University of Iowa

About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Abstract: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Different Contributions of the Human Amygdala and Ventromedial Prefrontal Cortex to Decision-Making

Abstract: The somatic marker hypothesis proposes that decision-making is a process that depends on emotion. Studies have shown that damage of the ventromedial prefrontal (VMF) cortex precludes the ability to use somatic (emotional) signals that are necessary for guiding decisions in the advantageous direction. However, given the role of the amygdala in emotional processing, we asked whether amygdala damage also would interfere with decision-making. Furthermore, we asked whether there might be a difference between the roles that the amygdala and VMF cortex play in decision-making. To address these two questions, we studied a group of patients with bilateral amygdala, but not VMF, damage and a group of patients with bilateral VMF, but not amygdala, damage. We used the "gambling task" to measure decision-making performance and electrodermal activity (skin conductance responses, SCR) as an index of somatic state activation. All patients, those with amygdala damage as well as those with VMF damage, were (1) impaired on the gambling task and (2) unable to develop anticipatory SCRs while they pondered risky choices. However, VMF patients were able to generate SCRs when they received a reward or a punishment (play money), whereas amygdala patients failed to do so. In a Pavlovian conditioning experiment the VMF patients acquired a conditioned SCR to visual stimuli paired with an aversive loud sound, whereas amygdala patients failed to do so. The results suggest that amygdala damage is associated with impairment in decision-making and that the roles played by the amygdala and VMF in decision-making are different.

Asian emissions in 2006 for the NASA INTEX-B mission

Abstract: . A new inventory of air pollutant emissions in Asia in the year 2006 is developed to support the Intercontinental Chemical Transport Experiment-Phase B (INTEX-B) funded by the National Aeronautics and Space Administration (NASA). Emissions are estimated for all major anthropogenic sources, excluding biomass burning. We estimate total Asian anthropogenic emissions in the year 2006 as follows: 47.1 Tg SO2, 36.7 Tg NOx, 298.2 Tg CO, 54.6 Tg NMVOC, 29.2 Tg PM10, 22.2 Tg PM2.5, 2.97 Tg BC, and 6.57 Tg OC. We emphasize emissions from China because they dominate the Asia pollutant outflow to the Pacific and the increase of emissions from China since 2000 is of great concern. We have implemented a series of improved methodologies to gain a better understanding of emissions from China, including a detailed technology-based approach, a dynamic methodology representing rapid technology renewal, critical examination of energy statistics, and a new scheme of NMVOC speciation for model-ready emissions. We estimate China's anthropogenic emissions in the year 2006 to be as follows: 31.0 Tg SO2, 20.8 Tg NOx, 166.9 Tg CO, 23.2 Tg NMVOC, 18.2 Tg PM10, 13.3 Tg PM2.5, 1.8 Tg BC, and 3.2 Tg OC. We have also estimated 2001 emissions for China using the same methodology and found that all species show an increasing trend during 2001–2006: 36% increase for SO2, 55% for NOx, 18% for CO, 29% for VOC, 13% for PM10, and 14% for PM2.5, BC, and OC. Emissions are gridded at a resolution of 30 min×30 min and can be accessed at our web site ( http://mic.greenresource.cn/intex-b2006 ).

Defining the role of common variation in the genomic and biological architecture of adult human height

Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Very fast empirical prediction and rationalization of protein pKa values

Abstract: A very fast empirical method is presented for structure-based protein pKa prediction and rationalization. The desolvation effects and intra-protein interactions, which cause variations in pKa values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pKa sites. A computer program is written to automatically predict pKa values based on these empirical relationships within a couple of seconds. Unusual pKa values at buried active sites, which are among the most interesting protein pKa values, are predicted very well with the empirical method. A test on 233 carboxyl, 12 cysteine, 45 histidine, and 24 lysine pKa values in various proteins shows a root-mean-square deviation (RMSD) of 0.89 from experimental values. Removal of the 29 pKa values that are upper or lower limits results in an RMSD = 0.79 for the remaining 285 pKa values.