CRISPR/Cas9 Mediated Generation and Analysis of N-Terminus Polymorphic Models of beta2-Adrenoreceptor in Isogenic hPSC Derived Cardiomyocytes

Investigators used CRISPR/Cas9 gene editing technology in human (h)PSCs to create a unique suite of four isogenic homozygous variants at amino acid positions 16(G/R) and 27(G/Q), which reside in the N-terminus of the β2AR.
[Molecular Therapy-Methods & Clinical Development]
Kondrashov, A., Yusof, N. A. N. M., Hasan, A., Goulding, J., Kodagoda, T., Hoang, D. M., Vo, N. T. N., Melarangi, T., Dolatshad, N., Gorelik, J., Hill, S., Harding, S. E., & Denning, C. (2020). CRISPR/Cas9 mediated generation and analysis of N-terminus polymorphic models of beta2-adrenoreceptor in isogenic hPSC derived cardiomyocytes. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.10.019 Cite
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A Multifunctional LNA Oligo-Based Strategy Blocks Androgen Receptor Expression and Transactivation Activity in Prostate Cancer Cells

The Androgen Receptor (AR) plays a critical role in the development of prostate cancer (PCa) through the activation of androgen-induced cellular proliferation genes. Using tailor-made splice switching Locked Nucleic Acid (LNA) oligos, scientists successfully redirected splicing of the AR pre-mRNA and destabilized the transcripts via the introduction of premature stop codons.
[Molecular Therapy-Nucleic Acids]
Castanotto, D., Zhang, X., Rüger, J., Alluin, J., Sharma, R., Pirrotte, P., Joenson, L., Ioannou, S., Nelson, M. S., Vikeså, J., Hansen, B. R., Koch, T., Jensen, M. A., Rossi, J. J., & Stein, C. A. (2020). A Multifunctional LNA Oligo-Based Strategy Blocks Androgen Receptor Expression And Transactivation Activity In Prostate Cancer Cells. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2020.10.032 Cite
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A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells

Polyphosphates (polyPs) are long chains of inorganic phosphates linked by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. Scientists demonstrated that internally produced polyP can activate diverse signaling pathways in human cells.
[Cell Reports]
Bondy-Chorney, E., Abramchuk, I., Nasser, R., Holinier, C., Denoncourt, A., Baijal, K., McCarthy, L., Khacho, M., Lavallée-Adam, M., & Downey, M. (2020). A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells. Cell Reports, 33(4). https://doi.org/10.1016/j.celrep.2020.108318 Cite
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Parallel Ascending Spinal Pathways for Affective Touch and Pain

Investigators showed two populations of projection neurons that expressed the structurally related G-protein-coupled receptors, TACR1 and GPR83 form parallel ascending circuit modules that cooperate to convey thermal, tactile and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons.
[Nature]
Choi, S., Hachisuka, J., Brett, M. A., Magee, A. R., Omori, Y., Iqbal, N.-A., Zhang, D., DeLisle, M. M., Wolfson, R. L., Bai, L., Santiago, C., Gong, S., Goulding, M., Heintz, N., Koerber, H. R., Ross, S. E., & Ginty, D. D. (2020). Parallel ascending spinal pathways for affective touch and pain. Nature, 1–6. https://doi.org/10.1038/s41586-020-2860-1 Cite
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T Cell-Intrinsic Role for Nod2 in Protection Against Th17-Mediated Uveiti

Scientists report a non-conventional, T cell-intrinsic function for Nod2 in suppression of Th17 immunity and experimental uveitis.
[Nature Communications]
Napier, R. J., Lee, E. J., Davey, M. P., Vance, E. E., Furtado, J. M., Snow, P. E., Samson, K. A., Lashley, S. J., Brown, B. R., Horai, R., Mattapallil, M. J., Xu, B., Callegan, M. C., Uebelhoer, L. S., Lancioni, C. L., Vehe, R. K., Binstadt, B. A., Smith, J. R., Caspi, R. R., & Rosenzweig, H. L. (2020). T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis. Nature Communications, 11(1), 5406. https://doi.org/10.1038/s41467-020-18961-0 Cite
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Proton-Driven Transformable Nanovaccine for Cancer Immunotherapy

The authors present a proton-driven nanotransformer-based vaccine, comprising a polymer–peptide conjugate-based nanotransformer and loaded antigenic peptide.
[Nature Nanotechnology]
Gong, N., Zhang, Y., Teng, X., Wang, Y., Huo, S., Qing, G., Ni, Q., Li, X., Wang, J., Ye, X., Zhang, T., Chen, S., Wang, Y., Yu, J., Wang, P. C., Gan, Y., Zhang, J., Mitchell, M. J., Li, J., & Liang, X.-J. (2020). Proton-driven transformable nanovaccine for cancer immunotherapy. Nature Nanotechnology, 1–12. https://doi.org/10.1038/s41565-020-00782-3 Cite
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A New Neutrophil Subset Promotes CNS Neuron Survival and Axon Regeneration

identify a unique granulocyte subset, with characteristics of an immature neutrophil, that had neuroprotective properties and drove CNS axon regeneration in vivo, in part via secretion of a cocktail of growth factors.
[Nature Immunology]
Sas, A. R., Carbajal, K. S., Jerome, A. D., Menon, R., Yoon, C., Kalinski, A. L., Giger, R. J., & Segal, B. M. (2020). A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nature Immunology, 1–10. https://doi.org/10.1038/s41590-020-00813-0 Cite
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Metabolic Regulation by PPARγ Is Required for IL-33-Mediated Activation of ILC2s in Lung and Adipose Tissue

Scientists found that the metabolic sensor peroxisome proliferator-activated receptor gamma was highly expressed in ILC2s of the lung and adipose tissue and increased responsiveness to IL-33.
[Mucosal Immunology]
Fali, T., Aychek, T., Ferhat, M., Jouzeau, J.-Y., Busslinger, M., Moulin, D., & Eberl, G. (2020). Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue. Mucosal Immunology, 1–9. https://doi.org/10.1038/s41385-020-00351-w Cite
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Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens

Using a model of cutaneous allergen exposure, scientists showed that allergens directly activated TRPV1 + sensory neurons leading to itch and pain behaviors.
[Immunity]
Perner, C., Flayer, C. H., Zhu, X., Aderhold, P. A., Dewan, Z. N. A., Voisin, T., Camire, R. B., Chow, O. A., Chiu, I. M., & Sokol, C. L. (2020). Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.10.001 Cite
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FoxO Maintains a Genuine Muscle Stem-Cell Quiescent State Until Geriatric Age

Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorated the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice.
[Nature Cell Biology]
García-Prat, L., Perdiguero, E., Alonso-Martín, S., Dell’Orso, S., Ravichandran, S., Brooks, S. R., Juan, A. H., Campanario, S., Jiang, K., Hong, X., Ortet, L., Ruiz-Bonilla, V., Flández, M., Moiseeva, V., Rebollo, E., Jardí, M., Sun, H.-W., Musarò, A., Sandri, M., … Muñoz-Cánoves, P. (2020). FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age. Nature Cell Biology, 1–12. https://doi.org/10.1038/s41556-020-00593-7 Cite
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Targeted CRISPR Screening Identifies PRMT5 As Synthetic Lethality Combinatorial Target wth Gemcitabine in Pancreatic Cancer Cellsescent State Until Geriatric Age

Scientists performed an in vivo CRISPR screen in an orthotopic patient-derived xenograft model to identify gene targets whose inhibition creates synergistic tumor growth inhibition with gemcitabine.
[Proceedings of the National Academy of Sciences of the United States of America]
Wei, X., Yang, J., Adair, S. J., Ozturk, H., Kuscu, C., Lee, K. Y., Kane, W. J., O’Hara, P. E., Liu, D., Demirlenk, Y. M., Habieb, A. H., Yilmaz, E., Dutta, A., Bauer, T. W., & Adli, M. (2020). Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2009899117 Cite
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