The complement system in neurodegenerative diseases

Complement is an important component of innate immune defence against pathogens and crucial for efficient immune complex disposal. These core protective activities are dependent in large part on properly regulated complement-mediated inflammation. Dysregulated complement activation, often driven by persistence of activating triggers, is a cause of pathological inflammation in numerous diseases, including neurological diseases. Increasingly, this has become apparent not only in well-recognized neuroinflammatory diseases like multiple sclerosis but also in neurodegenerative and neuropsychiatric diseases where inflammation was previously either ignored or dismissed as a secondary event. There is now a large and rapidly growing body of evidence implicating complement in neurological diseases that cannot be comprehensively addressed in a brief review. Here, we will focus on neurodegenerative diseases, including not only the ‘classical’ neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, but also two other neurological diseases where neurodegeneration is a neglected feature and complement is implicated, namely, schizophrenia, a neurodevelopmental disorder with many mechanistic features of neurodegeneration, and multiple sclerosis, a demyelinating disorder where neurodegeneration is a major cause of progressive decline. We will discuss the evidence implicating complement as a driver of pathology in these diverse diseases and address briefly the potential and pitfalls of anti-complement drug therapy for neurodegenerative diseases

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Embryogenesis: Pattern Formation from a Single Cell

During embryogenesis a single cell gives rise to a functional multicellular organism. In higher plants, as in many other multicellular systems, essential architectural features, such as body axes and major tissue layers are established early in embryogenesis and serve as a positional framework for subsequent pattern elaboration. In Arabidopsis, the apicalbasal axis and the radial pattern of tissues wrapped around it are already recognizable in young embryos of only about a hundred cells in size. This early axial pattern seems to provide a coordinate system for the embryonic initiation of shoot and root. Findings from genetic studies in Arabidopsis are revealing molecular mechanisms underlying the initial establishment of the axial core pattern and its subsequent elaboration into functional shoots and roots. The genetic programs operating in the early embryo organize functional cell patterns rapidly and reproducibly from minimal cell numbers. Understanding their molecular details could therefore greatly expand our ability to generate plant body patterns de novo, with important implications for plant breeding and biotechnology