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Cell Reports Methods
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Sep 19, 2022

Volume 2Issue 9
Open Access
On the cover: In this issue, two groups present tools to investigate the pathophysiology of Alzheimer's disease (AD)-related tau proteins in different model systems. Shimada et al. develop a method to make forebrain organoids from feeder-free human iPSCs, which they find can recapitulate early stages of AD and can be used to study pronounced cellular tauopathies. In parallel, Levy et al. develop a split-luciferase-based sensor to quantify and elucidate mechanisms of tau multimerization in adult, live Drosophila brains. The cover image highlighting these papers shows tau proteins (orange) being phosphorylated (in yellow) by kinases (blue purple). Cover image courtesy of Getty Images/Juan Gaertner/sciencephotolibrary....
On the cover: In this issue, two groups present tools to investigate the pathophysiology of Alzheimer's disease (AD)-related tau proteins in different model systems. Shimada et al. develop a method to make forebrain organoids from feeder-free human iPSCs, which they find can recapitulate early stages of AD and can be used to study pronounced cellular tauopathies. In parallel, Levy et al. develop a split-luciferase-based sensor to quantify and elucidate mechanisms of tau multimerization in adult, live Drosophila brains. The cover image highlighting these papers shows tau proteins (orange) being phosphorylated (in yellow) by kinases (blue purple). Cover image courtesy of Getty Images/Juan Gaertner/sciencephotolibrary.

Q&A

  • Meet the author: Martin Riccomagno

    In this Q&A, Cell Press Community Review Product Manager Matt Pavlovich talks to Martin Riccomagno about his paper “ A genetic tool for the longitudinal study of a subset of post-inflammatory reactive astrocytes ” and his experience with Cell Press Community Review.

Spotlight

Reports

Articles

  • Laser stimulation of the skin for quantitative study of decision-making and motivation

    • Julia Pai,
    • Takaya Ogasawara,
    • Ethan S. Bromberg-Martin,
    • Kei Ogasawara,
    • Robert W. Gereau,
    • Ilya E. Monosov
    Pai and Ogasawara et al. demonstrate that skin laser stimulation is a highly useful aversive stimulus for assessing how noxious experiences impact decisions. They then use it to study neural processing of appetitive and aversive information in the orbitofrontal cortex, an area crucial for value based decision making.
  • Deep-learning analysis of micropattern-based organoids enables high-throughput drug screening of Huntington’s disease models

    • Jakob J. Metzger,
    • Carlota Pereda,
    • Arjun Adhikari,
    • Tomomi Haremaki,
    • Szilvia Galgoczi,
    • Eric D. Siggia,
    • Ali H. Brivanlou,
    • Fred Etoc
    Metzger et al. describe a drug-screening platform based on micropatterned neural organoids. Deep-learning analysis can separate wild-type and disease organoids with high accuracy and can also quantify adverse effects of drugs. Bromodomain inhibitors are identified to rescue developmental phenotypes of Huntington’s disease in organoids.
  • Robust genome editing via modRNA-based Cas9 or base editor in human pluripotent stem cells

    • Tahir Haideri,
    • Alessandro Howells,
    • Yuqian Jiang,
    • Jian Yang,
    • Xiaoping Bao,
    • Xiaojun Lance Lian
    Haideri et al. develop non-integrating modRNA-based CRISPR systems for achieving robust and efficient gene knockouts in hPSCs. They further establish an ABE8e base editor modRNA protocol to disrupt the splice donor site. These non-integrating approaches can preserve genome integrity and significantly enhance knockout efficiency.
  • Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

    • Ivan Doykov,
    • Tomas Baldwin,
    • Justyna Spiewak,
    • Kimberly C. Gilmour,
    • Joseph M. Gibbons,
    • Corinna Pade,
    • Catherine J. Reynolds,
    • Áine McKnight,
    • Mahdad Noursadeghi,
    • Mala K. Maini,
    • Charlotte Manisty,
    • Thomas Treibel,
    • Gabriella Captur,
    • Marianna Fontana,
    • Rosemary J. Boyton,
    • Daniel M. Altmann,
    • Tim Brooks,
    • Amanda Semper,
    • UK COVIDsortium Investigators,
    • James C. Moon,
    • Kevin Mills,
    • Wendy E. Heywood
    Doykov et al. present an assay that reveals changes in immunoglobulin classes, subtypes, and complement in response to vaccination, infection, and variants of concern. The assay can provide insight into an individual’s immune response and aid vaccine design and delivery. It can also be applied to other antigens and diseases.
  • A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development

    • Dabbu Kumar Jaijyan,
    • Kavitha Govindasamy,
    • Moses Lee,
    • Hua Zhu
    Jaijyan et al. describe an efficient method to generate chemically live-attenuated, replication-defective DNA viruses for vaccine development. CM alkylates the genome of DNA viruses. Upon immunization, CM-treated viruses induce strong immune activation and provide protection against live virus challenges. The method developed here can be applied to all DNA viruses.
  • Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

    • Samantha L. Wilson,
    • Shu Yi Shen,
    • Lauren Harmon,
    • Justin M. Burgener,
    • Tim Triche Jr.,
    • Scott V. Bratman,
    • Daniel D. De Carvalho,
    • Michael M. Hoffman
    Wilson et al. developed synthetic DNA controls for normalizing cell-free methylation DNA immunoprecipitation sequencing (cfMeDIP-seq) assays used in liquid biopsies. These spike-in controls allow absolute quantification of methylated cell-free DNA in picomoles rather than arbitrary read counts. They also adjust for batch effects and reduce systematic noise related to technical biases.

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