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421.
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The sulfur inclusions from four strain ofBeggiatoa alba were observed by using a ruthenium red-glutaraldehyde technique and a modified Ryter-Kellenberger technique. Three of the four strains contained 4-to 5-nm-thick, single, electron-dense, layered sulfur inclusion envelopes. The fourth strain (B15LD) contained a complex pentalaminar sulfur inclusion envelope, 12–14 nm thick. The sulfur inclusions from all four strains were external to the cytoplasmic membrane but internal to the complexBeggiatoa cell walls. Freeze-etching of theB. alba strain B18LD trichomes revealed the unusual cross-fracture morphology of the sulfur in the inclusions. Fractures around the sulfur inclusions revealed a surface similar to that of the fractured cytoplasmic membrane.  相似文献   
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The aim of this hypothesis is to propose a new approach in targeted therapy of cancer: The simultaneous, dual targeting of two single molecules, Par-4 and G6PD, rather than inhibition of full-length signaling pathways. Rationale: Targeted inhibition of especially two survival signaling pathways (PI3K/AKT/mTOR and MAPK/ERK) is frequently tried, however, a major breakthrough has not yet been reported. Inhibition of complete pathways naturally goes along with a variety of dose-limiting side effects thus contributing to poor efficacy of the administered drugs. This essay offers a synopsis of relevant studies to support the above mentioned idea—targeting of two single molecules which either are crucial for tumor growth and cancer-cell-survival: on one side, Par-4-activation selectively triggers apoptosis of tumor cells thus reversing their characteristic feature—immortality. On the other side inhibition of G6PD breaks the energy supply of tumor cells, weakens their defence against oxidative stress and thereby enhances the sensitivity of tumor cells to oxidative agents (e.g. chemotherapy). Advantage of the proposed dual Par-4/G6PD-therapy is good tolerability and—especially when administered along with conventional therapy—less frequent emergence of resistance.  相似文献   
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Purpose

We have previously identified insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) as essential proteins for tip cell maintenance and sprouting angiogenesis. In this study, we aim to identify other IGF family members involved in endothelial sprouting angiogenesis.

Methods

Effects on sprouting were analyzed in human umbilical vein endothelial cells (HUVECs) using the spheroid-based sprouting model, and were quantified as mean number of sprouts per spheroid and average sprout length. RNA silencing technology was used to knockdown gene expression. Recombinant forms of the ligands (IGF1 and IGF2, insulin) and the IGF-binding proteins (IGFBP) 3 and 4 were used to induce excess effects. Effects on the tip cell phenotype were analyzed by measuring the fraction of CD34+ tip cells using flow cytometry and immunohistochemistry in a 3D angiogenesis model. Experiments were performed in the presence and absence of serum.

Results

Knockdown of IGF2 inhibited sprouting in HUVECs, in particular when cultured in the absence of serum, suggesting that components in serum influence the signaling of IGF2 in angiogenesis in vitro. We then determined the effects of IGFBP3 and IGFBP4, which are both present in serum, on IGF2-IGF1R signaling in sprouting angiogenesis in the absence of serum: knockdown of IGFBP3 significantly reduced sprouting angiogenesis, whereas knockdown of IGFBP4 resulted in increased sprouting angiogenesis in both flow cytometry analysis and immunohistochemical analysis of the 3D angiogenesis model. Other IGF family members except INSR did not affect IGF2-IGF1R signaling.

Conclusions

Serum components and IGF binding proteins regulate IGF2 effects on sprouting angiogenesis. Whereas IGFBP3 acts as co-factor for IGF2-IGF1R binding, IGFBP4 inhibits IGF2 signaling.

  相似文献   
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In this paper we report the in-planta activity of the ribosome-inactivating protein JIP60, a 60-kDa jasmonate-induced protein from barley (Hordeum vulgare L.), in transgenic tobacco (Nicotiana tabacum L.) plants. All plants expressing the complete JIP60 cDNA under the control of the cauliflower mosaic virus (CaMV) 35S promoter exhibited conspicuous and similar phenotypic alterations, such as slower growth, shorter internodes, lanceolate leaves, reduced root development, and premature senescence of leaves. Microscopic inspection of developing leaves showed a loss of residual meristems and higher degree of vacuolation of mesophyll cells as compared to the wild type. When probed with an antiserum which was immunoreactive against both the N- and the C-terminal half of JIP60, a polypeptide with a molecular mass of about 30 kDa, most probably a processed JIP60 product, could be detected. Phenotypic alterations could be correlated with the differences in the detectable amount of the JIP60 mRNA and processed JIP60 protein. The protein biosynthesis of the transformants was characterized by an increased polysome/monosome ratio but a decreased in-vivo translation activity. These findings suggest that JIP60 perturbs the translation machinery in planta. An immunohistological analysis using the JIP60 antiserum indicated that the immunoreactive polypeptide(s) are located mainly in the nucleus of transgenic tobacco leaf cells and to a minor extent in the cytoplasm. Received: 31 July 1996 / Accepted: 18 February 1997  相似文献   
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Zusammenfassung Die Möglichkeit einer experimentellen hormonalen Beeinflussung der Zugunruhe bei Vögeln in der Herbst- und Frühjahrszugphase, wie auch zur natürlichen Brutzeit wurde untersucht.Voraussetzung für die Untersuchungen zur sommerlichen Fortpflanzungszeit ist die Gefangenschaftserscheinung, daß ein Teil der gekäfigten Zugvögel (Grasmücken, Weindrosseln und Bergfinken) zu dieser Zeit die gleiche nächtliche Unruhe zeigen wie in den Zugphasen.Von der Arbeitshypothese ausgehend, daß die gleichen Wirkstoffe, die den Ablauf des Brutgeschäftes entscheidend beeinflussen, gleichzeitig die Blockierung des Zugimpulses übernehmen, wurden ziehende Vögel mit Gonaden- und hypophysären Hormonen behandelt.Injektionen mit dem synthetisch hergestellten Östrogen Cyren, dem Lutealhormon Progesteron und dem laktogenen Hormon Prolactin bewirkten uneinheitliche Ergebnisse. Die Versuchsvögel reagierten mit einem spontanen Auslöschen der Zugunruhe, einer kurzfristigen Herabsetzung oder negativ.Die Stärke des Zugimpulses und die Wirkung einer Hormoneinheit stehen in einem bestimmten Verhältnis zueinander.Während der natürlichen Fortpflanzungszeit ist der Anteil der positiv ansprechenden Vögel höher als während der Zugphasen. Für dieses Verhalten, wie auch für die individuell unterschiedliche Reaktionen zur gleichen Zeit dürfte eine ungleiche physiologische Stimmung der Vögel verantwortlich sein.Mit Unterstützung der Deutschen Forschungsgemeinschaft. — Herrn Dr. H. E. Voss, Mannheim, danken wir herzlichst für die kritische Durchsicht der Arbeit und fördernde Hinweise; den Werken Bayer, Hoechst, und der Schering AG. für die freundliche Überlassung ihrer Hormonpräparate.  相似文献   
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