870 resultados para antisense transformation


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This article examines attempts to negotiate a perceived residual dominance of settler populations in South Africa and Zimbabwe by means of developmental and cultural policies deemed necessary to restore sovereignty to Africans. Indigenisation has become a preferred strategy for reconstructing post-colonial states in Africa: indigenisation of the economy as part of a Third Chimurenga in Zimbabwe and Black Economic Empowerment in the socio-cultural context of Ubuntu in South Africa. These are issues arising from the regional legacy of contested and uneven transitions to majority rule. Identifying how governments frame the ‘settler problem’, and politicise space in doing so, is crucial for understanding post-colonial politics. Indigenisation in Zimbabwe allows the government to maintain a network of patronage and official rhetoric is highly divisive and exclusivist although couched in terms of reclaiming African values and sovereignty. Revival of Ubuntu as a cultural value system in South Africa facilitates a more positive approach to indigenisation, although Black Economic Empowerment displays elitist tendencies and cultural transformation remains controversial and elusive. The perceived need to anchor policy in socially acceptable (i.e., ostensibly indigenous/traditional) contexts has become a prominent feature of post-colonial politics and is indicative of an indigenous turn in Southern African politics.

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Noncoding RNA is emerging as an important regulator of gene expression in many organisms. We are characterizing RNA-mediated chromatin silencing of the Arabidopsis major floral repressor gene, FLC. Through suppressor mutagenesis, we identify a requirement for CstF64 and CstF77, two conserved RNA 3'-end-processing factors, in FLC silencing. However, FLC sense transcript 3' processing is not affected in the mutants. Instead, CstF64 and CstF77 are required for 3' processing of FLC antisense transcripts. A specific RNA-binding protein directs their activity to a proximal antisense polyadenylation site. This targeted processing triggers localized histone demethylase activity and results in reduced FLC sense transcription. Targeted 3' processing of antisense transcripts may be a common mechanism triggering transcriptional silencing of the corresponding sense gene.

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Transcription in eukaryotic genomes generates an extensive array of non-protein-coding RNA, the functional significance of which is mostly unknown. We are investigating the link between non-coding RNA and chromatin regulation through analysis of FLC - a regulator of flowering time in Arabidopsis and a target of several chromatin pathways. Here we use an unbiased strategy to characterize non-coding transcripts of FLC and show that sense/antisense transcript levels correlate in a range of mutants and treatments, but change independently in cold-treated plants. Prolonged cold epigenetically silences FLC in a Polycomb-mediated process called vernalization. Our data indicate that upregulation of long non-coding antisense transcripts covering the entire FLC locus may be part of the cold-sensing mechanism. Induction of these antisense transcripts occurs earlier than, and is independent of, other vernalization markers and coincides with a reduction in sense transcription. We show that addition of the FLC antisense promoter sequences to a reporter gene is sufficient to confer cold-induced silencing of the reporter. Our data indicate that cold-induced FLC antisense transcripts have an early role in the epigenetic silencing of FLC, acting to silence FLC transcription transiently. Recruitment of the Polycomb machinery then confers the epigenetic memory. Antisense transcription events originating from 3' ends of genes might be a general mechanism to regulate the corresponding sense transcription in a condition/stage-dependent manner.

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The article explores the extent to which criminal justice in Northern Ireland has been reconstructed over the past fifteen years. The focus is on the framework provided in the Good Friday Agreement (1998) and the range of transition processes that followed. Post-Agreement Inquiries are reviewed and the findings demonstrate the institutional rigidities facing the transformation of criminal justice. While the ideologies and practices of counter-terrorism no longer dominate the business of criminal justice, the extent of change in terms of social representativeness, scale and expenditure is variable, with the prison service proving the least changed.

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The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification model was investigated to distinguish the distinct subclasses of pediatric and adult leukemia, as well as MDS. Overall, the accuracy of the diagnostic classification model for subtyping leukemia was approximately 93%, but this was not reflected for the MDS samples giving only approximately 50% accuracy. Discordant samples of MDS were classified either into acute myeloid leukemia (AML) or

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Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure. We studied 16 patients with JAK2-mutant (7 of 16) or JAK2 wild-type (9 of 16) AML after a JAK2-mutant MPN. Primary myelofibrosis or myelofibrotic transformation preceded all 7 JAK2-mutant but only 1 of 9 JAK2 wild-type AMLs (P = .001), implying that JAK2-mutant AML is preceded by mutation(s) that give rise to a "myelofibrosis" phenotype. Loss of the JAK2 mutation by mitotic recombination, gene conversion, or deletion was excluded in all wild-type AMLs. A search for additional mutations identified alterations of RUNX1, WT1, TP53, CBL, NRAS, and TET2, without significant differences between JAK2-mutant and wild-type leukemias. In 4 patients, mutations in TP53, CBL, or TET2 were present in JAK2 wild-type leukemic blasts but absent from the JAK2-mutant MPN. By contrast in a chronic-phase patient, clones harboring mutations in JAK2 or MPL represented the progeny of a shared TET2-mutant ancestral clone. These results indicate that different pathogenetic mechanisms underlie transformation to JAK2 wild-type and JAK2-mutant AML, show that TET2 mutations may be present in a clone distinct from that harboring a JAK2 mutation, and emphasize the clonal heterogeneity of the MPNs.

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Following the 1998 Belfast Agreement in Northern Ireland, levels of paramilitary violence have declined substantially. Among loyalists, the Ulster Volunteer Force (UVF) and associated Red Hand Commando (RHC) have formally renounced violence, and dissolved their 'military structures', and perhaps the most reticent of all of the major paramilitary groupings, the Ulster Defence Association (UDA), has taken on board the central tenets of conflict transformation, and 'stood down' all of its 'active service units' in the Ulster Freedom Fighters (UFF). Thus, paramilitary violence now is mainly confined to the activities of 'dissident' republican groups, notably the Real and Continuity IRAs, although low-level sectarian violence remains a problem. Such dramatic societal and political change has resulted in a focus on the roles of formal party political leadership as agents of social change. This gaze, however, tends to obscure other important events such as the efforts, structures and approaches taken at the grassroots level to uphold and sustain conflict transformation and to maintain a reduction in violence. This article provides analysis of the role played by former loyalist paramilitary combatants in conflict transformation, and draws on material obtained through significant access to those former paramilitaries engaged in processes of societal shifts. In both personal and structural terms there is evidence of former combatants working to diminish the political tensions that remain as a result of the long-term inter-communal hostility developed across decades of violence and conflict.

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Drawing upon criminological studies in the field of prisoner rehabilitation, this essay explores the relevance of the Demobilisation, Disarmament and Reintegration (DDR) framework to the process of conflict transformation in Northern Ireland. In a similar fashion to the critique of 'passivity' offered by, for example, the 'strengths based' or 'good lives' approach to prisoner resettlement and reintegration more generally, the authors contend that the Northern Ireland peace process offers conspicuous examples of former prisoners and combatants as agents and indeed leaders in the process of conflict transformation. They draw out three broad styles of leadership which have emerged amongst ex-combatants over the course of the Northern Ireland transition from conflict-political, military and communal. They suggest that cumulatively such leadership speaks to the potential of ex-prisoners and ex-combatants as moral agents in conflict transformation around which peacemaking can be constructed rather than as obstacles which must be 'managed' out of existence.