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A fourth Phase III clinical trial evaluating an investigational vaccine for coronavirus disease 2019 has begun enrolling adult volunteers. The trial is designed to evaluate if the investigational Janssen COVID-19 vaccine can prevent symptomatic COVID-19 after a single dose regimen. Up to 60,000 volunteers will be enrolled in the trial at up to nearly 215 clinical research sites in the United States and internationally.
[National Institute of Allergy and Infectious Diseases]
Scientists report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative IgG-IgM SARS-CoV-2 serology and a positive RNAemia measured by digital PCR who were treated with four units of COVID-19 convalescent plasma.
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Hueso, T., Pouderoux, C., Péré, H., Beaumont, A.-L., Raillon, L.-A., Ader, F., Chatenoud, L., Eshagh, D., Szwebel, T.-A., Martinot, M., Camou, F., Crickx, E., Michel, M., Mahevas, M., Boutboul, D., Azoulay, E., Joseph, A., Hermine, O., Rouzaud, C., … Lacombe, K. (n.d.). Convalescent plasma therapy for B-cell depleted patients with protracted COVID-19 disease. Blood. https://doi.org/10.1182/blood.2020008423 Cite
Investigators observed accumulation of nuclear debris in the lungs of neutropenic mice exposed to acid-induced injury compared to wild-type. Size analysis of DNA-debris showed that neutropenic mice were unable to degrade extracellular DNA fragments.
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Divalent cations Cu2+ and Zn2+ could prevent the viral growth in mammalian cells during influenza infection, and viral titers decreased significantly on a copper surface. The underlying mechanisms included DNA damage by radicals, modulation of viral protease, M1 or neuraminidase, and morphological changes in viral particles.
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Papyrus Therapeutics, Inc. and Oxford Biomedica plc announced the signing of a research collaboration agreement, which includes the assessment of the impact and therapeutic benefit of Papyrus’ PYTX-002, a potential first-in-class gene replacement therapy.
[Papyrus Therapeutics, Inc.]
Scientists visualized inflammasome assembly by cellular imaging complemented by pharmacological inhibition and targeted deletion in cells and in mice.
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Magupalli, V. G., Negro, R., Tian, Y., Hauenstein, A. V., Caprio, G. D., Skillern, W., Deng, Q., Orning, P., Alam, H. B., Maliga, Z., Sharif, H., Hu, J. J., Evavold, C. L., Kagan, J. C., Schmidt, F. I., Fitzgerald, K. A., Kirchhausen, T., Li, Y., & Wu, H. (2020). HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation. Science, 369(6510). https://doi.org/10.1126/science.aas8995 Cite
Scientists validated cleavage at a putative furin substrate motif at SARS-CoV-2 spike by expressing it in VeroE6 cells and found prominent syncytium formation.
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Cheng, Y.-W., Chao, T.-L., Li, C.-L., Chiu, M.-F., Kao, H.-C., Wang, S.-H., Pang, Y.-H., Lin, C.-H., Tsai, Y.-M., Lee, W.-H., Tao, M.-H., Ho, T.-C., Wu, P.-Y., Jang, L.-T., Chen, P.-J., Chang, S.-Y., & Yeh, S.-H. (2020). Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects. Cell Reports, 0(0). https://doi.org/10.1016/j.celrep.2020.108254 Cite
Scientists investigated the effects of HIV infection on immune cell exhaustion at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from four healthy subjects and six HIV-infected donors.
[Emerging Microbes & Infections]
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To reduce or preclude the necessity for IL-2 use, scientists investigated whether genetic engineering of NK cells to express the erythropoietin receptor or thrombopoietin receptor could be used as a method to improve NK cell survival and function.
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Chanswangphuwana, C., Allan, D. S. J., Chakraborty, M., Reger, R. N., & Childs, R. W. (2020). Augmentation of NK Cell Proliferation and Anti-tumor Immunity by Transgenic Expression of Receptors for Erythropoietin or Thrombopoietin. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2020.09.023 Cite
Researchers isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer.
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Mager, L. F., Burkhard, R., Pett, N., Cooke, N. C. A., Brown, K., Ramay, H., Paik, S., Stagg, J., Groves, R. A., Gallo, M., Lewis, I. A., Geuking, M. B., & McCoy, K. D. (2020). Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science, 369(6510), 1481–1489. https://doi.org/10.1126/science.abc3421 Cite
Tmunity Therapeutics, Inc. announced that it has dosed the first patient in its Phase I CART-TnMUC1-01 clinical trial with the Tn/STn glycoform of mucin 1 chimeric antigen receptor T-cell therapy in patients with TnMUC1-positive advanced cancers.
[Tmunity Therapeutics, Inc.]