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  • 1
    Keywords: APOPTOSIS ; CANCER ; GROWTH ; GENE-EXPRESSION ; STEM-CELLS ; CENTRAL-NERVOUS-SYSTEM ; neuroblastoma ; N-MYC ; BRAIN-TUMORS ; TUMOR-SUPPRESSOR
    Abstract: Previous studies have evaluated the role of miRNAs in cancer initiation and progression. MiR-34a was found to be downregulated in several tumors, including medulloblastomas. Here we employed targeted transgenesis to analyze the function of miR-34a in vivo. We generated mice with a constitutive deletion of the miR-34a gene. These mice were devoid of mir-34a expression in all analyzed tissues, but were viable and fertile. A comprehensive standardized phenotypic analysis including more than 300 single parameters revealed no apparent phenotype. Analysis of miR-34a expression in human medulloblastomas and medulloblastoma cell lines revealed significantly lower levels than in normal human cerebellum. Re-expression of miR-34a in human medulloblastoma cells reduced cell viability and proliferation, induced apoptosis and downregulated the miR-34a target genes, MYCN and SIRT1. Activation of the Shh pathway by targeting SmoA1 transgene overexpression causes medulloblastoma in mice, which is dependent on the presence and upregulation of Mycn. Analysis of miR-34a in medulloblastomas derived from ND2:SmoA1(tg) mice revealed significant suppression of miR-34a compared to normal cerebellum. Tumor incidence was significantly increased and tumor formation was significantly accelerated in mice transgenic for SmoA1 and lacking miR-34a. Interestingly, Mycn and Sirt1 were strongly expressed in medulloblastomas derived from these mice. We here demonstrate that miR-34a is dispensable for normal development, but that its loss accelerates medulloblastomagenesis. Strategies aiming to re-express miR-34a in tumors could, therefore, represent an efficient therapeutic option. (c) 2014 Wiley Periodicals, Inc.
    Type of Publication: Journal article published
    PubMed ID: 25348795
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  • 2
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies were conducted to assess the normal tissue-associated levels of pristane (2,6,10,14-tetramethyl-pentadecane) in Copenhagen rats during ontogeny and adult life and to address whether or not dietary pristane can be adsorbed from the gut and disseminated throughout the body. During the course of this study the possible effects of dietary pristane on chromatin conformation of lymphoid cells were also examined by flow cytometry. The data indicated that 1) pristane crossed the placenta and accumulated in fetal tissues, 2) neonates were exposed to pristane via the colostrum, 3) there were significant increases in the amount of tissue-associated pristane in young adults and subsequent redistribution of the pristane to the muscle and adipose tissues in older rats and 4) after dietary exposure, significantly elevated levels of pristane were associated with the tissues and concomitant changes in chromatin conformation were observed. Collectively, these results suggest that pristane was adsorbed from dietary sources, disseminated to the tissues and exerted a transient, yet marked effect on chromatin of lymphoid cells in rats.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of pristane (2,6,10,14-tetramethylpentadecane) on the cellular DNA of lymphoid cells from Copenhagen rats were examined by flow cytometry. Significant reductions in the mean relative fluorescent intensities of propidium iodide (PI) stained lymphocytes from peripheral blood, spleen, thymus and lymph nodes were observed after a single intraperitoneal injection of pristane. The altered PI staining characteristics were observed as early as 4 days and reached a maximum decrease between 1–4 weeks (depending upon the lymphoid cells examined) post pristane treatment. The pristane-induced effects on peripheral blood lymphocytes were observed to be dose dependent, transient and reinducible by a subsequent exposure to pristane. Further analyses, using gas-liquid chromatography to detect pristane in the blood and lymphoid tissues of treated rats, indicated, significant increases over normal amounts of pristane. Furthermore, correlations existed between the times of maximum decrease in the fluorescence of PI stained cells and the amounts of pristane detected within the respective lymphoid tissues. By contrast no changes in the PI staining characteristics of kidney cells were observed, even though appreciable amounts of pristane, were detected in this organ. Diphenylamine analyses indicated no differences in the amounts of DNA in lymphoid cells from pristane treated and untreated rats. Furthermore, lymphocytes from pristane-treated rats did not exhibit decreased fluorescence when fixed at pH 10 rather than pH 7.4 prior to PI staining. Collectively these results suggest that pristane, may preferentially induce qualitative rather than quantitative changes in the DNA of lymphocytes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 66 (1995), S. 1104-1106 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The room-temperature photoinduced switching of an InGaAs/AlAs resonant-tunneling diode is demonstrated. When illuminated at an irradiance of greater than 20 W cm−2 using 1.3 μm radiation, the resonant-tunneling diode switches from a high-conductance to a low-conductance electrical state and exhibits a voltage swing of 600 mV. The switching characteristics are reversible and, in the absence of light, the detector returns to its original high conductance operating state. Small-signal optical measurements performed with the device biased prior to resonance demonstrate a 3 dB bandwidth of ∼1.5 GHz. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Industrial & engineering chemistry 41 (1949), S. 1341-1344 
    ISSN: 1520-5045
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0646
    Keywords: Doxil® ; mesothelioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Twenty-four patients with pleural mesotheliomareceived 50 mg/m2 of Doxil® every four weeks.At follow-up, the disease had stabilized in 43% percent ofpatients and had progressed in 57%. No objective responses wereobserved. Estimated median survival of all patients was 37 weeks.Major toxicities were erythrodysesthesia of hands and feet andmyelosuppression. No cardiac toxicity was observed. We concludedthat Doxil® at this dosage and schedule is inactiveagainst pleural mesothelioma.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 49 (1993), S. 877-883 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: A thermodynamic model for the equilibrial process zone ahead of a crack in polycarbonate is developed from the recently proposed Chudnovsky model and experimental characterization of the process zone. Based on the model, the force for evolution of the process zone is proposed from the consideration of irreversible thermodynamics and chemical reaction theories. The experimental data reported in our previous paper are well described by the equilibrial process zone model and a new kinetic equation. © 1993 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The process-zone evolution strongly influences the crack growth of polycarbonate. A methodology for determination of the kinetics of the process-zone evolution by decoupling these two processes was developed. This was achieved using constant displacement (stress-re-laxation) conditions under which the crack length remained constant. The morphology of the process zone was characterized using optical microscopy of cross sections and fracture surfaces produced with liquid nitrogen. The kinetics of process-zone evolution and stress relaxation were monitored and analyzed. The kinetics vary significantly with the level of displacement imposed. Thus, the challenge remains to construct a master curve for the kinetics. © 1993 John Wiley & Sons, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-689X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of computerized medical records for complex medical patients will depend upon the transfer of previous medical data from the manual record into the automated version. The complexity of these patients precludes the complete transfer of medical data into the automated record because of time requirements. This paper describes a method of transfer of medical data from the manual record to the computerized record that is efficient, accurate, and useful.
    Type of Medium: Electronic Resource
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  • 10
    Publication Date: 2018-05-26
    Description: Benzodiazepines are positive allosteric modulators of the GABAA receptor (GABAAR), acting at the α–γ subunit interface to enhance GABAAR function. GABA or benzodiazepine binding induces distinct conformational changes in the GABAAR. The molecular rearrangements in the GABAAR following benzodiazepine binding remain to be fully elucidated. Using two molecular models of the GABAAR, we identified electrostatic interactions between specific amino acids at the α–γ subunit interface that were broken by, or formed after, benzodiazepine binding. Using two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes, we investigated these interactions by substituting one or both amino acids of each potential pair. We found that Lys104 in the α1 subunit forms an electrostatic bond with Asp75 of the γ2 subunit after benzodiazepine binding and that this bond stabilizes the positively modified state of the receptor. Substitution of these two residues to cysteine and subsequent covalent linkage between them increased the receptor's sensitivity to low GABA concentrations and decreased its response to benzodiazepines, producing a GABAAR that resembles a benzodiazepine-bound WT GABAAR. Breaking this bond restored sensitivity to GABA to WT levels and increased the receptor's response to benzodiazepines. The α1 Lys104 and γ2 Asp75 interaction did not play a role in ethanol or neurosteroid modulation of GABAAR, suggesting that different modulators induce different conformational changes in the receptor. These findings may help explain the additive or synergistic effects of modulators acting at the GABAAR.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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