A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex

We quantified genome-wide patterns of lysine H3K27 acetylation (H3K27ac) in entorhinal cortex samples from Alzheimer’s disease (AD) cases and matched controls using chromatin immunoprecipitation and highly parallel sequencing. We observed widespread acetylomic variation associated with AD neuropathology, identifying 4,162 differential peaks (false discovery rate < 0.05) between AD cases and controls. Differentially acetylated peaks were enriched in disease-related biological pathways and included regions annotated to genes involved in the progression of amyloid-β and tau pathology (for example, APP, PSEN1, PSEN2, and MAPT), as well as regions containing variants associated with sporadic late-onset AD. Partitioned heritability analysis highlighted a highly significant enrichment of AD risk variants in entorhinal cortex H3K27ac peak regions. AD-associated variable H3K27ac was associated with transcriptional variation at proximal genes including CR1, GPR22, KMO, PIM3, PSEN1, and RGCC. In addition to identifying molecular pathways associated with AD neuropathology, we present a framework for genome-wide studies of histone modifications in complex disease

Optical spectroscopy of La3Ga5SiO14:Cr3+ crystals

The optical properties of trivalent chromium ions in La3Ga5SiO14 crystals have been investigated by means of absorption, emission, excitation, and lifetime measurements. The particular intermediate value of the octahedral crystal field Dq/B∼2.5 causes the overlapping of the 4T2 with the 2E and 2T1 levels. This overlap is the origin of Fano resonances in the absorption spectrum and of the simultaneous presence of broadband and narrow-line emissions. Polarized measurements have allowed the determinations of second-order effects such as the tetragonal or orthorhomic distortion of the octahedron of oxygen ions around the chromium ion. Moreover the temperature shift of the peak and the nonexponential decay of the broad emission band are indications of the disorder present in the crystal lattice. All these results produce a fairly complete picture of the energy levels of Cr3+ ions in a typical crystal of the Ca-gallogermanate family. © 1994 The American Physical Society