Gobeil, Sophie M-C Janowska, Katarzyna McDowell, Shana Mansouri, Katayoun Parks, Robert Manne, Kartik Stalls, Victoria Kopp, Megan F Henderson, Rory Edwards, Robert J
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Published in
Cell reports
The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S c...
Pensalfini, Anna Kim, Seonil Subbanna, Shivakumar Bleiwas, Cynthia Goulbourne, Chris N Stavrides, Philip H Jiang, Ying Lee, Ju-Hyun Darji, Sandipkumar Pawlik, Monika
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Published in
Cell reports
Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF i...
Lin, Lin Holmes, Benjamin Shen, Max W Kammeron, Darnell Geijsen, Niels Gifford, David K Sherwood, Richard I
Published in
Cell reports
Gene expression is controlled by the collective binding of transcription factors to cis-regulatory regions. Deciphering gene-centered regulatory networks is vital to understanding and controlling gene misexpression in human disease; however, systematic approaches to uncovering regulatory networks have been lacking. Here we present high-throughput i...
Christian, Diana L Wu, Dennis Y Martin, Jenna R Moore, J Russell Liu, Yiran R Clemens, Adam W Nettles, Sabin A Kirkland, Nicole M Papouin, Thomas Hill, Cheryl A
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Published in
Cell reports
Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Here, we define the effects of DNMT3A mutations associated with neurodevelopmental disease. We show that diverse mutations affect different aspects of protein activity but lead to sha...
Rawi, Reda Rutten, Lucy Lai, Yen-Ting Olia, Adam S Blokland, Sven Juraszek, Jarek Shen, Chen-Hsiang Tsybovsky, Yaroslav Verardi, Raffaello Yang, Yongping
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Published in
Cell reports
Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit neutralizing responses against HIV-1 strains closely related to the immunizing trimer. However, to date such stabilization has succeeded with only a limited number of HIV-1 strains. To address this issue, here we develop ADROITrimer, an automated procedure inv...
Opejin, Adeleye Surnov, Alexey Misulovin, Ziva Pherson, Michelle Gross, Cindy Iberg, Courtney A Fallahee, Ian Bourque, Jessica Dorsett, Dale Hawiger, Daniel
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Published in
Cell reports
Various processes induce and maintain immune tolerance, but effector T cells still arise under minimal perturbations of homeostasis through unclear mechanisms. We report that, contrary to the model postulating primarily tolerogenic mechanisms initiated under homeostatic conditions, effector programming is an integral part of T cell fate determinati...
Scheepers, Cathrine Bekker, Valerie Anthony, Colin Richardson, Simone I Oosthuysen, Brent Moyo, Thandeka Kgagudi, Prudence Kitchin, Dale Nonyane, Molati York, Talita
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Published in
Cell reports
Neutralizing antibodies (nAbs) to highly variable viral pathogens show remarkable diversification during infection, resulting in an "arms race" between virus and host. Studies of nAb lineages have shown how somatic hypermutation (SHM) in immunoglobulin (Ig)-variable regions enables maturing antibodies to neutralize emerging viral escape variants. H...
Roome, R Brian Bourojeni, Farin B Mona, Bishakha Rastegar-Pouyani, Shima Blain, Raphael Dumouchel, Annie Salesse, Charleen Thompson, W Scott Brookbank, Megan Gitton, Yorick
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Published in
Cell reports
Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Pair...
Jongkamonwiwat, Nopporn Ramirez, Miguel A Edassery, Seby Wong, Ann C Y Yu, Jintao Abbott, Tirzah Pak, Kwang Ryan, Allen F Savas, Jeffrey N
Published in
Cell reports
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundr...
Amcheslavsky, Alla Lindblad, Jillian L Bergmann, Andreas
Published in
Cell reports
We reveal surprising similarities between homeostatic cell turnover in adult Drosophila midguts and "undead" apoptosis-induced compensatory proliferation (AiP) in imaginal discs. During undead AiP, immortalized cells signal for AiP, allowing its analysis. Critical for undead AiP is the Myo1D-dependent localization of the initiator caspase Dronc to ...