Seismic Reflection Study of Upheaval Dome, Canyonlands National Park, Utah

The origin of Upheaval Dome, in Canyonlands National Park of southeastern Utah, has been a topic of controversy among geologists and planetary scientists. The structure has long been thought to have been created by salt diapirism from the underlying Paradox Formation. Recent studies have suggested that impact could have formed the dome. To test the various hypotheses, we acquired, processed, and interpreted seismic reflection data within and adjacent to the structure. Both conventionally stacked and prestack-migrated images show \u3c100 m relief in the Paradox Formation, contrary to salt diapirism hypotheses. Further, we have identified features within the images typical of impact structures, such as listric normal faults having displacements toward the center of the dome. Deformation occurs in two depth ranges, with the faulting that created the central uplift appearing only above the Hermosa Formation, in the upper 800 m of the structure. The images also suggest limited fracturing of the Hermosa and salt flow in the Paradox Formation, perhaps due to gravitational relaxation of the crater form. Our image of a nearly flat top of the Paradox salt strongly favors an impact origin for Upheaval Dome

Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear.</p> <p>Methods</p> <p>We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers.</p> <p>Results</p> <p>SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC.</p> <p>Conclusion</p> <p>Our data suggested that the down-regulation of SFRP1 as a candidate tumor suppressor gene, triggered by the epigenetic and/or genetic events, could contribute to the oncogenesis of HCC.</p

Myofibroblast-Derived SFRP1 as Potential Inhibitor of Colorectal Carcinoma Field Effect

Epigenetic changes of stromal-epithelial interactions are of key importance in the regulation of colorectal carcinoma (CRC) cells and morphologically normal, but genetically and epigenetically altered epithelium in normal adjacent tumor (NAT) areas. Here we demonstrated retained protein expression of well-known Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) in stromal myofibroblasts and decreasing epithelial expression from NAT tissues towards the tumor. SFRP1 was unmethylated in laser microdissected myofibroblasts and partially hypermethylated in epithelial cells in these areas. In contrast, we found epigenetically silenced myofibroblast-derived SFRP1 in CRC stroma. Our results suggest that the myofibroblast-derived SFRP1 protein might be a paracrine inhibitor of epithelial proliferation in NAT areas and loss of this signal may support tumor proliferation in CRC

Secreted Frizzled-related protein-1 is a negative regulator of androgen receptor activity in prostate cancer

Secreted Frizzled-related protein-1 (sFRP1) associates with Wnt proteins and its loss can lead to activation of Wnt/β-catenin signalling. It is frequently downregulated in cancer, including prostate cancer, but its function in prostate cancer is unclear because it can increase proliferation of prostate epithelial cells. We investigated the function of sFRP1 in androgen-dependent prostate cancer and found that sFRP1 inhibited androgen receptor (AR) transcriptional activity. In addition, sFRP1 inhibited the proliferation of androgen-dependent LNCaP cells but not of an androgen-independent subline LNCaP-r, suggesting a role in androgen-dependent growth. The inhibition of AR by sFRP1 was unaffected by co-expression of Wnt3a, stabilised β-catenin or β-catenin shRNA, suggesting it does not involve Wnt/β-catenin signalling. Wnt5a also inhibited AR and expression of Wnt5a and sFRP1 together did not further inhibit AR, suggesting that Wnt5a and sFRP1 activate the same signal(s) to inhibit AR. However, sFRP1 inhibition of AR was unaffected by inhibitors of kinases involved in Wnt/Ca2+ and Wnt/planar cell polarity non-canonical Wnt signalling. Interestingly, the cysteine-rich domain of sFRP1 interacted with Frizzled receptors expressed in prostate cancer cells, suggesting that sFRP1/Frizzled complexes activate a signal that leads to repression of AR. Taken together, these observations highlight the function of β-catenin-independent Wnt signalling in the control of AR activity and provide one explanation for sFRP1 downregulation in prostate cancer

EWS/ETS Regulates the Expression of the Dickkopf Family in Ewing Family Tumor Cells

BACKGROUND: The Dickkopf (DKK) family comprises a set of proteins that function as regulators of Wnt/beta-catenin signaling and has a crucial role in development. Recent studies have revealed the involvement of this family in tumorigenesis, however their role in tumorigenesis is still remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found increased expression of DKK2 but decreased expression of DKK1 in Ewing family tumor (EFT) cells. We showed that EFT-specific EWS/ETS fusion proteins enhance the DKK2 promoter activity, but not DKK1 promoter activity, via ets binding sites (EBSs) in the 5' upstream region. EWS/ETS-mediated transactivation of the promoter was suppressed by the deletion and mutation of EBSs located upstream of the DKK2 gene. Interestingly, the inducible expression of EWS/ETS resulted in the strong induction of DKK2 expression and inhibition of DKK1 expression in human primary mesenchymal progenitor cells that are thought to be a candidate of cell origin of EFT. In addition, using an EFT cell line SK-ES1 cells, we also demonstrated that the expression of DKK1 and DKK2 is mutually exclusive, and the ectopic expression of DKK1, but not DKK2, resulted in the suppression of tumor growth in immuno-deficient mice. CONCLUSIONS/SIGNIFICANCE: Our results suggested that DKK2 could not functionally substitute for DKK1 tumor-suppressive effect in EFT. Given the mutually exclusive expression of DKK1 and DKK2, EWS/ETS regulates the transcription of the DKK family, and the EWS/ETS-mediated DKK2 up-regulation could affect the tumorigenicity of EFT in an indirect manner

Aquaponics: alternative types and approaches

Whilst aquaponics may be considered in the mid-stage of development, there are a number of allied, novel methods of food production that are aligning alongside aquaponics and also which can be merged with aquaponics to deliver food efficiently and productively. These technologies include algaeponics, aeroponics, aeroaquaponics, maraponics, haloponics, biofloc technology and vertical aquaponics. Although some of these systems have undergone many years of trials and research, in most cases, much more scientific research is required to understand intrinsic processes within the systems, efficiency, design aspects, etc., apart from the capacity, capabilities and benefits of conjoining these systems with aquaponics

The effect of fasting on anti-inflammatory mediators, IL-1RA and IL-1R2, and their role in resistance to sickness behaviors in mice

Dietary regimens involving fasting have long been linked to beneficial health outcomes including; reduction in heart disease, diabetes, improved mood and cognition, and resistance to sickness behaviors such as anorexia and fever. The mechanisms underlying fasting-induced health benefits and alterations in immunity and sickness behavior continues to remain debated despite over 20 years of interest. This research project confirms that acute dietary restriction (24 h water-only fast) is able to attenuate IL-1β-induced anorexia, in addition to other sickness behaviors at early stages of the acute phase response. We previously reported that fasting was able to reduce gene expression of inflammatory IL-1α in the brain, here we looked at liver and adipose in addition to brain and uncovered a major up-regulation of IL-1 endogenous inhibitors, IL-1RA and IL-1R2 in peripheral tissues. These findings imply that attenuation in sickness behaviors observed may be due to counter-regulation of IL-1 via up-regulation of IL-1R2 and/or IL-1RA shown in metabolically active organs, which is capable of blunting the centrally-mediated effects of induced peripheral challenge. Our results further demonstrate that the mechanisms involved in IL-1R2 and IL-1RA up-regulation are independent of IL-1, TLR-4, IL-4 and glucocordicoid signaling. Here we also demonstrate that free fatty acids (FFA) are increased in the plasma as a consequence of fasting. Using palmitic acid injection to mimic fastings FFA increase, we elucidated a novel mechanism by which IL-1R2 is up-regulated. This method showed increased IL-1R2 gene transcripts in the liver of mice. FFA signaling, which produces an immune response, is shown here to be TLR-4-independent, implicating free fatty acid receptor 1 (FFAR1) as the key signaling receptor initiating the anti-inflammatory result of fasting documented in this study