The total burden of rare,non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability.     

The opioid systems - Panacea and nemesis

This mini-review outlines the opioid systems and their roles primarily as related to reward and compulsive drug/alcohol intake. The central role is taken by the mu-opioid receptor, target for opiate analgesics and also a central target in compulsive alcohol abuse, alcoholism. The mu-opioid receptor and the cognate opioid neuropeptides from proenkephalin and proopiomelancortin are members of a superfamily of opioid systems, each with unique and still to be defined roles in the central nervous system.     

Bikunin and α1-microglobulin in human zona pellucida and connective tissue

The occurrence of bikunin and ·₁-microglobuli n was investigated in human ovary and Fallopian tubes. Bikunin and ·₁-microglobulin are transcribed in the liver from a common gene. Bikunin immunoreactivity was detected in the zona pellucida. A positive reaction for bikunin was also observed in connective tissue of the oviduct. In addition, mast cells showed a more intense posi tive reaction than the surrounding connective tissue. Specific displaceable ·₁-microglobulin immunoreactivity was revealed in the zona pellucida. The data suggest that bikunin and ·₁- microglobulin are trapped in the zona pellucida. This revised version was published online in November 2006 with corrections to the Cover Date.     

Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype

Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd^-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd^-/- mice. Furthermore, Pdgfd^-/- mice also had a slightly elevated blood pressure. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis.     

Production of the lepidoptera-specific crystal protein by a local isolate of Bacillus thuringiensis

Summary A local isolate of Bacillus thuringiensis (B.t.81) produced crystal protein which was identified as a cry I gene of Class I. The synthesis and assembly of crystal complements were investigated at intervals throughout the growth cycle. Incubation temperature had a marked effect on toxin synthesis; production being the highest at 25°C and the lowest at 42°C. The mutants of B. t. 81, unable to synthesize crystal protein complements, have also been described.     

Apolipoprotein E and diets: a case of gene-nutrient interaction?

Apolipoprotein E has key functions in lipoprotein metabolism, and polymorphisms in the apolipoprotein E gene are associated with distinct lipoprotein patterns. The possibility of gene-nutrient interactions for apolipoprotein E has been addressed in many studies. Although results have generally been mixed, the indications for such an interaction have been more common in studies employing a metabolic challenge. Studies directly designed to examine apolipoprotein E gene-nutrient interactions are needed.     

Sampling and filtration efficiency of two commonly used plankton nets. A comparative study of the Nansen net and the Unesco WP 2 net

The paper presents the results from a study in which two commonlyused plankton nets, the Nansen net and the WP 2 net, were compared.The study was performed at six stations in the Baltic Sea andthe samples were collected during seasons of both high and lowparticle abundance. The comparison included both qualitativeand quantitative filtration capacity of the nets under differentenvironmental conditions. Different mesh sizes were also tested.The results show that the Nansen net has an efficiency of 50–70%compared to the WP 2 net under favourable conditions. When conditionsare unfavourable, i.e. during periods of high particle abundanceor during long hauls, the efficiency may be as low as 25–30%.The mesh size of the nets proved to be of decisive importancefor the qualitative composition of the samples. Most of thesmaller size fractions such as rotifers, copepod nauplii andyoung copepodites passed through the 160 and 200 µm meshes.The 90 µm nets sampled these fractions well but with thedrawback of retaining vast amounts of phytoplankton at certaintimes of the year.     

Large Alterations in Ganglioside and Neutral Glycosphingolipid Patterns in Brains from Cases with Infantile Neuronal Ceroid Lipofuscinosis/Polyunsaturated Fatty Acid Lipidosis

Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids.