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PNAS Papers on CRISPR-Edited Cancer Models, Multiple Sclerosis Neuroinflammation, Parasitic Wasps

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted this week.

For a paper slated to appear in PNAS this week, a Memorial Sloan Kettering Cancer Center-led team shares a multiplex gene editing-based approach aimed at developing cancer models and performing cell-of-origin analyses. Using freshly isolated prostate epithelial cells or organoid cultures, the researchers successfully introduced multi-gene alterations or chromosomal rearrangements associated with prostate cancer, which subsequently produced cancer in mouse models. "[W]e demonstrate highly efficient (50 to 90 percent) editing of primary prostate epithelial organoid cultures … through transient electroporation of Cas9-[single guide RNA] ribonucleoprotein (cRNP) complexes," they report, adding that "this approach can be used to address cancer cell-of-origin questions by multigenic editing selectively in luminal versus basal epithelial cells."

Researchers at the Sun Yat-sen University explore a role for the IFP35 family of extracellular proteins in multiple sclerosis (MS). Based on available transcriptome data for post-mortem brain samples from individuals with or without MS, the team saw a jump in the expression of the IFP35 family genes IFP35 and NMI in gray matter from those with the neuroinflammatory condition. A series of follow-up experiments in mouse models, including gene knockout experiments, suggested IFP35 and NMI may boost neuroinflammation by activating microglia and dendritic cells and prompting T cell differentiation. On the other hand, disease-related central nervous system demyelination and related encephalomyelitis symptoms dipped in mice missing IFP35 or NMI or in animals treated with IFP35-targeting neutralizing antibodies. "[O]ur study identified an additional mechanism for the pathogenesis of MS, one of the most severe autoimmune neurodegenerative diseases that affects millions of people worldwide," the authors report, "and reveals potential diagnostic and therapeutic targets suitable to combat this disease."

A team from China, Sweden, and Panama retraces the transition from mutualism to parasitism in Eupristina wasps and their Ficus microcarpa fig hosts in China. Using phylogenetic analyses, morphological and behavioral clues, and other approaches, the investigators compared a fig-pollinating wasp species called E. verticillata with a non-pollinating "cheater" species that appears to make its host plants less reproductively successful. Their results suggest the Eupristina wasps belong to sister taxa, with the parasitic wasps losing mutualistic specializations over time and becoming able to out-compete the pollinating E. verticillata wasps on the same plant. "By the strictest definition, the non-pollinating species represents a 'cheater' that has descended from a beneficial pollinating mutualist," the authors argue, noting that "the lack of sanctions in the local hosts promotes the loss of specialized morphologies and behaviors crucial for pollination and, thereby, the evolution of cheating."

The Scan

Booster for At-Risk

The New York Times reports that the US Food and Drug Administration has authorized a third dose of the Pfizer-BioNTech SARS-CoV-2 vaccine for people over 65 or at increased risk.

Preprints OK to Mention Again

Nature News reports the Australian Research Council has changed its new policy and now allows preprints to be cited in grant applications.

Hundreds of Millions More to Share

The US plans to purchase and donate 500 million additional SARS-CoV-2 vaccine doses, according to the Washington Post.

Nature Papers Examine Molecular Program Differences Influencing Neural Cells, Population History of Polynesia

In Nature this week: changes in molecular program during embryonic development leads to different neural cell types, and more.