Joint Metabonomic and Instrumental Analysis for the Classification of Migraine Patients with 677-MTHFR Mutations

Migraine is a neurological disorder that correlates with an increased risk of cerebrovascular lesions. Genetic mutations of the MTHFR gene are correlated to migraine and to the increased risk of artery pathologies. Also, migraine patients show altered hematochemical parameters, linked to an impaired platelet aggregation mechanism. Hence, the vascular assessment of migraineurs is of primary importance

Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis

Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single-cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease

Homocysteine and peripheral arterial disease: systematic review and meta-analysis.

AbstractObjectiveTo evaluate homocysteine (Hcy) levels in patients with peripheral arterial disease (PAD) as compared to unaffected controls, and to review the clinical effects of therapy aimed at lowering homocysteine in PAD patients.MethodsMEDLINE, EMBASE and Cochrane databases were searched from 1950 to December 2007. We selected observational studies and trials that evaluated Hcy levels in patients with PAD compared to unaffected controls. We also included trials on the effect of Hcy-lowering therapy (folate supplementation) in PAD patients. Continuous outcomes were pooled in a random effects meta-analysis of the weighted mean difference between comparator groups.ResultsWe retrieved 33 potentially suitable articles from our search. Meta-analysis of 14 relevant studies showed that Hcy was significantly elevated (pooled mean difference +4.31μmoll; 95% C.I. 1.71, 6.31, p<0.0001 with significant heterogeneity) in patients with PAD compared to controls. As all 14 studies consistently demonstrated raised plasma Hcy levels in PAD patients, the significant heterogeneity in this meta-analysis probably arises from differences in the degree of Hcy elevation.The effect of folate supplementation on PAD was tested in eight clinical trials but clinically important end points were inconsistently reported.ConclusionPatients with PAD have significantly higher Hcy levels than unaffected controls. However, we did not find any robust evidence on clinically beneficial effects of folate supplementation in PAD