8 research outputs found

    The dynamics of value system in 1998 and 2015 : Longitudinal research in Latvia

    Get PDF
    Values may change during life because a person obtains new life experience and competencies. In the past decade, many Latvian psychologists studied people's values and their connections with different factors like cultural, political, social, economic changes and other factors [1-3 and other]. Since 1994 Latvia has gone through different social-economic changes like crisis, economic growth, assumption to NATO and EU. and acceptation of euro currency. These changes can influence participants' values. The aim was to conduct a comparative longitudinal research in individuals' values in 1998 and 2015, at the beginning of their youth and then in adulthood, in order to answer the following questions: what values were in 1998 and 2015; what differences in values had appeared comparing 1998 and 2015 in same persons. Results showed that the most important values in 1998 and 2015 were "Family", "Love", "Responsibility". "Honesty" and "Cheerfulness". Significant changes appeared in "Health" that became significantly important in 2015 and replaced the importance of "Love". Most achievable values in 1998 and 2015 were "The beauty of nature and art" and "Cognition" but in 2015 also "Active life" which replaced "Self-confidence" that was important in 1998. Significant changes appeared in "Self-confidence", "Wisdom", "Active life", "Freedom", "Interesting job", "Learning" and "Friends" as well, where importance of some values increased and some decreased in 2015.publishersversionPeer reviewe

    Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh) signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI) prostate cancer cells.</p> <p>Results</p> <p>Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase) from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo) expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR) mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881) restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to grow in androgen depleted medium. AR protein co-immunoprecipitates with Gli2 protein from transfected 293T cell lysates.</p> <p>Conclusions</p> <p>Collectively, our results indicate that Hh/Gli signaling supports androgen signaling and AI growth in prostate cancer cells in a low androgen environment. The finding that Gli2 co-immunoprecipitates with AR protein suggests that an interaction between these proteins might be the basis for Hedgehog/Gli support of androgen signaling under this condition.</p

    Identification of Novel Genes That Regulate Androgen Receptor Signaling and Growth of Androgen-Deprived Prostate Cancer Cells

    Get PDF
    Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive promoter and then for altered expression of endogenous androgen-regulated genes in LNCaP cells. We identified 20 human genes whose silencing affected the expression of exogenous and endogenous androgen-responsive genes in prostate cancer cells grown in androgen-depleted medium. Knockdown of four of these genes upregulated the expression of endogenous AR targets and siRNAs targeting two of these genes (IGSF8 and RTN1) enabled androgen-independent proliferation of androgen-dependent cells. The effects of IGSF8 appear to be mediated through its interaction with a tetraspanin protein, CD9, previously implicated in prostate cancer progression. Remarkably, homozygous deletions of IGSF8 are found almost exclusively in prostate cancers but not in other cancer types. Our study shows that androgen independence can be achieved through the inhibition of specific genes and reveals a novel set of genes that regulate AR signaling in prostate cancers

    Climate change and Arctic ecosystems: 1. Vegetation changes north of 55°N between the last glacial maximum, mid-Holocene, and present

    Get PDF
    A unified scheme to assign pollen samples to vegetation types was used to reconstruct vegetation patterns north of 55°N at the last glacial maximum (LGM) and mid-Holocene (6000 years B.P.). The pollen data set assembled for this purpose represents a comprehensive compilation based on the work of many projects and research groups. Five tundra types (cushion forb tundra, graminoid and forb tundra, prostrate dwarf-shrub tundra, erect dwarf-shrub tundra, and low- and high-shrub tundra) were distinguished and mapped on the basis of modern pollen surface samples. The tundra-forest boundary and the distributions of boreal and temperate forest types today were realistically reconstructed. During the mid-Holocene the tundra-forest boundary was north of its present position in some regions, but the pattern of this shift was strongly asymmetrical around the pole, with the largest northward shift in central Siberia (?200 km), little change in Beringia, and a southward shift in Keewatin and Labrador (?200 km). Low- and high-shrub tundra extended farther north than today. At the LGM, forests were absent from high latitudes. Graminoid and forb tundra abutted on temperate steppe in northwestern Eurasia while prostrate dwarf-shrub, erect dwarf-shrub, and graminoid and forb tundra formed a mosaic in Beringia. Graminoid and forb tundra is restricted today and does not form a large continuous biome, but the pollen data show that it was far more extensive at the LGM, while low- and high-shrub tundra were greatly reduced, illustrating the potential for climate change to dramatically alter the relative areas occupied by different vegetation types
    corecore