Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the ...relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD‐specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, and proteomic data in AD. Metabolite co‐expression network analysis of the blood metabolomic data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) shows short‐chain acylcarnitines/amino acids and medium/long‐chain acylcarnitines are most associated with AD clinical outcomes, including episodic memory scores and disease severity. Integration of the gene expression data in both the blood from the ADNI and the brain from the Accelerating Medicines Partnership Alzheimer's Disease (AMP‐AD) program reveals ABCA1 and CPT1A are involved in the regulation of acylcarnitines and amino acids in AD. Gene co‐expression network analysis of the AMP‐AD brain RNA‐seq data suggests the CPT1A‐ and ABCA1‐centered subnetworks are associated with neuronal system and immune response, respectively. Increased ABCA1 gene expression and adiponectin protein, a regulator of ABCA1, correspond to decreased short‐chain acylcarnitines and amines in AD in the ADNI. In summary, our integrated analysis of large‐scale multiomics data in AD systematically identifies novel metabolites and their potential regulators in AD and the findings pave a way for not only developing sensitive and specific diagnostic biomarkers for AD but also identifying novel molecular mechanisms of AD pathogenesis.
The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by ...interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life.
CO
2
capture and recycle using microalgae was demonstrated at a coal-fired power plant (Duke Energy’s East Bend Station, Kentucky). Using an in-house designed closed loop, vertical tube ...photobioreactor,
Scenedesmus acutus
was cultured using flue gas as the CO
2
source. Algae productivity of 39 g/(m
2
day) in June–July was achieved at significant scale (18,000 L), while average daily productivity slightly in excess of 10 g/(m
2
day) was demonstrated in the month of December. A protocol for low-cost algae harvesting and dewatering was developed, and the conversion of algal lipids—extracted from the harvested biomass—to diesel-range hydrocarbons via catalytic deoxygenation was demonstrated. Assuming an amortization period of 10 years, calculations suggest that the current cost of capturing and recycling CO
2
using this approach will fall close to $1,600/ton CO
2
, the main expense corresponding to the capital cost of the photobioreactor system and the associated installation cost. From this it follows that future cost reduction measures should focus on the design of a culturing system which is less expensive to build and install. In even the most optimistic scenario, the cost of algae-based CO
2
capture is unlikely to fall below $225/ton, corresponding to a production cost of ~$400/ton biomass. Hence, the value of the algal biomass produced will be critical in determining the overall economics of CO
2
capture and recycle.
CO sub(2) capture and recycle using microalgae was demonstrated at a coal-fired power plant (Duke Energy's East Bend Station, Kentucky). Using an in-house designed closed loop, vertical tube ...photobioreactor, Scenedesmus acutus was cultured using flue gas as the CO sub(2) source. Algae productivity of 39 g/(m super(2) day) in June-July was achieved at significant scale (18,000 L), while average daily productivity slightly in excess of 10 g/(m super(2) day) was demonstrated in the month of December. A protocol for low-cost algae harvesting and dewatering was developed, and the conversion of algal lipids-extracted from the harvested biomass-to diesel-range hydrocarbons via catalytic deoxygenation was demonstrated. Assuming an amortization period of 10 years, calculations suggest that the current cost of capturing and recycling CO sub(2) using this approach will fall close to $1,600/ton CO sub(2), the main expense corresponding to the capital cost of the photobioreactor system and the associated installation cost. From this it follows that future cost reduction measures should focus on the design of a culturing system which is less expensive to build and install. In even the most optimistic scenario, the cost of algae-based CO sub(2) capture is unlikely to fall below $225/ton, corresponding to a production cost of ~$400/ton biomass. Hence, the value of the algal biomass produced will be critical in determining the overall economics of CO sub(2) capture and recycle.
Breakpoints and unit roots Christiano, Lawrence J; Zivot, Eric; Andrews, Donald W.K. ...
Journal of business & economic statistics,
07/1992, Letnik:
10, Številka:
3
Journal Article
PDF
