Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

Background: The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies.

Methods: We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance.

Interferon-γ blocks signalling through PDGFRβ in human brain pericytes.

Background: Neuroinflammation and blood-brain barrier (BBB) disruption are common features of many brain disorders, including Alzheimer's disease, epilepsy, and motor neuron disease. Inflammation is thought to be a driver of BBB breakdown, but the underlying mechanisms for this are unclear. Brain pericytes are critical cells for maintaining the BBB and are immunologically active.

Reduction of autophagy markers mediated protective effects of JNK inhibitor and bucladesine on memory deficit induced by Aβ in rats.

Autophagy, the process of self-degradation of cellular components, has an important role in neurodegenerative diseases, such as Alzheimer's disease. In this study, we investigated the effects of SP600125 as c-Jun N-terminal kinase (JNK) inhibitor and bucladesine as a cyclic adenosine 3',5'-monophosphate (cAMP) analog on spatial memory and expression of autophagic factors in Aβ-injected rats. Male Wistar rats were used.

Origin and evolution of the enhancer of split complex.

Background: The Enhancer of split complex is an unusual gene complex found in Arthropod genomes. Where known this complex of genes is often regulated by Notch cell signalling and is critically important for neurogenesis. The Enhancer of split complex is made up of two different classes of genes, basic helix-loop-helix-orange domain transcription factors and bearded class genes.

An anti-inflammatory role for C/EBPδ in human brain pericytes.

Neuroinflammation contributes to the pathogenesis of several neurological disorders and pericytes are implicated in brain inflammatory processes. Cellular inflammatory responses are orchestrated by transcription factors but information on transcriptional control in pericytes is lacking. Because the transcription factor CCAAT/enhancer binding protein delta (C/EBPδ) is induced in a number of inflammatory brain disorders, we sought to investigate its role in regulating pericyte immune responses.

Modeling the effect of insulin-like growth factor-1 on human cell growth.

Insulin-like growth factor-1 (IGF-1) plays a key role in human growth and development. The interactions of IGF-1 with IGF-1 receptors and IGF-1 binding proteins (IGFBPs) regulate IGF-1 function. Recent research suggests that a metabolite of IGF-1, cyclo-glycyl-proline (cGP), has a role in regulating IGF-1 homeostasis.

Early developmental conditioning of later health and disease: physiology or pathophysiology?

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later.

Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants.

Erythrocytes require glucose-6-phosphate dehydrogenase (G6PD) to generate NADPH and protect themselves against hemolytic anemia induced by oxidative stress. Peroxiredoxin 2 (Prx2) is a major antioxidant enzyme that requires NADPH to recycle its oxidized (disulfide-bonded) form. Our aims were to determine whether Prx2 is more highly oxidized in G6PD-deficient erythrocytes and whether these cells are able to recycle oxidized Prx2 after oxidant challenge.

Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1.

The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice.

The missing story behind Genome Wide Association Studies: single nucleotide polymorphisms in gene deserts have a story to tell.

Genome wide association studies are central to the evolution of personalized medicine. However, the propensity for single nucleotide polymorphisms (SNPs) to fall outside of genes means that understanding how these polymorphisms alter cellular function requires an expanded view of human genetics. Integrating the study of genome structure (chromosome conformation capture) into its function opens up new avenues of exploration.

The human side of microglia.

Despite increasing evidence of major differences between rodent and human immune and neurological function, relatively few biomedical studies are performed with human cells. This review takes the example of neuroimmunology research and the microglia cell type to illustrate the emerging differences between rodent and human research findings. Microglia are involved in disease states and normal aging processes of the adult human brain.

Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain.

DNA methylation (5-methylcytosine [5mC]) is one of several epigenetic markers altered in Alzheimer's disease (AD) brain. More recently, attention has been given to DNA hydroxymethylation (5-hydroxymethylcytosine [5hmC]), the oxidized form of 5mC. Whereas 5mC is generally associated with the inhibition of gene expression, 5hmC has been associated with increased gene expression and is involved in cellular processes such as differentiation, development, and aging.

Peroxiredoxins as biomarkers of oxidative stress.

Background: Peroxiredoxins (Prxs) are a class of abundant thiol peroxidases that degrade hydroperoxides to water. Prxs are sensitive to oxidation, and it is hypothesized that they also act as redox sensors. The accumulation of oxidized Prxs may indicate disruption of cellular redox homeostasis.

Hyperoxidation of peroxiredoxins 2 and 3: rate constants for the reactions of the sulfenic acid of the peroxidatic cysteine.

Typical 2-Cys peroxiredoxins (Prxs) react rapidly with H2O2 to form a sulfenic acid, which then condenses with the resolving cysteine of the adjacent Prx in the homodimer or reacts with another H2O2 to become hyperoxidized. Hyperoxidation inactivates the Prx and is implicated in cell signaling. Prxs vary in susceptibility to hyperoxidation.