The Spartan 1 mission

The first Spartan mission is documented. The Spartan program, an outgrowth of a joint Naval Research Laboratory (NRL)/National Aeronautics and Space Administration (NASA)-Goddard Space Flight Center (GSFC) development effort, was instituted by NASA for launching autonomous, recoverable payloads from the space shuttle. These payloads have a precise pointing system and are intended to support a wide range of space-science observations and experiments. The first Spartan, carrying an NRL X-ray astronomy instrument, was launched by the orbiter Discovery (STS51G) on June 20, 1985 and recovered successfully 45 h later, on June 22. During this period, Spartan 1 conducted a preprogrammed series of observations of two X-ray sources: the Perseus cluster of galaxies and the center of our galaxy. The mission was successful from both on engineering and a scientific viewpoint. Only one problem was encountered, the attitude control system (ACS) shut down earlier than planned because of high attitude control system gas consumption. A preplanned emergency mode then placed Spartan 1 into a stable, safe condition and allowed a safe recovery. The events are described of the mission and presents X-ray maps of the two observed sources, which were produced from the flight data

The not-so-barren ranges

© Thesis Eleven Pty, Ltd., SAGE Publications. This is an impressionistic and informal essay written near the end of a novelist's Australia Research Council funded research project: 'Developing narratives from language and stories indigenous to the south coast of Western Australia', and informed by how that research project morphed into an emphasis on revitalization of Noongar language, and the attempt to restore connections between a particular Creation Story and landscape in an area regarded as 'massacre territory'. A sympathetic reader might think of the topic as 'The Wirlomin Noongar Language and Stories Project meets The Barren Ranges'

MicroRNAs: Small but amazing, and their association with endothelin

MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the expressional regulation of genes by inhibiting gene translation. MicroRNAs are recruited and incorporated into the miRISC, ribonucleoprotein complex, targeting specific mRNAs through mechanisms specific for a miRNA sequence. Here we review the biogenesis, regulation, and monitoring of miRNAs, as well as the current evidence for potential roles of miRNAs in human diseases associated with activation of the endothelin system. These diseases include cancer, kidney disease, cardiovascular diseases, inflammatory diseases, infectious diseases, and blood diseases, that may all be aggravated by aberrant miRNA expression. In this review we will also discuss regulatory mechanisms determining production of miRNA as well as measuring or targeting miRNAs as potential novel approaches for diagnosis and treatment. Targeting miRNAs possibly will allow one to detect diseases or to interfere with the progression of diseases associated with activation of the endothelin system. (c) 2012 Elsevier Inc. All rights reserved

Endothelin-1 induced Mxi-2/Ago2 complex formation resulting in 5P536 downregulation promoting breast cancer development

Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors

ETS-dependent p16(INK4a) and p21(warf1/cip1) gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells

Aim: Cellular senescence, leading to cell death through prevention of regular cell renewal, is associated with the upregulation of the tumor suppressor gene p16(INK4a). While this mechanism has been described as leading to progressive nephron loss, p16(INK4a) upregulation in renal cell carcinoma has been linked to a diseasespecific improved patient survival rate. While in both conditions endothelin-1 is also upregulated, the signaling pathway connecting ET-1 to p16(INK4a) has not been characterized until this study. Main methods: Cell culture, qRT-PCR, Western Blot, immunoprecipitation (IP), proximity ligation assay (PLA), and non-radioactive electrophoretic mobility shift assay (EMSA). Key findings: In malignant renal proximal tumor cells (Caki-1), an activation of p16(INK4a) and p21(waf1/cip1) was observed. An increased expression of E-26 transformation-specific (ETS) transcription factors was detectable. Using specific antibodies, a complex formation between ETS1 and extracellular signal-regulated kinase-2 (ERK2) was shown. A further complex partner was Mxi2. EMSA with supershift analysis for ETS1 and Mxi2 indicated the involvement of both factors in the protein-DNA interaction. After specifically blocking the endothelin receptors, ETS1 expression was significantly downregulated. However, the endothelin B receptor dependent downregulation was stronger than that of the A receptor. In contrast, primary proximal tubule cells showed a nuclear decrease after ET-1 stimulation. This indicates that other ETS members may be involved in the observed p16(INK4a) upregulation (as described in the literature). Significance: ETS1, ERK2 and Mxi2 are important complex partners initiating increased p16(INK4a) and p21w(af1/cip1) activation in renal tumor cells. (c) 2012 Elsevier Inc. All rights reserved

Novel noninvasive marker of regression of clear cell renal cell carcinoma (ccRCC) (Publication with Expression of Concern. See vol. 48, pg. 392, 2022)

Objective: Analyzing protein kinase C (PKC) alpha, iota, and zeta as well as levels of Mxi-2 and Vim3 in regressive clear cell renal carcinomas (ccRCCs) and urine samples. Material and methods: Fresh samples of ccRCCs (predominantly pT1a/b) with different degrees of regression (= 70%) vs normal renal tissue and oncocytomas were studied by Western blot, using antibodies of different PKC isoforms. Urine samples from these tumors were analyzed by ELISA (PKC isoforms, Mxi-2, and Vim3). Results: With increasing degree of regression beyond 10%, nuclear Mxi-2 and Vim3 were highly overexpressed in fresh tumor samples. In urine samples, Vim3 was significantly overexpressed in oncocytoma and downregulated in RCCs with 70% regression. Western blot analysis shows that PKC alpha and iota levels were significantly increased in fresh tumor tissue samples (tumors with >= 30% regression). PKC zeta was expressed in normal kidney and significantly increased in oncocytoma but not found in ccRCCs. In patients' urines, Mxi-2 was significantly reduced (regression > 50%), while PKC isofonn alpha was significantly increased by advanced regression rate. PKC iota in patients' urine was overexpressed in oncocytoma and reduced in all ccRCC urines. Conclusion: Tumor regression in ccRCC tissue shows strong nuclear overexpression of Mxi-2, Vim3, and PKC alpha and iota. In respective urines, PKC alpha was overexpressed; PKC iota was decreased. Mxi-2 and Vim3 decreased with increasing regression rates. These reagents could serve as noninvasive ccRCC markers for regression

Protein kinase C alpha regulates nuclear pri-microRNA 15a release as part of endothelin signaling

Endothelin-1 induced signaling is characterized by an early induction of a nuclear factor-kappa B p65/mitogen-activated phosphokinase p38 transcription complex via its A-receptor versus a late induction via diacylglycerol, and protein kinase C. A possible interaction between these two pathways and a potential function for protein kinase C in this context has not previously been elucidated. Here we report that in Caki-1 tumor cells, protein kinase C alpha is a part of the transcription complex. With importin alpha 4 and alpha 5 as chaperones, the transcription complex transmigrates into the nucleus. Protein kinase C alpha blocks the nuclear release of primicroRNA 15a by direct binding shown by electrophoretic mobility shift assay and Duolink immune histology. The expression levels of miRNA 15a can be further manipulated by transfection of si-protein kinase C alpha, or an expression vector containing protein kinase C alpha or miRNA 15. The miRNA 15a regulation by protein kinase C alpha is detectable in different malignant human tumor cell lines (renal cell carcinoma, breast carcinoma, and melanoma). Furthermore, all three cell lines harbor both endothelin receptors (ETAR/ETBR). Specific blockage of each receptor leads to major reduction of miRNA 15a expression due to increased nuclear protein kinase C alpha translocation. We conclude that the nuclear binding of pri-microRNA 15a is a novel function of protein kinase C alpha, which plays an important role in endothelin-1 mediated signaling. Since several endothelin-sensitive, malignant tumor cell lines harbor this regulation, it could indicate a more general role in tumor biology. (C) 2011 Elsevier B.V. All rights reserved