Blog

  • ‘The Witcher’ Season 4 Footage Reveals Liam Hemsworth as Geralt

    ‘The Witcher’ Season 4 Footage Reveals Liam Hemsworth as Geralt

    Ready to meet the new Geralt of Rivia?

    Netflix has released the first footage (below) introducing Liam Hemsworth taking over the fantasy drama’s role for the show’s fourth season. This marks the first video of The Hunger Games star as the grim monster slayer following Henry Cavill’s announcement that he was departed the role three years ago. Also, Netflix revealed the season’s premiere date as Oct. 30.

    The new season’s official description: “After the Continent-altering events of Season Three, Geralt, Yennefer (Anya Chalotra), and Ciri (Freya Allan) find themselves separated by a raging war and countless enemies. As their paths diverge and their goals sharpen, they stumble on unexpected allies eager to join their journeys. And if they can accept these found families, they just might have a chance at reuniting for good.”

    The season will consist of eight episodes, the same as prior seasons. The series is from showrunner and executive producer Lauren Schmidt The season will consist of eight episodes, the same as previous seasons. The series is from showrunner and executive producer Lauren Schmidt Hissrich and the new season’s directors are Sergio Mimica-Gezzan, Tricia Brock, Alex Garcia Lopez and Jeremy Webb.

    The season will consist of eight episodes, the same as previous seasons. The series is from showrunner and executive producer Lauren Schmidt Hissrich and the new season’s directors are Sergio Mimica-Gezzan, Tricia Brock, Alex Garcia Lopez and Jeremy Webb.

    Netflix has previously announced the show will end with season five. “This is the beginning of a two-season journey for our family to finally reunite and be together — hopefully forever,” Hissrich says.

    When Cavill announced he was quitting the series, later suggesting it was over creative differences, he posted the following statement: “My journey as Geralt of Rivia has been filled with both monsters and adventures, and alas, I will be laying down my medallion and my swords for Season 4. In my stead, the fantastic Mr Liam Hemsworth will be taking up the mantle of the White Wolf. As with the greatest of literary characters, I pass the torch with reverence for the time spent embodying Geralt and enthusiasm to see Liam’s take on this most fascinating and nuanced of men.”

    For his part, Hemsworth has said he is “over the moon” to be stepping in as Geralt of Rivia. “Henry Cavill has been an incredible Geralt, and I’m honoured that he’s handing me the reins and allowing me to take up the White Wolf’s blades for the next chapter of his adventure,” Hemsworth’s statement read. “Henry, I’ve been a fan of yours for years and was inspired by what you brought to this beloved character. I may have some big boots to fill, but I’m truly excited to be stepping into The Witcher world.”

    In The Hollywood Reporter’s cover story with Cavill from November 2021, Cavill said he planned to follow through with The Witcher series through at least seven seasons. “Absolutely,” Cavill said at the time. “As long as we can keep telling great stories which honor Sapkowski’s work.”

    Cavill is currently working on another sword-swinging epic, a remake of Highlander, though a recent injury has caused the production to be pushed to 2026.
     

    Continue Reading

  • Liam Hemsworth In for Henry Cavill, Sets Release Date

    Liam Hemsworth In for Henry Cavill, Sets Release Date

    Toss a coin to your witcher because Geralt of Rivia is back on the hunt. Netflix has released the first look at Season 4 of “The Witcher,” the fantasy drama series adapted from CD Projekt Red’s video game franchise and Andrzej Sapkowski’s novels of the same name. The eight-episode season will arrive on Netflix on Oct. 30.

    Though the show’s white-haired protagonist Geralt was played by Henry Cavill in the first three seasons of the Netflix series, Cavill took to Instagram in October 2022 to announce that he was departing the series and that Liam Hemsworth would take over the role of the titular witcher. Season 3, which was released in two parts in June and July 2023, was Cavill’s final outing as the character.

    “My journey as Geralt of Rivia has been filled with both monsters and adventures, and alas, I will be laying down my medallion and my swords for Season 4,” Cavill wrote. “In my stead, the fantastic Mr. Liam Hemsworth will be taking up the mantle of the White Wolf.”

    The first teaser shows Hemsworth’s Geralt, who looks very similar to Cavill’s version, vanquish a ghostly wraith. The logline reads: “After the Continent-altering events of Season 3, Geralt, Yennefer, and Ciri find themselves separated by a raging war and countless enemies. As their paths diverge, and their goals sharpen, they stumble on unexpected allies eager to join their journeys. And if they can accept these found families, they just might have a chance at reuniting for good.”

    In addition to Hemsworth, the cast includes Anya Chalotra (Yennefer of Vengerberg), Freya Allan (Princess Cirilla of Cintra), Joey Batey (Jaskier), Laurence Fishburne (Regis), Eamon Farren (Cahir), Anna Shaffer (Triss Merigold), Mimî M Khayisa (Fringilla), Cassie Clare (Philippa), Mahesh Jadu (Vilgefortz), Meng’er Zhang (Milva), Graham McTavish (Dijkstra), Royce Pierreson (Istredd), Mecia Simson (Francesca), Sharlto Copley (Leo Bonhart), Danny Woodburn (Zoltan) Jeremy Crawford (Yarpen), Bart Edwards (Emhyr), Hugh Skinner (Radovid), James Purefoy (Skellen), Christelle Elwin (Mistle), Fabian McCallum (Kayleigh), Juliette Alexandra (Reef), Ben Radcliffe (Giselher), Connor Crawford (Asse), Aggy K. Adams (Iskra), Linden Porco (Percival Schuttenbach), Therica Wilson-Read (Sabrina), Rochelle Rose (Margarita), Safiyya Ingar (Keira) and more

    As previously announced, Season 4 will be the penultimate season of “The Witcher,” with the series coming to a close after Season 5. The two remaining seasons of the series were shot back to back and have three novels’ worth of material left to cover: “Baptism of Fire,” “The Tower of the Swallow” and “Lady of the Lake.”

    “This is the beginning of a two-season journey for our family to finally reunite and be together — hopefully forever,” said creator, showrunner and executive producer Lauren Schmidt Hissrich.

    Watch the trailer below:

    Continue Reading

  • iPhone 17 price: How much extra Indians pay compared to other countries – Explained

    iPhone 17 price: How much extra Indians pay compared to other countries – Explained

    Apple recently unveiled its new iPhone 17 lineup, including the iPhone 17, iPhone 17 Pro, iPhone 17 Pro Max, and iPhone Air, at the “Awe Dropping” event on September 9. The base iPhone 17 now comes with 256GB of storage, doubling the capacity offered in the iPhone 16.

    Here’s how much the iPhone 17 series costs in the US, Dubai, and other regions compared to India.(Apple)

    All models will be available for pre-order in India starting September 12, with in-store and online sales beginning September 19. This year, we’ve seen a slight price increase across the series. The base iPhone 17 starts at Rs. 82,900, while the iPhone 17 Pro and iPhone 17 Pro Max are priced at Rs. 34,900 and Rs. 1,49,900, respectively. These prices are higher than in the U.S, where the same models are significantly cheaper. If you’re planning to buy or upgrade to the new iPhone, then check the price comparison below across key markets to get the best deal.

    Also read: Thinking of upgrading? Here’s why iPhone 17 is Apple’s best deal right now

    Price Comparison Across Key Markets

    When converted to Indian Rupees using approximate September 2025 exchange rates, the iPhone 17 series shows notable variations across markets. The iPhone 17 costs around Rs. 70,500 in the US, Rs. 81,700 in Dubai, Rs. 87,900 in the UK, and Rs. 128,800 in Vietnam. The iPhone Air starts at Rs. 88,200 in the US, Rs. 103,300 in Dubai, Rs. 109,900 in the UK, and Rs.105,400 in Vietnam. The iPhone 17 Pro is priced at Rs. 97,000 in the US, Rs.113,000 in Dubai, Rs. 120,900 in the UK, and Rs. 115,500 in Vietnam. The iPhone 17 Pro Max costs Rs. 105,800 in the US, Rs. 122,500 in Dubai, Rs. 131,900 in the UK, and Rs. 125,400 in Vietnam.

    Also read: Apple Watch SE 3 price in India: What’s new? Sale date and more

    Other countries also show differences in pricing. For instance, the iPhone 17 series costs less in the US, Canada, Japan, Australia, and Hong Kong compared to India. France, Germany, and Denmark have prices slightly higher than in India for some models.

    Buying iPhones from Outside India?

    International versions of the iPhone 17 series generally work in India, but there are some considerations. US models do not include a physical SIM slot and support eSIM only, while the Indian versions come with both nano SIM and eSIM options. Some international iPhones are carrier-locked and may not function with Indian SIM cards. However, Apple offers a global warranty, which helps with repairs and service without returning the iPhone to its purchase country.

    Also read: iPhone Air, Apple’s thinnest iPhone yet, launched in India: Price, specs and more

    Cheaper Options for Indian Buyers

    The US offers the most affordable prices for all models. The iPhone 17 starts at around Rs. 70,500, while the iPhone 17 Pro and Pro Max are available for Rs. 97,000 and Rs. 105,800, respectively. Canada follows closely, with prices slightly higher than in the US. Hong Kong also provides competitive pricing for the Pro and Pro Max models. Buyers can consider asking friends or relatives travelling from these countries to bring the devices, rather than visiting in person.

    Continue Reading

  • From digestive issues to hormone problems: 4 health conditions acne reveals

    From digestive issues to hormone problems: 4 health conditions acne reveals

    Skin is the mirror of our health. What goes on inside is reflected outside on our faces. It is more than a cosmetic concern; it might be trying to tell us something. In ancient Ayurveda and Chinese medicine, there is a concept known as acne face mapping, which suggests the locations of the acne on the face and what issues they indicate. Which scientific research is limited, below are the common interpretations of acne locations and the corresponding health concerns they are believed to reflect.

    Why does acne occur

    Acne develops as a result of hypersensitivity of the sebaceous glands to normal levels of circulating androgens. This process is further exacerbated by the presence of Cutibacterium acnes (C acnes), a bacterial species, and subsequent inflammation.

    6 Yoga poses to practice every winter morning for improved digestion

    Hormonal acne: Chin and jawline

    2

    The study titled “”Hormonal treatment of acne vulgaris: an update,” published in the Clinical, Cosmetic and Investigational Dermatology journal provides significant insights into the relationship between hormonal imbalances and acne, particularly in women. Its key findings suggests that hormonal fluctuations in the body can lead to increased sebum production and the excess sebum (oil) can clog the pores, leading to acne flair ups. It very well recognised that hormonal acne concentrates itself in the lower third of the face, along chin and jawline.

    Digestive issues: Cheeks

    3

    Clinical research suggests that individuals with acne vulgaris often exhibit gut microbiota profiles compared to healthy individuals. An imbalance in gut bacteria can lead to inflammation and an overproduction of sebum (skin oils), which can clog pores and cause breakouts, especially on cheeks. Further the research claims that if the gut-barrier function is enhanced, it can offer a complementary strategy in managing acne.

    Liver functionality: Between the eyebrows

    While traditional Chinese medicine supports the idea that pimples between the eyebrows are linked to proper liver health and functioning, modern science doesn’t show a direct connection. Breakouts in this particular area might suggest that the liver is under strain, possibly from an unhealthy diet, emotional stress or alcohol.

    Hairline and temples

    In traditional Chinese medicine, “face mapping”, breakouts on the hairline and temples are often interpreted as signs of liver or bladder function imbalance. However, dermatology says that acne in this particular region is largely due to external factors and clogged pores, which is known as pomade acne. Some researchers argue that the correlation between kidney function and temple acne is not fully proven. It is believed that when these organs are struggling, perhaps due to dehydration or infection, the skin on the temples could respond with breakouts.

    What can possibly be done to avoid acne

    4

    • Maintain a consistent skincare routine
    • Consume a healthy diet
    • Manage chronic stress
    • Avoid common triggers and beware of sweat

    In cases where acne can be persistent, working with a dermat, nutritionist or functional medicine practitioner can help uncover the root cause.


    Continue Reading

  • Parents report life changing benefits of mobility assistance dogs for children with walking impairments

    Parents report life changing benefits of mobility assistance dogs for children with walking impairments

    Parents of children with variable levels of walking impairment perceive significant quality of life improvements in their children after six months of living with a mobility assistance dog, according to the first qualitative assessment of its type that provides important evidence in an area of growing therapeutic interest.

    Specifically, the parents of 10 children aged 6-12 with neurological and/or physical impairments in their walking perceived improvements in most of the childrens’ physical activity levels, as well as in their social engagement and family life.

    The findings are reported in the journal Physical Therapy Reviews.

    The six-month study was led by researchers from Trinity College Dublin, who were interested in the qualitative impacts of this novel therapy where children lived with specially trained mobility assistance dogs, provided by the national charity Dogs for Disabled. 

    Regarding physical activity, parents said their children walked for longer periods, had improved quality of walking, and had greater endurance. In addition, all parents said their children had increased steadiness and balance and most said they were able to negotiate difference surfaces better, such as walking on a beach.

    Socially, parents felt the dogs facilitated interactions with other children and the public. They helped their children engage with others, with the dogs providing a topic of conversation.

    In family life, parents noted the dogs had brought a positive energy and happiness to their homes, and families walked more together. And while all families reported extra work in the responsibility of caring for the dogs they felt the overall benefits outweighed any challenges and they were happy to take these on.

    Children with physical impairments often participate in significantly lower levels of habitual physical activity than their peers – below recommended guidelines – which state that therapies to improve function, participation and quality of life in children with additional needs should be fun, involve family, encourage fitness, improve function and develop future goals.”


    Dr. Heather Kennedy, first author of the research, Trinity’s School of Engineering

    Michelle Spirtos, Head of Discipline of Occupational Therapy at Trinity, and senior author, added:  “This research provides cause for optimism that mobility assistance dogs can improve the quality of life for children with walking impairments, as well as their families, in a number of different ways. Longer-term studies involving more participants will be helpful for us to learn more, but the early signs are very encouraging.”

    Ciaran Simms, Professor in Trinity’s School of Engineering, is the principal investigator of the research. He said: “Related research from this group recently showed that physical improvements were greater in children whose walking impairments were less severe than those with more pronounced mobility issues, so this new research underlining parents’ perceived improvement in quality of life for all the children in our cohort is particularly noteworthy.”

    “In addition to the perceived improvements in physical activity, social engagement and family life, some of the parents noted the dogs helped to motivate their children to be more active, while all of them said their children had greater confidence and self-belief, as well as linking the dogs to reducing anxiety.”

    Jennifer Dowler, CEO and Founder of Irish Dogs for Disabled, said: “It is a profound privilege for Dogs for the Disabled to embark on this first-of-its-kind research, a milestone made possible through the unwavering support of Trinity College Dublin, the CRC – Central Remedial Clinic – and the generosity of our valued funders. Their commitment empowers us to push the boundaries of knowledge, ensuring pioneering ideas flourish with lasting impacts for our children.”

    Source:

    Journal reference:

    Curtin, H., et al. (2025). Parental perceptions of the impact of mobility assistance dogs for children with neurological impairment. Physical Therapy Reviews. doi.org/10.1080/10833196.2025.2546686

    Continue Reading

  • Maternal depression and offspring neurodevelopmental impairments in wild rodents induced by ecologically relevant prenatal stress

    Maternal depression and offspring neurodevelopmental impairments in wild rodents induced by ecologically relevant prenatal stress

  • Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev. 2008;32:1073–86.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Karnwal R, Sharmila K. Perspective view of stress, anxiety, and depression among pregnant women: a review. JEOH. 2024;24:7–19.

    Article 

    Google Scholar 

  • Weinstock M. Prenatal stressors in rodents: effects on behavior. Neurobiol Stress. 2017;6:3–13.

    Article 
    PubMed 

    Google Scholar 

  • Ross LE, McLean LM. Anxiety disorders during pregnancy and the postpartum period: a systematic review. J Clin Psychiatry. 2006;67:1285–98.

    Article 
    PubMed 

    Google Scholar 

  • Lebel C, MacKinnon A, Bagshawe M, Tomfohr-Madsen L, Giesbrecht G. Elevated depression and anxiety symptoms among pregnant individuals during the COVID-19 pandemic. J Affect Disord. 2020;277:5–13.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Luo Y, Zhang K, Huang M, Qiu C. Risk factors for depression and anxiety in pregnant women during the COVID-19 pandemic: evidence from meta-analysis. PLoS One. 2022;17:e0265021.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fisher J, Cabral de Mello M, Patel V, Rahman A, Tran T, Holton S, et al. Prevalence and determinants of common perinatal mental disorders in women in low- and lower-middle-income countries: a systematic review. Bull World Health Organ. 2012;90:139G–149G.

    Article 
    PubMed 

    Google Scholar 

  • Woody CA, Ferrari AJ, Siskind DJ, Whiteford HA, Harris MG. A systematic review and meta-regression of the prevalence and incidence of perinatal depression. J Affect Disord. 2017;219:86–92.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Benoit JD, Rakic P, Frick KM. Prenatal stress induces spatial memory deficits and epigenetic changes in the hippocampus indicative of heterochromatin formation and reduced gene expression. Behav Brain Res. 2015;281:1–8.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Markham JA, Taylor AR, Taylor SB, Bell DB, Koenig JI. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat. Front Behav Neurosci. 2010;4:173.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang J, Han H, Cao J, Li L, Xu L. Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus. 2006;16:431–6.

    Article 
    PubMed 

    Google Scholar 

  • Matrisciano F, Tueting P, Dalal I, Kadriu B, Grayson DR, Davis JM, et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology. 2013;68:184–94.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Brachetta V, Schleich CE, Cutrera AP, Merlo JL, Kittlein MJ, Zenuto RR. Prenatal predatory stress in a wild species of subterranean rodent: do ecological stressors always have a negative effect on the offspring? Dev Psychobiol. 2018;60:567–81.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Holson RR, Gough B, Sullivan P, Badger T, Sheehan DM. Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. Neurotoxicol Teratol. 1995;17:393–401.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Merlot E, Couret D, Otten W. Prenatal stress, fetal imprinting and immunity. Brain Behav Immun. 2008;22:42–51.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • St-Pierre J, Laurent L, King S, Vaillancourt C. Effects of prenatal maternal stress on serotonin and fetal development. Placenta. 2016;48:S66–S71.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008;28:9055–65.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dong E, Guidotti A, Zhang H, Pandey SC. Prenatal stress leads to chromatin and synaptic remodeling and excessive alcohol intake comorbid with anxiety-like behaviors in adult offspring. Neuropharmacology. 2018;140:76–85.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Matrisciano F, Dong E, Nicoletti F, Guidotti A. Epigenetic alterations in prenatal stress mice as an endophenotype model for schizophrenia: role of metabotropic glutamate 2/3 receptors. Front Mol Neurosci. 2018;11:423.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sheriff MJ, Bell A, Boonstra R, Dantzer B, Lavergne SG, McGhee KE, et al. Integrating ecological and evolutionary context in the study of maternal stress. Integr Comp Biol. 2017;57:437–49.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Verdolin JL. Meta-analysis of foraging and predation risk trade-offs in terrestrial systems. Behav Ecol Sociobiol. 2006;60:457–64.

    Article 

    Google Scholar 

  • St-Cyr S, McGowan PO. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor. Front Behav Neurosci. 2015;9:145.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • St-Cyr S, Abuaish S, Spinieli RL, McGowan PO. Maternal predator odor exposure in mice programs adult offspring social behavior and increases stress-induced behaviors in semi-naturalistic and commonly-used laboratory tasks. Front Behav Neurosci. 2018;12:136.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • St-Cyr S, Abuaish S, Sivanathan S, McGowan PO. Maternal programming of sex-specific responses to predator odor stress in adult rats. Horm Behav. 2017;94:1–12.

    Article 
    PubMed 

    Google Scholar 

  • Wu Y, Bian J, Liu J. Effects of predator-induced maternal stress on offspring’s locomotor activity and exploring behavior in root voles. Acta Theriol Sin. 2006;26:235–40.

    Google Scholar 

  • Chen G, Shi D. Study on reproductive behavior of different social hierarchy of Brandt’s voles (Lasiopodomys Brandtii). Acta Theriol Sin. 2003;23:220–4.

    Google Scholar 

  • Liu Z, Sun R. Study on physiological age structure of Brandt’s voles (Microtus brandti). Acta Theriol Sin. 1993;13:50–60.

    Google Scholar 

  • Yu X, Sun R, Fang J. Effect of kinship on social behaviors in Brandt’s voles (Microtus brandti). J Ethol. 2004;22:17–22.

    Article 

    Google Scholar 

  • Liu XH, Yue LF, Wang DW, Li N, Cong L. Inbreeding avoidance drives consistent variation of fine-scale genetic structure caused by dispersal in the seasonal mating system of Brandt’s voles. PloS one. 2013;8:e58101.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu R, Jiang X, Wu X, Pang J, Tang Y, Ren Z, et al. Interspecific differences in sociability, social novelty preference, anxiety- and depression-like behaviors between Brandt’s voles and C57BL/6J mice. Behav Processes. 2022;197:104624.

    Article 
    PubMed 

    Google Scholar 

  • Hegab IM, Wang A, Yin B, Yang S, Wei W. Behavioral and neuroendocrine response of Brandt’s voles, Lasiopodomys brandtii, to odors of different species. Eur J Wildlife Res. 2014;60:331–40.

    Article 

    Google Scholar 

  • Hegab IM, Shang G, Ye M, Jin Y, Wang A, Yin B, et al. Defensive responses of Brandt’s voles (Lasiopodomys brandtii) to chronic predatory stress. Physiol Behav. 2014;126:1–7.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Peng Y, Wu Y, Gu C, Yang S, Yin B, Wei W. Effects of repeated exposure to cat odor on anti-predator and anxiety-like behaviors of juvenile Brandt’s voles (Lasiopodomys brandtii). Acta Theriol Sin. 2021;41:451–8.

    Google Scholar 

  • Gu C, Wang W, Ding X, Yang S, Wang A, Yin B, et al. Effects of maternal stress induced by predator odors during gestation on behavioral and physiological responses of offspring in Brandt’s vole (Lasiopodomys brandtii). Integr Zool. 2018;13:723–34.

    Article 
    PubMed 

    Google Scholar 

  • Gu C, Xu Z, Chen L, Gu M, Yang S, Wang A, et al. Effects of maternal stress on the behavioral and HPA responses of offspring exposed to the predator or non-predator odor in Brandt’s voles. Pakistan J Zool. 2023;55:2151–61.

    Article 
    CAS 

    Google Scholar 

  • Pang J, Li S, Liu Y, Yang S, Wu R, Wei W. Adolescent predatory risk alters the antipredator behavior and basal HPA axis activity of future offspring in Brandt’s voles. Acta Theriol Sin. 2022;42:177–88.

    Google Scholar 

  • Wu R, Li S, Huang Y, Pang J, Cai Y, Zhang X, et al. Postpartum maternal exposure to predator odor alters offspring antipredator behavior, basal HPA axis activity and immunoglobulin levels in adult Brandt’s voles. Behav Brain Res. 2022;416:113532.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu R, Wang W, Zheng Y, Li S, Zhang L, Pang J, et al. Maternal predation risk during pregnancy alters various social behaviors in the offspring of Brandt’s voles. Behav Ecol Sociobiol. 2023;77:121.

    Article 

    Google Scholar 

  • Anacker C, Luna VM, Stevens GS, Millette A, Shores R, Jimenez JC, et al. Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature. 2018;559:98–102.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yagi S, Galea LAM. Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology. 2019;44:200–13.

    Article 
    PubMed 

    Google Scholar 

  • Liu MY, Wei LL, Zhu XH, Ding HC, Liu XH, Li H, et al. Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor. Mol Psychiatry. 2023;28:1383–95.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Christie BR, Cameron HA. Neurogenesis in the adult hippocampus. Hippocampus. 2006;16:199–207.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–7.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • McEwen BS. Redefining neuroendocrinology: epigenetics of brain-body communication over the life course. Front Neuroendocrinol. 2018;49:8–30.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Artola A, von Frijtag JC, Fermont PCJ, Gispen WH, Schrama LH, Kamal A, et al. Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Eur J Neurosci. 2006;23:261–72.

    Article 
    PubMed 

    Google Scholar 

  • Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA. 2000;97:11032–7.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Belnoue L, Grosjean N, Ladeveze E, Abrous DN, Koehl M. Prenatal stress inhibits hippocampal neurogenesis but spares olfactory bulb neurogenesis. PLoS One. 2013;8:e72972.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zheng X, Wang X, Wang T, Zhang H, Wu H, Zhang C, et al. Gestational exposure to particulate matter 2.5 (PM2.5) leads to spatial memory dysfunction and neurodevelopmental impairment in hippocampus of mice offspring. Front Neurosci. 2019;12:1000.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bock J, Murmu MS, Biala Y, Weinstock M, Braun K. Prenatal stress and neonatal handling induce sex-specific changes in dendritic complexity and dendritic spine density in hippocampal subregions of prepubertal rats. Neuroscience. 2011;193:34–43.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu YP, Gao HY, Ouyang SH, Kurihara H, He RR, Li YF. Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice. Neural Regen Res. 2019;14:298–305.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cohen H, Matar MA, Todder D, Cohen C, Zohar J, Hawlena H, et al. Sounds of danger and post-traumatic stress responses in wild rodents: ecological validity of a translational model of post-traumatic stress disorder. Mol Psychiatry. 2023;28:4719–28.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu R, Huang Y, Liu Y, Shen Q, Han Y, Yang S, et al. Repeated predator odor exposure alters maternal behavior of postpartum Brandt’s voles and offspring’s locomotor activity. Behav Processes. 2020;177:104143.

    Article 
    PubMed 

    Google Scholar 

  • Markus EJ, Zecevic M. Sex differences and estrous cycle changes in hippocampus-dependent fear conditioning. Psychobiology. 1997;25:246–52.

    Article 

    Google Scholar 

  • Paris JJ, Frye CA. Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks. Reproduction. 2008;136:105–15.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu R, Pang J, Xu Z, Wu X, Wang W, Zheng Y, et al. Adolescence predatory risk alters social behaviors and cognitive ability and central oxytocin and vasopressin expression in adult Brandt’s voles. Neuroendocrinology. 2023;113:519–34.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pascual R, Valencia M, Bustamante C. Antenatal betamethasone produces protracted changes in anxiety-like behaviors and in the expression of microtubule-associated protein 2, brain-derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex. Int J Dev Neurosci. 2015;43:78–85.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kiryanova V, Meunier SJ, Dyck RH. Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure. Behav Brain Res. 2017;331:84–91.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Akatsu S, Ishikawa C, Takemura K, Ohtani A, Shiga T. Effects of prenatal stress and neonatal handling on anxiety, spatial learning and serotonergic system of male offspring mice. Neurosci Res. 2015;101:15–23.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Coe CL, Kramer M, Czeh B, Gould E, Reeves AJ, Kirschbaum C, et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol Psychiatry. 2003;54:1025–34.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Willner P, Scheel-Kruger J, Belzung C. The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev. 2013;37:2331–71.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zoladz PR, Diamond DM. Predator-based psychosocial stress animal model of PTSD: preclinical assessment of traumatic stress at cognitive, hormonal, pharmacological, cardiovascular and epigenetic levels of analysis. Exp Neurol. 2016;284:211–9.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Righetti-Veltema M, Conne-Perreard E, Bousquet A, Manzano J. Postpartum depression and mother-infant relationship at 3 months old. J Affect Disord. 2002;70:291–306.

    Article 
    PubMed 

    Google Scholar 

  • Bauer CM, Hayes LD, Ebensperger LA, Ramirez-Estrada J, Leon C, Davis GT, et al. Maternal stress and plural breeding with communal care affect development of the endocrine stress response in a wild rodent. Horm Behav. 2015;75:18–24.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mashoodh R, Sinal CJ, Perrot-Sinal TS. Predation threat exerts specific effects on rat maternal behaviour and anxiety-related behaviour of male and female offspring. Physiol Behav. 2009;96:693–702.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bosch OJ, Pohl TT, Neumann ID, Young LJ. Abandoned prairie vole mothers show normal maternal care but altered emotionality: Potential influence of the brain corticotropin-releasing factor system. Behav Brain Res. 2018;341:114–21.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Alves RL, Portugal CC, Lopes IM, Oliveira P, Alves CJ, Barbosa F, et al. Maternal stress and vulnerability to depression: coping and maternal care strategies and its consequences on adolescent offspring. Transl Psychiatry. 2022;12:463.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sullivan EL, Smith MS, Grove KL. Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology. 2011;93:1–8.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cottrell EC, Holmes MC, Livingstone DE, Kenyon CJ, Seckl JR. Reconciling the nutritional and glucocorticoid hypotheses of fetal programming. FASEB J. 2012;26:1866–74.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Curley JP, Champagne FA. Influence of maternal care on the developing brain: Mechanisms, temporal dynamics and sensitive periods. Front Neuroendocrinol. 2016;40:52–66.

    Article 
    PubMed 

    Google Scholar 

  • Moore CL, Morelli GA. Mother rats interact differently with male and female offspring. J Comp Physiol Psychol. 1979;93:677–84.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hiroi R, Carbone DL, Zuloaga DG, Bimonte-Nelson HA, Handa RJ. Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood. Neuroscience. 2016;320:43–56.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Krusemark EA, Novak LR, Gitelman DR, Li W. When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation. J Neurosci. 2013;33:15324–32.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bontempi C, Jacquot L, Brand G. A study on the relationship between odor hedonic ratings and individual odor detection threshold. Sci Rep. 2022;12:18482.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shah A, Oxley G, Lovic V, Fleming AS. Effects of preweaning exposure to novel maternal odors on maternal responsiveness and selectivity in adulthood. Dev Psychobiol. 2002;41:187–96.

    Article 
    PubMed 

    Google Scholar 

  • Marr JN, Gardner Jr LE. Early olfactory experience and later social behavior in the rat: preference, sexual responsiveness, and care of young. J Genet Psychol. 1965;107:167–74.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. 2014;17:89–96.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, Ikeda T, et al. Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis. Neurosci Res. 2007;59:145–51.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jia N, Li Q, Sun H, Song Q, Tang G, Sun Q, et al. Alterations of group I mGluRs and BDNF associated with behavioral abnormity in prenatally stressed offspring rats. Neurochem Res. 2015;40:1074–82.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zohar I, Dosoretz-Abittan L, Shoham S, Weinstock M. Sex dependent reduction by prenatal stress of the expression of 5HT1A receptors in the prefrontal cortex and CRF type 2 receptors in the raphe nucleus in rats: reversal by citalopram. Psychopharmacology (Berl). 2015;232:1643–53.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pawluski JL, Csaszar E, Savage E, Martinez-Claros M, Steinbusch HWM, van den Hove D. Effects of stress early in gestation on hippocampal neurogenesis and glucocorticoid receptor density in pregnant rats. Neuroscience. 2015;290:379–88.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bock J, Wainstock T, Braun K, Segal M. Stress in utero: prenatal programming of brain plasticity and cognition. Biol Psychiatry. 2015;78:315–26.

    Article 
    PubMed 

    Google Scholar 

  • Iribarne J, Brachetta V, Kittlein M, Schleich C, Zenuto R. Effects of acute maternal stress induced by predator cues on spatial learning and memory of offspring in the subterranean rodent Ctenomys talarum. Anim Cogn. 2023;26:1997–2008.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lian B, Gao J, Sui N, Feng T, Li M. Object, spatial and social recognition testing in a single test paradigm. Neurobiol Learn Mem. 2018;152:39–49.

    Article 
    PubMed 

    Google Scholar 

  • Grundwald NJ, Benitez DP, Brunton PJ. Sex-dependent effects of prenatal stress on social memory in rats: a role for differential expression of central vasopressin-1a receptors. J Neuroendocrinol. 2016;28:n/a.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI. Prenatal stress generates deficits in rat social behavior: reversal by oxytocin. Brain Res. 2007;1156:152–67.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wilson CA, Terry Jr AV. Variable maternal stress in rats alters locomotor activity, social behavior, and recognition memory in the adult offspring. Pharmacol Biochem Behav. 2013;104:47–61.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ehrlich DE, Rainnie DG. Prenatal stress alters the development of socioemotional behavior and amygdala neuron excitability in rats. Neuropsychopharmacology. 2015;40:2135–45.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gur TL, Palkar AV, Rajasekera T, Allen J, Niraula A, Godbout J, et al. Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring. Behav Brain Res. 2019;359:886–94.

    Article 
    PubMed 

    Google Scholar 

  • Gur TL, Shay L, Palkar AV, Fisher S, Varaljay VA, Dowd S, et al. Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring. Brain Behav Immun. 2017;64:50–8.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Beery AK, Kaufer D. Stress, social behavior, and resilience: insights from rodents. Neurobiol Stress. 2015;1:116–27.

    Article 
    PubMed 

    Google Scholar 

  • Sams-Dodd F. Phencyclidine in the social interaction test: an animal model of schizophrenia with face and predictive validity. Rev Neurosci. 1999;10:59–90.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sapolsky RM. Is impaired neurogenesis relevant to the affective symptoms of depression? Biol Psychiatry. 2004;56:137–9.

    Article 
    PubMed 

    Google Scholar 

  • Drew MR, Hen R. Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurol Disord Drug Targets. 2007;6:205–18.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature. 2011;476:458–61.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sorra KE, Harris KM. Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus. 2000;10:501–11.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Koehl M, Lemaire V, Le Moal M, Abrous DN. Age-dependent effect of prenatal stress on hippocampal cell proliferation in female rats. Eur J Neurosci. 2009;29:635–40.

    Article 
    PubMed 

    Google Scholar 

  • Lucassen PJ, Bosch OJ, Jousma E, Kromer SA, Andrew R, Seckl JR, et al. Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11beta-hydroxysteroid dehydrogenase type 2. Eur J Neurosci. 2009;29:97–103.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Paris JJ, Frye CA. Juvenile offspring of rats exposed to restraint stress in late gestation have impaired cognitive performance and dysregulated progestogen formation. Stress. 2011;14:23–32.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hosseini-Sharifabad M, Hadinedoushan H. Prenatal stress induces learning deficits and is associated with a decrease in granules and CA3 cell dendritic tree size in rat hippocampus. Anat Sci Int. 2007;82:211–7.

    Article 
    PubMed 

    Google Scholar 

  • Martinez-Tellez RI, Hernandez-Torres E, Gamboa C, Flores G. Prenatal stress alters spine density and dendritic length of nucleus accumbens and hippocampus neurons in rat offspring. Synapse. 2009;63:794–804.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jia N, Yang K, Sun Q, Cai Q, Li H, Cheng D, et al. Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats. Dev Neurobiol. 2010;70:114–25.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bustamante C, Valencia M, Torres C, Gonzalez MJ, Carvajal C, Sandoval D, et al. Effects of a single course of prenatal betamethasone on dendritic development in dentate gyrus granular neurons and on spatial memory in rat offspring. Neuropediatrics. 2014;45:354–61.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu Y, De Asis-Cruz J, Limperopoulos C. Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy. Mol Psychiatry. 2024;29:2223–40.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

Continue Reading

  • US Fed poised for first rate cut of 2025 as political tension mounts – France 24

    1. US Fed poised for first rate cut of 2025 as political tension mounts  France 24
    2. StanChart expects Fed to cut rates by 50 bps next week after weak jobs data  Reuters
    3. Why traders priced in a 90% chance of US interest rate cut  Finimize
    4. Take Five: Regular, or super-sized? By Reuters  Investing.com
    5. The ‘Super Week for Central Banks’ is here — traders will be working around the clock for these 36 hours.  富途牛牛

    Continue Reading

  • ‘Roofman’s Channing Tatum Was Nude First Time Meeting Peter Dinklage

    ‘Roofman’s Channing Tatum Was Nude First Time Meeting Peter Dinklage

    While filming their latest crime comedy-drama Roofman, Peter Dinklage became quickly acquainted with co-star Channing Tatum.

    Director Derek Cianfrance recalled the actors’ first time meeting during a scene in which Tatum was “full monty” while portraying fugitive Jeffrey Manchester, a father and U.S. Army Reserve officer who broke out of jail and hid in the walls of a Toys ‘R’ Us.

    “There’s this big scene in the movie where [Dinklage] catches Channing Tatum showering in the middle of the night,” Cianfrance told People. “You can write that scene, but then you have to shoot it. And it’s… Channing had to show up.”

    Related Stories

    The movie, which premiered at TIFF, stars Dinklage as store manager Mitch and Kirsten Dunst as Leigh, a Toys ‘R’ Us employee who develops a romance with the fugitive.

    Noting “there was nothing to hide behind,” Cianfrance confirmed that Tatum was fully nude during the scene, which was also the first time Dinklage met his co-star.

    Juno Temple, LaKeith Stanfield, Derek Cianfrance, Kirsten Dunst and Channing Tatum attend the premiere of ‘Roofman’ during the 2025 Toronto International Film Festival on Sept. 6, 2025 in Toronto, Ontario. (Emma McIntyre/Getty Images)

    “It was pretty fun having Peter and Channing interact that way. That was the first time they met because I tried to keep my actors apart because I wanted them to be surprised,” said Cianfrance. “So, Channing and Peter never saw each other. The first time Peter ever saw Channing was full monty.”

    Following the film’s debut last week at Toronto International Film Festival, Roofman premieres Oct. 10 in U.S. theaters.


    Continue Reading

  • Owen Cooper fights to make Emmy history as youngest male winner

    Owen Cooper fights to make Emmy history as youngest male winner



    Owen Cooper fights to make Emmy history as youngest male winner

    Owen Cooper, rising Hollywood star who has won millions of hearts with his performance at such young age, was on the brink of making television history as he prepared for the Emmy Awards.

    The 15 year old actor from Warrington was nominated for Best Supporting Actor for his role in Netflix’s hit drama Adolescence. 

    A win would make him the youngest male Emmy winner in the award show’s 76 year history.

    Adolescence, which told the story of a teenager accused of murder, became one of the most acclaimed shows of the year. 

    Netflix hit secured 13 nominations and already proven its success at the National TV Awards, where it picked up Best New Drama. 

    However, Cooper also won Best Drama Performance for his portrayal of Jamie Miller, a troubled teen at the heart of the story.

    The little star filmed the series at just 14 and quickly caught the attention of critics for his powerful performance. 

    Ahead of the Emmys, the actor attended parties in Hollywood with his parents, Noreen and Andy, who both work outside the entertainment industry. 

    Speaking about the moment, he said he would never forget it and admitted that the show changed his life in ways he never imagined.

    Other British stars also lined up for Emmy recognition, including Stephen Graham, who played Cooper’s on-screen father, as well as Gary Oldman, Bella Ramsey and Colin Farrell. 

    But all eyes were on the teenager, whose nomination was hailed as a major breakthrough. 

    Moreover, industry experts called Owen’s category placement a smart move that could give him the edge in one of the most competitive races of the night.

    Continue Reading

  • Cryo-EM reveals how blood clotting proteins fit together to trigger clot formation

    Cryo-EM reveals how blood clotting proteins fit together to trigger clot formation

    If you’ve ever accidentally sliced yourself on a broken glass or a piece of paper, you may have noticed that the bleeding can be hard to stop.

    Scientists have long wondered how the cascade of events that leads to blood clotting is triggered, especially since the process has life and death consequences. Too little clotting and you bleed out, while too much can cause a heart attack or stroke.

    New detailed 3D structures of blood clotting proteins, made possible through cryogenic-electron microscopy (Cryo-EM), have solved a mystery vexing biological chemists for more than 30 years.

    Cryo-EM is a structural approach where biological samples are trapped in a layer of non-crystalline ice and imaged using powerful electron microscopes.

    The U-M Life Sciences Institute, with support from the U-M Bioscience Initiative and Arnold and Mabel Beckman Foundation, established a state-of-the art cryo-EM facility that made this research possible.

    James Morrissey, Ph.D., professor of biochemistry at U-M Medical School, has been studying the various proteins involved in clotting since the 1980s. To uncover their structure, he teamed up with cryo-EM expert Melanie Ohi, Ph.D., a professor of cell and developmental biology at U-M Medical School and research professor in the U-M Life Sciences Institute.

    Most of the blood clotting proteins are soluble proteins that circulate in your blood, and there’s one missing protein that is housed on the surface of cells outside of the vasculature.”


    James Morrissey, Ph.D., professor of biochemistry, U-M Medical School

    The normal clotting process involves an enzyme with two sub-units, tissue factor and factor VIIa. When that combo links up on a cell surface, it kicks off the clotting cascade, he said. The cell membrane plays an important role in whether clotting will happen.

    “A happy, healthy resting cell won’t bind these blood clotting proteins,” he said. But an injury causes the particular phospholipids from the lipid bilayer that makes up the cell membrane to flip to the outside of the cell, where the blood clotting proteins bind to them, he explained.

    In the case of a profusely bleeding paper cut, “it could be that if you don’t damage enough cells and don’t expose enough of these phospholipids of the surface of the damaged cells to recruit blood clotting proteins, then clotting is slowed,” Morrissey noted.

    This process has been exceedingly hard to study, so Morrissey and his colleagues used cryo-EM to determine 3D structures that allowed them to build an atomic model of the protein interactions when associated with a lipid nanodisc.

    They found that the tissue factor/factor VIIa complex binds to the second protein in the clotting cascade, called factor X, by moving a small site on tissue factor out of the way, changing the structure so that factor X can dock onto that site, like two puzzle pieces fitting together (see movie).

    “It was exciting to determine a structure that helps solve the long-standing mystery for why tissue factor can activate the blood clotting cascade only when specific lipids are found on the outside of a cell. For me this work highlights two strengths of doing research at the University of Michigan – the ease at establishing successful cross-disciplinary collaborations and access to one of the best cryo-electron microscopy facilities in the world. Working in this type of environment makes it fun to tackle challenging structural questions,” said Ohi.

    Their results are published in a recent issue of the American Society of Hematology journal, Blood.

    The findings help explain “something that people have known about for years: that this part of tissue factor was important in recognizing the substrate and allowing the reaction to go. But nobody came up with how the proteins actually dock together,” said Morrissey.

    Anticoagulant drugs like Warfarin, prescribed to treat dangerous blood clotting, work by weakening the ability of these proteins to interact at the cell membrane, but they worked without scientists fully understanding what was happening. This basic science work finally provides new insights into the mechanism behind it.

    Source:

    Michigan Medicine – University of Michigan

    Journal reference:

    Sedzro, J. C., et al. (2025). Cryo-EM structure of the tissue factor/factor VIIa complex with a factor X mimetic reveals a novel allosteric mechanism. Blood Journal. doi.org/10.1182/blood.2025029430

    Continue Reading