28 research outputs found
Double helical conformation and extreme rigidity in a rodlike polyelectrolyte
The ubiquitous biomacromolecule DNA has an axial rigidity persistence length
of ~50 nm, driven by its elegant double helical structure. While double and
multiple helix structures appear widely in nature, only rarely are these found
in synthetic non-chiral macromolecules. Here we describe a double helical
conformation in the densely charged aromatic polyamide
poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) or PBDT. This double helix
macromolecule represents one of the most rigid simple molecular structures
known, exhibiting an extremely high axial persistence length (~1 micrometer).
We present X-ray diffraction, NMR spectroscopy, and molecular dynamics (MD)
simulations that reveal and confirm the double helical conformation. The
discovery of this extreme rigidity in combination with high charge density
gives insight into the self-assembly of molecular ionic composites with high
mechanical modulus (~1 GPa) yet with liquid-like ion motions inside, and
provides fodder for formation of new 1D-reinforced composites.Comment: Accepted for publication by Nature Communication
Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels
Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis