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  1. Article: A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors.

    Menon, Indu / Sych, Taras / Son, Yeeun / Morizumi, Takefumi / Lee, Joon / Ernst, Oliver P / Khelashvili, George / Sezgin, Erdinc / Levitz, Joshua / Menon, Anant K

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors ...

    Abstract Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs, yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the β1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.24.568580
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  2. Article ; Online: A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors.

    Menon, Indu / Sych, Taras / Son, Yeeun / Morizumi, Takefumi / Lee, Joon / Ernst, Oliver P / Khelashvili, George / Sezgin, Erdinc / Levitz, Joshua / Menon, Anant K

    The Journal of biological chemistry

    2024  Volume 300, Issue 2, Page(s) 105649

    Abstract: Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors ...

    Abstract Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the β1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.
    MeSH term(s) Animals ; Biological Transport ; Cholesterol ; Phospholipid Transfer Proteins/metabolism ; Phospholipids/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Cattle ; Turkeys
    Chemical Substances Cholesterol (97C5T2UQ7J) ; Phospholipid Transfer Proteins ; Phospholipids ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2024.105649
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  3. Article ; Online: Phospholipid Scrambling by G Protein-Coupled Receptors.

    Khelashvili, George / Menon, Anant K

    Annual review of biophysics

    2021  Volume 51, Page(s) 39–61

    Abstract: ... flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein-coupled receptors ...

    Abstract Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. In liposomes, opsin scrambles lipids at a unitary rate of >100,000 per second. Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions that expose a polar groove between transmembrane helices 6 and 7. This groove enables transbilayer lipid movement, conceptualized as the swiping of a credit card (lipid) through a card reader (GPCR). Conformational changes that facilitate scrambling are distinct from those associated with GPCR signaling. In this review, we discuss the physiological significance of GPCR scramblase activity and the modes of its regulation in cells.
    MeSH term(s) Biological Transport ; Opsins/metabolism ; Phospholipid Transfer Proteins/metabolism ; Phospholipids/metabolism ; Receptors, G-Protein-Coupled
    Chemical Substances Opsins ; Phospholipid Transfer Proteins ; Phospholipids ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2434725-5
    ISSN 1936-1238 ; 1936-122X
    ISSN (online) 1936-1238
    ISSN 1936-122X
    DOI 10.1146/annurev-biophys-090821-083030
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  4. Article ; Online: Cholesterol occupies the lipid translocation pathway to block phospholipid scrambling by a G protein-coupled receptor.

    Morra, Giulia / Razavi, Asghar M / Menon, Anant K / Khelashvili, George

    Structure (London, England : 1993)

    2022  Volume 30, Issue 8, Page(s) 1208–1217.e2

    Abstract: Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid ...

    Abstract Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid scramblases as evinced after their reconstitution into liposomes. Yet phospholipid scrambling is not detectable in the resting plasma membrane of mammalian cells that is replete with GPCRs. We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids. Our previous Markov State Model (MSM) analysis of molecular dynamics simulations of membrane-embedded opsin indicated that phospholipid headgroups traverse a dynamically revealed hydrophilic groove between transmembrane helices (TM) 6 and 7 while their tails remain in the bilayer. Here, we present comparative MSM analyses of 150-μs simulations of opsin in cholesterol-free and cholesterol-rich membranes. Our analyses reveal that cholesterol inhibits phospholipid scrambling by occupying the TM6/7 interface and stabilizing the closed groove conformation while itself undergoing flip-flop. This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane.
    MeSH term(s) Animals ; Biological Transport ; Cholesterol ; Lipid Bilayers ; Mammals/metabolism ; Opsins/metabolism ; Phospholipid Transfer Proteins/genetics ; Phospholipid Transfer Proteins/metabolism ; Phospholipids/metabolism ; Receptors, G-Protein-Coupled/metabolism
    Chemical Substances Lipid Bilayers ; Opsins ; Phospholipid Transfer Proteins ; Phospholipids ; Receptors, G-Protein-Coupled ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1213087-4
    ISSN 1878-4186 ; 0969-2126
    ISSN (online) 1878-4186
    ISSN 0969-2126
    DOI 10.1016/j.str.2022.05.010
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  5. Article ; Online: Structure and function of skin in the pelagic sea snake, Hydrophis platurus.

    Lillywhite, Harvey B / Menon, Gopinathan K

    Journal of morphology

    2019  Volume 280, Issue 4, Page(s) 544–554

    Abstract: ... scales ('hinge') entrap and wick water over the body surface, with mean retention of 5.1 g/cm of skin ...

    Abstract We describe and interpret the functional morphology of skin of the Yellow-bellied sea snake, Hydrophis platurus. This is the only pelagic sea snake, and its integument differs from what is known for other species of snakes. In gross appearance, the scales of H. platurus consist of non-overlapping, polygonal knobs with flattened outer surfaces bearing presumptive filamentous sensillae. The deep recesses between scales ('hinge') entrap and wick water over the body surface, with mean retention of 5.1 g/cm of skin surface, similar to that determined previously for the roughened, spiny skin of marine file snakes, Acrochordus granulatus. This feature possibly serves to maintain the skin wet when the dorsal body protrudes above water while floating on calm oceanic slicks where they forage. In contrast with other snakes, including three species of amphibious, semi-marine sea kraits (Laticauda spp.), the outer corneous β-protein layer consists of a syncytium that is thinner than seen in most other species. The subjacent α-layer is also thin, and lipid droplets and lamellar bodies are seen among the immature, cornifying α-cells. A characteristic mesos layer, comprising the water permeability barrier, is either absent or very thin. These features are possibly related to (1) permeability requirements for cutaneous gas exchange, (2) reduced gradient for water efflux compared with terrestrial environments, (3) less need for physical protection in water compared with terrestrial ground environments, and (4) increased frequency of ecdysis thought to be an anti-fouling mechanism. The lipogenic features of the α-layer possibly compensate for the reduced or absent mesos layer, or produce layers of cells that comprise what functionally might be termed a mesos layer, but where the organization of barrier lipids nonetheless appears less robust than what is characteristically seen in squamates.
    MeSH term(s) Animal Scales/anatomy & histology ; Animal Scales/ultrastructure ; Animals ; Epidermis/ultrastructure ; Hydrophiidae/anatomy & histology ; Molting ; Skin/anatomy & histology ; Skin/ultrastructure
    Language English
    Publishing date 2019-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3084-3
    ISSN 1097-4687 ; 0022-2887 ; 0362-2525
    ISSN (online) 1097-4687
    ISSN 0022-2887 ; 0362-2525
    DOI 10.1002/jmor.20963
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  6. Article: Dora's mother: a housewife's psychosis.

    Menon, Anuradha

    BJPsych bulletin

    2022  Volume 47, Issue 4, Page(s) 220–224

    Abstract: ... the apparently sanctioned entry of another couple, Frau and Herr K, into the parental relationship. In particular ...

    Abstract I examine a speculative diagnosis made by Sigmund Freud regarding his patient's mother in his landmark 1905 paper describing a hysterical illness. Freud considered the impact of Dora's mother's mental state on her daughter, wondering whether the mother might suffer from a 'housewife's psychosis'. Here was an emphasis on the social structures of the times and differences between the parents in terms of sexual freedom and societal limitations placed on women. Freud's description drew attention to Dora's anxieties in relation to her parents, in particular the state of their sexual relationship and the apparently sanctioned entry of another couple, Frau and Herr K, into the parental relationship. In particular, the role of syphilis in the aetiology of sexual disturbances was considered, affecting men and their sexual partners, specifically their wives, who faced lifelong risks of morbidity, inadequate treatment and psychic disturbances at this time in 19th century Vienna.
    Language English
    Publishing date 2022-10-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2816886-0
    ISSN 2056-4708 ; 2056-4694
    ISSN (online) 2056-4708
    ISSN 2056-4694
    DOI 10.1192/bjb.2022.64
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  7. Article ; Online: Will Electronic Skins Be the Next Miraculous Skin Care Devices?

    Menon, Gopinathan K / Wakefield, Joan S / Elias, Peter M / Denda, Mitsuhiro

    The Journal of investigative dermatology

    2023  Volume 143, Issue 11, Page(s) 2102–2104

    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2023.06.196
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  8. Book ; Online ; E-Book: Robotics in genitourinary surgery

    Hemal, Ashok K. / Menon, Mani

    2018  

    Author's details Ashok K. Hemal, Mani Menon editors
    Keywords Urology ; Endoscopic surgery
    Subject code 616.6
    Language English
    Size 1 Online-Ressource (XXII, 961 Seiten), Illustrationen
    Edition Second edition
    Publisher Springer
    Publishing place Cham
    Publishing country Switzerland
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT019847959
    ISBN 978-3-319-20645-5 ; 9783319206448 ; 3-319-20645-1 ; 3319206443
    DOI 10.1007/978-3-319-20645-5
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  9. Article ; Online: Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

    Teske, Arco J / Moudgil, Rohit / López-Fernández, Teresa / Barac, Ana / Brown, Sherry Ann / Deswal, Anita / Neilan, Tomas G / Ganatra, Sarju / Abdel Qadir, Husam / Menon, Venu / Sverdlov, Aaron L / Cheng, Richard K / Makhoul, Silvia / Ghosh, Arjun K / Szmit, Sebastian / Zaha, Vlad / Addison, Daniel / Zhang, Lili / Herrmann, Joerg /
    Chong, Jun H / Agarwala, Vivek / Iakobishvili, Zaza / Guerrero, Patricia / Yang, Eric H / Leja, Monika / Akhter, Nausheen / Guha, Avirup / Okwuosa, Tochukwu M / Silva, Carolina Carvalho / Collier, Patrick / DeCara, Jeanne / Bauer, Brenton / Lenneman, Carrie E / Sadler, Diego

    Circulation. Cardiovascular quality and outcomes

    2023  Volume 16, Issue 10, Page(s) e009905

    Abstract: Background: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the ... ...

    Abstract Background: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry.
    Methods: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative.
    Results: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment.
    Conclusions: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.
    MeSH term(s) Humans ; Female ; Cardiology ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/therapy ; Medical Oncology ; Cardiologists ; Breast Neoplasms ; Registries ; Multicenter Studies as Topic
    Language English
    Publishing date 2023-09-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2483197-9
    ISSN 1941-7705 ; 1941-7713
    ISSN (online) 1941-7705
    ISSN 1941-7713
    DOI 10.1161/CIRCOUTCOMES.123.009905
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    Zs.A 6744: Show issues Location:
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  10. Article ; Online: Evidence for the holocrine nature of lipoid secretion by avian epidermal cells: A histochemical and fine structural study of rictus and the uropygial gland.

    Menon, G K / Aggarwal, S K / Lucas, A M

    Journal of morphology

    2018  Volume 167, Issue 2, Page(s) 185–199

    Abstract: Cells of the avian epidermis (rictus of the chicken), when examined under the light microscope following suitable fat staining, show similarities to epithelial cells of the uropygial gland of chicken and pigeon, an organ which is recognized both ... ...

    Abstract Cells of the avian epidermis (rictus of the chicken), when examined under the light microscope following suitable fat staining, show similarities to epithelial cells of the uropygial gland of chicken and pigeon, an organ which is recognized both morphologically and functionally as a holocrine gland. Evidence thus far from electron microscopic studies strongly suggests that the skin of the bird is also a holocrine gland, although details of cytogenesis and secretion differ somewhat in the two organs.
    Language English
    Publishing date 2018-06-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3084-3
    ISSN 1097-4687 ; 0022-2887 ; 0362-2525
    ISSN (online) 1097-4687
    ISSN 0022-2887 ; 0362-2525
    DOI 10.1002/jmor.1051670204
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