Genome Researchers Question Security Provisions in New US Senate Bill

Buried in a bill approved by the US Senate to help the United States compete with China is language that is drawing fire from human genome researchers. It would require the NIH to develop new security protocols aimed at preventing the misuse of US-funded genomic data by China and other nations.
[Science]
Editorial
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The Costimulatory Activity of Tim-3 Requires Akt and MAPK Signaling and Its Recruitment to the Immune Synapse

Investigators examined the upstream signaling pathways that control Tim-3–mediated increases in phosphorylated S6 in T cells. They defined the localization of Tim-3 relative to the T cell immune synapse and its effects on downstream signaling.
[Science Signaling]
Kataoka, S., Manandhar, P., Lee, J., Workman, C. J., Banerjee, H., Szymczak-Workman, A. L., Kvorjak, M., Lohmueller, J., & Kane, L. P. (2021). The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse. Science Signaling, 14(687). https://doi.org/10.1126/scisignal.aba0717 Cite
Abstract
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Integrin β7 Inhibits Colorectal Cancer Pathogenesis via Maintaining Anti-Tumor Immunity

Researchers found that the number of β7+ cells decreased significantly in tumor tissue compared with adjacent normal tissue. β7 expression decreased in tumor-derived compared to normal tissue-derived CD8+ T cells.
[Cancer Immunology Research]
Zhang, Y., Xie, R., Zhang, H., Zheng, Y., Lin, C., Yang, L., Huang, M., Li, M., Song, F., Lu, L., Yang, M., Liu, Y., Wei, Q., Li, J., & Chen, J. (2021). Integrin β7 inhibits colorectal cancer pathogenesis via maintaining anti-tumor immunity. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0879 Cite
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Inhibition of the DNA Damage Response Phosphatase PPM1D Reprograms Neutrophils to Enhance Anti-Tumor Immune Responses

Scientists showed that mice with genetic knockout of Ppm1d or with conditional knockout of Ppm1d in the hematopoietic system, in myeloid cells, or in neutrophils all displayed significantly reduced growth of syngeneic melanoma or lung carcinoma tumors.
[Nature Communications]
Uyanik, B., Goloudina, A. R., Akbarali, A., Grigorash, B. B., Petukhov, A. V., Singhal, S., Eruslanov, E., Chaloyard, J., Lagorgette, L., Hadi, T., Baidyuk, E. V., Sakai, H., Tessarollo, L., Ryffel, B., Mazur, S. J., Lirussi, F., Garrido, C., Appella, E., & Demidov, O. N. (2021). Inhibition of the DNA damage response phosphatase PPM1D reprograms neutrophils to enhance anti-tumor immune responses. Nature Communications, 12(1), 3622. https://doi.org/10.1038/s41467-021-23330-6 Cite
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Sorrento Announces Clinical Research Agreement With Mayo Clinic and FDA Clearance for the First Phase Ib Pilot Study Using Sofusa Lymphatic Drug Delivery Technology to Deliver Ipilimumab in Patients With Melanoma

Sorrento Therapeutics, Inc. announced a research collaboration agreement with Mayo Clinic to conduct human clinical proof of concept studies using the Sofusa Lymphatic Drug Delivery System technology across multiple products and indications.
[Sorrento Therapeutics, Inc.]
Press Release
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Omeros Announces Preliminary Results from Phase I Clinical Trial of OMS906

Omeros Corporation announced preliminary results from the Phase I clinical trial of its MASP-3 inhibitor OMS906. The ongoing trial is designed as a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous and subcutaneous administration of OMS906 to healthy adult volunteers.
[Omeros Corporation]
Press Release
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Neutrophil Extracellular Traps Impair Intestinal Barrier Functions in Sepsis by Regulating TLR9-Mediated Endoplasmic Reticulum Stress Pathway

Neutrophil extracellular traps treatment induced intestinal epithelial monolayer barrier disruption and endoplasmic reticulum (ER) stress activation in a dose-dependent manner in vitro, and ER stress inhibition markedly attenuated intestinal apoptosis and tight junction injury.
[Cell Death & Disease]
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Alternative Activation of Macrophages by Prostacyclin Synthase Ameliorates Alcohol Induced Liver Injury

Investigators demonstrated that PTGIS was downregulated in alchoholic liver disease and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed prostacyclin synthase overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice.
[Laboratory Investigation]
Pan, X., Wang, L., You, H., Cheng, M., Yang, Y., Huang, C., & Li, J. (2021). Alternative activation of macrophages by prostacyclin synthase ameliorates alcohol induced liver injury. Laboratory Investigation, 1–15. https://doi.org/10.1038/s41374-021-00531-7 Cite
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Lentiviral Vector Induces High-Quality Memory T Cells via Dendritic Cells Transduction

With a mycobacterial immunogen, scientists observed distinct functional signatures and memory phenotype in lentiviral vector- or Adenovirus type 5-immunized mice, despite comparable antigen-specific CD8+ T cell magnitudes.
[Communications Biology]
Ku, M. W., Authié, P., Nevo, F., Souque, P., Bourgine, M., Romano, M., Charneau, P., & Majlessi, L. (2021). Lentiviral vector induces high-quality memory T cells via dendritic cells transduction. Communications Biology, 4(1), 1–16. https://doi.org/10.1038/s42003-021-02251-6 Cite
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Targeting Monoamine Oxidase A-Regulated Tumor-Associated Macrophage Polarization for Cancer Immunotherapy

Scientists observed monoamine oxidase A (MAO-A) induction in mouse and human tumor-associated macrophages (tAMs). MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity.
[Nature Communications]
Wang, Y.-C., Wang, X., Yu, J., Ma, F., Li, Z., Zhou, Y., Zeng, S., Ma, X., Li, Y.-R., Neal, A., Huang, J., To, A., Clarke, N., Memarzadeh, S., Pellegrini, M., & Yang, L. (2021). Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy. Nature Communications, 12(1), 3530. https://doi.org/10.1038/s41467-021-23164-2 Cite
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Serum Free Culture for the Expansion and Study of Type 2 Innate Lymphoid Cells

Researchers demonstrated for the first time a methodology allowing mouse type 2 innate lymphoid cells to be cultured, and their numbers expanded in serum-free medium supplemented with Interleukins IL-33, IL-2, IL-7 and TSLP.
[Scientific Reports]
de Lucía Finkel, P., Sherwood, C., Saranchova, I., Xia, W., Munro, L., Pfeifer, C. G., Piret, J. M., & Jefferies, W. A. (2021). Serum free culture for the expansion and study of type 2 innate lymphoid cells. Scientific Reports, 11(1), 12233. https://doi.org/10.1038/s41598-021-91500-z Cite
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