Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis

Common diseases such as endometriosis (ED), Alzheimer's disease (AD) and multiple sclerosis (MS) account for a significant proportion of the health care burden in many countries. Genome-wide association studies (GWASs) for these diseases have identified a number of individual genetic variants contributing to the risk of those diseases. However, the effect size for most variants is small and collectively the known variants explain only a small proportion of the estimated heritability. We used a linear mixed model to fit all single nucleotide polymorphisms (SNPs) simultaneously, and estimated genetic variances on the liability scale using SNPs from GWASs in unrelated individuals for these three diseases. For each of the three diseases, case and control samples were not all genotyped in the same laboratory. We demonstrate that a careful analysis can obtain robust estimates, but also that insufficient quality control (QC) of SNPs can lead to spurious results and that too stringent QC is likely to remove real genetic signals. Our estimates show that common SNPs on commercially available genotyping chips capture significant variation contributing to liability for all three diseases. The estimated proportion of total variation tagged by all SNPs was 0.26 (SE 0.04) for ED, 0.24 (SE 0.03) for AD and 0.30 (SE 0.03) for MS. Further, we partitioned the genetic variance explained into five categories by a minor allele frequency (MAF), by chromosomes and gene annotation. We provide strong evidence that a substantial proportion of variation in liability is explained by common SNPs, and thereby give insights into the genetic architecture of the diseases.

Partitioning of dioxins (PCDDs/Fs) in ambient air at urban residential locations

In this work, 17-polychlorinated dibenzo-pdioxin/furan (PCDD/Fs) isomers were measured in ambient air at four urban sites in Seoul, Korea (from February to June 2009). The concentrations of their summed values RPCDD/Fs) across all four sites ranged from 1,947 (271 WHO05 TEQ) (Jong Ro) to 2,600 (349 WHO05 TEQ) fg/m3 (Yang Jae) with a mean of 2,125 ± 317) fg/m3 (292 WHO05 TEQ fg/m3). The sum values for the two isomer groups of RPCDD and RPCDF were 527 (30 WHO05 TEQ) and 1,598 (263 WHO05 TEQ) fg/m3, respectively. The concentration profile of individual species was dominated by the 2,3,4,7,8-PeCDF isomer, which contributed approximately 36 % of the RPCDD/Fs value. The observed temporal trends in PCDD/F concentrations were characterized by relative enhancement in the winter and spring. The relative contribution of different sources, when assessed by principal component analysis, is explained by the dominance of vehicular emissions along with coal (or gas) burning as the key source of ambient PCDD/Fs in the residential areas studied.

Partitioning the variation in stream fish assemblages within a spatio-temporal hierarchy

This paper describes the relative influence of: (i) landscape scale environmental and hydrological factors; (ii) local scale environmental conditions including recent flow history, and; (iii) spatial effects (proximity of sites to one another) on the spatial and temporal variation in local freshwater fish assemblages in the Mary River, south-eastern Queensland, Australia. Using canonical correspondence analysis, each of the three sets of variables explained similar amounts of variation in fish assemblages (ranging from 44 to 52%). Variation in fish assemblages was partitioned into eight unique components: pure environmental, pure spatial, pure temporal, spatially structured environmental variation, temporally structured environmental variation, spatially structured temporal variation, the combined spatial/temporal component of environmental variation and unexplained variation. The total variation explained by these components was 65%. The combined spatial/temporal/environmental component explained the largest component (30%) of the total variation in fish assemblages, whereas pure environmental (6%), temporal (9%) and spatial (2%) effects were relatively unimportant. The high degree of intercorrelation between the three different groups of explanatory variables indicates that our understanding of the importance to fish assemblages of hydrological variation (often highlighted as the major structuring force in river systems) is dependent on the environmental context in which this role is examined.

Effects of fertilizer type and rate on partitioning of soil organic matter into pools of different stability

Type and rate of fertilizers influence the level of soil organic carbon (Corg) and total nitrogen (Nt) markedly, but the effect on C and N partitioning into different pools is open to question. The objectives of the present work were to: (i) quantify the impact of fertilizer type and rate on labile, intermediate and passive C and N pools by using a combination of biological, chemical and mathematical methods; (ii) explain previously reported differences in the soil organic matter (SOM) levels between soils receiving farmyard manure with or without biodynamic preparations by using Corg time series and information on SOM partitioning; and (iii) quantify the long-term and short-term dynamics of SOM in density fractions and microbial biomass as affected by fertilizer type and rate and determine the incorporation of crop residues into labile SOM fractions. Samples were taken from a sandy Cambisol from the long-term fertilization trial in Darmstadt, Germany, founded in 1980. The nine treatments (four field replicates) were: straw incorporation plus application of mineral fertilizer (MSI) and application of rotted farmyard manure with (DYN) or without (FYM) addition of biodynamic preparations, each at high (140 – 150 kg N ha-1 year-1; MSIH, DYNH, FYMH), medium (100 kg N ha-1 year-1; MSIM, DYNM, FYMM) and low (50 – 60 kg N ha-1 year-1; MSIL, DYNL, FYML) rates. The main findings were: (i) The stocks of Corg (t ha-1) were affected by fertilizer type and rate and increased in the order MSIL (23.6), MSIM (23.7), MSIH (24.2) < FYML (25.3) < FYMM (28.1), FYMH (28.1). Stocks of Nt were affected in the same way (C/N ratio: 11). Storage of C and N in the modelled labile pools (turnover times: 462 and 153 days for C and N, respectively) were not influenced by the type of fertilizer (FYM and MSI) but depended significantly (p ≤ 0.05) on the application rate and ranged from 1.8 to 3.2 t C ha 1 (7 – 13% of Corg) and from 90 to 140 kg N ha-1 (4-5% of Nt). In the calculated intermediate pool (C/N ratio 7), stocks of C were markedly higher in FYM treatments (15-18 t ha-1) compared to MSI treatments (12-14 t ha-1). This showed that differences in SOM stocks in the sandy Cambisol induced by fertilizer rate may be short-lived in case of changing management, but differences induced by fertilizer type may persist for decades. (ii) Crop yields, estimated C inputs (1.5 t ha-1 year-1) with crop residue, microbial bio¬mass C (Cmic, 118 – 150 mg kg-1), microbial biomass N (17 – 20 mg kg-1) and labile C and N pools did not differ significantly between FYM and DYN treatments. However, labile C increased linearly with application rate (R2 = 0.53) from 7 to 11% of Corg. This also applied for labile N (3.5 to 4.9% of Nt). The higher contents of Corg in DYN treatments existed since 1982, when the first sampling was conducted for all individual treatments. Contents of Corg between DYN and FYM treatments con-verged slightly since then. Furthermore, at least 30% of the difference in Corg was located in the passive pool where a treatment effect could be excluded. Therefore, the reported differences in Corg contents existed most likely since the beginning of the experiment and, as a single factor of biodynamic agriculture, application of bio-dynamic preparations had no effect on SOM stocks. (iii) Stocks of SOM, light fraction organic C (LFOC, ρ ≤ 2.0 g cm-3), light fraction organic N and Cmic decreased in the order FYMH > FYML > MSIH, MSIL for all sampling dates in 2008 (March, May, September, December). However, statistical significance of treatment effects differed between the dates, probably due to dif-ferences in the spatial variation throughout the year. The high proportion of LFOC on total Corg stocks (45 – 55%) highlighted the importance of selective preservation of OM as a stabilization mechanism in this sandy Cambisol. The apparent turnover time of LFOC was between 21 and 32 years, which agreed very well with studies with substantially longer vegetation change compared to our study. Overall, both approaches; (I) the combination of incubation, chemical fractionation and simple modelling and (II) the density fractionation; provided complementary information on the partitioning of SOM into pools of different stability. The density fractionation showed that differences in Corg stocks between FYM and MSI treatments were mainly located in the light fraction, i.e. induced by higher recalcitrance of the organic input in the FYM treatments. Moreover, the use of the combination of biological, chemical and mathematical methods indicated that effects of fertilizer rate on total Corg and Nt stocks may be short-lived, but that the effect of fertilizer type may persist for longer time spans in the sandy Cambisol.

Variance partitioning of deconstructed periphyton communities: does the use of biological traits matter?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Formalin fixation affects equilibrium partitioning of an ionic contrast agent-microcomputed tomography (EPIC-[mu]CT) imaging of osteochondral samples

Equilibrium Partitioning of an Ionic Contrast agent with microcomputed tomography (EPIC-[mu]CT) is a non-invasive technique to quantify and visualize the three-dimensional distribution of glycosaminoglycans (GAGs) in fresh cartilage tissue. However, it is unclear whether this technique is applicable to already fixed tissues. Therefore, this study aimed at investigating whether formalin fixation of bovine cartilage affects X-ray attenuation, and thus the interpretation of EPIC-[mu]CT data.Design Osteochondral samples (n = 24) were incubated with ioxaglate, an ionic contrast agent, for 22 h prior to [mu]CT scanning. The samples were scanned in both formalin-fixed and fresh conditions. GAG content was measured using a biochemical assay and normalized to wet weight, dry weight, and water content to determine potential reasons for differences in X-ray attenuation.Results The expected zonal distribution of contrast agent/GAGs was observed for both fixed and fresh cartilage specimens. However, despite no significant differences in GAG concentrations or physical properties between fixed and fresh samples, the average attenuation levels of formalin-fixed cartilage were 14.3% lower than in fresh samples.Conclusions EPIC-[mu]CT is useful for three-dimensional visualization of GAGs in formalin-fixed cartilage. However, a significant reduction in X-ray attenuation for fixed (compared to fresh) cartilage must be taken into account and adjusted for accordingly when quantifying GAG concentrations using EPIC-[mu]CT.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Partitioning of persistent organic pollutants (POPs) between human serum and breast milk : a literature review

The literature was reviewed to assess the relationship between the lipid adjusted concentration in human serum and breast milk (expressed as the serum/milk ratio) of a broad range of POPs in paired samples. Thirteen studies were identified, including seven studies that reported serum/milk ratios for polychlorinated dibenzo-dioxins and -furans (PCDD/Fs), ten for polychlorinated biphenyls (PCBs), five for polybrominated diphenyl ethers (PBDEs), and five for organochlorine pesticides (OCPs). Mean serum/milk ratios ranged between 0.7 and 25 depending on the compound and congener. For PCDD/Fs, PCBs and PBDEs, a clear trend of increasing mean serum/milk ratio by increasing molar volume, hydrophobicity and number of halogen substitutes was observed. The mean serum/milk ratios reported by the 13 studies summarized here will aid comparison between human POPs exposure studies using either serum or milk samples. More studies are needed to allow a valid comparison between data obtained from analysis of breast milk and serum samples for a broader range of POPs. Furthermore such studies may shed light on compound specific factors as well as other determinants that may affect the partitioning and partition kinetics of POPs between serum and breast milk.

A threshold concepts focus to curriculum design: supporting student learning through application of variation theory

This project develops and evaluates a model of curriculum design that aims to assist student learning of foundational disciplinary ‘Threshold Concepts’. The project uses phenomenographic action research, cross-institutional peer collaboration and the Variation Theory of Learning to develop and trial the model. Two contrasting disciplines (Physics and Law) and four institutions (two research-intensive and two universities of technology) were involved in the project, to ensure broad applicability of the model across different disciplines and contexts. The Threshold Concepts that were selected for curriculum design attention were measurement uncertainty in Physics and legal reasoning in Law. Threshold Concepts are key disciplinary concepts that are inherently troublesome, transformative and integrative in nature. Once understood, such concepts transform students’ views of the discipline because they enable students to coherently integrate what were previously seen as unrelated aspects of the subject, providing new ways of thinking about it (Meyer & Land 2003, 2005, 2006; Land et al. 2008). However, the integrative and transformative nature of such threshold concepts make them inherently difficult for students to learn, with resulting misunderstandings of concepts being prevalent...

ESR measurements of the partitioning of some new spin probes in n-octanol-water

The stable free radical 1,1,3,3-tetramethylisoindolin-2-yloxyl (TMIO) has proved to be very suitable for use as a spin probe for a number of applications. Because it is soluble mainly in non-polar liquids, there is a need for new derivatives that can be used in a variety of environments. This has been done by introducing substituents in the 5-position of the aromatic ring, namely carboxyl (CTMIO), trimethylamino (TMTMIOI) and sodium sulphonate (NaTMIOS). An accurate ESR method was developed for the measurement of partition coefficients in n-octanol–water. For comparison purposes the method was also applied to some Tempo derivatives. The effect of temperature on the rotational correlation times and the nitrogen-14 hyperfine coupling constant of some of the spin probes was investigated. There is evidence for dimerization of CTMIO to form a biradical

Growth analysis and biomass partitioning of Cyperus iria in response to rice planting density and nitrogen rate

Cyperus iria is a weed of rice with widespread occurrence throughout the world. Because of concerns about excessive and injudicious use of herbicides, cultural weed management approaches that are safe and economical are needed. Developing such approaches will require a better understanding of weed biology and ecology, as well as of weed response to increases in crop density and nutrition. Knowledge of the effects of nitrogen (N) fertilizer on crop-weed competitive interactions could also help in the development of integrated weed management strategies. The present study was conducted in a screenhouse to determine the effects of rice planting density (0, 5, 10, and 20 plants pot−1) and N rate (0, 50, 100, and 150 kg ha−1) on the growth of C. iria. Tiller number per plant decreased by 73–88%, leaf number by 85–94%, leaf area by 85–98%, leaf biomass by 92–99%, and inflorescence biomass by 96–99% when weed plants were grown at 20 rice plants pot−1 (i.e., 400 plants m−2) compared with weed plants grown alone. All of these parameters increased when N rates were increased. On average, weed biomass increased by 118–389% and rice biomass by 121–275% with application of 50–150 kg N ha−1, compared to control. Addition of N favored weed biomass production relative to rice biomass. Increased N rates reduced the root-to-shoot weight ratio of C. iria. Rice interference reduced weed growth and biomass and completely suppressed C. iria when no N was applied at high planting densities (i.e., 20 plants pot−1). The weed showed phenotypic plasticity in response to N application, and the addition of N increased the competitive ability of the weed over rice at densities of 5 and 10 rice plants pot−1 compared with 20 plants pot−1. The results of the present study suggest that high rice density (i.e., 400 plants m−2) can help suppress C. iria growth even at high N rates (150 kg ha−1).

Causes and consequences of variation in nestling immune function

Defence against pathogens is a vital need of all living organisms that has led to the evolution of complex immune mechanisms. However, although immunocompetence the ability to resist pathogens and control infection has in recent decades become a focus for research in evolutionary ecology, the variation in immune function observed in natural populations is relatively little understood. This thesis examines sources of this variation (environmental, genetic and maternal effects) during the nestling stage and its fitness consequences in wild populations of passerines: the blue tit (Cyanistes caeruleus) and the collared flycatcher (Ficedula albicollis). A developing organism may face a dilemma as to whether to allocate limited resources to growth or to immune defences. The optimal level of investment in immunity is shaped inherently by specific requirements of the environment. If the probability of contracting infection is low, maintaining high growth rates even at the expense of immune function may be advantageous for nestlings, as body mass is usually a good predictor of post-fledging survival. In experiments with blue tits and haematophagous hen fleas (Ceratophyllus gallinae) using two methods, methionine supplementation (to manipulate nestlings resource allocation to cellular immune function) and food supplementation (to increase resource availability), I confirmed that there is a trade-off between growth and immunity and that the abundance of ectoparasites is an environmental factor affecting allocation of resources to immune function. A cross-fostering experiment also revealed that environmental heterogeneity in terms of abundance of ectoparasites may contribute to maintaining additive genetic variation in immunity and other traits. Animal model analysis of extensive data collected from the population of collared flycatchers on Gotland (Sweden) allowed examination of the narrow-sense heritability of PHA-response the most commonly used index of cellular immunocompetence in avian studies. PHA-response is not heritable in this population, but is subject to a non-heritable origin (presumably maternal) effect. However, experimental manipulation of yolk androgen levels indicates that the mechanism of the maternal effect in PHA-response is not in ovo deposition of androgens. The relationship between PHA-response and recruitment was studied for over 1300 collared flycatcher nestlings. Multivariate selection analysis shows that it is body mass, not PHA-response, that is under direct selection. PHA-response appears to be related to recruitment because of its positive relationship with body mass. These results imply that either PHA-response fails to capture the immune mechanisms that are relevant for defence against pathogens encountered by fledglings or that the selection pressure from parasites is not as strong as commonly assumed.

Denitrification losses from an intensively managed sub-tropical pasture: Impact of soil moisture on the partitioning of N2 and N2O emissions

Intensively managed pastures in subtropical Australia under dairy production are nitrogen (N) loaded agro-ecosystems, with an increased pool of N available for denitrification. The magnitude of denitrification losses and N2:N2O partitioning in these agro-ecosystems is largely unknown, representing a major uncertainty when estimating total N loss and replacement. This study investigated the influence of different soil moisture contents on N2 and N2O emissions from a subtropical dairy pasture in Queensland, Australia. Intact soil cores were incubated over 15 days at 80% and 100% water-filled pore space (WFPS), after the application of 15N labelled nitrate, equivalent to 50 kg N ha−1. This setup enabled the direct quantification of N2 and N2O emissions following fertilisation using the 15N gas flux method. The main product of denitrification in both treatments was N2. N2 emissions exceeded N2O emissions by a factor of 8 ± 1 at 80% WFPS and a factor of 17 ± 2 at 100% WFPS. The total amount of N-N2 lost over the incubation period was 21.27 kg ± 2.10 N2-N ha−1 at 80% WFPS and 25.26 kg ± 2.79 kg ha−1 at 100% WFPS respectively. N2 emissions remained high at 100% WFPS, while related N2O emissions decreased. At 80% WFPS, N2 emissions increased constantly over time while N2O fluxes declined. Consequently, N2/(N2 + N2O) product ratios increased over the incubation period in both treatments. N2/(N2 + N2O) product ratios responded significantly to soil moisture, confirming WFPS as a key driver of denitrification. The substantial amount of fertiliser lost as N2 reveals the agronomic significance of denitrification as a major pathway of N loss for sub-tropical pastures at high WFPS and may explain the low fertiliser N use efficiency observed for these agro-ecosystems.

Factors affecting partitioning of private forest holdings in Finland.

Questions of the small size of non-industrial private forest (NIPF) holdings in Finland are considered and factors affecting their partitioning are analyzed. This work arises out of Finnish forest policy statements in which the small average size of holdings has been seen to have a negative influence on the economics of forestry. A survey of the literature indicates that the size of holdings is an important factor determining the costs of logging and silvicultural operations, while its influence on the timber supply is slight. The empirical data are based on a sample of 314 holdings collected by interviewing forest owners in the years 1980-86. In 1990-91 the same holdings were resurveyed by means of a postal inquiry and partly by interviewing forest owners. The principal objective in compiling the data is to assist in quantifying ownership factors that influence partitioning among different kinds of NIPF holdings. Thus the mechanism of partitioning were described and a maximum likelihood logistic regression model was constructed using seven independent holding and ownership variables. One out of four holdings had undergone partitioning in conjunction with a change in ownership, one fifth among family owned holdings and nearly a half among jointly owned holdings. The results of the logistic regression model indicate, for instance, that the odds on partitioning is about three times greater for jointly owned holdings than for family owned ones. Also, the probabilities of partitioning were estimated and the impact of independent dichotomous variables on the probability of partitioning ranged between 0.02 and 0.10. The low value of the Hosmer-Lemeshow test statistic indicates a good fit of the model and the rate of correct classification was estimated to be 88 per cent with a cutoff point of 0.5. The average size of holdings undergoing ownership changes decreased from 29.9 ha to 28.7 ha over the approximate interval 1983-90. In addition, the transition probability matrix showed that the trends towards smaller size categories mostly involved in the small size categories, less than 20 ha. The results of the study can be used in considering the effects of the small size of holdings for forestry and if the purpose is to influence partitioning through forest or rural policy.