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Browsing by Author "Dixon, Richard A."

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    Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice
    Wang, Jun; Hodes, Georgia E.; Zhang, Hongxing; Zhang, Song; Zhao, Wei; Golden, Sam A.; Bi, Weina; Menard, Caroline; Kana, Veronika; Leboeuf, Marylene; Xie, Marc; Bregman, Dana; Pfau, Madeline L.; Flanigan, Meghan E.; Estebam-Fernández, Adelaida; Yemul, Shrishailam; Sharma, Ali; Ho, Lap; Dixon, Richard A.; Merad, Miriam; Han, Ming-Hu; Russo, Scott J.; Pasinetti, Giulio M. (Nature, 2018)
    Major depressive disorder is associated with abnormalities in the brain and the immune system. Chronic stress in animals showed that epigenetic and inflammatory mechanisms play important roles in mediating resilience and susceptibility to depression. Here, through a highthroughput screening, we identify two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3′-O-glucoside (Mal-gluc) that are effective in promoting resilience against stress by modulating brain synaptic plasticity and peripheral inflammation. DHCA/Mal-gluc also significantly reduces depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of hematopoietic progenitor cells from stresssusceptible mice. DHCA reduces pro-inflammatory interleukin 6 (IL-6) generations by inhibiting DNA methylation at the CpG-rich IL-6 sequences introns 1 and 3, while Mal-gluc modulates synaptic plasticity by increasing histone acetylation of the regulatory sequences of the Rac1 gene. Peripheral inflammation and synaptic maladaptation are in line with newly hypothesized clinical intervention targets for depression that are not addressed by currently available antidepressants.
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    An “ideal lignin” facilitates full biomass utilization
    Li, Yanding; Shuai, Li; Kim, Hoon; Motagamwala, Ali Hussain; Mobley, Justin K.; Yue, Fengxia; Tobimatsu, Yuki; Havkin-Frenkel, Daphna; Chen, Fang; Dixon, Richard A.; Luterbacher, Jeremy S.; Dumesic, James A.; Ralph, John (AAAS, 2018-09-28)
    Lignin, a major component of lignocellulosic biomass, is crucial to plant growth and development but is a major impediment to efficient biomass utilization in various processes. Valorizing lignin is increasingly realized as being essential. However, rapid condensation of lignin during acidic extraction leads to the formation of recalcitrant condensed units that, along with similar units and structural heterogeneity in native lignin, drastically limits product yield and selectivity. Catechyl lignin (C-lignin), which is essentially a benzodioxane homopolymer without condensed units, might represent an ideal lignin for valorization, as it circumvents these issues. We discovered that C-lignin is highly acid-resistant. Hydrogenolysis of C-lignin resulted in the cleavage of all benzodioxane structures to produce catechyl-type monomers in near-quantitative yield with a selectivity of 90% to a single monomer.