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51.
Kieu Trinh Do Simone Wahl Johannes Raffler Sophie Molnos Michael Laimighofer Jerzy Adamski Karsten Suhre Konstantin Strauch Annette Peters Christian Gieger Claudia Langenberg Isobel D. Stewart Fabian J. Theis Harald Grallert Gabi Kastenmüller Jan Krumsiek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):128
Background
Untargeted mass spectrometry (MS)-based metabolomics data often contain missing values that reduce statistical power and can introduce bias in biomedical studies. However, a systematic assessment of the various sources of missing values and strategies to handle these data has received little attention. Missing data can occur systematically, e.g. from run day-dependent effects due to limits of detection (LOD); or it can be random as, for instance, a consequence of sample preparation.Methods
We investigated patterns of missing data in an MS-based metabolomics experiment of serum samples from the German KORA F4 cohort (n?=?1750). We then evaluated 31 imputation methods in a simulation framework and biologically validated the results by applying all imputation approaches to real metabolomics data. We examined the ability of each method to reconstruct biochemical pathways from data-driven correlation networks, and the ability of the method to increase statistical power while preserving the strength of established metabolic quantitative trait loci.Results
Run day-dependent LOD-based missing data accounts for most missing values in the metabolomics dataset. Although multiple imputation by chained equations performed well in many scenarios, it is computationally and statistically challenging. K-nearest neighbors (KNN) imputation on observations with variable pre-selection showed robust performance across all evaluation schemes and is computationally more tractable.Conclusion
Missing data in untargeted MS-based metabolomics data occur for various reasons. Based on our results, we recommend that KNN-based imputation is performed on observations with variable pre-selection since it showed robust results in all evaluation schemes.52.
Ross IA 《Bioethics》1996,10(4):310-323
A clinical scenario is described where an anaesthetist is concerned about the seemingly high risk/benefit ratio relating to laparoscopic versus standard inguinal hernia operations. Some options for further action by the anaesthetist are introduced. The remainder of the paper explores the question of who can legitimately assess the acceptability of risk/benefit ratios, and defends the use of practice guidelines at the expense of so called clinical freedom. It is argued that respect for persons is not breached by limiting the treatment options offered to patients to those therapies which have a 'reasonable' risk/benefit ratio. This 'reasonableness' is context dependent, and should be properly decided by those with expertise in the field. 相似文献
53.
Sanjaya Gyawali Myrtle Harrington Jonathan Durkin Kyla Horner Isobel A. P. Parkin Dwayne D. Hegedus Diana Bekkaoui Lone Buchwaldt 《Molecular breeding : new strategies in plant improvement》2016,36(6):72
The fungal pathogen Sclerotinia sclerotiorum causes stem rot of oilseed rape (Brassica napus) worldwide. In preparation for genome-wide association mapping (GWAM) of sclerotinia resistance in B. napus, 152 accessions from diverse geographical regions were screened with a single Canadian isolate, #321. Plants were inoculated by attaching mycelium plugs to the main stem at full flower. Lesion lengths measured 7, 14 and 21 days after inoculation were used to calculate the area under the disease progress curve (AUDPC). Depth of penetration was noted and used to calculate percent soft and collapsed lesions (% s + c). The two disease traits were highly correlated (r = 0.93). Partially resistant accessions (AUDPC <7 and % s + c <2) were identified primarily from South Korea and Japan with a few from Pakistan, China and Europe. Genotyping of accessions with 84 simple sequence repeat markers provided 690 polymorphic loci for GWAM. The general linear model in TASSEL best fitted the data when adjusted for population structure (STRUCTURE), GLM + Q. After correction for positive false discovery rate, 34 loci were significantly associated with both disease traits of which 21 alleles contributed to resistance, while the remaining enhanced susceptibility. The phenotypic variation explained by the loci ranged from 6 to 25 %. Five loci mapped to published quantitative trait loci conferring sclerotinia resistance in Chinese lines. 相似文献
54.
Mate guarding and frequent copulation in birds: A meta‐analysis of their relationship to paternity and male phenotype 下载免费PDF全文
Anna M. F. Harts Isobel Booksmythe Michael D. Jennions 《Evolution; international journal of organic evolution》2016,70(12):2789-2808
In many birds, males are presumed to protect their paternity by closely guarding their mate or copulating frequently with her. Both these costly behaviors are assumed to reduce the risk and/or intensity of sperm competition. However, despite many studies on avian extra‐pair paternity, it remains unclear how strongly these behaviors are related to fitness and other key life‐history traits. Here, we conduct meta‐analyses to address two questions. First, are mate guarding and/or frequent copulation positively correlated with a male's share of paternity at his nest? We find a significant positive correlation between both presumed paternity protection behaviors and paternity share. The relationship is, however, weak (r = 0.08–0.23). This is perhaps unsurprising if the risk of partner infidelity, hence the need to protect paternity, varies among males. For example, more attractive males might have less need to protect their paternity. Second, do males with higher indices of so‐called male “quality” (phenotypic measures, usually subjectively defined by researchers as predictors of male attractiveness) exhibit lower levels of paternity protection behavior? We find a negative correlation between male quality and paternity protection. This finding might partly explain the weak relationship between paternity protection and paternity, although we discuss other, nonmutually exclusive possibilities. 相似文献
55.
Summary A fifty-three metre inter-tidal transect on a headland near Sydney, New South Wales, has been studied. Its profile, fauna and flora are illustrated and described.Figures were prepared indicating the herbivore standing crop on this transect at various seasons, and some evidence of seasonal changes in the marine algal flora is presented.All macroscopic herbivorous animals were removed from the transect at two-weekly intervals during a twelve month period. After the initiation of this treatment no species of alga in the transect appeared outside the zone in which it normally occurred. There was thus no indication that animal browsing normally restricts algae to particular (vertical) zones on this rock platform. The abundance of certain species was, however, affected by the removal of the herbivores. First to flourish were the green algae; contrary to results obtained in other parts of the world, brown algae did not then become established to form a climax community. It is suggested that the rapid reinvasion by herbivores noted at Cape Banks may account for differences in these results from those recorded elsewhere.Some algal taxonomic notes are appended. 相似文献
56.
Summary The mature vesicle of the Hippophaë rhamnoides root nodule endophyte is spherical, approximately 3–4 m in diameter and exhibits a high degree of apparently random septation. Electron micrographs are presented which show that this vesicular form in the endophytic development within the host cell originates as a swelling of the hyphal tip. The young vesicle is non-septate and in general attains a minimum diameter of 3 m before septation becomes evident. The number of septa then increases with vesicle maturity. 相似文献
57.
The uptake of [3H]adrenaline and [3H]noradrenaline into rat hypothalamic slices was compared for determination of whether adrenaline uptake was independent of uptake into noradrenergic neurones. Kinetic analysis revealed a similar high-affinity uptake process for both adrenaline and noradrenaline, with Km and Vmax values within similar ranges. These uptakes were inhibited by desipramine and maprotiline in a dose-dependent manner, but the selective dopamine and 5-hydroxytryptamine uptake inhibitors benztropine and fluoxetine, respectively, were without effect. Competition for uptake sites by unlabelled adrenaline with [3H]adrenaline and [3H]-noradrenaline and by unlabelled noradrenaline with [3H]-adrenaline and [3H]noradrenaline was very similar. Lesioning of the major adrenaline-containing cell group (C1 cell group) decreased the hypothalamic adrenaline concentration but had no effect on hypothalamic [3H]adrenaline or [3H]noradrenaline uptake. The results suggest that exogenous adrenaline is largely taken up by high-affinity sites on noradrenergic nerve terminals. 相似文献
58.
59.
Amyloid is a highly ordered form of aggregate comprising long, straight and unbranched proteinaceous fibrils that are formed with characteristic nucleation-dependent kinetics in vitro. Currently, the structural molecular mechanism of fibril nucleation and elongation is poorly understood. Here, we investigate the role of the sequence and structure of the initial monomeric precursor in determining the rates of nucleation and elongation of human β2-microglobulin (β2m). We describe the kinetics of seeded and spontaneous (unseeded) fibril growth of wild-type β2m and 12 variants at pH 2.5, targeting specifically an aromatic-rich region of the polypeptide chain (residues 62-70) that has been predicted to be highly amyloidogenic. The results reveal the importance of aromatic residues in this part of the β2m sequence in fibril formation under the conditions explored and show that this region of the polypeptide chain is involved in both the nucleation and the elongation phases of fibril formation. Structural analysis of the conformational properties of the unfolded monomer for each variant using NMR relaxation methods revealed that all variants contain significant non-random structure involving two hydrophobic clusters comprising regions 29-51 and 58-79, the extent of which is critically dependent on the sequence. No direct correlation was observed, however, between the extent of non-random structure in the unfolded state and the rates of fibril nucleation and elongation, suggesting that the early stages of aggregation involve significant conformational changes from the initial unfolded state. Together, the data suggest a model for β2m amyloid formation in which structurally specific interactions involving the highly hydrophobic and aromatic-rich region comprising residues 62-70 provide a complementary interface that is key to the generation of amyloid fibrils for this protein at acidic pH. 相似文献
60.
Mapping of homoeologous chromosome exchanges influencing quantitative trait variation in Brassica napus 下载免费PDF全文
Anna Stein Olivier Coriton Mathieu Rousseau‐Gueutin Birgit Samans Sarah V. Schiessl Christian Obermeier Isobel A.P. Parkin Anne‐Marie Chèvre Rod J. Snowdon 《Plant biotechnology journal》2017,15(11):1478-1489
Genomic rearrangements arising during polyploidization are an important source of genetic and phenotypic variation in the recent allopolyploid crop Brassica napus. Exchanges among homoeologous chromosomes, due to interhomoeologue pairing, and deletions without compensating homoeologous duplications are observed in both natural B. napus and synthetic B. napus. Rearrangements of large or small chromosome segments induce gene copy number variation (CNV) and can potentially cause phenotypic changes. Unfortunately, complex genome restructuring is difficult to deal with in linkage mapping studies. Here, we demonstrate how high‐density genetic mapping with codominant, physically anchored SNP markers can detect segmental homoeologous exchanges (HE) as well as deletions and accurately link these to QTL. We validated rearrangements detected in genetic mapping data by whole‐genome resequencing of parental lines along with cytogenetic analysis using fluorescence in situ hybridization with bacterial artificial chromosome probes (BAC‐FISH) coupled with PCR using primers specific to the rearranged region. Using a well‐known QTL region influencing seed quality traits as an example, we confirmed that HE underlies the trait variation in a DH population involving a synthetic B. napus trait donor, and succeeded in narrowing the QTL to a small defined interval that enables delineation of key candidate genes. 相似文献