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Sökning: WFRF:(Welham J)

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1.
  • El-Saadi, O, et al. (författare)
  • Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia
  • 2004
  • Ingår i: Schizophrenia Research. - 0920-9964. ; 67:2-3, s. 227-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: While the association between increased maternal age and congenital disorders has long been recognized, the offspring of older fathers are also at increased risk of congenital disorders related to DNA errors during spermatogenesis. Recent studies have drawn attention to an association between increased paternal age and increased risk of schizophrenia. The aim of the current study was to examine both paternal and maternal age as risk factors for the broader category of psychosis. Method: We used data from three sources examining psychosis: a population-based cohort study (Denmark), and two case-control studies (Sweden and Australia). Results: When controlling for the effect of maternal age, increased paternal age was significantly associated with increased risk of psychosis in the Danish and Swedish studies. The Australian study found no association between adjusted paternal age and risk of psychosis. When controlling for the effect of paternal age, younger maternal a-e was associated with an increased risk of psychoses in the Danish study alone. Conclusions: The offspring of older fathers are at increased risk of developing psychosis. The role of paternally derived mutations and/or psychosocial factors associated with older paternal age warrants further research. (C) 2003 Elsevier B.V. All rights reserved.
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2.
  • Kia, Richard, et al. (författare)
  • MicroRNA-122 : a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity
  • 2015
  • Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 144:1, s. 173-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.
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3.
  • Barta, Z, et al. (författare)
  • Annual routines of non-migratory birds: optimal moult strategies
  • 2006
  • Ingår i: Oikos. - : Wiley. - 1600-0706 .- 0030-1299. ; 112:3, s. 580-593
  • Tidskriftsartikel (refereegranskat)abstract
    • In a periodically changing environment it is important for animals to properly time the major events of their life in order to maximise their lifetime fitness. For a non-migratory bird the timing of breeding and moult are thought to be the most crucial. We develop a state-dependent optimal annual routine model that incorporates explicit density dependence in the food supply. In the model the birds' decisions depend on the time of year, their energy reserves, breeding status, experience, and the quality of two types of feathers (outer and inner primaries). Our model predicts that, under a seasonal environment, feathers with large effects on flight ability, higher abrasion rate and lower energetic cost of moult should be moulted closer to the winter (i.e. later) than those with the opposite attributes. Therefore, we argue that the sequence of moult may be an adaptive response to the problem of optimal timing of moult of differing feathers within the same feather tract. The model also predicts that environmental seasonality greatly affects optimal annual routines. Under high seasonality birds breed first then immediately moult, whereas under low seasonality an alternation occurs between breeding and moulting some of the feathers in one year and having a complete moult but no breeding in the other year. Increasing food abundance has a similar effect.
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