung tablet and phone, I was really surprised when I copied text on one device and it automatically beamed over to the other. It made me wish that Windows had a feature like that, where I could copy text either on my PC or my Android device and have it appear on the other. I couldn’t find anything that did it automatically, so I had to settle for mirroring apps that could handle it for me.
Well, it turns out that Microsoft is working on a feature that does just that. And while it’s not quite ready for release just yet, it’s already looking very promising.
Microsoft is working on a shared clipboard between Windows and Android
Windows Latest spotted this cool feature within the new Windows 11 Dev build. Apparently, Microsoft attempted to launch the feature last month, but an issue arose, and it was subsequently removed until the problem was resolved. Now, the shared clipboard feature has made its glorious return, and if Windows Latest’s tests are anything to go by, it’s already shaping up to be a killer new feature.
To get the feature running, Windows Latest had to have both devices connected via the Link to Windows app. Once done, it then downloaded the new Windows 11 Dev build and enabled a new feature in the mobile devices section called “Access PC’s clipboard.” Windows Latest noted that it didn’t have to enable anything on the Android side.
Once the feature was all set up, the tests began. According to Windows Latest, the feature appears to be already implemented and performs surprisingly well. As quoted in their article:
Next, I copied a chunk of text from a webpage, and the text immediately appeared in my Gboard keyboard on my Android phone. I tried it a bunch of times, and the sync was instantaneous. In our tests, Windows Latest noticed that the clipboard sync is not limited to any specific keyboard app. It works with the Samsung keyboard too.
That last bit is especially important to me. I think if it only worked on Microsoft’s own keyboard, SwiftKey, it wouldn’t have been nearly as exciting. Making the feature keyboard-agnostic was an excellent move, and now I can see a ton of people using the tool to share complex passwords, move contact details, or just send a website from one device to another.
Unfortunately, although the feature appears to be largely complete, it’s still in the Dev testing branch and will take some time to reach the Release channel. After all, there’s always the chance that some bugs will emerge and will need squishing before it’s ready to go. Until then, you can always take the manual route.
The spontaneous coalescence of the molecules that led to life on primordial Earth, some 4 billion years ago, may have finally been observed in a laboratory.
Replicating the likely conditions of our newborn planet, chemists have joined together RNA and amino acids – the crucial first step that would eventually lead to the proliferation of living organisms that crawl all over Earth today.
The experimental work could yield important clues about the origins of one of the most important biological relationships: the one between nucleic acids and proteins.
Related: Building Blocks of Life Can Be Forged by ‘Dark Chemistry’ Far From Stars or Planets
“Life today uses an immensely complex molecular machine, the ribosome, to synthesize proteins. This machine requires chemical instructions written in messenger RNA, which carries a gene’s sequence from a cell’s DNA to the ribosome. The ribosome then, like a factory assembly line, reads this RNA and links together amino acids, one by one, to create a protein,” explains chemist Matthew Powner of University College London.
“We have achieved the first part of that complex process, using very simple chemistry in water at neutral pH to link amino acids to RNA. The chemistry is spontaneous, selective, and could have occurred on the early Earth.”
A complex process using biochemical machinery known as a ribosome ‘reads’ nucleic acid templates and produces proteins. (selvanegra/Getty Images/Canva)
Although we know that life must have wriggled its way out of Earth’s primordial ooze – after all, here we are – scientists are not as sure about how it happened. One growing school of thought invests in RNA as a self-replicating nucleic acid, which, thanks to its knack for also performing mechanical work, can catalyze other chemical reactions. This is known as the RNA world hypothesis.
Proteins cannot self-replicate; the instructions for their exact sequencing of amino acids are encoded in sequences of nucleic acid, such as RNA.
So while proteins play a necessary role in many biological processes, molecules of nucleic acid provide a crucial template for their production. Still, this means that the two molecular components would have needed to find a way to join together in the soggy, steamy conditions of early Earth.
“Life relies on the ability to synthesize proteins – they are life’s key functional molecules. Understanding the origin of protein synthesis is fundamental to understanding where life came from,” Powner says.
“Our study is a big step towards this goal, showing how RNA might have first come to control protein synthesis.”
Many attempts have been made to replicate the natural coalescence of amino acids and RNA. This process requires a high-energy mediator, and past studies have found that some highly reactive molecules are not fit for this purpose, since they tend to break down in water, leading the amino acids to react with each other rather than the RNA.
Led by chemist Jyoti Singh of University College London, the research team took their cues instead from biology. As a mediator, they tried a thioester, a high-energy, highly reactive compound that contains carbon, oxygen, hydrogen, and sulfur – four of the six elements that are thought to be vital to life.
Thioesters are known to play a key intermediary role in some biological processes, and are thought to have been abundant in the ‘primordial organic soup’. Some scientists believe their proliferation preceded the RNA world, known as the thioester world hypothesis.
In their simulated organic soup, the researchers found that thioester provided the necessary external energy to allow the amino acid to bind to the RNA – a pretty significant breakthrough that neatly unifies the two hypotheses.
“Our study unites two prominent origin of life theories – the ‘RNA world’, where self-replicating RNA is proposed to be fundamental, and the ‘thioester world’, in which thioesters are seen as the energy source for the earliest forms of life,” Powner says.
To be clear, we’re still quite far from having a detailed, comprehensive understanding of the origins of life. The new research shows that it’s possible these components can come together with a high-energy mediator; the next step is to see if RNA will preferentially bind to the specific amino acids that would facilitate the emergence of genetic code.
“Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulphur atoms, and from these Lego pieces form molecules capable of self-replication. This would be a monumental step towards solving the question of life’s origin,” Singh says.
“Our study brings us closer to that goal by demonstrating how two primordial chemical Lego pieces (activated amino acids and RNA) could have built peptides, short chains of amino acids that are essential to life.”
The spontaneous coalescence of the molecules that led to life on primordial Earth, some 4 billion years ago, may have finally been observed in a laboratory.
Replicating the likely conditions of our newborn planet, chemists have joined together RNA and amino acids – the crucial first step that would eventually lead to the proliferation of living organisms that crawl all over Earth today.
The experimental work could yield important clues about the origins of one of the most important biological relationships: the one between nucleic acids and proteins.
Related: Building Blocks of Life Can Be Forged by ‘Dark Chemistry’ Far From Stars or Planets
“Life today uses an immensely complex molecular machine, the ribosome, to synthesize proteins. This machine requires chemical instructions written in messenger RNA, which carries a gene’s sequence from a cell’s DNA to the ribosome. The ribosome then, like a factory assembly line, reads this RNA and links together amino acids, one by one, to create a protein,” explains chemist Matthew Powner of University College London.
“We have achieved the first part of that complex process, using very simple chemistry in water at neutral pH to link amino acids to RNA. The chemistry is spontaneous, selective, and could have occurred on the early Earth.”
A complex process using biochemical machinery known as a ribosome ‘reads’ nucleic acid templates and produces proteins. (selvanegra/Getty Images/Canva)
Although we know that life must have wriggled its way out of Earth’s primordial ooze – after all, here we are – scientists are not as sure about how it happened. One growing school of thought invests in RNA as a self-replicating nucleic acid, which, thanks to its knack for also performing mechanical work, can catalyze other chemical reactions. This is known as the RNA world hypothesis.
Proteins cannot self-replicate; the instructions for their exact sequencing of amino acids are encoded in sequences of nucleic acid, such as RNA.
So while proteins play a necessary role in many biological processes, molecules of nucleic acid provide a crucial template for their production. Still, this means that the two molecular components would have needed to find a way to join together in the soggy, steamy conditions of early Earth.
“Life relies on the ability to synthesize proteins – they are life’s key functional molecules. Understanding the origin of protein synthesis is fundamental to understanding where life came from,” Powner says.
“Our study is a big step towards this goal, showing how RNA might have first come to control protein synthesis.”
Many attempts have been made to replicate the natural coalescence of amino acids and RNA. This process requires a high-energy mediator, and past studies have found that some highly reactive molecules are not fit for this purpose, since they tend to break down in water, leading the amino acids to react with each other rather than the RNA.
Led by chemist Jyoti Singh of University College London, the research team took their cues instead from biology. As a mediator, they tried a thioester, a high-energy, highly reactive compound that contains carbon, oxygen, hydrogen, and sulfur – four of the six elements that are thought to be vital to life.
Thioesters are known to play a key intermediary role in some biological processes, and are thought to have been abundant in the ‘primordial organic soup’. Some scientists believe their proliferation preceded the RNA world, known as the thioester world hypothesis.
In their simulated organic soup, the researchers found that thioester provided the necessary external energy to allow the amino acid to bind to the RNA – a pretty significant breakthrough that neatly unifies the two hypotheses.
“Our study unites two prominent origin of life theories – the ‘RNA world’, where self-replicating RNA is proposed to be fundamental, and the ‘thioester world’, in which thioesters are seen as the energy source for the earliest forms of life,” Powner says.
To be clear, we’re still quite far from having a detailed, comprehensive understanding of the origins of life. The new research shows that it’s possible these components can come together with a high-energy mediator; the next step is to see if RNA will preferentially bind to the specific amino acids that would facilitate the emergence of genetic code.
“Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulphur atoms, and from these Lego pieces form molecules capable of self-replication. This would be a monumental step towards solving the question of life’s origin,” Singh says.
“Our study brings us closer to that goal by demonstrating how two primordial chemical Lego pieces (activated amino acids and RNA) could have built peptides, short chains of amino acids that are essential to life.”
The moon is appearing bigger and brighter to us every night right now. This is due to where we are in the lunar cycle.
The lunar cycle is a series of eight unique phases of the moon’s visibility. The whole cycle takes about 29.5 days, according to NASA, and these different phases happen as the Sun lights up different parts of the moon whilst it orbits Earth.
So, let’s see what’s happening with the moon tonight, Sept. 2.
What is today’s moon phase?
As of Tuesday, Sept. 2, the moon phase is Waxing Gibbous, and 72% will be lit up to us on Earth, according to NASA’s Daily Moon Observation.
We’re getting closer and closer to the Full Moon, and with each night there’s more and more to see on the moon’s surface. Tonight with no visual aids, you’ll see the Mare Imbrium, Mare Serenitatis, and the Mare Vaporum. With binoculars, you’ll also get a glimpse of the Clavius Crater, the Alphonsus Crater, and the Apennine Mountains. If you have a telescope too, enjoy glimpses of the Apollo 12, Apollo 17, and the Rima Ariadaeus.
When is the next full moon?
The next full moon will be on Sept. 7. The last full moon was on Aug. 9.
What are moon phases?
According to NASA, moon phases are caused by the 29.5-day cycle of the moon’s orbit, which changes the angles between the Sun, Moon, and Earth. Moon phases are how the moon looks from Earth as it goes around us. We always see the same side of the moon, but how much of it is lit up by the Sun changes depending on where it is in its orbit. This is how we get full moons, half moons, and moons that appear completely invisible. There are eight main moon phases, and they follow a repeating cycle:
Mashable Light Speed
New Moon – The moon is between Earth and the sun, so the side we see is dark (in other words, it’s invisible to the eye).
Waxing Crescent – A small sliver of light appears on the right side (Northern Hemisphere).
First Quarter – Half of the moon is lit on the right side. It looks like a half-moon.
Waxing Gibbous – More than half is lit up, but it’s not quite full yet.
Full Moon – The whole face of the moon is illuminated and fully visible.
Waning Gibbous – The moon starts losing light on the right side.
Last Quarter (or Third Quarter) – Another half-moon, but now the left side is lit.
Waning Crescent – A thin sliver of light remains on the left side before going dark again.
This is a descriptive, cross-sectional study, conducted at the Respiratory Viruses Unit of the Institute Pasteur of Côte d’Ivoire. This unit houses the World Health Organization (WHO) National Reference Laboratory for influenza and other respiratory viruses. We analyzed the epidemiological data and biological samples from the national sentinel influenza surveillance network. The network was built according to WHO guidelines [16] and consists of nine health centers located in health areas covering a population of approximately 1.9 million inhabitants. These sites are located in several geographical areas of the country (Supplementary Fig. 1), and data was collected during the period between January 1 st, 2013 and December 31 st, 2015.
Study population
Each sentinel site recruited five patients per week, who met the influenza-like illness (ILI) or severe acute respiratory infection (SARI) case definition and were 5 years of age or younger and whose guardians gave consent for the survey. All subjects with fever (temperature ≥ 38 °C) and coughing for less than 10 days were admitted as ILI cases. SARI was evoked in all subjects feeling feverish or with fever and cough, or breathing difficulties that had been going on for less than 10 days and whose condition required hospitalization. We excluded from the study children with a real-time reverse transcription-polymerase chain reaction (RT-PCR) result positive for influenza virus and RSV.
Sample and environmental data collection
A total of 3,899 nasopharyngeal swabs were collected using the Copan Universal transport medium (UTM-RT) system. The samples were obtained during consultation or hospitalization, and were immediately stored in a cooler with a cold accumulator or a refrigerator at + 4 °C before their transfer to the reference laboratory at the Institute Pasteur. An epidemiological fact sheet with demographic data, patient history, signs of severity, and risk factors for influenza infection was completed for all subjects included in the study, as samples were obtained as part of the national influenza sentinel surveillance framework. For each site, climate data (temperature, humidity, and rainfall) were collected from the Société d’Exploitation et de Développement Aéroportuaire, Aéronautique et Météorologique (SODEXAM) in order to determine the correlation between positive cases of hMPV and these different climatic parameters.
Statistical analysis
Data management and analysis were performed using R software (version 2.15.1) after initial data entry in Epi-info® (version 3.5). Descriptive statistics were used to summarize the data; quantitative variables were described by their medians, while categorical variables were presented as counts and proportions.
To analyze associations between categorical variables (e.g., hMPV positivity by sex, age group, or clinical presentation), the chi-square (χ2) test or Fisher’s exact test was used as appropriate. The relationship between monthly hMPV case counts and climatological factors (temperature, humidity, rainfall) was assessed using Spearman’s correlation and a multiple linear regression model. A p-value < 0.05 was considered statistically significant for all tests.
RNA extraction and real time RT-PCR for hMPV detection
RNA was extracted from 200 μL of the collected nasopharyngeal secretion in Universal Transport Medium (UTM-RT). Extraction was performed using the QIAamp Viral RNA Mini kit (QIAGEN®, Hilden, Germany) as per the manufacturer’s instructions with RNA elution into a final volume of 80 μL of AVE buffer. Nuclease-free water was included for each extraction run as a negative control. Two aliquots of each extracted RNA sample were made, one of the aliquots was used for RT-PCR targeting the N gene of hMPV, and the second was stored at −20°C for future analyses.
The master-mix for RT-PCR was made with the Invitrogen™ SuperScript™ III Platinum™ Kit One-step quantitative RT-PCR System with the following primers and probes:
The cycling conditions were 30 min (min) at 50 °C, 2 min at 95 °C, 45 cycles of 15 s (s) at 95 °C, 15 s at 55 °C, and 15 s at 55 °C; and a final incubation at 55 °C for 10 min.
Amplification and sequencing of the F and G genes
Conventional RT-PCR was also used to amplify a fragment of the F and G gene open reading frames (ORFs) of 243 positive samples obtained by real time PCR, from hMPV samples. The amplification RT-PCR was performed using the Qiagen One-Step RT-PCR kit (Qiagen) as per the manufacturers’ instructions, using the following primer sequences:
F gene Fwd-5’-CAATGCAGGTATAACACCAGCAATATC-3’,
F gene Rev-5’-GCAACAATTGAACTGATCTTCAGGAAAC-3’ [17].
G gene Fwd-5’-GAGAACATTCGRRCRATAGAYATG-3’ [18].
G gene Rev-5’-AGATAGACATTRACAGTGGATTCA-3’.
Thermocycling was performed following reverse transcription at 50 °C for 30 min, PCR activation at 94 °C for 15 min, 40 cycles of denaturation at 94 °C for 30 s, annealing at 55 °C for 1 min, extension at 72 °C for 1 min, followed by a final extension at 72 °C for 10 min. All PCR products were visualized using the flashgel system of Lonza® with 1.5% agarose gel. Sequencing was performed in both directions using an ABI 3500 XL Genetic Analyzer with BigDye terminators (Applied Biosystems) at a contract sequencing facility (Genewiz sequencing, Germany). The complete genome sequences of the reference prototypes of each lineage were available in GenBank (under the accession numbers AF371337 [A1], FJ168779 [A2], AY525843 [B1] and FJ168778 [B2]).
Dataset assembly
In order to supplement the Côte d’Ivoire hMPV datasets of 20 F gene lineage A, 43 F gene lineage B, 21 G gene lineage A, and 29 G gene lineage B sequences, we retrieved all available hMPV sequences from GenBank on September 6, 2019, that were annotated with location and collection date. This initial background dataset consisted of 2,345 F and 1,554 G sequences.
The sequence were aligned using MAFFT v7.409 [19] and subsequently manually inspected in AliView v1.25. During manual editing, one Côte d’Ivoire sequence was removed from the G gene dataset because of a duplication not seen in other Côte d’Ivoire or background sequences. We also removed 145 nucleotides (nt) from G2403 and G357 in the G: B2 dataset out of concern that the 145-nt were the result of recombination [20].
We noted the 180-nt and 111-nt duplications in G gene samples reported by Saikusa et al. [21] and preserved them in the initial G gene alignments. Any background sequences that were noted as nonfunctional in their GenBank entries or had premature stop codons that would likely impair function were also removed.
Because the Côte d’Ivoire sequences are fragments, we trimmed the total dataset of each gene to match the length of the Côte d’Ivoire sequences. The F dataset was trimmed to 686-nt positions and the G dataset to 868-nt positions. After each dataset was trimmed, we removed samples shorter than 75% of the length of the longest sequence.
After editing the alignments, maximum-likelihood (ML) trees were inferred using RAxML v7.2.6. [22] incorporating a general time reversible (GTR) model of nucleotide substitution with a gamma-distributed (Γ) rate variation among sites. We investigated the temporal signal of the datasets using TempEst [23]. A few background sequences showing incongruent temporal patterns were excluded (Supplementary Fig. 2). In order to confidently identify clades within each gene, each ML tree was run with 5,000 bootstrap replicates. We extracted clades encompassing the Côte d’Ivoire samples at nodes with high bootstrap support (> 70%). In the F gene ML tree, we identified three clades of interest (A, B1, B2; Supplementary Fig. 3) and in the G gene ML tree, four clades (A, B Early, B1, and B2) were selected. The “B Early” clade was designated to describe a phylogenetically distinct group of G gene sequences that could not be classified within the canonical B1 or B2 clades. As shown in the phylogenetic tree (Supplementary Figure S4), this clade occupies a basal position relative to the other B lineages, meaning it diverges from the main trunk of the B genotype before the common ancestor of the B1 and B2 clades. The name “B Early” was therefore chosen to reflect this early-diverging characteristic. We extracted the sequences for each new tree to create “gene: clade” specific datasets, which were subsequently aligned and manually edited. Duplicate sequences with identical countries, collection dates, and nucleotide sequences were removed (Supplementary Figs. 5–8). Specific to the G: A dataset, the region caused by the 180-nt insertion, encompassing the 111-nt insertion, was removed. We used RAxML to generate “gene: clade” ML trees which were examined in TempEst for outliers (see Fig. 2 below).
Phylogenetic analysis
To reconstruct the evolutionary history and spatial diffusion of the virus, we employed a Bayesian phylogenetic and phylogeographic framework for each of the “gene: clade” datasets separately using the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (http://biowulf.nih.gov). Evolutionary rate variation across lineages was accounted for using an uncorrelated relaxed molecular clock model with branch rates drawn from a log-normal distribution. Changes in the viral effective population size (Ne) over time were inferred using a Skygrid demographic prior [24]. Nucleotide substitution was modeled using a general time reversible (GTR) model with gamma-distributed rate variation among sites. For sequences where only the year of collection was available, tip dates were accommodated by uniform sampling within a one-year window (January 1 st to December 31 st).
Markov chain Monte Carlo (MCMC) analyses were conducted using BEAST v1.10.4, with computational performance enhanced by the BEAGLE library [25]. Each dataset was analyzed in at least three independent MCMC runs of 400 million iterations, with sampling every 40,000 iterations. Convergence of all parameters was assessed visually using Tracer v1.7.1, and statistical uncertainty was quantified using 95% highest posterior density (HPD) intervals. A burn-in of at least 10% was applied to each chain.
Given the independent modeling of the diffusion and substitution processes, we adopted a two-step inference approach. First, we focused on the sequence evolution process to generate an empirical distribution of phylogenetic trees. Subsequently, this distribution of trees was used as a condition for inferring the discrete location diffusion process. A subset of 500 trees was randomly selected from the combined posterior distribution of trees to represent the empirical distribution for spatial diffusion analysis [26].
Spatial diffusion dynamics among specified countries were estimated for each “gene: clade” dataset using a Bayesian discrete phylogeographic approach [27]. This approach models location transitions as a continuous-time Markov chain (CTMC) process, allowing for the inference of ancestral location states. A nonreversible CTMC model [28] was employed, and Bayesian stochastic search variable selection (BSSVS) was incorporated to identify a sparse set of significant transition rates, representing epidemiological connectivity [29]. Furthermore, Markov jump histories for location traits were mapped across the posterior tree distribution using stochastic mapping techniques [30], and the number of jumps was summarized.
Maximum clade credibility (MCC) trees were generated using Tree Annotator v1.10.4, and visualizations were produced using FigTree v1.4.3.
GUJRAT: The Sialkot International Airport is open to flight operations after remaining suspended for five days due to flooding.
According to the officials, though the flight operations were restored by 6pm on Monday, the floodwater from Chenab is still accumulated in the parking area. There were no flights scheduled on Monday.
An official told Dawn that the passengers would be taken to the airport terminal by buses from the main entry point outside the airport as the vehicles couldn’t be parked in the flooded parking lot.
The airport management as well as the Sialkot administration joined hands to drain the floodwater out.
The suspension of flights had caused disturbance to the air passengers from Gujranwala region as the airlines had shifted their passengers to Lahore, Faisalabad and Islamabad airports.
The Sialkot airport spokesperson Umair Khan said the main airport terminal building, runway, taxiway as well as the equipment remained secure in the flood.
