Mass Spectrometry-Based Methodology for Identification of Native Histone Variant Modifications From Mammalian Tissues and Solid Tumors.

Histone posttranslational modifications (PTMs) are key epigenetic marks involved in gene silencing or activation. Histone modifications impact chromatin organization and transcriptional processes through the changes in charge density between histones and DNA. They also serve as recognition and binding sites for specific binding proteins. Histone tails and globular cores contain many basic amino acid residues, which are subject to various dynamic modifications, making the modification repertoire extremely diverse. Consequently, determination of histone PTM identity and quantity has been a challenging task. In recent years, mass spectrometry-based methods have proven useful in histone PTM characterization. This chapter provides a brief overview of these methods and describes the approach to analyze the PTMs of the histone variant CENP-A, essential for the cell cycle progression, when present in minute amounts from tumor and mammalian tissues. Because this method does not rely on antibody-based immunopurification, we anticipate that these tools could be readily adaptable to the investigation to other histone variants in a range of mammalian tissues and solid tumors.

Atrial fibrillation and mild cognitive impairment: what correlation?

AIM: Atrial fibrillation (AF), in addition to macroembolic complications, may also produce multiple cerebral ischemic areas due to microembolic phenomena and transient hypoperfusion, eventually leading to a progressive cognitive impairment and even to acclaimed vascular dementia. The aim of this study was to evaluate the prevalence of cognitive impairment in patients with AF. The reported results concern data obtained at the moment of recruitment. METHODS: The authors studied 42 patients with a history of non valvular AF (paroxysmal, persistent, recurrent or permanent) and 40 homogenous controls in sinus rhythm without previous AF. All subjects underwent anamnesis, physical examination, biochemical and instrumental tests. To investigate the cognitive status, subjects underwent the following neuropsychological rating scales: Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR),Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL) Global Deterioration Scale (GLDS), Geriatric Depression Scale (GDS) and Hachinski Ischemic Score (HIS). RESULTS: AF Patients had worse scores versus controls at GLDS (P=0.0001), HIS (P=0.001), CDR (P=0.07) and GDS (P=0.07); no significant differences were found for MMSE even after correction for age and education. AF patients treated with warfarin showed better scores at CDR (P=0.04),GLDS (P=0.03) and GDS (P=0.007), compared to those in aspirin-treatment. Corrected MMSE scores did not differ. CONCLUSIONS: The authors identified a slight cognitive impairment in the AF group; patients with paroxysmal, persistent or recurrent AF showed worse cognitive performances than permanent ones, suggesting a possible microembolic pathogenesis. Anticoagulation therapy could play a protective role, however more evidence is needed.