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51.
19 To whom correspondence should be addressed at: Department of Medical Genetics, University of Turku, Kiinamyllykatu 10, FIN-20520 Turku, Finland. E-mail: hkaaria{at}utu.fi* Reprinted from European Journal of Human Genetics (2006) 1–58 with permission. The views expressed in this study do not necessarily reflect those of the European Commission (EC). The interface between assisted reproductive technologies (ART)and genetics comprises several sensitive and important issuesthat affect infertile couples, families with severe geneticdiseases, potential children, professionals in ART and genetics,health care, researchers and the society in general. Geneticcauses have a considerable involvement in infertility. Geneticconditions may also be transmitted to the offspring and hencecreate transgenerational infertility or other serious healthproblems. Several studies also suggest a slightly elevated riskof birth defects in children born following ART. PGD has becomewidely practiced throughout the world for various medical indications,but its limits are being debated. The attitudes towards ARTand PGD vary substantially within Europe. The purpose of thisarticle was to outline a framework for development of guidelinesto be issued jointly by European Society of Human Genetics (ESHG)and European Society of Human Reproduction and Embryology (ESHRE)for the interface between genetics and ART. Technical, social,ethical and legal issues of ART and genetics will be reviewed.  相似文献   
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Inner ear develops from an induced surface ectoderm placode that invaginates and closes to form the otic vesicle, which then undergoes a complex morphogenetic process to form the membranous labyrinth. Inner ear morphogenesis is severely affected in Gata3 deficient mouse embryos, but the onset and basis of the phenotype has not been known. We show here that Gata3 deficiency leads to severe and unique abnormalities during otic placode invagination. The invagination problems are accompanied often by the formation of a morphological boundary between the dorsal and ventral otic cup and by the precocious appearance of dorsal endolymphatic characteristics. In addition, the endolymphatic domain often detaches from the rest of the otic epithelium during epithelial closure. The expression of several cell adhesion mediating genes is altered in Gata3 deficient ears suggesting that Gata3 controls adhesion and morphogenetic movements in early otic epithelium. Inactivation of Gata3 leads also to a loss of Fgf10 expression in otic epithelium and auditory ganglion demonstrating that Gata3 is an important regulator of Fgf-signalling during otic development.  相似文献   
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The insulin-like growth factors (IGFs) are well known mitogens, both in vivo and in vitro, while functions in cellular differentiation have also been indicated. Here, we demonstrate a new role for the IGF pathway in regulating head formation in Xenopus embryos. Both IGF-1 and IGF-2, along with their receptor IGF-1R, are expressed early during embryogenesis, and the IGF-1R is present particularly in anterior and dorsal structures. Overexpression of IGF-1 leads to anterior expansion of head neural tissue as well as formation of ectopic eyes and cement gland, while IGF-1 receptor depletion using antisense morpholino oligonucleotides drastically reduces head structures. Furthermore, we demonstrate that IGF signaling exerts this effect by antagonizing the activity of the Wnt signal transduction pathway in the early embryo, at the level of beta-catenin. Thus, the IGF pathway is required for head formation during embryogenesis.  相似文献   
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Methylprednisolone (MP), a synthetic glucocorticoid, is widely used clinically and experimentally as acute antiinflammatory treatment. The molecular actions of MP indicate that pretreatment with this drug may be cardioprotective. We investigated if giving rats MP prior to excising their hearts for Langendorff-perfusion protected cardiac function against oxidative stress, and if this was mediated by increasing antioxidant defence or influencing myocardial nitric oxide synthase (NOS). Rats (n=6-11 in each group) were injected with MP (40 mg/kg i.m.) or vehicle 24 and 12 h before Langendorff-perfusion with 30 min global ischaemia and 60 min reperfusion, or 10 min perfusion with 180 μmol/L hydrogen peroxide. Other hearts were exposed to 30 min global ischaemia 5 days after MP-injection. Additional hearts were sampled before, during, and after ischaemia for analyzing tissue activity of antioxidant enzymes. Tissue endothelial and inducible NOS (eNOS and iNOS) were investigated by immunoblotting and semiquantitative RT-PCR in a time-course after MP injection. Pretreatment with MP improved left ventricular function and increased coronary flow during postischaemic reperfusion, and this effect was sustained 5 days afterwards. When exposing hearts to hydrogen peroxide, MP improved coronary flow. Catalase, glutathione peroxidase, and oxidized glutathione were increased during reperfusion of MP-treated hearts compared to vehicle only. MP did not influence eNOS at protein or mRNA level. iNOS could not be detected by immunoblotting, indicating low cardiac enzyme content. Its mRNA initially increased the first hour after injection, thereafter decreased. In conclusions, pretreating rats with MP protects the heart against ischaemia-reperfusion dysfunction. This effect could be due to increase of tissue antioxidant activity during reperfusion. MP did not influence cardiac eNOS. mRNA for iNOS was influenced by MP, but the corresponding protein could not be detected.  相似文献   
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Glutathione (GSH) is the major low-molecular weight antioxidant in mammalian cells. Thus, its analogues carrying similar and/or additional positive properties might have clinical perspectives. Here, we report the design and synthesis of a library of tetrapeptidic GSH analogues called UPF peptides. Compared to cellular GSH our designed peptidic analogues showed remarkably higher hydroxyl radical scavenging ability (EC(50) of GSH: 1,231.0 +/- 311.8 microM; EC(50) of UPF peptides: from 0.03 to 35 microM) and improved antiradical efficiency towards a stable alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical. The best of UPF peptides was 370-fold effective hydroxyl radical scavengers than melatonin (EC(50): 11.4 +/- 1.0 microM). We also found that UPF peptides do not influence the viability and membrane integrity of K562 human erythroleukemia cells even at 200 microM concentration. Dimerization of GSH and UPF peptides was compared in water and in 0.9% saline solutions. The results, together with an earlier finding that UPF1 showed protective effects in global cerebral ischemia model in rats, suggest that UPF peptides might serve both as potent antioxidants as well as leads for design of powerful non-peptidic antioxidants that correct oxidative stress-driven events.  相似文献   
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During the Fennoscandian ice recession from the eastern Baltic area, the water level in the Lake Peipsi basin was decreasing and reached a minimum at the end of the Younger Dryas Chronozone. The low lake level episode is represented in the basal deposits by a ca. 0.8 m thick bed of coarse detritus gyttja dated to 9.6–9.1 ka 14C BP. The gyttja lies at an elevation of 20–21 m a.s.l., i.e. about 9 m below the present lake level (30 m a.s.l.), and is buried under a 1.5–2 m bed of fine to medium-grained sand. The overall pollen data indicate a shallow-water littoral environment during the gyttja accumulation in the area studied. The diatom flora in the gyttja is dominated by shallow-water benthic and epiphytic taxa, indicating eutrophic littoral conditions at the time of gyttja accumulation. In the uppermost portion of the gyttja sequence the pollen and diatom successions indicate a short period of land emergence when swampy conditions prevailed in the surroundings.  相似文献   
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