Structural characterisation of neutrophil glycans by ultra sensitive mass spectrometric glycomics methodology

Neutrophils are the most abundant white blood cells in humans and play a vital role in several aspects of the immune response. Numerous reports have implicated neutrophil glycosylation as an important factor in mediating these interactions. We report here the application of high sensitivity glycomics methodologies, including matrix assisted laser desorption ionisation (MALDI-TOF) and MALDI-TOF/TOF analyses, to the structural analysis of N- and O-linked carbohydrates released from two samples of neutrophils, prepared by two separate and geographically remote laboratories. The data produced demonstrates that the cells display a diverse range of sialylated and fucosylated complex glycans, with a high level of similarity between the two preparations

A review of diagnostic and functional imaging in headache

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache — the posterior hypothalamic grey matter — and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele