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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 376 (1995), S. 88-91 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Immunopurified human p53 protein was phosphorylated in vitro by several immunopurified cyclin-dependent kinase complexes: cyclin Dl/Cdk4, cyclin B/Cdc2, cyclin A/Cdk2 or cyclin E/Cdk2 (Fig. \d). Purified Rb protein (Fig. 10, bottom panel) was used to standardize the activity of the four ...
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  • 2
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Several strains of mice have been created which have reproductive defects secondary to disruption of the hypothalamic-pituitary-gonadal axis3,4. Although these mouse models are useful for studying reproductive function, many of these mice have multiple defects. For example, targeted disruption of ...
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been widely demonstrated that Eph receptors and their ephrin ligands play multiple pivotal roles in the development of the nervous system. However, less is known about their roles in the adult brain. Here we reported the expression of ephrin-B1 and its cognate EphB receptors in the adult mouse hippocampus at 3, 7, 15, 30 and 60 days after transections of the entorhinal afferents. In situ hybridization and immunohistochemistry showed the time-dependent up-regulation of ephrin-B1 in the denervated areas of the hippocampus, which initiated at 3 days postlesion (dpl), reached maximal levels at 7–15 dpl, remained slightly elevated at 30 dpl and recovered to normal levels by 60 dpl. Double labeling of ephrin-B1 and glial fibrillary acidic protein revealed that ephrin-B1-expressing cells in the denervated areas were reactive astrocytes. Furthermore, a ligand-binding assay using ephrin-B1/Fc chimera protein also displayed the up-regulation of EphB receptors in the denervated areas of the hippocampus in a similar manner to that of ephrin-B1. Within the first week postlesion, the EphB receptors were expressed by reactive astrocytes. After 7 dpl, however, EphB receptors were expressed not only by reactive astrocytes but also first by sprouting axons and later by regrowing dendrites. These results suggest that the ephrin-B1/EphB system may participate in the lesion-induced plasticity processes in the adult mouse hippocampus.
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: On the basis of anatomical and pharmacological evidence, we have proposed that D3 receptor antagonism plays a role in the mediation of clozapine-, but not haloperidol-, induced immediate-early gene expression in the striatum. To test this hypothesis directly, we compared the effects of repeated administration of vehicle (8 mL/kg/day), clozapine (20 mg/kg/day) and haloperidol (2 mg/kg/day) for 17 days on expression of ΔFosB-like immunoreactivity (ΔFosB-Ir) in the island of Calleja major, nucleus accumbens and caudate-putamen of wild-type C57Bl6 (WT) and D3 receptor knockout (D3KO) mice. In vehicle-treated mice, the number of ΔFosB-Ir neurons in the nucleus accumbens was greater in D3KO than in WT mice. This finding is consistent with results implicating D3 receptor activation in the tonic inhibition of this limbic structure. Unlike rats, clozapine significantly increased the number of ΔFosB-Ir neurons in both the nucleus accumbens and the caudate-putamen of WT mice albeit to a lesser extent in the caudate-putamen than nucleus accumbens. Similar to rats, however, ΔFosB-Ir in the island of Calleja major of WT mice was elevated by clozapine but not by haloperidol. In the nucleus accumbens and caudate-putamen, haloperidol produced similar increases in ΔFosB-Ir in WT and D3KO mice. By contrast, clozapine-induced increases in ΔFosB-Ir in the island of Calleja major, nucleus accumbens and caudate-putamen of WT mice were absent in D3KO mice. These findings, which indicate that D3 receptor blockade is essential for clozapine-induced increases in striatal ΔFosB-Ir, suggest that D3 receptor antagonism may contribute to the unique therapeutic profile of this atypical antipsychotic.
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been proposed to be attenuated by sequestration into intracellular vesicles by the vesicular monoamine transporter (VMAT2). The purpose of this study was to determine if mice with genetically reduced levels of VMAT2 (heterozygote knockout; VMAT2 +/−) were more vulnerable to MPTP. Striatal dopamine (DA) content, the levels of DA transporter (DAT) protein, and the expression of glial fibrillary acidic protein (GFAP) mRNA, a marker of gliosis, were assessed as markers of MPTP neurotoxicity. In all parameters measured VMAT2 +/− mice were more sensitive than their wild-type littermates (VMAT2 +/+). Administration of MPTP (7.5, 15, or 30 mg/kg, b.i.d.) resulted in dose-dependent reductions in striatal DA levels in both VMAT2 +/− and VMAT2 +/+ animals, but the neurotoxic potency of MPTP was approximately doubled in the VMAT2 +/− mice: 59 versus 23% DA loss 7 days after 7.5 mg/kg dose for VMAT2 +/− and VMAT2 +/+ mice, respectively. Dopaminergic nerve terminal integrity, as assessed by DAT protein expression, also revealed more drastic reductions in the VMAT2 +/− mice: 59 versus 35% loss at 7.5 mg/kg and 95 versus 58% loss at 15 mg/kg for VMAT2 +/− and VMAT2 +/+ mice, respectively. Expression of GFAP mRNA 2 days after MPTP was higher in the VMAT2 +/− mice than in the wild-type: 15.8- versus 7.8-fold increase at 7.5 mg/kg and 20.1- versus 9.6-fold at 15 mg/kg for VMAT2 +/− and VMAT2 +/+ mice, respectively. These observations clearly demonstrate that VMAT2 +/− mice are more susceptible to the neurotoxic effects of MPTP, suggesting that VMAT2-mediated sequestration of the neurotoxin into vesicles may play an important role in attenuating MPTP toxicity in vivo.
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  • 6
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Haptoglobin (Hp) is an acute-phase reactant, known to be produced mainly in the liver. Haptoglobin can also be detected in the cytoplasm of normal epidermal Langerhans cells (LCs), and can prevent their functional maturation. The synthesis of Hp in skin cells has not been well studied.Methods  We examined Hp expression at mRNA and protein levels by in situ hybridization and immunohistochemistry, respectively, in normal human skin and in the skin of patients with psoriasis, lichen planus, erythroderma, seborrheic keratosis, verruca vulgaris, basal cell carcinoma, systemic lupus erythematosus, pemphigus and bullous pemphigoid.Results  (1) Haptoglobin mRNA was expressed in the epidermal keratinocytes (KCs), the epithelial cells of hair follicles, sebaceous glands and eccrine glands in normal skin and all dermatoses investigated. (2) Whereas compared with normal skin, the Hp mRNA in KCs of patients with psoriasis, lichen planus, erythroderma, seborrhoea keratosis and verruca vulgaris was significantly intensified, it was weaker in patients with systemic lupus erythematosus, pemphigus and bullous pemphigoid. (3) Haptoglobin protein only stained positively in some KCs of patients with psoriasis, lichen planus and erythroderma. (4) Although some but not all epidermal LCs were positively stained with anti-Hp antibody in normal skin and in skin samples from all patients, the ratios of Hp-positive LCs/total LCs were significantly higher in those diseases with intensified Hp mRNA in KCs.Conclusions  Skin is another extrahepatic organ where Hp can be synthesized by KCs. The expression of Hp mRNA in KCs and the Hp protein in both LCs and KCs appears to be correlated with the amount of inflammation, which might indicate that skin itself is involved in down-regulating the local inflammatory reaction by KC-synthesized Hp.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 49 (2003), S. 0 
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Saccharomyces cerevisiae Spa2p is a component of polarisome that controls cell polarity. Here, we have characterized the role of its homologue, CaSpa2p, in the polarized growth in Candida albicans. During yeast growth, GFP-tagged CaSpa2p localized to distinct growth sites in a cell cycle-dependent manner, while during hyphal growth it persistently localized to hyphal tips throughout the cell cycle. Persistent tip localization of the protein was also observed in Catup1Δ and Canrg1Δ, mutants constitutive for filamentous growth. Caspa2Δ exhibited defects in polarity establishment and maintenance, such as random budding and failure to confine growth to a small surface area leading to round cells with wide, elongated bud necks and markedly thicker hyphae. It was also defective in nuclear positioning, presumably a result of defective interactions between cytoplasmic microtubules with certain polarity determinants. The highly conserved SHD-I and SHD-V domains were found to be important and responsible for different aspects of CaSpa2p function. Caspa2Δ exhibited no virulence in the mouse systemic candidiasis model. Because of the existence of distinct growth forms and the easy control of the switch between them in vitro, C. albicans may serve as a useful model in cell polarity research.
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