Chronic hypoxia in the human neuroblastoma SH-SY5Y causes reduced expression of the putative alpha-secretases, ADAM10 and TACE, without altering their mRNA levels

Alzheimer's disease is more frequent following an ischemic or hypoxic episode, with levels of beta-amyloid peptides elevated in brains from patients. Similar increases are found after experimental ischemia in animals. It is possible that increased beta-amyloid deposition arises from alterations in amyloid precursor protein (APP) metabolism, indeed, we have shown that exposing cells of neuronal origin to chronic hypoxia decreased the secretion of soluble APP (sAPPalpha) derived by action of alpha-secretase on APP, coinciding with a decrease in protein levels of ADAM10, a disintegrin metalloprotease which is thought to be the major alpha-secretase. In the current study, we extended those observations to determine whether the expression of ADAM10 and another putative alpha-secretase, TACE, as well as the beta-secretase, BACE1 were regulated by chronic hypoxia at the level of protein and mRNA. Using Western blotting and RT-PCR, we demonstrate that after 48 h chronic hypoxia, such that sAPPalpha secretion is decreased by over 50%, protein levels of ADAM10 and TACE and by approximately 60% and 40% respectively with no significant decrease in BACE1 levels. In contrast, no change in the expression of the mRNA for these proteins could be detected. Thus, we conclude that under CH the level of the putative alpha-secretases, ADAM10 and TACE are regulated by post-translational mechanisms, most probably proteolysis, rather than at the level of transcription.

Investigation of the faecal microbiota associated with canine chronic diarrhoea.

Diarrhoea is a common problem in dogs and can result in disturbance of the normal intestinal microbiota. However, little is known about the gastrointestinal microbiota of dogs with chronic diarrhoea and controlled canine studies of dietary management are scarce. The aims of this study were to investigate the predominant faecal microbiota of chronic diarrhoea dogs and to examine the effect(s) of a fibre blend on the canine faecal microbiota. A 3-week fibre supplementation feeding study was performed in nine chronic diarrhoea and eight control dogs. Atopobium cluster, Lactobacillus-Enterococcus group and Clostridium cluster XIV were the predominant bacterial groups in all dogs. Chronic diarrhoea dogs had significantly higher Bacteroides counts at baseline and significantly lower Atopobium cluster counts following fibre supplementation compared with control dogs. Atopobium cluster levels increased significantly in control dogs, while counts of sulphate-reducing bacteria decreased significantly and Clostridium clusters I and II counts increased significantly in chronic diarrhoea dogs during fibre supplementation. Microbial profiles (detected by denaturing gradient gel electrophoresis) demonstrated interindividual variation, with greater similarity seen between the chronic diarrhoea and control dogs' profiles after fibre supplementation compared with baseline. In conclusion, fibre supplementation induced changes in the canine faecal microbiota, with greater resemblance between the microbiota of chronic diarrhoea and control dogs after this dietary modulation.

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error.

Progressive erosion of genetic and epigenetic variation in callus-derived cocoa (Theobroma cacao) plants

Relatively little is known about the timing of genetic and epigenetic forms of somaclonal variation arising from callus growth. We surveyed for both types of change in cocoa (Theobroma cacao) plants regenerated from calli of various ages, and also between tissues from the source trees. For genetic change, we used 15 single sequence repeat (SSR) markers from four source trees and from 233 regenerated plants. For epigenetic change, we used 386 methylation-sensitive amplified polymorphism (MSAP) markers on leaf and explant (staminode) DNA from two source trees and on leaf DNA from 114 regenerants. Genetic variation within source trees was limited to one slippage mutation in one leaf. Regenerants were far more variable, with 35% exhibiting at least one mutation. Genetic variation initially accumulated with culture age but subsequently declined. MSAP (epigenetic) profiles diverged between leaf and staminode samples from source trees. Multivariate analysis revealed that leaves from regenerants occupied intermediate eigenspace between leaves and staminodes of source plants but became progressively more similar to source tree leaves with culture age. Statistical analysis confirmed this rather counterintuitive finding that leaves of ‘late regenerants’ exhibited significantly less genetic and epigenetic divergence from source leaves than those exposed to short periods of callus growth.

Chronic disease risk associated with different dietary saturated fatty acids

This chapter compares the risks of chronic disease, and cardiovascular disease in particular, associated with consumption of different saturated fatty acids. Emphasis is placed on the effects of stearic acid as this has potential to replace trans fatty acids in certain manufactured food products. The chapter first reviews the effects of individual saturated fatty acids on blood lipids, including cholesterol, as these are commonly used as markers of disease risk. It then looks directly at evidence in relation to health outcomes. Finally, recent evidence specifically on the effect of stearic acid relative to other fatty acids, including trans fatty acids, is summarised.

A prospective longitudinal study of the impact of early postnatal vs. chronic maternal depressive symptoms on child development

Background Few studies of the effects of postnatal depression on child development have considered the chronicity of depressive symptoms. We investigated whether early postnatal depressive symptoms (PNDS) predicted child developmental outcome independently of later maternal depressive symptoms. Methods In a prospective, longitudinal study, mothers and children were followed-up from birth to 2 years; repeated measures of PNDS were made using the Edinburgh Postnatal Depression Scale (EPDS); child development was assessed using the Bayley Scales II. Multilevel modelling techniques were used to examine the association between 6 week PNDS, and child development, taking subsequent depressive symptoms into account. Results Children of mothers with 6 week PNDS were significantly more likely than children of non-symptomatic mothers to have poor cognitive outcome; however, this association was reduced to trend level when adjusted for later maternal depressive symptoms. Conclusion Effects of early PNDS on infant development may be partly explained by subsequent depressive symptoms.

The role of corticospinal tract damage in chronic motor recovery and neurorehabilitation: a pilot study

Background. With diffusion-tensor imaging (DTi) it is possible to estimate the structural characteristics of fiber bundles in vivo. This study used DTi to infer damage to the corticospinal tract (CST) and relates this parameter to (a) the level of residual motor ability at least 1 year poststroke and (b) the outcome of intensive motor rehabilitation with constraint-induced movement therapy (CIMT). Objective. To explore the role of CST damage in recovery and CIMT efficacy. Methods. Ten patients with low-functioning hemiparesis were scanned and tested at baseline, before and after CIMT. Lesion overlap with the CST was indexed as reduced anisotropy compared with a CST variability map derived from 26 controls. Residual motor ability was measured through the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL) acquired at baseline. CIMT benefit was assessed through the pre—post treatment comparison of WMFT and MAL performance. Results. Lesion overlap with the CST correlated with residual motor ability at baseline, with greater deficits observed in patients with more extended CST damage. Infarct volume showed no systematic association with residual motor ability. CIMT led to significant improvements in motor function but outcome was not associated with the extent of CST damage or infarct volume. Conclusion. The study gives in vivo support for the proposition that structural CST damage, not infarct volume, is a major predictor for residual functional ability in the chronic state. The results provide initial evidence for positive effects of CIMT in patients with varying, including more severe, CST damage.