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PNAS Papers Explore Neurogenesis Exosomes, More

Researchers at the Scripps Research Institute, the University of California, San Diego, and elsewhere outline a potential role for exosomes in neuronal circuit development. The team tracked the effects of isolated exosomes, demonstrating that exosomes released by human induced pluripotent stem cells (hiPSC) could prompt neural cell cultures to proliferate and differentiate, for example, while rodent exosomes appeared to boost neuronal proliferation in the dentate gyrus region of the mouse brain. The authors subsequently used quantitative mass spectrometry to profile proteomic patterns in exosomes from cells with or without the Rett syndrome-related gene MECP2, which also appeared to have a role in neuronal development. "Treating MECP-knockdown human primary neural cultures with control exosomes rescues deficits in neuronal proliferation, differentiation, synaptogenesis, and synchronized firing," they report, "whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capability."  

A team from the UK and the US describes a Mycobacterium tuberculosis enzyme that appears to contribute to pathways involved in resistance to the host macrophage-produced antimicrobial metabolite itaconate and breakdown of the amino acid L-leucine. Using in vitro enzymatic assays, phylogenetics, mouse infection models, and other approaches, the researchers characterized an essential enzyme called Rv2498c, demonstrating that it acts as a bifunctional oxoacid lyase enzyme that affects tuberculosis infection in a mouse model. "Importantly, deletion of rv2498c from the [M. tuberculosis] genome led to a defect during murine infection," the authors report, "indicating that one or more of its enzymatic functions are important during infection." 

German researchers report on results from a targeted mutagenesis study aimed at understanding insect receptor and plant volatile compound interactions between the hawkmoth, Manduca sexta, and the Sacred datura or Western jimsonweed (Datura wrightii), a perennial plant it pollinates and feeds on in southwestern North America. After systematically mutating the hawkmoth odorant co-receptor gene called Orco with help from the CHOPCHOP v2 genome editing web tool and CRISPR-Cas9-based targeted mutagenesis, the team looked at flight, foraging, and other hawkmoth responses to its host plant's pheromones. Based on results from these and other experiments, the authors suggest that odorant receptor-mediated insect olfaction "is essential for foraging and pollination behaviors, but plant-seeking and oviposition behaviors are sustained through additional [odorant receptor]-independent sensory cues."