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Berkeley, CA, United States

Totir M.,University of California at Berkeley | Echols N.,University of California at Berkeley | Echols N.,Lawrence Berkeley National Laboratory | Nanao M.,European Molecular Biology Laboratory | And 11 more authors.
PLoS ONE | Year: 2012

Structural biology and structural genomics projects routinely rely on recombinantly expressed proteins, but many proteins and complexes are difficult to obtain by this approach. We investigated native source proteins for high-throughput protein crystallography applications. The Escherichia coli proteome was fractionated, purified, crystallized, and structurally characterized. Macro-scale fermentation and fractionation were used to subdivide the soluble proteome into 408 unique fractions of which 295 fractions yielded crystals in microfluidic crystallization chips. Of the 295 crystals, 152 were selected for optimization, diffraction screening, and data collection. Twenty-three structures were determined, four of which were novel. This study demonstrates the utility of native source proteins for high-throughput crystallography. © 2012 Totir et al.

Elabd C.,QB3 Institute | Elabd C.,University of California at Berkeley | Cousin W.,QB3 Institute | Cousin W.,University of California at Berkeley | And 14 more authors.
Nature Communications | Year: 2014

The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation; however, systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin - a hormone best known for its role in lactation, parturition and social behaviours - is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signalling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation through activation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle but instead leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle ageing. © 2014 Macmillan Publishers Limited. All rights reserved.

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