The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for pre-mortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrPSc detection to allow in vivo diagnosis at low abundances of PrPSc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis.     

Intersubject synchronization of cortical activity during natural vision

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.     

Application of gas chromatography-mass spectrometry metabolite profiling techniques to the analysis of heathland plant diets of sheep

Little is known about how plant biochemistry influences the grazing behavior of animals consuming heterogeneous plant communities. The biochemical profiles of grassland species are mostly restricted to major nutritional characteristics, although recent developments in analytical techniques and data analysis have made possible the detailed analysis of minor components that may influence animal feeding preferences, performance, and health. In the present study, gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF/MS) was used to profile the abundances of metabolites in nine specific heathland plant groups and in three mixed forage diets containing 10, 20, or 30% heather (Calluna vulgaris) and also in plasma and feces from sheep offered one of the three diets. Statistical and chemometric approaches, that is, principal component analysis (PCA) and hierarchical cluster analysis (HCA), were used to discriminate between these diets and between individual animals maintained on these diets. It is shown that GC-TOF/MS analysis of sheep plasma allowed distinction between the very similar diets by PCA and HCA, and, moreover, the plant metabolites responsible for the differences observed have been identified. Furthermore, metabolite markers of herbage mixtures and individual plant groups have been identified, and markers have been detected in sheep plasma and feces.     

Constitutive expression of feedback-insensitive cystathionine γ-synthase increases methionine levels in soybean leaves and seeds

Soybean(Glycine max(L.) Merr.) is a major crop that provides plant-origin protein and oil for humans and livestock.Although the soybean vegetative tissues and seeds provide a major source of high-quality protein,they suffer from low concentration of an essential sulfur-containing amino acid,methionine,which significantly limits their nutritional quality.The level of methionine is mainly controlled by the first unique enzyme of methionine synthesis,cystathione γ-synthase(CGS).Aiming to elevate methionine level in vegetative tissues and seeds,we constitutively over-expressed a feedback-insensitive Arabidopsis CGS(At D-CGS) in soybean cultivars,Zigongdongdou(ZD) and Jilinxiaoli 1(JX).The levels of soluble methionine increased remarkably in leaves of transgenic soybeans compared to wild-type plants(6.6-and 7.3-fold in two transgenic ZD lines,and 3.7-fold in one transgenic JX line).Furthermore,the total methionine contents were significantly increased in seeds of the transgenic ZD lines(1.5-to 4.8-fold increase) and the transgenic JX lines(1.3-to 2.3-fold increase) than in the wild type.The protein contents of the transgenic soybean seeds were significantly elevated compared to the wild type,suggesting that the scarcity of methionine in soybeans may limit protein accumulation in soybean seeds.The increased protein content did not alter the profile of major storage proteins in the seeds.Generally,this study provides a promising strategy to increase the levels of methionine and protein in soybean through the breeding programs.