135 research outputs found
Media(ted) discourses and climate change : a focus on political subjectivity and (dis)engagement
Research has shown that the media are the main source of information and the main factor shaping peopleβs awareness and concern in relation to climate change and therefore have an important role in setting the public agenda. As a key forum for the production, reproduction and transformation of the meaning of public issues, the media influence understandings of risks, responsibilities, as well as of the functioning of democratic politics. This article argues that the media also matter to citizensβ perception of their (potential) political agency or their political subjectivity. Media representations construct particular βsubject positionsβ for individuals and cultivate dispositions to action or inaction. The article discusses the importance of citizensβ political engagement with climate change and points out some aspects of media(ted) discourses that may constrain the perceived possibilities of participation in the politics of climate change. While engagement with climate change has multiple dimensions and a number of barriers have been identified through empirical studies, this article offers a critique of the role of the media in political engagement with the problem and suggests avenues for future research.The author is grateful to the Portuguese Funda A, o para a CiIncia e a Tecnologia for funding the project 'The Politics of Climate Change: Discourses and Representations' (POCI/COM56973/2004), to Jan Zienkowski for relevant comments on this paper, and to the reviewers who provided detailed feedback
High level expression of differentially localized BAG-1 isoforms in some oestrogen receptor-positive human breast cancers
Sensitivity to oestrogens and apoptosis are critical determinants of the development and progression of breast cancer and reflect closely linked pathways in breast epithelial cells. For example, induction of BCL-2 oncoprotein expression by oestrogen contributes to suppression of apoptosis and BCL-2 and oestrogen receptor (ER) are frequently co-expressed in tumours. BAG-1/HAP is a multifunctional protein which complexes with BCL-2 and steroid hormone receptors (including the ER), and can suppress apoptosis and influence steroid hormone-dependent transcription. Therefore, analysis of expression of BAG-1 in human breast cancer is of considerable interest. BAG-1 was readily detected by immunostaining in normal breast epithelial cells and most ER-positive tumours, but was undetectable or weakly expressed in ER-negative tumours. BAG-1 positive cells showed a predominantly cytoplasmic or cytoplasmic plus nuclear distribution of staining. A correlation between ER and BAG-1 was also evident in breast cancer derived cell lines, as all lines examined with functional ER expression also expressed high levels of BAG-1. In addition to the prototypical 36 kDa BAG-1 isoform, breast cancer cells expressed higher molecular weight isoforms and, in contrast to BCL-2, BAG-1 expression was independent of oestrogens. BAG-1 isoforms were differentially localized to the nucleus or cytoplasm and this was also independent of oestrogens. These results demonstrate a close association between BAG-1 and functional ER expression and suggest BAG-1 may be useful as a therapeutic target or prognostic marker in breast cancer. Β© 1999 Cancer Research Campaig
Identification of Novel High-Frequency DNA Methylation Changes in Breast Cancer
Recent data have revealed that epigenetic alterations, including DNA methylation and chromatin structure changes, are among the earliest molecular abnormalities to occur during tumorigenesis. The inherent thermodynamic stability of cytosine methylation and the apparent high specificity of the alterations for disease may accelerate the development of powerful molecular diagnostics for cancer. We report a genome-wide analysis of DNA methylation alterations in breast cancer. The approach efficiently identified a large collection of novel differentially DNA methylated loci (βΌ200), a subset of which was independently validated across a panel of over 230 clinical samples. The differential cytosine methylation events were independent of patient age, tumor stage, estrogen receptor status or family history of breast cancer. The power of the global approach for discovery is underscored by the identification of a single differentially methylated locus, associated with the GHSR gene, capable of distinguishing infiltrating ductal breast carcinoma from normal and benign breast tissues with a sensitivity and specificity of 90% and 96%, respectively. Notably, the frequency of these molecular abnormalities in breast tumors substantially exceeds the frequency of any other single genetic or epigenetic change reported to date. The discovery of over 50 novel DNA methylation-based biomarkers of breast cancer may provide new routes for development of DNA methylation-based diagnostics and prognostics, as well as reveal epigenetically regulated mechanism involved in breast tumorigenesis
Toward a Theory of Child Well-Being
Assuring the well-being of children has emerged over the past several decades as an important goal for health and social policymakers. Although the concept of child well-being has been operationalized and measured in different ways by different child-serving entities, there are few unifying theories that could undergird and inform these various conceptual and measurement efforts. In this paper, we attempt to construct a theory of child well-being. We first review the social and policy history of the concept of child well-being, and briefly review its measurement based on these conceptualizations. We then examine three types of theories of well-being extant in philosophy - mental states theories, desire-based theories and needs-based theories - and investigate their suitability to serve as prototypes of a theory of child well-being. We develop a constraint that child well-being is important in and of itself and not merely as a way station to future adult well-being (we call this a non-reduction constraint). Using this constraint, we identify the limitations of each of the three sets of theories to serve as a basis for a theory of child well-being. Based on a developmentalist approach, we then articulate a theory of child well-being that contains two conditions. First, a child's stage-appropriate capacities that equip her for successful adulthood, given her environment; and, second, an engagement with the world in child-appropriate ways. We conclude by reviewing seven implications of this theoretical approach for the measurement of child well-being. Key Words Child well-being, philosophy, social policy, child developmentNoneThis is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11205-014-0665-
The Study of Rule-Governed Behavior and Derived Stimulus Relations: Bridging the Gap
The concept of rule-governed behavior or instructional control has been widely recognized for many decades within the behavior-analytic literature. It has also been argued that the human capacity to formulate and follow increasingly complex rules may undermine sensitivity to direct contingencies of reinforcement, and that excessive reliance upon rules may be an important variable in human psychological suffering. Although the concept of rules would appear to have been relatively useful within behavior analysis, it seems wise from time to time to reflect upon the utility of even well-established concepts within a scientific discipline. Doing so may be particularly important if it begins to emerge that the existing concept does not readily orient researchers toward potentially important variables associated with that very concept. The primary purpose of this article is to engage in this reflection. In particular, we will focus on the link that has been made between rule-governed behavior and derived relational responding, and consider the extent to which it might be useful to supplement talk of rules or instructions with terms that refer to the dynamics of derived relational responding
RNA Is an Integral Component of Chromatin that Contributes to Its Structural Organization
Chromatin structure is influenced by multiples factors, such as pH, temperature, nature and concentration of counterions, post-translational modifications of histones and binding of structural non-histone proteins. RNA is also known to contribute to the regulation of chromatin structure as chromatin-induced gene silencing was shown to depend on the RNAi machinery in S. pombe, plants and Drosophila. Moreover, both in Drosophila and mammals, dosage compensation requires the contribution of specific non-coding RNAs. However, whether RNA itself plays a direct structural role in chromatin is not known. Here, we report results that indicate a general structural role for RNA in eukaryotic chromatin. RNA is found associated to purified chromatin prepared from chicken liver, or cultured Drosophila S2 cells, and treatment with RNase A alters the structural properties of chromatin. Our results indicate that chromatin-associated RNAs, which account for 2%β5% of total chromatin-associated nucleic acids, are polyAβ and show a size similar to that of the DNA contained in the corresponding chromatin fragments. Chromatin-associated RNA(s) are not likely to correspond to nascent transcripts as they are also found bound to chromatin when cells are treated with Ξ±-amanitin. After treatment with RNase A, chromatin fragments of molecular weight >3.000 bp of DNA showed reduced sedimentation through sucrose gradients and increased sensitivity to micrococcal nuclease digestion. This structural transition, which is observed both at euchromatic and heterochromatic regions, proceeds without loss of histone H1 or any significant change in core-histone composition and integrity
Arabidopsis RPT2a, 19S Proteasome Subunit, Regulates Gene Silencing via DNA Methylation
The ubiquitin/proteasome pathway plays a crucial role in many biological processes. Here we report a novel role for the Arabidopsis 19S proteasome subunit RPT2a in regulating gene activity at the transcriptional level via DNA methylation. Knockout mutation of the RPT2a gene did not alter global protein levels; however, the transcriptional activities of reporter transgenes were severely reduced compared to those in the wild type. This transcriptional gene silencing (TGS) was observed for transgenes under control of either the constitutive CaMV 35S promoter or the cold-inducible RD29A promoter. Bisulfite sequencing analysis revealed that both the transgene and endogenous RD29A promoter regions were hypermethylated at CG and non-CG contexts in the rpt2a mutant. Moreover, the TGS of transgenes driven by the CaMV 35S promoters was released by treatment with the DNA methylation inhibitor 5-aza-2β²-deoxycytidine, but not by application of the inhibitor of histone deacetylase Trichostatin A. Genetic crosses with the DNA methyltransferase met1 single or drm1drm2cmt3 triple mutants also resulted in a release of CaMV 35S transgene TGS in the rpt2a mutant background. Increased methylation was also found at transposon sequences, suggesting that the 19S proteasome containing AtRPT2a negatively regulates TGS at transgenes and at specific endogenous genes through DNA methylation
Physcomitrella patens DCL3 Is Required for 22β24 nt siRNA Accumulation, Suppression of Retrotransposon-Derived Transcripts, and Normal Development
Endogenous 24 nt short interfering RNAs (siRNAs), derived mostly from intergenic and repetitive genomic regions, constitute a major class of endogenous small RNAs in flowering plants. Accumulation of Arabidopsis thaliana 24 nt siRNAs requires the Dicer family member DCL3, and clear homologs of DCL3 exist in both flowering and non-flowering plants. However, the absence of a conspicuous 24 nt peak in the total RNA populations of several non-flowering plants has raised the question of whether this class of siRNAs might, in contrast to the ancient 21 nt microRNAs (miRNAs) and 21β22 nt trans-acting siRNAs (tasiRNAs), be an angiosperm-specific innovation. Analysis of non-miRNA, non-tasiRNA hotspots of small RNA production within the genome of the moss Physcomitrella patens revealed multiple loci that consistently produced a mixture of 21β24 nt siRNAs with a peak at 23 nt. These Pp23SR loci were significantly enriched in transposon content, depleted in overlap with annotated genes, and typified by dense concentrations of the 5-methyl cytosine (5 mC) DNA modification. Deep sequencing of small RNAs from two independent Ppdcl3 mutants showed that the P. patens DCL3 homolog is required for the accumulation of 22β24 nt siRNAs, but not 21 nt siRNAs, at Pp23SR loci. The 21 nt component of Pp23SR-derived siRNAs was also unaffected by a mutation in the RNA-dependent RNA polymerase mutant Pprdr6. Transcriptome-wide, Ppdcl3 mutants failed to accumulate 22β24 nt small RNAs from repetitive regions while transcripts from two abundant families of long terminal repeat (LTR) retrotransposon-associated reverse transcriptases were up-regulated. Ppdcl3 mutants also displayed an acceleration of leafy gametophore production, suggesting that repetitive siRNAs may play a role in the development of P. patens. We conclude that intergenic/repeat-derived siRNAs are indeed a broadly conserved, distinct class of small regulatory RNAs within land plants
Bisulfite Sequencing Reveals That Aspergillus flavus Holds a Hollow in DNA Methylation
Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species
Review of the literature and suggestions for the design of rodent survival studies for the identification of compounds that increase health and life span
Much of the literature describing the search for agents that increase the life span of rodents was found to suffer from confounds. One-hundred-six studies, absent 20 contradictory melatonin studies, of compounds or combinations of compounds were reviewed. Only six studies reported both life span extension and food consumption data, thereby excluding the potential effects of caloric restriction. Six other studies reported life span extension without a change in body weight. However, weight can be an unreliable surrogate measure of caloric consumption. Twenty studies reported that food consumption or weight was unchanged, but it was unclear whether these data were anecdotal or systematic. Twenty-nine reported extended life span likely due to induced caloric restriction. Thirty-six studies reported no effect on life span, and three a decrease. The remaining studies suffer from more serious confounds. Though still widely cited, studies showing life span extension using short-lived or βenfeebledβ rodents have not been shown to predict longevity effects in long-lived animals. We suggest improvements in experimental design that will enhance the reliability of the rodent life span literature. First, animals should receive measured quantities of food and its consumption monitored, preferably daily, and reported. Weights should be measured regularly and reported. Second, a genetically heterogeneous, long-lived rodent should be utilized. Third, chemically defined diets should be used. Fourth, a positive control (e.g., a calorically restricted group) is highly desirable. Fifth, drug dosages should be chosen based on surrogate endpoints or accepted cross-species scaling factors. These procedures should improve the reliability of the scientific literature and accelerate the identification of longevity and health span-enhancing agents
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