Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancer

<p>Abstract</p> <p>Background</p> <p>The lipogenic enzyme fatty acid synthase (FAS) is up-regulated in a wide variety of cancers, and is considered a potential metabolic oncogene by virtue of its ability to enhance tumor cell survival. Inhibition of tumor FAS causes both cell cycle arrest and apoptosis, indicating FAS is a promising target for cancer treatment.</p> <p>Results</p> <p>Here, we used gene expression profiling to conduct a global study of the cellular processes affected by siRNA mediated knockdown of FAS in MDA-MB-435 mammary carcinoma cells. The study identified 169 up-regulated genes (≥ 1.5 fold) and 110 down-regulated genes (≤ 0.67 fold) in response to knockdown of FAS. These genes regulate several aspects of tumor function, including metabolism, cell survival/proliferation, DNA replication/transcription, and protein degradation. Quantitative pathway analysis using Gene Set Enrichment Analysis software further revealed that the most pronounced effect of FAS knockdown was down-regulation in pathways that regulate lipid metabolism, glycolysis, the TCA cycle and oxidative phosphorylation. These changes were coupled with up-regulation in genes involved in cell cycle arrest and death receptor mediated apoptotic pathways.</p> <p>Conclusion</p> <p>Together these findings reveal a wide network of pathways that are influenced in response to FAS knockdown and provide new insight into the role of this enzyme in tumor cell survival and proliferation.</p

Antiferromagnetic critical pressure in URu2Si2 under hydrostatic conditions

The onset of antiferromagnetic order in URu2Si2 has been studied via neutron diffraction in a helium pressure medium, which most closely approximates hydrostatic conditions. The antiferromagnetic critical pressure is 0.80 GPa, considerably higher than values previously reported. Complementary electrical resistivity measurements imply that the hidden order-antiferromagnetic bicritical point far exceeds 1.02 GPa. Moreover, the redefined pressure-temperature phase diagram suggests that the superconducting and antiferromagnetic phase boundaries actually meet at a common critical pressure at zero temperature.Comment: 5 pgs, 4 figs; AFM ordered moment revised to 0.5 muB, added and corrected citations and reference

Magnetic form factor of SrFe2_2As2_2

Neutron diffraction measurements have been carried out to investigate the magnetic form factor of the parent SrFe2As2 system of the iron-based superconductors. The general feature is that the form factor is approximately isotropic in wave vector, indicating that multiple d-orbitals of the iron atoms are occupied as expected based on band theory. Inversion of the diffraction data suggests that there is some elongation of the spin density toward the As atoms. We have also extended the diffraction measurements to investigate a possible jump in the c-axis lattice parameter at the structural phase transition, but find no detectable change within the experimental uncertainties

Spin gap and magnetic resonance in superconducting BaFe1.9_{1.9}Ni%_{0.1}As2_{2}

We use neutron spectroscopy to determine the nature of the magnetic excitations in superconducting BaFe$_{1.9}$Ni$_{0.1}$As$_{2}$ ($T_{c}=20$ K). Above $T_{c}$ the excitations are gapless and centered at the commensurate antiferromagnetic wave vector of the parent compound, while the intensity exhibits a sinusoidal modulation along the c-axis. As the superconducting state is entered a spin gap gradually opens, whose magnitude tracks the $T$-dependence of the superconducting gap observed by angle resolved photoemission. Both the spin gap and magnetic resonance energies are temperature \textit{and} wave vector dependent, but their ratio is the same within uncertainties. These results suggest that the spin resonance is a singlet-triplet excitation related to electron pairing and superconductivity.Comment: 4 pages, 4 figure