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  • Conch blowing could help to alleviate sleep apnoea, study suggests | Sleep apnoea

    Conch blowing could help to alleviate sleep apnoea, study suggests | Sleep apnoea

    Blowing into a conch shell could help tackle the symptoms of a sleep disorder that affects millions of people across the UK, according to a study.

    Conch blowing, also known as shankh blowing, is an ancient ritual that involves breathing in deeply and exhaling into the spiral-shaped shell.

    The practice could improve sleep for patients with obstructive sleep apnoea (OSA), which usually needs to be treated with uncomfortable machinery, according to the research.

    OSA occurs when breathing starts and stops during sleep. Symptoms include loud snoring and making gasping or choking noises.

    Thirty people living with the disorder and aged between 19 and 65 were involved in the trial, led by researchers at the Eternal Heart Care Centre and Research Institute in Jaipur, India.

    About half of the group were taught how to use the shell, while the others carried out deep breathing exercises. Both groups were encouraged to practise their techniques for at least 15 minutes, five days a week.

    Six months later, the trial found that those who had practiced shankh blowing were 34% less sleepy during the day. They also had higher blood oxygen levels during the night, and four to five fewer OSA episodes an hour on average.

    “Shankh blowing is a simple low-cost breathing technique that could help improve sleep and reduce symptoms without the need for machines or medication,” said Dr Krishna K Sharma, who led the research.

    “The way the shankh is blown is quite distinctive. This action creates strong vibrations and airflow resistance, which likely strengthens the muscles of the upper airway, including the throat and soft palate, areas that often collapse during sleep in people with OSA.”

    The most common form of treatment for sleep apnoea is a continuous positive airway pressure (Cpap) machine, which involves patients wearing a mask that blows pressurised air into the nose and throat while asleep. Previous research has also found that playing a woodwind instrument could help with the condition.

    Although the machines are effective, they can be uncomfortable, leading the researchers to suggest that shankh blowing could be a promising alternative.

    A larger trial involving several hospitals is being planned.

    “The findings of this trial are encouraging, but the small scale of the trial means it’s too soon to say for certain that conch blowing can help people manage their obstructive sleep apnoea,” said Dr Erika Kennington, the head of research and innovation at Asthma + Lung UK.

    “It’s also not clear from this research why blowing through a conch shell regularly might improve someone’s symptoms. It would be good to see the conch blowing approach tested on a larger scale and compared with other proven strategies, such as limiting alcohol, staying active and maintaining good bedtime habits.

    “OSA is a long-term condition, but with the right treatments and lifestyle changes, people can make a real difference to their symptoms.”

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  • Colin Farrell to Receive Zurich’s Golden Icon Award

    Colin Farrell to Receive Zurich’s Golden Icon Award

    Colin Farrell will receive the Golden Icon Award at the 2025 Zurich Film Festival, recognizing his performance in Ballad of a Small Player and his career achievements. The Oscar-nominated Irish actor will attend the festival on September 27 for the award presentation and gala premiere of the film, and will participate in a ZFF Masters discussion the following day.

    Directed by Edward Berger, Ballad of a Small Player is based on Lawrence Osborne’s 2014 novel and follows a gambler in Macau whose past catches up with him. The screening marks Berger’s third consecutive ZFF selection, following All Quiet on the Western Front and Conclave.

    Farrell, known for roles in In Bruges, The Banshees of Inisherin, The Lobster, The Batman, and Minority Report, has collaborated with directors including Sofia Coppola, Yorgos Lanthimos, Steven Spielberg, and Tim Burton. His portrayal in The Banshees of Inisherin earned him a Golden Globe, Venice Best Actor award, and an Academy Award nomination.

    Zurich festival director Christian Jungen praised Farrell’s range, noting his ability to play villains, romantic leads, and complex characters, and called his work in Ballad of a Small Player “irresistible.”

    Farrell can currently be seen in HBO’s The Penguin and is filming season two of Apple TV+’s Sugar.

    Previous Zurich Golden Icon Award recipients include Kate Winslet, Jessica Chastain, Hugh Jackman, Cate Blanchett, and Hugh Grant.

    The 2025 Zurich film festival runs Sept. 25 to Oct. 5.

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  • Saudi VC Impact46 expands gaming portfolio with multi-studio investments

    Saudi VC Impact46 expands gaming portfolio with multi-studio investments

    • Impact46 invests over $6.6 million in five gaming studios—Fahy, NJD, Game Cooks, Starvania, and Alpaka—as part of its $40 million Gaming Fund launched in March 2024.
    • Studios span mobile, PC, console, VR, and hybrid-casual game development, with culturally localised and globally appealing content.
    • This investment builds on earlier 2025 investments in Spoilz and Spekter Games, expanding Impact46’s gaming portfolio to seven active companies.
    • Investment aligns with Saudi Arabia’s National Gaming and Esports Strategy and Vision 2030, positioning the Kingdom as a global gaming hub.

    Press release:

    Impact46 has announced investments exceeding SAR 25 million in five gaming studios—Fahy, NJD, Game Cooks, Starvania, and Alpaka—as part of its SAR 150 million Gaming Fund, launched in March 2024. The fund reflects Impact46’s long-term commitment to backing high-potential founders shaping the future of digital content and gaming experiences in the region.  

    The studios span a diverse slate of gaming innovation, from culturally grounded mobile gameplay to immersive console/PC experiences and next-generation hybrid-casual action games, highlighting the creative and technical depth emerging from MENA’s game development ecosystem.

    “We see gaming as more than a sector; it’s a language of youth, culture, and creation,” said Basmah Alsinaidi, Managing Partner at Impact46. “Through these investments, we’re backing builders who aren’t just launching games but creating the infrastructure, stories, and platforms that define the next era of content in the region.”

    This announcement builds on Impact46’s growing portfolio in gaming, following earlier 2025 investments in Spoilz, a mobile game studio developing engaging IPs, and Spekter Games, a next-gen studio bringing mobile games to chat-based super apps, seamlessly blending traditional gameplay with Web3 incentive layers. Together, these nine companies represent a new wave of MENA gaming ventures redefining how content is created, distributed, and experienced across the region.

    This momentum aligns with the Kingdom’s rise as a global leader in gaming and interactive entertainment, in step with the National Gaming and Esports Strategy and Vision 2030’s push to diversify the economy and enable homegrown innovation. From national enabler programs such as the National Development Fund, Social Development Fund, CODE by the Ministry of Communication and Information Technology, and Saudi Esports Federation, to global initiatives by the Esports World Cup Foundation and Savvy Games Group, Saudi Arabia is positioned to become a launchpad for the region’s gaming ecosystem.

    About the startups:

    • Fahy – A Saudi-based mobile game development studio crafting experiences that are instantly fun yet endlessly rewarding.
    • NJD Games – A Saudi mobile game studio that creates joy and lasting memories through mobile gaming.
    • Game Cooks – A dynamic game development and publishing studio specialising in Virtual Reality (VR), Mobile, and PC video games. With a signature blend of action, adventure, and puzzle elements, the studio has released over 22 original titles and earned numerous international awards for its creativity and innovation. Now proudly establishing its base in Riyadh, Game Cooks is entering a new chapter—focused on delivering localised, culturally tailored, and globally engaging gaming experiences.
    • Starvania – A Saudi indie game studio dedicated to creating fantasy universes from fresh perspectives, where worlds are rich with thoughtfulness and inspiring concepts. Specialises in PC and console games.
    • Alpaka – A mobile gaming studio producing and developing next-generation hybrid-casual games in the action genre.
    • Spoilz (earlier investment) – Games that spark joy and connect cultures everywhere.
    • Spekter Games (earlier investment) – A next-gen game publisher blending Web2 and Web3 to supercharge games at scale.

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  • Colin Farrell To Receive Zurich Film Festival’s Golden Icon Award

    Colin Farrell To Receive Zurich Film Festival’s Golden Icon Award

    Oscar-nominated Irish actor Colin Farrell will be honored with the Zurich Film Festival’s Golden Icon Award at its upcoming edition, running from September 25 to October 5.

    The award acknowledges the actor’s performance in Edward Berger’s psychological thriller Ballad Of A Small Player as well as his overall career.

    Farrell will be presented with the award on September 27 ahead of a gala premiere for the upcoming film, which will also be attended by Swiss director and Oscar winner Berger. The following day Farrell will give a masterclass on his career.

    The Irish born actor is internationally renowned for films such as Miami Vice, Minority Report, In Bruges, The Batman, The Lobster, The Killing of a Sacred Deer, and The Banshees of Inisherin.

    He follows in the wake of a long line of illustrious Golden Icon Award recipients who also include Kate Winslet, Jessica Chastain, Hugh Jackman, Cate Blanchett and Hugh Grant.

    Ballad of a Small Player marks the third consecutive film from Berger to be showcased at Zurich following All Quiet on the Western Front and Conclave. Berger also received the prestigious A Tribute to… Award at the 2024 edition of the festival.

    His new film is adapted from the 2014 novel by Lawrence Osborne and is set in Macau. It tells the story of a high-stakes gambler whose past and debts start to catch up with him, but whilst laying low in Macau he encounters a kindred spirit who might just hold the key to his salvation.

    “Colin Farrell is one of the most passionate and charismatic character actors in auteur cinema,” says Festival Director Christian Jungen.

    “He’s just as convincing as a villain as he is a romantic lead, or in complex roles that fall somewhere in between, like in Edward Berger’s irresistible tragicomedy Ballad of a Small Player, where Colin captivates us as a roguish gambler and makes us root for his character.

    “Colin Farrell has already worked with many great filmmakers, but under Edward Berger’s direction, he truly reaches new heights. He carries the film from beginning to end and takes us on an emotional roller coaster that makes us laugh, cry, and marvel. For this outstanding performance, which could earn him another Oscar nomination, and for his invaluable contribution to auteur cinema, we are honoring Colin Farrell with the Golden Icon Award.”

    Farrell welcomed the news of the honor and said he was looking forward to the opportunity to visit Zurich for the first time.

    “I’d like to thank Zurich Film Festival for inviting Ballad of a Small Player to the festival, and for honoring me with the Golden Icon Award,” he said.

    It’ll be my first time visiting the beautiful city of Zurich and I’m beyond excited to walk its streets, drink its coffee and move amongst its people. It’s both generous and humbling to have my years of making film recognized by such a storied festival, one that champions film from all corners of the globe. It will be an absolute pleasure to visit later this year and we are thrilled to be bringing Ballad of a Small Player to audiences there,” he continued.

    Farrell was seen recently in HBO’s The Penguin, reprising his acclaimed role as Ozwald Cobblepot.

    He won a string of awards for the performance including a Golden Globe for Best Actor in a Limited Series, a Screen Actors Guild Award, and a Critics Choice Award. He is currently shooting season 2 of the Apple TV+ series Sugar, returning as private detective John Sugar.

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  • Selective deletion or preservation of tissue components via enzymatic digestion monitored by scanning acoustic microscopy

    Selective deletion or preservation of tissue components via enzymatic digestion monitored by scanning acoustic microscopy

    Human and mouse specimen Preparation

    Tissue samples were fixed in a 10% buffered formalin solution, embedded in paraffin and sliced into flat Sect. (10-µm-thick sections were prepared for SAM, whereas 4-µm-thick sections were prepared for LM). Enzymatic digestion makes the surface irregular and causes the section to detach from the glass slide. To protect the detachment, we used an immune-coated slide for immunostaining (Muto Pure Chemicals, Tokyo, Japan).

    For mouse bone tissue, the bones were provided by Dr. Y. Enomoto from the Department of Regenerative & Infectious Pathology and fixed and soaked in a 0.5 mol/L ethylenediaminetetraacetic acid (EDTA) solution (Fujifilm Wako chemicals, Tokyo, Japan) for 2 days for decalcification.

    For the cytology section, residual free cells from ascites or pleural effusions were prepared to make single-cell-layer slides using a previously reported liquid-based cytology method (BD CytoRich™; Franklin Lakes, NJ, USA)12. The slides were fixed in 95% ethanol for 10 min and postfixed in 10% buffered formalin for 45 min.

    Enzyme digestion

    To digest the sections, various enzymes were used, including actinase E (pronase E) (Funakoshi, Tokyo, Japan), collagenase type 2 (Worthington, Lakewood, NJ, USA), DNase 1 (Merck, Darmstadt, Germany) and α-amylase (Fujifilm Wako, Osaka, Japan). Actinase and collagenase type 2 were dissolved at 1 mg/mL in phosphate-buffered saline (PBS) containing 0.5 mM CaCl2. α-Amylase (10 mg/mL) was dissolved in PBS (pH 7.4), and DNase 1 (0.1 mg/mL) was dissolved in 20 mM HCl containing 1 mM MgCl2 and 1 mM CaCl2. The enzyme solution was mounted on the section and incubated at 37 °C. The activity of each enzyme determined the incubation duration. The sections were washed in distilled water at each time point and observed with SAM. After observation, the same section was reincubated in the enzyme solution.

    SAM observations

    We used a SAM system (AMS-50AI; Honda Electronics, Toyohashi, Aichi, Japan) with a central frequency of 320 MHz and a lateral resolution of 3.8 μm, as previously reported24,25,26. The tissue or cytology section was placed on the stage, and distilled water was used as the coupling fluid between the transducer and the section. The waveforms reflected from the surface and bottom of the sample were compared to measure the AOS at each point8. The waveform from the glass surface without a specimen was considered the zero AOS area (black) and was used as the reference. The transducer scanned the sections along the X- and Y-axis for a few minutes to capture the images. The plotted AOS value at each point generated an AOS image.

    LM observation

    LM slides taken from near the SAM section locations or the same section as for the SAM observation were prepared for comparison with the corresponding AOS images. Staining methods, including haematoxylin and eosin, Elastica Masson trichrome, Congo red and periodic acid-Schiff (PAS), were the same as the routine histology methods employed in the pathology laboratory.

    Immunohistochemistry

    We utilised the Dako REAL EnVision detection system using the peroxidase reaction with DAB for immunohistochemistry and followed the analysis procedure. The primary antibody was anti-Ki67 (MIB-1, DAKO). For antigen retrieval, histological and cytological sections were soaked in 10 mM Tris-EDTA buffer (pH 9.0) (Abcam, Tokyo, Japan) at 95 °C for 40 min. After immunostaining, the sections were counterstained with haematoxylin.

    Transmission electron microscopic observation of paraffin sections

    TEM observation of formalin-fixed paraffin sections was performed using previously reported methods27,28. DAB-stained sections were fixed with 2% glutaraldehyde for 60 min for pre-fixation and then incubated with 2% osmium tetroxide for 15 min for post-fixation. The sections were dehydrated with an alcohol gradient and embedded in epoxy resin (Quetol 812, Nisshin EM, Tokyo, Japan) by heating at 60 °C for 48 h. Ultrathin 70-nm-thick sections were prepared, stained with lead and uranium acetate (Merck), and observed by JEM 1400 Plus (JEOL, Tokyo, Japan).

    Statistical analysis

    The means and standard deviations (SD) of the AOS values were calculated from at least five areas per slide. Mean AOS values between different tissue components and at different time points following protease digestion were compared using Student’s t-test or Welch’s t-test, as appropriate. A commercial statistical software package (BellCurve for Excel; Social Survey Research Information, Tokyo, Japan) was used to calculate the mean values for areas-of-interest, generate dot plot graphs and perform t-test analyses. Before statistical analysis, all continuous datasets were tested for normal distribution. A p-value of < 0.05 was considered statistically significant.

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  • Ancient shankh blowing practice found to improve sleep and alertness in OSA patients

    Ancient shankh blowing practice found to improve sleep and alertness in OSA patients

    People who practised blowing through a conch shell regularly for six months experienced a reduction in their symptoms of obstructive sleep apnoea (OSA), according to a small randomised controlled trial published today (Monday) in ERJ Open Research.

    OSA is a common sleep disorder where breathing repeatedly stops during the night due to a blocked airway. It leads to loud snoring, restless sleep and daytime sleepiness. It also increases the risk of high blood pressure, heart disease, and stroke.

    Blowing the conch shell, or shankh blowing, has been part of Indian culture for thousands of years. The new research showed that people with moderate OSA who practised shankh blowing slept better, felt more alert during the day and had fewer breathing interruptions at night. The researchers say conch blowing is a simple, low-cost intervention that could help reduce symptoms without the need for medication or machines.

    The study was led by Dr. Krishna K Sharma from the Eternal Heart Care Centre and Research Institute in Jaipur, India.

    The standard treatment for OSA is a continuous positive airway pressure machine, or CPAP, which keeps the patient’s airway open by blowing air through a facemask throughout the night. While effective, many patients find it uncomfortable and struggle to use it consistently.


    In my clinical practice, several patients reported feeling more rested and experiencing fewer symptoms after regularly practising shankh blowing – a traditional yogic breathing exercise involving exhaling through a conch shell. These observations led us to design a scientific study to rigorously test whether this simple, ancient practice could serve as a meaningful therapy for people with OSA.”


    Dr. Krishna K Sharma, Eternal Heart Care Centre and Research Institute, India

    The study included 30 people with moderate OSA, aged between 19 and 65, who were assessed at the Eternal Heart Care Centre and Research Institute between May 2022 and January 2024. They were tested with polysomnography, meaning they are monitored throughout a night’s sleep, and asked questions about the quality of their sleep and how sleepy they feel during the day.

    They were randomly assigned to either be trained to practise blowing through a conch shell (16 patients) or to practise a deep breathing exercise (14 patients). Participants were provided with a traditional shankh used in yogic practices. They were trained in person at the clinic by a study team member before beginning home-based practice. Participants were encouraged to practise at home for a minimum of 15 minutes, five days per week. After six months, the patients were reassessed.

    Compared to the people who practised deep breathing, the people who practised shankh blowing were 34% less sleepy during the daytime, they reported sleeping better and polysomnography revealed that they had four to five fewer apnoeas (where breathing stops during sleep) per hour on average. They also had higher levels of oxygen in their blood during the night.

    Dr. Sharma said: “The way the shankh is blown is quite distinctive. It involves a deep inhalation followed by a forceful, sustained exhalation through tightly pursed lips. This action creates strong vibrations and airflow resistance, which likely strengthens the muscles of the upper airway, including the throat and soft palate – areas that often collapse during sleep in people with OSA. The shankh’s unique spiralling structure may also contribute to specific acoustic and mechanical effects that further stimulate and tone these muscles.

    “For people living with OSA, especially those who find CPAP uncomfortable, unaffordable, or inaccessible, our findings offer a promising alternative. Shankh blowing is a simple low-cost, breathing technique that could help improve sleep and reduce symptoms without the need for machines or medication.

    “This is a small study, but we are now planning a larger trial involving several hospitals. This next phase will allow us to validate and expand on our findings in a broader, more diverse population and assess how shankh blowing performs over longer periods. We also want to study how this practice affects airway muscle tone, oxygen levels and sleep in greater detail. We’re particularly interested in comparing shankh blowing with standard treatments like CPAP, and in examining its potential help in more severe forms of OSA.”

    Professor Sophia Schiza, Head of the ERS group on sleep disordered breathing, based at the University of Crete, Greece, who was not involved in the research said: “Obstructive sleep apnoea is a common disease around the world. We know that OSA patients have poor quality of sleep, and higher risks of high blood pressure, strokes and heart disease. A proportion of patients experience sleepiness during the day. While CPAP and other treatments are available based on careful diagnosis of disease severity, there is still need for new treatments.

    “This is an intriguing study that shows the ancient practice of shankh blowing could potentially offer an OSA treatment for selected patients by targeting muscles training. A larger study will help provide more evidence for this intervention which could be of benefit as a treatment option or in combination with other treatments in selected OSA patients.”

    Source:

    European Respiratory Society

    Journal reference:

    Sharma, K. K., et al. (2025) Efficacy of blowing shankh on moderate sleep apnea: a randomised control trial. ERJ Open Research. doi.org/10.1183/23120541.00258-2025.

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  • BCCI undecided over Virat, Rohit future in ODIs amid reports of international retirement during Australia tour

    BCCI undecided over Virat, Rohit future in ODIs amid reports of international retirement during Australia tour

    India’s upcoming tour to Australia in October could be a defining one for the futures of veteran stars Virat Kohli and Rohit Sharma, as reports have surfaced regarding their potential retirement from international cricket. Already retired from T20Is and Test cricket, reports have suggested that Virat and Rohit’s tour Down Under in Australia will be their last with the Indian team on Sunday (August 10). However, those reports have now been put on hold after the Board of Control for Cricket in India (BCCI) has hinted that the apex body is currently undecided on the duo’s future.

    BCCI still not decided on Virat, Rohit

    “Obviously, if they (Rohit and Kohli) have something in mind, they would tell the BCCI brass like they did before the England Test tour. But from an Indian team’s perspective, the next big assignment is the T20 World Cup in February and preparations before that. The immediate focus will be on sending the best team for the Asia Cup T20 tournament, hoping all players are fit and available,” a BCCI source privy to the developments told PTI on condition of anonymity.

    On Sunday, it emerged that neither Rohit nor Virat will be in the plans for the 2027 ODI World Cup set-up, as preparations are already underway to build a team. The Dainik Bhaskar report stated that Rohit and Virat are likely to announce their retirements from the ODI format and, therefore, altogether from international cricket in the Australia tour, which begins on October 19.

    However, those reports are temporarily on hold as BCCI has refused to comment on the situation, while the source suggests the focus is now on the T20 World Cup.

    Interestingly, India were earlier scheduled to play Bangladesh as both Virat and Rohit would have played in the home series. Unfortunately for the duo, the series was postponed to 2026, meaning the Aussie tour remains India’s next ODI series. In case the retirement rumours are true, then neither Rohit nor Virat will get a home farewell.

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  • European XFEL reveals quantum fluctuations in complex molecules

    European XFEL reveals quantum fluctuations in complex molecules

    Due to the Heisenberg uncertainty principle of quantum physics, atoms and molecules never come completely to rest, even in their lowest energy state. Researchers at European XFEL in Schenefeld near Hamburg have now been able to directly measure this quantum motion in a complex molecule for the first time. For this, however, as they report in the journal Science, they had to make the molecule explode in the process.

    Absolute standstill only exists in classical physics. In the quantum world, even the ground state with the lowest energy is characterised by persistent fluctuations. This is due to a quantum-mechanical principle discovered by Werner Heisenberg a hundred years ago during the development of quantum mechanics. The so-called zero-point fluctuations are a quantum effect that prevents atoms from remaining precisely at a fixed position, even at temperatures near absolute zero. At European XFEL in Schenefeld, researchers have now made the previously invisible directly observable – and the quantum world a bit more tangible.

    An international team led by Rebecca Boll from the SQS (Small Quantum Systems) instrument at European XFEL in Schenefeld, Ludger Inhester from the DESY research centre, and Till Jahnke from the Max Planck Institute for Nuclear Physics in Heidelberg, succeeded in visualising the collective trembling of an entire molecule. Using a sophisticated experiment and refined data analysis, they were able to measure the quantum fluctuations of the 2-iodopyridine molecule (C5H4IN), which consists of eleven atoms – a milestone in molecular imaging. They describe their work in the renowned journal Science.

    The researchers employed a method as spectacular as its name: Coulomb Explosion Imaging. The ultrashort, extremely intense X-ray laser pulses of European XFEL strip numerous electrons from the atoms of individual 2-iodopyridine molecules very rapidly. The remaining atomic cores become positively charged, repelling each other. The result resembles a microscopic big bang: the atomic cores fly apart in an explosion.

    Nonetheless, from the measured flight directions and velocities of the fragments, the researchers can reconstruct the original arrangement of the atoms – and more than that: they can even visualise the tiny quantum-mechanical fluctuations.

    The 2-iodopyridine molecule is a so-called pyridine ring. It consists of a carbon ring incorporating a nitrogen atom. An iodine atom is attached to this pyridine ring. From a classical perspective, the entire molecule is perfectly planar – meaning that all its atoms lie exactly within one plane. If the molecule would be a classical object, then after a Coulomb explosion, all atoms and fragments would fly off exactly within the molecular plane. As the researchers studied the molecule in its ground state, deviations due to possible molecular vibrations can be excluded.

    Nevertheless, the team detected charged atoms outside the classically expected molecular plane. Their measurements matched detailed simulation calculations that also included machine learning methods. “In these calculations, we explicitly had to include the quantum fluctuations in order to reproduce the data,” says Benoît Richard from DESY and the University of Hamburg, first author of the Science paper.

    “We could furthermore see the collective nature of the quantum fluctuations in the measurement data,” Ludger Inhester adds. “That is, the atoms in the molecule do not tremble independently of each other, but move in coordinated patterns.”

    The measurement data were recorded with a detector called a COLTRIMS (REMI) reaction microscope – one of the endstations available to users at the SQS instrument. With this device, many of the fragments can be recognised and spatially assigned at the same time.

    “We already saw first indications of this correlated behaviour of the atoms in the data back in 2021, but it took a while to really understand everything and convince our colleagues of this remarkable finding,” says Till Jahnke from the Max Planck Institute for Nuclear Physics in Heidelberg. One challenge was that not all fragments of the molecule can be detected in every X-ray pulse. The researchers overcame this obstacle by using a new statistical analysis method developed by Benoît Richard, which can reconstruct the complete momentum distribution of the molecule even from such fragmentary datasets. “Furthermore, the very intense X-ray flashes from European XFEL make each molecule explode very efficiently and in a very similar way,” emphasises Rebecca Boll. “With this method, we were able to decipher the structure of the entire molecule,” explains Robin Santra from DESY and the University of Hamburg. The researchers also clearly detected the “fingerprints” of the atoms’ quantum fluctuations.

    The new method opens entirely new avenues for exploring complex quantum mechanical systems. “Coulomb Explosion Imaging does not just provide averaged values, such as X-ray crystallography for example, but allows us to investigate individual molecules,” says Boll. “In the future, this technique could be used to study even larger molecules, and time-resolved movies of their internal motions are now possible,” explains Michael Meyer, leading scientist at the SQS instrument: “And this with a time resolution of less than one femtosecond, that is, within a quadrillionth of a second.”

    A follow-up project will be funded next year within the Excellence Strategy of the German federal and state governments as part of the recently extended Excellence Cluster “CUI: Advanced Imaging of Matter”. This cluster at the University of Hamburg is a cooperation with DESY, the Max Planck Institute for the Structure and Dynamics of Matter (MPSD), and European XFEL.

    The newly published work impressively demonstrates what is possible when cutting-edge laser technology, quantum mechanics, and sophisticated data analysis come together.

    Original publication

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  • Tokyo researchers reveal key role of Fen1 in resisting antiviral and anticancer drug effects

    Tokyo researchers reveal key role of Fen1 in resisting antiviral and anticancer drug effects

    Researchers from Tokyo Metropolitan University have discovered a new pathway by which cells counteract the action of alovudine, an important antiviral and anticancer drug. The protein flap endonuclease-1 (Fen1) was found to improve cell tolerance by counteracting the toxic accumulation of another protein, 53BP1. A renewed spotlight on the underappreciated role of Fen1 promises not only new cancer treatments, but a way to gauge the efficacy of existing treatments.

    Chain-terminating nucleoside analogs (CTNAs) are molecules which closely resemble nucleosides, the building blocks of DNA. They have been used as antiviral and cancer treatments since the 1980s due to their ability to bind to DNA as they are replicated. Since replication rates are abnormally high in infected or cancerous cells, these cells take up more of the drug, suppressing their growth. However, there is much that we don’t know about how healthy cells resist the action of CTNA toxicity, limiting how we put them to good use. For example, alovudine, a CTNA containing fluorine, was envisioned as an HIV treatment, but clinical trials were stopped at phase II due to their toxicity.

    A team led by Professor Kouji Hirota of Tokyo Metropolitan University have been looking at the pathways by which healthy cells resist the action of CTNAs. In previous work on alovudine, they had discovered the important role played by breast cancer type I susceptibility protein (BRCA1), a key player in DNA repair. Now, they have turned to the underappreciated role played by flap endonuclease-1 (Fen1), another DNA repair protein responsible for cutting off short, single-stranded DNA sections hanging off a replicating section of DNA known as an Okazaki fragment.

    In their experiments with genetically modified chicken DT40 cells, a common model system, the team discovered that suppression of Fen1 made cells extremely susceptible to alovudine toxicity, with replication speeds significantly reduced. Strikingly, they discovered that the further loss of a gene encoding for an entirely different protein led to recovery of alovudine tolerance. Known as 53BP1, this protein is known to collect at nicks in double-stranded DNA. This suggests a mechanism where a lack of Fen1 firstly leads to long overhangs, or “flaps”, being left on replicating DNA. When alovudine is incorporated, the 53BP1 accumulates around the flap, impeding other available mechanisms for cleaving off the overhang, effectively terminating DNA replication.

    The team also carried out experiments extending their previous work on BRCA1. At the time, they found that homologous recombination (HR), a key DNA repair pathway involving BRCA1, was significant in their alovudine tolerance. While having either Fen1 or HR suppressed led to lowered resistance, having both led to significantly more suppression. This suggests that the newly found significance of Fen1 is independent of the previous role identified for BRCA1.

    A deeper understanding of CTNA tolerance might yield not only promising new treatments but also effect biomarking of cancerous cells which often have a Fen1 deficiency, and a way to ascertain how effective drugs like alovudine might be. The team aims to move to studies in human cells, and work on how such treatments might be applied to different cancerous tissues, such as solid tumors.

    This work was supported by JSPS KAKENHI Grants-in-Aid (JP25K02256, JP21K19235, JP20H04337, JP22K15040, and 19KK0210), Tokyo Metropolitan Government Advanced Research Grant Number (R3-[2]), the Takeda Science Foundation, and the Uehara Memorial Foundation.

    Source:

    Tokyo Metropolitan University

    Journal reference:

    Bayejid Hosen, Md., et al. (2025). The flap endonuclease-1 promotes cellular tolerance to a chain-terminating nucleoside analog, alovudine, by counteracting the toxic effect of 53BP1. Nucleic Acids Research. doi.org/10.1093/nar/gkaf617.

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  • Special von Economo neurons may hold key to super-sharp memory in 80+ superagers

    Special von Economo neurons may hold key to super-sharp memory in 80+ superagers

    A 25-year study of ‘superagers’ reveals the brain and lifestyle factors that help some older adults defy typical memory decline, offering clues for boosting cognitive resilience across the lifespan.

    ​​​​​​​Participants in the Northwestern University SuperAging study gathered on May 24, 2013, to mingle and socialize. Photograph by Ben Kesling, at the time with The Wall Street Journal. Study: The first 25 years of the Northwestern University SuperAging Program

    In a recent article published in the journal Alzheimer’s & Dementia, researchers at the Northwestern University Alzheimer’s Disease Research Center (ADRC) investigated ‘superaging’, a specific, operationally defined biological and cognitive phenotype in people over 80 who perform as well as individuals who are 20–30 years younger on memory tests.

    Superagers, they found, show cellular characteristics and brain structures that resist typical declines associated with age, including reduced inflammation, distinct patterns of “resistance” to the development of pathology and “resilience” to its cognitive impact, and higher densities of certain specialized neurons.

    The term “superaging” (no space between “super” and “ager”) was deliberately chosen as a symbolic designation for this quantitative threshold rather than a generic description.

    Background

    The human brain changes over time through both constructive and regressive processes. Early in life, adaptive changes dominate, but with age, these are gradually undermined by biological factors.

    Neurons are particularly vulnerable because they do not regenerate, work intensely to transmit information, and consume large amounts of energy, leading to cumulative wear and tear. Aging is often linked to brain shrinkage, loss of neurons and synapses, and accumulation of harmful proteins, which has reinforced the view that cognitive decline is inevitable.

    Historically, perspectives on aging have ranged from pessimism to a belief in the enduring value of judgment and wisdom. Modern neuroscience has largely emphasized the negative view, especially due to Alzheimer’s disease research showing that most older adults develop some brain changes linked to this condition.

    The Northwestern University SuperAging Program began in the mid-1990s after an unusual autopsy of an 81-year-old woman with exceptional memory and minimal Alzheimer’s disease-related pathology.

    This discovery suggested that significant memory loss is not unavoidable and inspired a research program to identify the biological traits that protect certain older adults from cognitive decline.

    About the Study

    Researchers defined superagers as individuals aged 80 and above who scored at least 9 out of 15 on the Rey Auditory Verbal Learning Test (RAVLT) delayed recall, matching the average performance of 56–66-year-olds but well above the typical score for their age of 5 out of 15.

    Candidates also had to perform at least at an age-appropriate level on other cognitive tests. Episodic memory was chosen as the main criterion because it is the domain most affected by aging.

    Participants were recruited from cognitively normal controls in the Northwestern ADRC Clinical Core and via referrals, though only about 10% of referrals met the superaging criteria.

    The study eventually enrolled 290 participants, including 101 superagers and 32 neurotypical peers, with a mean age of around 90. Brain donation was encouraged, resulting in 77 autopsies.

    Researchers also collected data on social engagement, lifestyle, and personality. While superagers did not have healthier medical profiles or consistently follow “healthy” lifestyles, they tended to be highly sociable, report positive relationships, and score higher in extraversion. The researchers also noted that these personality characteristics align with the anterior cingulate cortex’s role in social and emotional processing, one of the brain regions preserved in superagers.

    Longitudinal follow-up assessed neuropathology, brain imaging, and cognitive stability. Neuroimaging focused on cortical thickness, especially in the anterior cingulate. Neuropathological analysis examined neuron density, protein accumulations, cholinergic system integrity, and microglial activity.

    Key Findings

    Neuroimaging showed that, unlike typical older adults, superagers had no cortical thinning compared to much younger adults, and thinning occurred more slowly over time.

    Surprisingly, their anterior cingulate cortex was thicker than in 50–60-year-olds and contained more von Economo neurons, which are specialized cells linked to social and emotional processing. The authors note that superagers may be born with a higher density of these neurons, as this did not appear to decline with age in neurotypical adults.

    Post-mortem studies revealed fewer Alzheimer’s disease-related neurofibrillary tangles in memory-critical regions such as the entorhinal cortex and hippocampus. The authors emphasised two possible mechanisms: resistance to the development of such tangles and resilience to their cognitive effects. In some cases, neuron size in the entorhinal layer two was larger, possibly conferring resistance or resilience to age-related changes. Superagers also had lower blood levels of phosphorylated tau, specifically p-tau181, supporting reduced pathology.

    The basal forebrain cholinergic system, important for attention and memory, showed fewer tangles and axonal abnormalities in superagers, along with a lower density of acetylcholinesterase-rich neurons—potentially increasing the effect of acetylcholine by reducing its breakdown.

    Microglial activation in white matter was also reduced, suggesting a lower inflammatory burden. Preliminary work also found that microglia from superager brains have unique characteristics and different proliferation patterns in culture.

    A detailed case study demonstrated remarkable cognitive stability over 15 years, minimal brain atrophy, normal hippocampal and amygdala volumes, and sparse tau pathology without amyloid deposits or other common age-related brain diseases.

    These findings suggest that superaging involves both structural preservation and biological resistance to common neurodegenerative processes, supporting exceptional memory performance well into advanced age.

    Conclusions

    The Northwestern University SuperAging Program has demonstrated that it is possible to identify individuals in their 80s and beyond who retain memory performance comparable to those decades younger and who exhibit a distinctive neurobiological profile.

    This clinicobiological phenotype, characterized by preserved brain morphology, greater von Economo neuron density, robust cholinergic systems, reduced neurofibrillary degeneration, and lower white matter inflammation, offers a valuable contrast for understanding the mechanisms driving typical cognitive decline.

    A key strength is the program’s integration of longitudinal clinical, neuroimaging, and post-mortem data, enabling robust phenotype characterization. Findings suggest that superaging reflects a relative dominance of constructive neuroplasticity over involutional processes, potentially modulated by genetic, epigenetic, and environmental factors. Candidate genes such as KLOTHO, BDNF, APOE, REST, and TMEM106b have been proposed as possible contributors, although their role in superaging remains to be determined.

    Limitations include the small proportion of the population meeting superaging criteria and uncertainty over whether protective traits are innate or modifiable. The authors also caution that conventional neuropathological staging systems, such as Braak stages, may underestimate preserved neurons that contribute to maintained function in superagers.

    Future research should clarify causal mechanisms, assess interventions to delay regressive brain changes, and explore pharmacological pathways to enhance resilience and resistance, potentially benefiting cognitive longevity in the broader aging population.

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