2,914 research outputs found
Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.
Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF-II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway
Man muss nur wollen? : Zur Ambivalenz von Verantwortung
Rechtssoziologie am Institut für Sozialforschung Im Mittelpunkt des aktuellen Forschungsprogramms des Frankfurter Instituts für Sozialforschung stehen die Paradoxien und Ambivalenzen der kapitalistischen Modernisierung. Grund legend hierfür ist die Beobachtung, dass sich fortschrittliche soziale Prozesse im Nachhinein unter den Bedingungen einer gewandelten Moderne in ihr Gegenteil verkehren können. Mit dieser These beschäftigt sich auch der Forschungsschwerpunkt »Politische Öffentlichkeit und Recht«. Mit Bezugnahme auf die gegenwärtige Rechtsentwicklung interessiert vor allem die Frage, ob und wie das Recht auf Veränderungen im Verhältnis von Individuum und Gesellschaft und auf die fortschreitende Individualisierung reagiert. Auch interessiert, wie die Rechtsentwicklung im Alltagsverständnis wahrgenommen wird. Antworten auf diese Fragestellungen werden derzeit aus den Ergebnissen des DFG-Projekts »Die Zuschreibung von Verantwortung in den Rechtsmeinungen von Bürgerinnen und Bürgern« wie auch aus der fortlaufenden Diskussion über »Verantwortung und Gerechtigkeit« im Arbeitskreis Rechtssoziologie gewonnen. Im Rahmen des Forschungsprojektes unter der Projektleitung von Prof. Dr. Klaus Günther und Prof. Dr. Axel Honneth wurden in 45 qualitativen, Leitfaden-gestützten Einzelinterviews Befragte um ihre Urteile zu drei vorgegebenen Rechtsfällen gebeten. Der Arbeitskreis Rechtssoziologie beschäftigt sich vor allem mit den in vielen gesellschaftlichen Lebensbereichen häufig aufgestellten Postulaten der Eigen- oder Selbstverantwortung; dabei soll untersucht werden, welche Konzepte einer verantwortlich handelnden Person damit einhergehen und in welchem Verhältnis sie zu den gesellschaftlichen Bedingungen verantwortlichen Handelns stehen. Die Ergebnisse der Diskussionen und des empirischen Projektes sollen ein Fundament für eine normative Theorie liefern, die Kriterien für eine gerechtfertigte Verteilung von Verantwortung in der Gesellschaft begründen soll
Schlüssel zur Einteilung von Neophyten in der Schweiz in die Schwarze Liste oder die Watch-Liste
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Zur Entwicklung der Hausarbeit: Bericht über das Forschungsvorhaben "Anzahl und Situation der zu Hause lebenden Pflegebedürftigen in der Bundesrepublik Deutschland"
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Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice.
BACKGROUND: Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. OBJECTIVES: We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. METHODS: Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; <3-μg silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). RESULTS: The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. CONCLUSIONS: These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model
Transcriptional and distributional profiling of microglia in retinal angiomatous proliferation
Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors
ICON in Climate Limited-area Mode (ICON release version 2.6.1): a new regional climate model
For the first time, the Limited-Area Mode of the new ICON (Icosahedral Nonhydrostatic) weather and climate model has been used for a continuous long-term regional climate simulation over Europe. Built upon the Limited-Area Mode of ICON (ICON-LAM), ICON-CLM (ICON in Climate Limited-area Mode, hereafter ICON-CLM, available in ICON release version 2.6.1) is an adaptation for climate applications. A first version of ICON-CLM is now available and has already been integrated into a starter package (ICON-CLM_SP_betal). The starter package provides users with a technical infrastructure that facilitates long-term simulations as well as model evaluation and test routines. ICON-CLM and ICON-CLM_SP were successfully installed and tested on two different computing systems. Tests with different domain decompositions showed bit-identical results, and no systematic outstanding differences were found in the results with different model time steps. ICON-CLM was also able to reproduce the large-scale atmospheric information from the global driving model. Comparison was done between ICON-CLM and the COnsortium for Small-scale MOdeling (COSMO)-CLM (the recommended model configuration by the CLM-Community) performance. For that, an evaluation run of ICON-CLM with ERA-Interim boundary conditions was carried out with the setup similar to the COSMO-CLM recommended optimal setup. ICON-CLM results showed biases in the same range as those of COSMO-CLM for all evaluated surface variables. While this COSMO-CLM simulation was carried out with the latest model version which has been developed and was carefully tuned for climate simulations on the European domain, ICON-CLM was not tuned yet. Nevertheless, ICON-CLM showed a better performance for air temperature and its daily extremes, and slightly better performance for total cloud cover. For precipitation and mean sea level pressure, COSMO-CLM was closer to observations than ICON-CLM. However, as ICON-CLM is still in the early stage of development, there is still much room for improvement
Successful Treatment with Miltefosine of Disseminated Cutaneous Leishmaniasis in a Severely Immunocompromised Patient Infected with HIV-1
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