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10 results

  • Integrin force loading rate in mechanobiology: From model to molecular measurement

  • Part of
  • Hongyuan Zhang, Micah Yang, Seong Ho Kim, Isaac T.S. Li
  • Journal:
    QRB Discovery / Volume 6 / 2025
    Published online by Cambridge University Press:
    16 January 2025, e9
    Print publication:
    2025
    • Article
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      • Open access
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  • Integrins are critical transmembrane receptors that connect the extracellular matrix (ECM) to the intracellular cytoskeleton, playing a central role in mechanotransduction – the process by which cells convert mechanical stimuli into biochemical signals. The dynamic assembly and disassembly of integrin-mediated adhesions enable cells to adapt continuously to changing mechanical cues, regulating essential processes such as adhesion, migration, and proliferation. In this review, we explore the molecular clutch model as a framework for understanding the dynamics of integrin – ECM interactions, emphasizing the critical importance of force loading rate. We discuss how force loading rate bridges internal actomyosin-generated forces and ECM mechanical properties like stiffness and ligand density, determining whether sufficient force is transmitted to mechanosensitive proteins such as talin. This force transmission leads to talin unfolding and activation of downstream signalling pathways, ultimately influencing cellular responses. We also examine recent advances in single-molecule DNA tension sensors that have enabled direct measurements of integrin loading rates, refining the range to approximately 0.5–4 pN/s. These findings deepen our understanding of force-mediated mechanotransduction and underscore the need for improved sensor designs to overcome current limitations.

  • If Long-Term Suppression is not Possible, how do we Minimize Mortality for Infectious Disease Outbreaks?

  • Andreas Handel, Joel C. Miller, Yang Ge, Isaac Chun-Hai Fung
  • Journal:
    Disaster Medicine and Public Health Preparedness / Volume 17 / 2023
    Published online by Cambridge University Press:
    01 December 2023, e547
  • Objective:

    For any emerging pathogen, the preferred approach is to drive it to extinction with non-pharmaceutical interventions (NPI) or suppress its spread until effective drugs or vaccines are available. However, this might not always be possible. If containment is infeasible, the best people can hope for is pathogen transmission until population level immunity is achieved, with as little morbidity and mortality as possible.

    Methods:

    A simple computational model was used to explore how people should choose NPI in a non-containment scenario to minimize mortality if mortality risk differs by age.

    Results:

    Results show that strong NPI might be worse overall if they cannot be sustained compared to weaker NPI of the same duration. It was also shown that targeting NPI at different age groups can lead to similar reductions in the total number of infected, but can have strong differences regarding the reduction in mortality.

    Conclusions:

    Strong NPI that can be sustained until drugs or vaccines become available are always preferred for preventing infection and mortality. However, if people encounter a worst-case scenario where interventions cannot be sustained, allowing some infections to occur in lower-risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally.

  • Chapter 7 - Neurological and Neurosurgical Disorders and Wellness

  • from Part II - From Illness to Wellness by Organ Systems/Disorders
  • Edited by Waguih William IsHak
  • Book:
    The Handbook of Wellness Medicine
    Published online:
    18 September 2020
    Print publication:
    20 August 2020, pp 66-78

  • Summary

    Neurological and neurosurgical disorders represent a particularly salient area for interventions using practices of wellness medicine. Due to the complex physiology and functions of the nervous system, disease processes can have a wide range of clinical presentations, each with unique hardships. Because the nervous system itself provides individuals with cognition, sense of self, and identity, the loss of normal neurological function in day-to-day activities can elicit substantial emotional distress. Neurological disorders are also somewhat unique in that a large number of conditions lack curative treatments and require lifelong symptom management and supportive care [1]. Medical and surgical interventions for such diseases often come with their own set of complications, side effects, and impacts on quality of life [2]. It is therefore important for care providers to understand the ways in which patients can improve their health by seeking personalized cognitive, behavioral, physical, and spiritual interventions alongside their standard course of treatment.

  • P-495 - Gender Difference in Antidepressant-related Sexual Dysfunction in Patients With Major Depressive Disorder (mdd)

  • J. Isaac, T. Lee, K. Chin Chen, T. Lieh Yeh, I. Hui Lee, P. See Chen, S.-H. Lin, Y. Kuang Yang
  • Journal:
    European Psychiatry / Volume 27 / Issue S1 / 2012
    Published online by Cambridge University Press:
    15 April 2020, p. 1
    • Article
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  • Introduction:

    It is known that Sexual Dysfunction (SD) is higher in patient with depression than in the general population. Though antidepressant seems to worsen the situation, there are also indications that the gender may play a role on it.

    Objective:

    Evaluate the gender effect of sexual function among unmedicated MDD, MDD receiving antidepressant, and healthy controls.

    Methods:

    The sample was formed by male and female Taiwanese outpatients in three age and sex matched groups, with sixty nine participants per group: unmedicated MDD, MDD receiving antidepressant, and healthy controls. the diagnoses of depressions were performed according DSM-IV and Taiwanese Depression Questionnaire. SD was evaluated with the Chinese version of the Changes in Sexual Functioning Questionnaire. Finally, the data was analyzed using SPSS software v17. Mixed designed ANOVA was used.

    Results:

    There are significant differences between males and females CSFQ results (sex main effect F = 82.44, p < 0.001) and between groups (group main effect F = 3.48, p = 0.034). Additionally, the 2-way interaction between sex and group was also significant (F = 3.40, p = 0.036). Simple main effect analysis shows differences among male participants, between healthy and medicated males (F = 11.41, p = 0.002), but not in female (F = 1.58, p = 0.21). However the statistics weren’t different between females groups, the medicated expresses better results (similar to healthy group) than the unmedicated one.

    Conclusions:

    SD is different between genders in each of the groups. Antidepressant seems to increase SD in man, while improves sexual satisfaction/function among depressive woman. We speculate that psychological improvement after treatment may have different impact between genders on sexual satisfaction.

  • Direct collapse to SMBH seeds in cosmological halos with radiation transfer

  • Kentaro Nagamine, Isaac Shlosman, Yang Luo
  • Journal:
    Proceedings of the International Astronomical Union / Volume 15 / Issue S341 / November 2019
    Published online by Cambridge University Press:
    10 June 2020, pp. 289-291
    Print publication:
    November 2019
    • Article
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  • We present results of our zoom-in cosmological hydrodynamic simulations of direct collapse (DC) to supermassive black hole (SMBH) seeds with radiative transfer (RT). The DC has been modeled in dark matter halos of ∼108M⊙, using adaptive mesh refinement (AMR) code Enzo. For the first time, the baryonic collapse has been followed down to 10−7 pc (∼0.01 AU) with on-the-fly RT and the flux-limited diffusion (FLD) approximation. We find a complex behavior involving accretion flow and associated outflows driven by the radiation force. The resulting gas dynamics around the central density peak differs profoundly from that in previous works which adopted adiabatic approximation in the core. The core forms with a photosphere at ∼1 AU, and its growth starts to saturate at ∼100M⊙. The unrelaxed core radiates intermittently near the Eddington luminosity, correlated with strong anisotropic outflows.