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  • What You Get at the Most Expensive Hotels in the World

    What You Get at the Most Expensive Hotels in the World

    The hotels below are among the most expensive in their cities, a collection of places around the world known for robust food and hospitality scenes. But this page is not just about eye-popping penthouse suites and butler service. The hotels here command nightly rates well into the thousands, and at this level, the infinity pools and MICHELIN-Starred restaurants practically come standard. What’s more interesting is just how differently luxury manifests from place to place.

    In New York, the most expensive hotels are where celebrities hide away in a fantasy version of Old New York. In Madrid, they’re the palaces once exclusive to nobility. And in Tokyo, top dollar buys you either a room in a sleek, hyper-modern skyscraper or a historic, distinctly Japanese mansion.

    The prices below are approximate, based on mid-week rates in peak season. Visit in the off-season for excellent deals. But even if you never stay the night, the hotels below are home to some of their city’s best restaurants, bars and lounges — places that define a city’s highest aspirations, where history has unfolded and watershed moments have played out for centuries.

    And yes, they also have some truly outlandish amenities. That said, this list kicks off in Dubai.

    DUBAI

    At One&Only One Za'abeel, a 120-meter infinity pool connects two skyscapers.

    At One&Only One Za’abeel, a 120-meter infinity pool connects two skyscapers.

    In Dubai, an idea of what the luxury hotel market may look like in the year 3000. By then, perhaps every hotel will be hosted in giant glass, H-shaped buildings like the One&Only One Za’abeel (from $800/night) or in shining, sailboat-like buildings on the water like the Burj Al Arab (from $1900/night).

    Besides the outlandish architecture, both exemplify another feature of Dubai’s top of the top hotels: outrageous suites. At the One & Only, the penthouse comes with a private cinema and private infinity lap pool (from $20,000/night). At the Burj Al Arab, expect multiple rotating beds, amenities like hair driers and lamp shades made of actual gold, and bathrooms with full-size Jacuzzis in the presidential duplex suite (from $40,000/night).

    Expect cutting-edge design and almost-unlimited amenities at every hotel at this level in Dubai.

    NEW YORK CITY

    A Garden Suite Terrace at the Lowell — set on an unassuming block on the ritzy and residential Upper East Side.
    A Garden Suite Terrace at the Lowell — set on an unassuming block on the ritzy and residential Upper East Side.

    A Garden Suite Terrace at the Lowell — set on an unassuming block on the ritzy and residential Upper East Side.

    Here’s what to expect at New York City’s most expensive hotels: celebrities. Yes, you’ll find the well‑heeled, the rich and the famous at any hotel on this list, anywhere in the world. But a hotel like the Lowell (from $1,400/night), recently host to Michelle Obama, and the Carlyle (from $1,400/night) aren’t the shiny objects grubbed at by just any a‑lister. These are the quiet, apartment‑like residences where guests pay primarily for the elegance and discretion of what feels like Old New York in the most romantic vision of the word.

    Granted, there are plenty of flashier haunts in our Complete Guide to New York City at this price level. Shall we list them? Here are two: the Mark (from $1,000/night) — unofficial second venue of the MET Gala — and the Robert De Niro‑owned Greenwich Hotel (from $1,200/night).

    MADRID

    This Royal Suite at the Mandarin Oriental Madrid is located in a turret of the Belle Époque palace.
    This Royal Suite at the Mandarin Oriental Madrid is located in a turret of the Belle Époque palace.

    This Royal Suite at the Mandarin Oriental Madrid is located in a turret of the Belle Époque palace.

    Many of the best luxury hotels in Madrid were once actual palaces. Splurge here and you’re in for design details like the Italian marble fireplaces and Persian rugs of the French-style neoclassical residence once home to a duke, at Santo Mauro hotel, or the expansive, refurbished gardens at Rosewood Villa Magna (both from $1,000/night), a tribute to the original aristocratic residence that stood here — and recreated with the same flora that once thrived on its grounds. 

    And while the gold and silver leaves that drip down from the lobby ceiling at the Mandarin Oriental Ritz (from $1,200/night) feel regal, even though this particular Belle Époque landmark was purpose built as a luxury hotel in 1910, that may be because the hotel was built with the explicit encouragement of King Alfonso XIII. The highest end of the hotel scene in Madrid, then, is all about history: places to sip a cocktail in residences once frequented by counts and countesses.

    PARIS

    The Cheval Blanc Paris — set in a remade Art Deco apartment store, directly overlooking the Seine.
    The Cheval Blanc Paris — set in a remade Art Deco apartment store, directly overlooking the Seine.

    The Cheval Blanc Paris — set in a remade Art Deco apartment store, directly overlooking the Seine.

    What do you get at the most expensive hotels in Paris? Largely, a palace. But these are not the historic palaces of Madrid — at least, not by definition. France, nearly alone among nations, grants an official, government‑backed title for hotels they judge the very best.

    To gain the formal, prestigious designation of “palace” from the French Ministry of Tourism, hotels must first meet basic criteria like the inclusion of a spa, a multilingual staff and concierge service onsite. 12 of the 31 palace hotels in France are in Paris, and they represent some of the highest in luxury in the country.

    At Cheval Blanc Paris (from $2,600/night), set in the remade Art Deco department store La Samaritaine, the 7,000‑square‑foot Quintessence Suite has its own swimming pool (from $55,000/night). At The Peninsula Paris (from $1,700/night), a fleet of stylish sedans includes a 1934 Rolls‑Royce Phantom II to whisk guests to the opera or a VIP tour of Versailles.

    LONDON

    The lobby at Claridge’s — a quintessential example of the posh standards at London’s most luxurious hotels.
    The lobby at Claridge’s — a quintessential example of the posh standards at London’s most luxurious hotels.

    The lobby at Claridge’s — a quintessential example of the posh standards at London’s most luxurious hotels.

    No city in the world does formal luxury quite like London. And no neighborhood in London does it quite like Mayfair. Here, you’ll find the kind of world-class service deployed by a place like Brown’s Hotel (from $900/night), where doormen in top hats have been escorting guests inside the hotel’s Georgian townhouses since 1837.

    The Ritz, Claridge’s and the Connaught (all from $1,000/night) have more than a century to their names as well, each a Mayfair icon at the highest end of posh London. At Claridge’s, members of the royal family waited out World War II. At the Three MICHELIN Key Connaught, a Three MICHELIN Star restaurant awaits guests as well, a fitting meal to caper a day of butler service and treatments at the Aman Spa.

    TOKYO

    The Janu Suite — with a clear-eyed view of Tokyo Tower.
    The Janu Suite — with a clear-eyed view of Tokyo Tower.

    The Janu Suite — with a clear-eyed view of Tokyo Tower.

    The luxury hotel scene in Tokyo is one of the more difficult to fit in a single box. That’s not just because these hotels are physically massive. The spare-no-expense skyscrapers typical of many an Asian metropolis — like the Bvlgari Hotel (from $2,000/night) and its 400‑square‑meter signature Bvlgari Suite (from $30,000/night) filled with gold lamps and unspeakable views, or JANU Tokyo (from $1,500/night), its massive suites offering private balconies for guests who can pull themselves away from the 4,000‑square‑meter wellness complex — are undoubtedly here.

    But here too are spots like the Palace Hotel (from $1,000/night) and the Trunk (from $1,200/night), more uniquely Japanese hotels with an aesthetic that resembles an ultra‑luxurious private residence in a privileged corner of the city rather than a giant tower of sleek and divine perks.

    BANGKOK

    One of two pools at the Mandarin Oriental — outdoor spaces come standard at Bangkok's luxury hotels.
    One of two pools at the Mandarin Oriental — outdoor spaces come standard at Bangkok's luxury hotels.

    One of two pools at the Mandarin Oriental — outdoor spaces come standard at Bangkok’s luxury hotels.

    The most distinctive splurge in Bangkok is the Mandarin Oriental (from $1,000/night). Here it’s not just the kings and queens who formed the guest list of this late 19th‑century hotel — it is where Joseph Conrad, Somerset Maugham, Noël Coward and so many famous British writers stayed at the peak of the colonial era in Southeast Asia.

    Paired with such illustrious history and sumptuous nods to the past is the cutting‑edge luxury defined by the Mandarin Oriental brand, and which justifies its inclusion at the very top of so many hotel scenes around the world — things like Star dining, an award‑winning spa and an endless list of amenities.

    Many of Bangkok’s hotels in or around this price range have another excellent perk: outdoor space and private gardens.

    CHICAGO

    The Langham is one of many top brands operating in Downtown Chicago.
    The Langham is one of many top brands operating in Downtown Chicago.

    The Langham is one of many top brands operating in Downtown Chicago.

    In Chicago, as with many of the world’s “second” cities, you can find some of the most world-renowned brands, operating at their typical standards of excellence, at prices significantly more reasonable than their counterparts in places like Paris, London or New York.

    At the Pendry (from $500/night), a sleek and dignified style appears behind the architectural‑masterwork facade that is the 1929 Art Deco Carbide & Carbon Building. The Langham (from $600/night), similarly, puts its excellent spa, lounge and state‑of‑the‑art rooms within an architectural masterpiece — this one by modernist icon Ludwig Mies van der Rohe.

    HONG KONG

    The hyper-luxury Peninsula brand began in Hong Kong.
    The hyper-luxury Peninsula brand began in Hong Kong.

    The hyper-luxury Peninsula brand began in Hong Kong.

    It makes sense that in Hong Kong, the massive, high-end luxury hotels reign supreme at the top of the market. The Peninsula (from $500/night) makes several appearances on this list, after all, and the brand’s illustrious story began here in Hong Kong — long considered one of the best city hotels in the world, with its massive, gilded lobby and staffers so attentive you can forget that in the real world you’re actually expected to fend for yourself.

    The Peninsula Suite (from $18,000/night) has its own grand piano, private gym and gallery‑level artworks to go with one in a million panoramic views. There is a Four Seasons and Rosewood (both from $800/night) here as well, but an underrated boutique luxury scene, too. The Upper House (from $400/night) is a skyscraper with just over a hundred rooms and design by the renowned Andre Fu, who, for that matter, did the design on K11 Artus (from $600/night) as well — a residential‑style hotel with the same kind of amenities (personal shoppers, limo service, infinity pool) you might expect from the highest‑luxury outfits.

    Hero image: Peak maximalism in the lobby of the soaring Burj Al Arab Jumeirah in Dubai


    Written by
    Mitchell Friedman

    Based in New York City, Mitchell Friedman is the Global Hotel Editor of The MICHELIN Guide.

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  • Senior PTI leaders jailed in May 9 cases urge talks with govt – Samaa TV

    1. Senior PTI leaders jailed in May 9 cases urge talks with govt  Samaa TV
    2. Dialogue only way out of crisis, say incarcerated PTI leaders  The Express Tribune
    3. How Prisons Become Spaces of Quiet Erasure  SabrangIndia
    4. Jailed PTI leaders urge national dialogue to end crises  Dunya News
    5. Jailed PTI leaders urge leadership to begin ‘dialogue process’  Geo.tv

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  • Reverse Evolution Reveals a Hidden Defense in Tomatoes

    Reverse Evolution Reveals a Hidden Defense in Tomatoes

    A rare chemical reversion in Galápagos tomatoes is challenging how we think about bitterness, toxicity and crop resilience.

    On the rocky western shores of the Galápagos Islands, wild tomatoes are doing something evolutionary theory once considered nearly impossible: they’re going backward. Scientists call it a rare case of “reverse evolution,” but what matters most to the future of agriculture is the chemistry behind the change—and what it could mean for breeders, seed companies, and farmers trying to build more resilient crops.

    Adam Jozwiak, Assistant Professor of Molecular Biochemistry, Botany and Plant Sciences (UCR/Stan Lim)

    At the center of this breakthrough is Solanum cheesmaniae, a wild tomato species native to the archipelago. On newer islands formed by volcanic activity, this plant has developed a molecular profile that closely resembles its ancient ancestors. According to University of California-Riverside assistant professor of molecular biochemistry Adam Jozwiak, it’s not just an oddity, it’s a potential roadmap for strengthening tomato defenses in an era of mounting pest pressure and reduced pesticide use.

    Unlocking Ancestral Chemistry

    “Commercial tomato varieties could easily be screened for the presence of both stereoisomeric forms of steroidal glycoalkaloids using standard metabolite profiling techniques such as LC-MS,” Jozwiak explains. “That’s straightforward. However, detecting whether a variety is ‘primed’ to revert to ancestral chemistry is a different story.”

    And that story is complicated. Tomatoes, like many crops in the Solanaceae family, produce steroidal glycoalkaloids (SGAs) — bitter-tasting, toxic compounds that protect the plant from insects, fungi and pathogens. In modern breeding, those compounds have been systematically reduced in ripe fruit to satisfy consumer preferences for sweeter, milder tomatoes.

    Just four amino acid changes can flip the chemical signature from modern to ancestral. Photo: UCR

    “Tomato breeders have worked to reduce bitterness in cultivated varieties for decades,” Jozwiak says. “But by reducing these compounds for the sake of flavor, we may have unintentionally compromised the plant’s natural ‘immune system.’”

    The Four-Amino-Acid Switch

    That’s where the Galápagos tomatoes come in. On newer islands like Fernandina and Isabela, S. cheesmaniae plants produce alkaloids with a stereochemistry not seen in cultivated tomatoes for millions of years. These compounds resemble the bitter, bioactive chemicals found in eggplants, and they’re synthesized through an altered version of the GAME8 enzyme.

    The kicker? It only takes four amino acid substitutions in that enzyme to flip the chemical signature from modern to ancestral.

    “The fact that just four amino acid changes in the GAME8 enzyme can flip the stereochemistry of these compounds shows how precise and targeted this kind of trait manipulation could be,” Jozwiak says. “In theory, we could use CRISPR gene editing to introduce specific mutations that shift the chemical profiles.”

    His team didn’t stop at tomatoes. They introduced the modified GAME8 gene into tobacco plants, which then produced the same ancestral alkaloids. It was a rare, clear demonstration that evolution doesn’t always move in one direction, and that reversing a major plant chemistry pathway is both possible and predictable.

    A New Frontier for Crop Defense

    That level of biochemical control opens the door for what Jozwiak calls “designer plant chemistry,” where breeders and biotech firms could tailor alkaloid profiles to balance pest resistance, flavor, safety, and shelf life.

    “If the goal were to make plants more resistant to pests, then a logical approach would be to upregulate key biosynthetic enzymes, particularly GAME8, GAME6 and GAME15,” he says. “But do so in a tissue-specific or developmental-stage-specific way.”

    For example, boosting SGAs in leaves and stems (the parts of the plant that aren’t consumed) could increase pest deterrence without compromising fruit quality. Alternatively, delaying the natural conversion of α-tomatine (a bitter, toxic compound) into its non-toxic form, esculeoside A, might allow for better protection during early fruit development while preserving taste at harvest.

    “Another approach could involve fine-tuning the timing of alkaloid conversion during ripening, to maximize pest resistance early in fruit development while ensuring a palatable product at harvest,” Jozwiak explains.

    Balancing Flavor and Function

    But any strategy involving increased SGAs would need careful testing and regulatory scrutiny. These compounds, while natural, can be toxic to humans and animals at high doses. In modern tomatoes, they’re typically present in unripe fruit and vegetative tissue—but the ripe fruit contains little to none.

    “Yes, I think targeted alkaloid manipulation has real potential to reduce pesticide use, but it would require a careful, science-based approach,” Jozwiak says. “Any commercial application would need to be precisely controlled and subjected to rigorous regulatory safety assessments, especially if the edible parts of the plant are affected.”

    The opportunity goes beyond tomatoes. Other nightshade crops, like potatoes and eggplants, also use steroidal glycoalkaloids for defense. And they use the same family of enzymes — GAME8-like proteins — to build them.

    “Because these compounds play important roles in plant defense, manipulating their biosynthesis could be useful for breeding more pest-resistant or disease-tolerant varieties,” he says. “However, efforts to reduce alkaloid content for safety or flavor often come with a trade-off—lower defense capacity. So, there’s a balance to be struck between taste, safety, and resilience.”

    Environmental Hurdles and Genetic Drift

    That balance could be achieved through gene editing or even marker-assisted breeding, using enzyme structure as a guide.

    But there’s another challenge: ecology. In the Galápagos, Jozwiak’s team found the reversion trait to be stable across multiple populations, likely due to strong local selective pressure, whether from herbivores, microbes or climate. In commercial settings, those pressures might not exist.

    “It’s unclear whether this trait would remain stable in other environments,” he says. “The expression and retention of these alkaloids could be influenced by many factors: the surrounding ecosystem, the presence or absence of certain pests, soil microbiota and climate conditions.”

    Gene flow is another risk. In places like North America or Europe, where tomatoes are grown commercially alongside many varieties, pollination could spread or dilute the trait.

    “There’s a chance of gene flow through pollination. This could dilute or disrupt the trait in subsequent generations unless strict breeding controls are maintained,” he explains.

    Bitterness with a Purpose

    Still, the potential is real. Breeding tomatoes that are better able to fend for themselves, without a chemical crutch, could help reduce reliance on synthetic pesticides, lower input costs and protect pollinators and soil health.

    “Instead of eliminating SGAs altogether, we could explore strategic reintroduction or modulation,” Jozwiak says. “This could pave the way for a more nuanced, defense-aware approach to tomato breeding, where bitterness is not viewed solely as a defect but as a tool.”

    As researchers continue to explore the precise effects of SGA stereochemistry on taste receptors, insect deterrence, and microbial interactions, the path forward may depend on looking back.

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  • F1 Movie: How Martin Donnelly’s crash inspired Brad Pitt film

    F1 Movie: How Martin Donnelly’s crash inspired Brad Pitt film

    Just hours before his accident, Lotus had taken up an option on Donnelly to drive for them the following season with Jordan, Tyrrell and Arrows vying for his signature.

    However, the crash meant he barely scratched the surface of what would have been a lucrative contract.

    Donnelly had competed against, and often beaten, the likes of Damon Hill, David Coulthard, and Eddie Irvine in the junior ranks, but had to watch their careers grow while his own F1 dreams came to an end.

    He added the death of Ayrton Senna at Imola in 1994 was the moment he knew it was time to halt his pursuit.

    The pair were friends after racing through the junior categories together, and Senna, who stopped at the scene of Donnelly’s accident and visited him in hospital, had even offered financial support in his recovery.

    “Ayrton had his millions made and he was a three-time world champion, but he had nobody to leave it to.

    “He had no offspring, no wife. I thought, I’ve died three times, I’m still involved in the sport I love and had a young son at the time, so I just let it go.”

    Donnelly is still involved in the sport he loves, just in a different capacity. He was a drivers’ steward for Formula 1, and still competes in the national racing and runs his own Martin Donnelly Academy in Norfolk.

    “Time is a healer and you adjust your way of life.

    “I have three great kids and I’m still involved in motorsport. Life goes on.”

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  • France car registrations down 6.7% in June, Tesla sales drop 10%

    France car registrations down 6.7% in June, Tesla sales drop 10%

    PARIS (Reuters) -New car registrations in France slid 6.7% in June from a year earlier to 169,504 vehicles, data from French car body PFA showed on Tuesday.

    Tesla sales fell 10.04% to 3,646 vehicles last month. Since the beginning of the year, Tesla’s sales have slumped by 39.59% while the French market overall has shrunk by 7.94% over the same period.

    (Reporting by Makini Brice, Editing by Dominique vidalon)

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  • What do ancient mummies smell like? Scientists finally find out

    What do ancient mummies smell like? Scientists finally find out

    Sensory heritage is the study of how we connect with historical objects using senses beyond just sight, like smell or touch.

    Ancient Egyptians used special oils, waxes, and balms to preserve bodies for the afterlife through a process called mummification. Until now, most studies of mummies have focused on collections in European museums.

    But a new study, led by researchers from the University of Ljubljana, the University of Krakow, and the Egyptian Museum in Cairo, explored mummies in Cairo’s collection.

    The goal: To determine what mummified bodies smell like.

    Scientists digitally unwrapped the almost 2,300-year-old undisturbed mummy of a teenage boy

    Researchers wanted to know if today’s mummies still carry traces of the original embalming materials. And if so, could those scents help museums better preserve and explain these ancient remains?

    To find out, they studied nine mummies at the Egyptian Museum in Cairo. Some were on display while others were tucked away in storage. These mummies came from different periods (the oldest is 3,500 years old) and had been preserved and stored in various ways.

    Because the mummies are so fragile, the team followed strict non-destructive methods to protect them while gathering scent data.

    To explore the scents of ancient mummies, researchers used a mix of sensory testing, chemical analysis (GC-MS-O), microbiology, and historical research. But first, they had to make sure it was safe.

    Sound of a mummy heard again for the first time in 3,000 years

    Many mummies had been treated with synthetic pesticides decades ago, which can be harmful. So, any bodies with high levels of these chemicals were excluded from the study.

    For the remaining nine mummies, the team gently opened their sarcophagi just enough to insert tiny pipes and collect air samples. These samples were sealed in special bags and taken to a separate room, where researchers could smell them directly, a rare, nose-to-nose encounter with the past.

    To dig deeper into what ancient mummies smell like, researchers captured more air samples using metal tubes filled with a special material that traps scent molecules.

    These samples were taken to a lab, where scientists used chromatography to separate the smells into individual components, so trained sniffers could describe each one in detail.

    Despite differences in how strong the smells were, most mummies shared a familiar scent palette: woody, floral, sweet, spicy, stale, and resin-like.

    Scientists revealed the faces of 3 Egyptian mummies

    Chemical tests also revealed traces of ancient embalming ingredients like conifer oils, frankincense, myrrh, and cinnamon. All of these were used by the museum recently for preservation.

    They also detected degraded animal fats used in the mummification process, the scent of the human remains themselves, and both modern synthetic pesticides and natural plant-based oils used by the museum for preservation.

    Mummies on display gave off stronger scents than those kept in storage. Although none were overpowering like modern perfumes. One mummy even surprised researchers with a smell that reminded them of black tea. The likely culprit? A natural compound called caryophyllene, also found in cloves and cinnamon.

    Now, the team is taking things a step further. They plan to recreate these ancient aromas so that visitors to the Egyptian Museum in Cairo can experience the scent of history, literally.

    Authors noted, “The results also revealed close similarities between mummified bodies from the Late Period, indicating that with a larger set with more detailed information on the mummified bodies, it may be possible to differentiate by the period (or at least by the mummification practice) based on chemical and olfactory profiles and to achieve a better understanding of the different practices.”

    Journal Reference

    1. Emma Paolin, Cecilia Bembibre, Fabiana Di Gianvincenzo, Julio Cesar Torres-Elguera, Randa Deraz, Ida Kraševec, Ahmed Abdellah, Asmaa Ahmed, Irena Kralj Cigić, Abdelrazek Elnaggar, Ali Abdelhalim, Tomasz Sawoszczuk, and Matija Strlič. Ancient Egyptian Mummified Bodies: Cross-Disciplinary Analysis of Their Smell. Journal of the American Chemical Society. DOI: 10.1021/jacs.4c15769

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  • 2 ‘new stars’ have exploded into the night sky in recent weeks — and both are visible to the naked eye

    2 ‘new stars’ have exploded into the night sky in recent weeks — and both are visible to the naked eye

    A second “new star” has unexpectedly appeared in the night sky, less than two weeks after a near-identical point of light first burst into view without warning.

    These never-before-seen “stars” are made of light coming from rare stellar explosions known as classical novas. Scientists believe this may be the first time in recorded history that more than one of these luminous outbursts have been visible with the naked eye at the same time.

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  • The role of cd8+ t cells in tissue regeneration

    The role of cd8+ t cells in tissue regeneration

    In this interview, News Med talks to Prof. Uwe Ritter about the role of advanced imaging techniques in uncovering the role of CD8+ T cells in tissue regeneration.

    What are the main goals of your research into immune cell interactions and tissue regeneration?

    My work focuses on exploring immune cell interactions and tissue regeneration through cutting-edge imaging technologies, most notably the image processing and analysis pipelines of 3D skin models. These models are beneficial for characterizing regular T cells (Tregs) in wound healing.

    I am also using machine learning to analyze organoid cultures, particularly focused on investigating the impact of CD8+ T cells on tissue remodeling and the decryption of cell-cell interactions in situ.

    Mouse experiments involving the depletion of Tregs (pan depletion, subset-specific depletion, or induced depletion) have shown that Tregs are involved in immune regulation, metabolism, and tissue repair. These Tregs are characterized by the expression of amphiregulin and Foxp3.

    The repair function in murine systems is well established, but we would like to know whether or not there are equivalent tissue repair Tregs in humans.

    Michael Sforer’s group analyzed mouse and human tissues to investigate this equivalence. They analyzed blood, subcutaneous fat, and skin, performing single-cell attacks to look for any overlap in markers expressed by human or mouse Tregs to detect the phenotype of tissue repair Tregs in humans.

    This research revealed that it was possible to detect tissue Tregs in humans that express CCR8 and are positive for basic leucine zipper ATF-like transcription factor (BATF). These are comparable to tissue Tregs from the mouse immune system.

    Could you explain how imaging pipelines support the investigation of tissue regeneration processes?

    In the example I discussed, molecular analysis revealed that these tissue Tregs included Tfh, a molecular helper T cell differentiation program. This discovery offers a major advantage because we can generate Tfh-like tissue Tregs and naive T cells and look for functional analysis or tissue repair functions.

    The pipeline for this experiment involved isolating the tissue Tregs from PBMCs from blood and enriching them with CD25. We performed FACS sorting for the markers CD45 and CD45RA. We isolated antigen-naive Tregs and stimulated those naive Tregs with IL-2 to generate IL-2-derived Tregs. This allowed us to use Tfh-like Tregs similar to tissue Tregs, adding components such as IL-2, IL-12, IL-21, IL-23, and TGF-b.

    We added TransAct IL-2 to these T cells, allowing us to further activate and harvest the supernatant from these Tregs. This process gave us two supernatants from the IL-2 Tregs and putative repair Tregs from the tissue itself.

    What makes 3D skin models particularly useful for studying Tregs in wound healing? Could you expand on your work in this area?

    We contacted Florian Gruber in Vienna and Dirk Becker in Würzburg because this group had established a very useful 3D skin model involving growing human epidermal keratinocytes in plastic (PET) tubes.

    As the keratinocytes grow, they build up a strong epidermal compartment. A dermal punch can then be used to punch a hole into the epidermal compartment, and the keratinocytes start to close this area. This is essentially wound healing.

    We aimed to determine whether supernatants from Tfh-like Tregs or IL-2 Tregs better accelerate wound healing. Using a time kinetic approach, we cut the epidermal pieces in a cryostat.

    We aimed to measure the newly built stratum corneum in this structure. We needed to develop a software-based solution for dissecting structures from this epidermal compartment because we wanted to quantify the new stratum corneum in relation to the root healing effect of supernatant from the different Tregs I mentioned.

    The challenge was achieving the sophisticated color and structural separation to properly discern the epidermal tissue, the stratum granulosum, the stratum basale, and the polycarbonate matrix of the 3D skin model.

    The software detected the structures present in the epidermal compartment, reducing the impact of the background by subtracting the shades that do not correlate with the epidermal compartment. This is what allowed the stratum corneum to be detected.

    The software can be used to measure the number of keratinocytes in the epidermal compartment, and it is possible to use advanced color separation using special settings for tissue detection, polycarbonate detection, and more.

    The software’s capabilities were key to answering whether the supernatant could increase the wound healing in the system. The results showed that the IL-2 Treg supernatants did not have a significant impact on wound healing, but the Tfh-like cells supernatant saw the square micrometer of the stratum corneum become normalized.

    This technique can be reproduced via other methods such as trans-epithelial electrical resistance (TEER) measurements. Comparing these measurements showed similarity between the different approaches, confirming that the technique was working.

    We developed a detection algorithm that could dissect the pink shades of tissue. We also showed that tissue Tregs from humans are CCR8- and BAFT-positive and that these Tregs could accelerate wound healing in more complex wound-healing systems.

    Image Credit: Komsan Loonprom/Shutterstock.com

    How are you using machine learning with organoid cultures to study CD8+ T cells?

    CD8+ T cells are well known for their ability to kill virus-infected cells or tumor cells. CD8+ T cells in the dysfunctional state (called exhaustion) are positive for PD1, TIGIT, and other markers.

    Immunity is not black and white, however. In systems like liver hepatocellular carcinoma or NASH, it has been shown that CD8+ T cells that are PD1+ and TIGIT+ are reactive. They are not exhausted and can promote fibrosis or tumor progression.

    We want to know whether these CD8+ T cells are involved in tissue reconstruction. When CD8+ T cells kill infected cells, we see tissue destruction that requires remodeling. Therefore, we can ask whether CD8+ T cells can also induce tissue regeneration.

    To investigate this, we isolated those T cells and stimulated those CD8+ T cells using CD3 and CD28 beads. We took the resulting supernatant and performed an easy scratch assay. Activated naive T cells are not useful in wound healing, but we did observe that activated PD1+, TIGIT+, and activated central memory T cells can induce wound healing.

    We also wanted to know whether CD8+ cells can promote organoids’ reorganization. To investigate this, we isolated CD8+ T cells using the TexMACS medium, activated those T cells (because only activated CD8+ T cells can induce wound healing), and added them to organoids.

    Organoids are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structures and functions of corresponding in vivo tissues. Organoids are tissue-derived and we can derive them from adult stem cells.

    Cancer stem cells are induced through pretense stem cells, so this is not a problem. We can generate organoids in a Matrigel dome, so we opted to use this approach.

    For example, we wanted to know what happens when the organoids come into close contact with lymphocytes. This had not been done before our study because measuring and dissecting organoids from lymphoids is very difficult.

    With this in mind, our goal was to develop a machine learning pipeline suitable for detecting organ structures within the complex co-culture and high-throughput conditions. This had to include the characterization of organ formation, including numbers, size, and shape.

    We began by deriving organoids from the bile duct and combining them with CD8+ T cells. Then, we started working in collaboration with TissueGnostics to develop an organoid detection app.

    A number of problems had to be addressed at the beginning of this process. For example, we saw contour mimicry whereby cells look like organoids but are not organoids. We also saw contour fusion, with a fusion of two organoids that are difficult to dissect, and contour disruption, which makes it difficult for the algorithm to detect the organoid structure.

    The software takes the organoid image, converts it to grayscale, and performs a background correction. The software then allows one to see the membrane of the organoids, distinguishing between the membrane and the organoids and the background of the lymphocytes and other structures. Corrections can be applied as required to better split the background from the organoids and implement a layer specification of the organoids.

    It is also possible to adjust size and compactness when you are not confident or happy with the results.

    We used the classifier machine learning system to improve this new system. For example, it is possible to train the algorithm by manually marking the tissue and marking the organoid boundary.

    This type of manual delineation is time-consuming, but it was a useful quality control measure. We used a linear regression model to compare organoid size using both manual detection and software detection, confirming that the app is very precise and that it can be used to perform studies.

    Results showed an increase in CD8+ cells from different donors. We measured the total area and sum of the organoids, showing an increase in organoid development in the presence of CD8+ T cells.

    Our findings also indicate that the cytotoxic effector program of CD8+ cells is closely linked to a regeneration program, both of which are evoked upon a teaser stimulation. CD8+ T cells can kill other cells, but they also induce a tissue regeneration program.

    What are your visions for decoding cell-cell interactions in situ using advanced imaging technologies?

    I think we will be able to effectively decode cell-cell interactions in a few years. Cell communication between immunological cells such as T cells or dendritic cells is often based on autocrine signaling or juxtaposition processes. These processes influence tissue homeostasis and immune response to tumors and pathogens.

    There are signaling molecules involved, for example, cytokines, metabolites, receptor proteins that bind specific surface molecules, signaling pairs, cell junctions, and secondary messengers. In terms of understanding this communication, we know the alphabet, but we do not currently understand the sentences.

    Many people are already working with single-cell RNA-seqs and single-cell FACS analysis, allowing them to describe the transcriptome and phenotype of each single cell. However, we still do not know which cell has been in contact with other cells or which cell is responsible for activating other cells. These questions cannot be answered via single-cell analysis.

    We can generate single-cell raw data at the transcriptome, proteome, or metabolome level, but this is the limit at the moment.

    We can perform very simple in vitro experiments. For example, we can evaluate OT-1 T cells specific for ovalbumin by adding ovalbumin to an in vitro culture with dendritic cells and measuring the immune response of the dendritic and T cells.

    We can also use laser scanning microscopy to measure the membrane overlaps of cells (immunological synapse) to characterize the phenotype of cells that interact with dendritic cells. This approach is very precise, but it only describes the phenotypes.

    We can also do this in situ, measuring cell boundaries via the StrataQuest software. This allows us to calculate the potential contact area of cells, analyzing the cells that are in direct contact with the analyzed cell to characterize its neighbors. However, this method does not show whether cells are in communication.

    We have performed experiments. We took APCs, defined endogen, a T cell receptor, and added ovalbumin. We then measured single-cell and double-cell effects with RNAseq and dcRNAseq. After sorting the droplets, we analyzed the phenotype modification or the transcriptome of those cells interacting in terms of their phenotype modification or non-phenotype modification.

    How does your work in this area correlate with the PIC-seq methods developed by Ido Amit’s lab?

    It is closely aligned. In 2020, an excellent publication by Ido Amit described a similar approach to ours. They did exactly the same. They kept it simple, used APCs, defined a TCR receptor, isolated the T cells and dendritic cells, and then conjugated doublets. They then performed single-cell analysis and physically interacting cells (PIC) analysis.

    This allowed them to develop a PIC-seq algorithm that enabled the dissection of dendritic cells and T cells. This PIC-seq approach allowed the team to analyze the core signature of the attached dendritic cells or T cells.

    This is very important because this approach removes the need to isolate and dissect doublets, allowing us to begin to characterize the crosstalk of physically interacting cells.

    However, it is important to note that this approach is only possible when the two cell subsets are transcriptionally distant. When they are transcriptionally related, this technique is not functional.

    I became fascinated with this technique and wrote an opinion article about it that was published this year. I explained that it is possible to analyze single cells, analyze PICs, sequence single cells on the PICs, and run the PIC-seq. This is based on the pre-processing, integration, deconvolution, and differentiation of the data.

    My idea was that it is also possible to define the gene expression profiles of PICs grouped by the contributing T cell or myeloid identity. For example, it would be possible to characterize migratory DCs based on their genes, plasmacytoid DCs, DC-1, DC-2, or monocytes. A similar definition is possible with T cells, for example, characterizing a naive T cell, CD4+ Treg, CD8+ CTL, or an activated T cell.

    When we know the profile of physically interacting cells based on experimental data with ovalbumin or other antigens, we can determine the gene profiles of migratory antigen-presenting TCs and know exactly what they are producing.

    This allows us to create a panel, choosing antibodies with fluorescence, for example, and performing multiplex staining.

    This requires a microscope capable of imaging multiple channels. The key advantage of this approach is that we can detect the cells that are genuinely interacting based on the presence of specific markers.

    What types of research do you see potentially evolving from these approaches?

    This approach is potentially valuable for mouse systems where, for example, we can infect mice with pathogens, and because we know we have a resistant phenotype and a chronic phenotype, we can detect the gene modules that correlate to adaptive immunity by T cells or dendritic cells that correlate to immune pathology.

    There are differences between viruses, protozoans, and bacteria, but this approach could lead to the creation of a multicenter-based contextual and PIC atlas, featuring relevant gene modules and a pathogen-specific background.

    For example, during the immune response of the PICs, we may see shared expressions of genes also induced by protozoans or bacteria. The software could be used to detect genes that are exclusively induced by virus infection. We could isolate these genes using future software packages, demonstrate these findings, and relate these back to the in situ situation, clearly showing or describing the cells in communication in a pathogen-specific manner.

    These findings could also eliminate the need to work with dendritic and T-cells. We may see this concept expand into other systems, such as tumor immunology. It may become possible to characterize gene models associated with tumor-killing based on the interaction between cells and the expression of genes that are specifically induced during tumor-killing processes.

    This type of computational analysis will allow us to pinpoint biomarkers, for example, that are associated with tumor immune cell interaction. The advantages of these systems are clear: they allow us to deepen our understanding of tumor immune communications, identify tumor gene modules, and characterize tumor escape mechanisms.

    I also think this will improve the interpretation of tumor-effector cell interactions in situ, which will be crucial for evaluating tumor progression and treatment activities.

    About Prof. Uwe Ritter

    Prof. Uwe Ritter is a principal investigator in the Department of Immunology, Leibniz institute for Immunotherapy. His research is focused on studying the immune system’s response to various antigens in the skin-associated lymphatic tissue (SALT). He and his team aim to manipulate critical immune checkpoints in myeloid cells to potentially reprogram dysfunctional immune reactions. Their work integrates cutting-edge technologies – notably in-situ contextual tissue cytometry and high-resolution imaging – to gain deeper insights into tissue structure and function.

    About TissueGnostics

    TissueGnostics (TG) is an Austrian company focusing on integrated solutions for high content and/or high throughput scanning and analysis of biomedical, veterinary, natural sciences, and technical microscopy samples.

    TG has been founded by scientists from the Vienna University Hospital (AKH) in 2003. It is now a globally active company with subsidiaries in the EU, the USA, and China, and customers in 30 countries.

    TissueGnostics portfolio

    TG scanning systems are currently based on versatile automated microscopy systems with or without image analysis capabilities. We strive to provide cutting-edge technology solutions, such as multispectral imaging and context-based image analysis as well as established features like Z-Stacking and Extended Focus. This is combined with a strong emphasis on automation, ease of use of all solutions, and the production of publication-ready data.

    The TG systems offer integrated workflows, i.e. scan and analysis, for digital slides or images of tissue sections, Tissue Microarrays (TMA), cell culture monolayers, smears, and other samples on slides and oversized slides, in Microtiter plates, Petri dishes and specialized sample containers. TG also provides dedicated workflows for FISH, CISH, and other dot structures.

    TG analysis software apart from being integrated into full systems is fully standalone capable and supports a wide variety of scanner image formats as well as digital images taken with any microscope.

    TG cooperations

    TG continuously cooperates with research groups and other companies in the industry to provide novel tools and applications to its customers.

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  • Lakshya Chahar, Jaismine Lamboria in quarter-finals

    Lakshya Chahar, Jaismine Lamboria in quarter-finals

    Manish Rathore, however, exited the competition after a closely-contested loss against Rui Yamaguchi of Japan in the men’s 55kg category.

    Sakshi, Lakshya and Jaismine will join fellow Indian boxers Sachin Siwach, Hitesh Gulia, Muskan, Minakshi and Sanju in the next round.

    Back in April, India had won six medals at the previous World Boxing Cup leg in Brazil. The Indian women, however, did not compete in Brazil on account of the national championships.

    The tournament in Astana is the second and last of two scheduled World Boxing Cup meets for the year.

    Boxers accumulate ranking points through their performances at these two meets with the top pugilists qualifying for the World Boxing Cup Finals scheduled in India in November.

    The Kazakhstan leg will run until July 7, with over 400 boxers from 31 countries, including Olympians, competing across 10 weight categories in both men’s and women’s divisions. India have sent a 20-member team.

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  • ENG-W VS IND-W Live Streaming: When And Where To Watch England vs 2nd Women’s T20I On TV and Online?

    ENG-W VS IND-W Live Streaming: When And Where To Watch England vs 2nd Women’s T20I On TV and Online?

    India will play Englnad in the second match of the five-match series |Courtesy – BCCI

    After a rousing 97-run victory in the first match, the Indian women’s cricket team will face the England women’s cricket team in the second T20I of a five-match series at the County Ground in Bristol on Tuesday (July 1) as they aim to continue their winning run.

    Smriti Mandhana led the women in blue to victory in the series opener in the absence of Harmanpreet Kaur. The Indian captain is suffering from an illness, and a call on her availability is only expected to be taken just before the match.

    Mandhana created history in the first match at Trent Bridge with a knock of 112. She became only the second Indian after Harmanpreet to score a century in the shortest format of the game. The 28-year-old is also the first Indian to score a century in all formats of the game and the fifth player from across the world to complete the rare feat.

    The Indian women’s team are in England for a five-match series in the T20 format, which is key for the team ahead of the Women’s T20 World Cup in 2026, which will be hosted in England. Later, the two teams will play each other in three ODIs as focus shifts to the 50-over format ahead of the Women’s Cricket World Cup this year from September 30 to November 2, which will take place in India and Sri Lanka.

    Here is all you need to know about the England women vs India women 2nd T20I match

    Where is England women vs India women 2nd T20I match being played?

    The England women vs India women 2nd T20I match at the County Ground in Bristol

    What time does England women vs India women 2nd T20I match begin?

    Real Madrid Vs Juventus FIFA Club World Cup 2025 will begin at 11:00 PM IST on July 2.

    Which TV channels will broadcast England women vs India women 2nd T20I match?

    England women vs India women 2nd T20I match will be telecasted on Sony Sports 1 and Sony Sports 3.

    Where to live stream England women vs India women 2nd T20I match?

    England women vs India women 2nd T20I match will be available on the Sony Liv App and Website in India.


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