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

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

An evaluation of carbon indicators of soil health in long-term agricultural experiments

Soil organic carbon (SOC) is closely tied to soil health. However, additional biological indicators may also provide insight about C dynamics and microbial activity. We used SOC and the other C indicators (potential C mineralization, permanganate oxidizable C, water extractable organic C, and β-glucosidase enzyme activity) from the North American Project to Evaluate Soil Health Measurements to examine the continental-scale drivers of these indicators, the relationships among indicators, and the effects of soil health practices on indicator values. All indicators had greater values at cooler temperatures, and most were greater with increased precipitation and clay content. The indicators were strongly correlated with each other at the site-level, with the strongest relationship between SOC and permanganate oxidizable C. The indicator values responded positively to decreased tillage, inclusion of cover crops, application of organic nutrients, and retention of crop residue, but not the number of harvested crops in a rotation. The effect of decreased tillage on the C indicators was generally greater at sites with higher precipitation. The magnitude and direction of the response to soil health practices was consistent across indicators within a site but measuring at least two indicators would provide additional confidence of the effects of management, especially for tillage. All C indicators responded to management, an essential criterion for evaluating soil health. Balancing the cost, sensitivity, interpretability, and availability at commercial labs, a 24-hr potential C mineralization assay could deliver the most benefit to measure in conjunction with SOC.Samuel Roberts Noble FoundationOpen access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Evaluation of aggregate stability methods for soil health

Aggregate stability is a commonly used indicator of soil health because improvements in aggregate stability are related to reduced erodibility and improved soil–water dynamics. During the past 80 to 90 years, numerous methods have been developed to assess aggregate stability. Limited comparisons among the methods have resulted in varied magnitudes of response to soil health management practices and varied influences of inherent soil properties and climate. It is not clear whether selection of a specific method creates any advantage to the investigator. This study assessed four commonly used methods of measuring aggregate stability using data collected as part of the North American Project to Evaluate Soil Health Measurements. The methods included water stable aggregates using the Cornell Rainfall Simulator (WSACASH), wet sieved water stable aggregates (WSAARS), slaking captured and adapted from SLAKES smart-phone image recognition software (STAB10), and the mean weight diameter of water stable aggregates (MWD). Influence of climate and inherent soil properties at the continental scale were analyzed in addition to method responses to rotation diversity, cash crop count, residue management, organic nutrient amendments, cover crops, and tillage. The four methods were moderately correlated with each other. All methods were sensitive to differences in climate and inherent soil properties between sites, although to different degrees. None measured significant effects from rotation diversity or crop count, but all methods detected significant increases in aggregate stability resulting from reduced tillage. Significant increases or positive trends were observed for all methods in relation to cover cropping, increased residue retention, and organic amendments, except for STAB10, which expressed a slightly negative response to organic amendments. Considering these results, no single method was clearly superior and all four are viable options for measuring aggregate stability. Therefore, secondary considerations (e.g., cost, method availability, increased sensitivity to a specific management practice, or minimal within-treatment variability) driven by the needs of the investigator, should determine the most suitable method.General Mills IncOpen access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]