Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease

Background: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer’s disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation. Methodology/Principal Findings: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter was hypermethylated more in MCI than in advanced AD. The cytosine methylation of total genomic DNA was similar in AD, MCI, and control samples. Consistent with a notion that hypermethylation-mediated silencing of the nucleolar chromatin stabilizes rDNA loci, preventing their senescence-associated loss, genomic rDNA content was elevated in cerebrocortical samples from MCI and AD groups. Conclusions/Significance: In conclusion, rDNA hypermethylation could be a new epigenetic marker of AD. Moreover, silencing of nucleolar chromatin may occur during early stages of AD pathology and play a role in AD-related ribosoma

Atomic spectrometry update: Review of advances in the analysis of metals, chemicals and materials

There has been a large increase in the number of papers published that are relevant to this review over this review period. The growth in popularity of LIBS is rapid, with applications being published for most sample types. This is undoubtedly because of its capability to analyse in situ on a production line (hence saving time and money) and its minimally destructive nature meaning that both forensic and cultural heritage samples may be analysed. It also has a standoff analysis capability meaning that hazardous materials, e.g. explosives or nuclear materials, may be analysed from a safe distance. The use of mathematical algorithms in conjunction with LIBS to enable improved accuracy has proved a popular area of research. This is especially true for ferrous and non-ferrous samples. Similarly, chemometric techniques have been used with LIBS to aid in the sorting of polymers and other materials. An increase in the number of papers in the subject area of alternative fuels was noted. This was at the expense of papers describing methods for the analysis of crude oils. For nanomaterials, previous years have seen a huge number of single particle and field flow fractionation characterisations. Although several such papers are still being published, the focus seems to be switching to applications of the nanoparticles and the mechanistic aspects of how they retain or bind with other analytes. This is the latest review covering the topic of advances in the analysis of metals, chemicals and materials. It follows on from last year's review1-6 and is part of the Atomic Spectrometry Updates series