Impaired Inhibitory GABAergic Synaptic Transmission and Transcription Studied in Single Neurons by Patch-Seq in Huntington’s Disease

we demonstrated that Patch-seq technology can be applied both to better understand molecular mechanisms underlying a complex neurological disease at the single-cell level and to provide a platform for screening for therapeutics for the disease.
[Proceedings of the National Academy of Sciences of the United States of America]
Paraskevopoulou, F., Parvizi, P., Senger, G., Tuncbag, N., Rosenmund, C., & Yildirim, F. (2021). Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington’s disease. Proceedings of the National Academy of Sciences, 118(19). https://doi.org/10.1073/pnas.2020293118 Cite
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Neuromodulator Release in Neurons Requires Two Functionally Redundant Calcium Sensors

we show that in mouse hippocampal neurons, dense core vesicles fusion is strongly and equally reduced in synaptotagmin-1 (Syt1)- or Syt7-deficient neurons, but combined Syt1/Syt7 deficiency did not reduce fusion further.
[Proceedings of the National Academy of Sciences of the United States of America]
Westen, R. van, Poppinga, J., Arazola, R. D., Toonen, R. F., & Verhage, M. (2021). Neuromodulator release in neurons requires two functionally redundant calcium sensors. Proceedings of the National Academy of Sciences, 118(18). https://doi.org/10.1073/pnas.2012137118 Cite
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Optogenetic Pacing of Medial Septum Parvalbumin-Positive Cells Disrupts Temporal but Not Spatial Firing in Grid Cells

we show that optogenetic activation of parvalbumin-positive cells in the medial septal area enabled selective pacing of local field potential oscillations in medial entorhinal cortex.
[Science Advances]
Lepperød, M. E., Christensen, A. C., Lensjø, K. K., Buccino, A. P., Yu, J., Fyhn, M., & Hafting, T. (2021). Optogenetic pacing of medial septum parvalbumin-positive cells disrupts temporal but not spatial firing in grid cells. Science Advances, 7(19), eabd5684. https://doi.org/10.1126/sciadv.abd5684 Cite
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SynNotch-CAR T Cells Overcome Challenges of Specificity, Heterogeneity, and Persistence in Treating Glioblastoma

developed synthetic notch (synNotch)–CAR T cells targeting solid tumor antigens and used them to treat mouse models of mesothelioma, ovarian cancer, and glioblastoma.
[Science Translational Medicine]
Choe, J. H., Watchmaker, P. B., Simic, M. S., Gilbert, R. D., Li, A. W., Krasnow, N. A., Downey, K. M., Yu, W., Carrera, D. A., Celli, A., Cho, J., Briones, J. D., Duecker, J. M., Goretsky, Y. E., Dannenfelser, R., Cardarelli, L., Troyanskaya, O., Sidhu, S. S., Roybal, K. T., … Lim, W. A. (2021). SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Science Translational Medicine, 13(591). https://doi.org/10.1126/scitranslmed.abe7378 Cite
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Novel Dopamine Receptor 3 Antagonists Inhibit the Growth of Primary and Temozolomide Resistant Glioblastoma Cells

To improve treatment of glioblastoma, including those resistant to temozolomide , we explored the potential of targeting dopamine receptor signaling.
[PLoS One]
Williford, S. E., Libby, C. J., Ayokanmbi, A., Otamias, A., Gordillo, J. J., Gordon, E. R., Cooper, S. J., Redmann, M., Li, Y., Griguer, C., Zhang, J., Napierala, M., Ananthan, S., & Hjelmeland, A. B. (2021). Novel dopamine receptor 3 antagonists inhibit the growth of primary and temozolomide resistant glioblastoma cells. PLOS ONE, 16(5), e0250649. https://doi.org/10.1371/journal.pone.0250649 Cite
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STAG2 Mutations Alter CTCF-Anchored Loop Extrusion, Reduce Cis-Regulatory Interactions and EWSR1-FLI1 Activity in Ewing Sarcoma

Using isogenic Ewing cells, researchers showed STAG2 loss of function profoundly changed the transcriptome but it did not significantly impact EWSR1-FLI1, CTCF/cohesin, or acetylated H3K27 DNA binding patterns.
[Cancer Cell]
Surdez, D., Zaidi, S., Grossetête, S., Laud-Duval, K., Ferre, A. S., Mous, L., Vourc’h, T., Tirode, F., Pierron, G., Raynal, V., Baulande, S., Brunet, E., Hill, V., & Delattre, O. (2021). STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2021.04.001 Cite
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Researchers report that CRISPR–RfxCas13d could effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction sites featured in RNA circles.
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Scientists conducted a bioinformatics analysis of COVID-19 comorbidity-associated gene sets, identifying genes and pathways shared among the comorbidities, and evaluated current knowledge about these genes and pathways as related to current information about SARS-CoV-2 infection.
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