New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Modeling ammonia accumulation and color changes of arugula (Diplotaxis tenuifolia) leaves in relation to temperature, storage time and cultiva

Leafy greens produce ammonia under stressful conditions during postharvest handling. The objective of this study was to understand the relationship between ammonia accumulation and color variation of arugula leaves in relation to cultivar and storage temperature and time. Leaves of five cultivars ('Bellezia', 'Grazia', 'Letizia', 'Tricia', and 'Wild Thing') were washed, centrifuged, placed in unsealed plastic bags, and stored at 0, 5 or 10°C for 28, 20 and 12 days, respectively. Visual quality score, color (hue angle) and ammonia accumulation were monitored every 4 or 8 days, depending on temperature. Ammonia increased from 11-15 μg g-1 fresh weight (FW) to 150-220 at 0°C, 340-450 at 5°C and >590 μg g-1 FW at 10°C by the end of storage-life. While there were some differences among cultivars, temperature played the major role in ammonia accumulation. Color varied due to leaf yellowing, which increased with increasing temperature. Both hue angle and ammonia changes were fitted with traditional (first- and zero-order kinetics) and Weibullian models, with the latter explaining a higher percentage of experimental data variance. Moreover, considering that time was the common variable between the two kinetics, a new mathematical equation describing ammonia versus hue angle for each cultivar/temperature was obtained. In all cases, there was a good correlation between ammonia content and color changes, with more accurate results at 5 and 10°C (r>0.98), since color at 0°C was quite stable (r>0.72). These results demonstrate that ammonia may be a good indicator of senescence in arugula, since it correlated well to color change with storage temperature and time