SOIL HEALTH EFFECTS AND STAKEHOLDER PERCEPTIONS OF MANURE AND WOODY BIOMASS APPLICATION TO CROPLAND IN NEBRASKA

Organic products that have historically been viewed as waste products may improve soil health by adding carbon (C) and nutrients to soil. Two such products are woodchips, generated from forest or rangeland management activities, and livestock manure. In Nebraska, eastern redcedar (Juniperus virginiana L.) is a native but invasive tree species inhibiting rangeland productivity. Livestock manure that is underutilized while inorganic fertilizers are imported for crop production presents a water quality risk by contributing to local- and regional-scale nutrient imbalances. Increasing the responsible use of livestock manure in crop fertility programs to improve sustainability of both livestock and crop farms necessitates equipping farmers and their advisors to recognize fields with the greatest potential for economic and natural resource benefits from manure. This dissertation included evaluating the body of research reporting effects of manure and municipal biosolids on soil health properties. Further, the effects of eastern redcedar woodchips applied as a soil amendment alone or co-mingled with swine manure, cattle manure, or inorganic nitrogen (N) on soil health properties, water quality indicators, and greenhouse gas emissions were assessed. Manure application increases soil microbial abundance, improves nutrient cycling and enhances soil structure. Results from field and laboratory studies indicated that surface application of woodchips, with or without other amendments, did not affect soil nor leachate nitrate-N concentrations. Woodchip amendments increased soil organic matter concentration and decreased soil bulk density in less than three years. Methane and nitrous oxide emissions from soil were unaffected by woodchip application, but carbon dioxide emissions increased. Because the field plots were irrigated, no differences in soil moisture were observed by treatment, but soil temperature fluctuations under the woodchips were diminished. Overall, manure and woodchips are viable amendments for improving soil health. A survey of stakeholders revealed that improving soil health is important to them, and they recognize the risks of eastern redcedar to sustainability. Thus, adoption of this novel conservation practice is likely with continued stakeholder engagement. Advisor: Dr. Amy M. Schmid

Impact of Drainage Water Management on Crop Yield, Drainage Volume, and Nitrate Loss

The objectives of this study were to determine the impact of shallow, controlled, conventional, and no drainage on crop yields, subsurface drainage volumes, and nitrate loss through subsurface drainage. This research investigates whether drainage water management reduces nitrate loadings to downstream surface waters

Impact of nitrogen application timing and source on nitrate leaching and crop yield

Nutrient reduction strategies were developed and are being implemented across Midwest to reduce nutrient loading to local and downstream waters. State-wide strategies developed in response to the 2008 Gulf Hypoxia Action Plan. In order to reduce nitrate-nitrogen leaching through subsurface drainage systems, the Iowa Nutrient Reduction Strategy suggests implementation of in-field management practices including nitrogen application timing, source of nitrogen fertilizer, nitrogen application rate, and use of a nitrification inhibitor. The objectives of this study were to document the effects of nitrogen application timing (fall versus spring) and source (aqua-ammonia, urea, and poly-coated urea) on nitrate-nitrogen leaching and crop yield. Field experiments were conducted at the Agricultural Drainage and Water Quality Research and Demonstration site located near Gilmore City in Pocahontas County, Iowa, from 2011 to 2015. Treatments included in this study consisted of 32 experimental plots with both phases of a corn (Zea mays L.) and soybean (Glycine max [L.] Merr.) rotation to simulate a typical cropping system for Iowa conditions. This study showed limited impact of nitrogen application timing on nitrate-nitrogen concentrations. However, five-year average annual flow-weighted nitrate-nitrogen concentration for the soybean phase with fall applied nitrogen to the previous corn crop had significantly lower nitrate levels when compared to the spring application treatment. The use of poly-coated urea as a source of nitrogen fertilizer showed some potential to reduce nitrate-nitrogen concentrations in subsurface drainage

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Variation in dopamine D2 and serotonin 5-HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n¼63 and n¼54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Peer reviewe

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted