933 resultados para NONGENOMIC ACTIONS


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Resource-intensive, high-carbon, Western lifestyles are frequently criticised as unsustainable and deeply unsatisfying. However, these lifestyles are still attractive to the majority of Westerners and to a high proportion of the developing world’s middle classes. This paper argues that the imminent threat of catastrophic climate change constitutes an immediate political, economic and ethical challenge for citizens of the developed world that cannot be tackled by appeals to asceticism or restraint. There can be no solution to climate change until sustainable conceptions of the good life are developed that those in the west want to live and which others might want to live. While the ultimate solution to climate change is the development of low carbon lifestyles, it is important that government initiatives, governance arrangements and economic incentives support rather than undermine that search. Like the global financial crisis, the climate change crisis also demonstrates what happens when weaknesses in national, corporate and professional governance are exacerbated by weaknesses in global governance. In tackling the latter, it is critical the mistakes now evidenced in the former are avoided – including a rethinking of carbon market and carbon tax alternatives. It is also critical that individuals must take responsibility for their actions as consumers, voters and investors.

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In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

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Abstract This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder. RÉSUMÉ Cette étude a investigué les symptômes dépressifs et les relations interpersonnels d'une thérapie narrative en huit séances chez 47 adultes souffrant d'un trouble dépressif majeur. Après la thérapie, l'amélioration des symptômes dépressifs (d=1.36) et la proportion de clients atteignant un changement significatif (74%), le mouvement vers la population fonctionnelle (61%), enfin l'amélioration clinique significative (53%) étaient comparables aux performances des études de résultats. L'amélioration des relations interpersonnelles (d=0.62) était inférieure à l'amélioration symptomatique. Le suivi à trois mois montrait un maintien des gains symptomatiques mais pas pour les relations interpersonnelles. L’évaluation des performances et les analyses de significativité clinique modèrent les limitations du plan de recherche à mesures répétées et apportent une preuve empirique qui étaie l'efficacité des thérapies narratives pour des adultes avec un trouble dépressif majeur. Este estudo investigou sintomas depressivos e resultados interpessoais relacionados em oito sessões de terapia narrativa manualizada para 47 adultos com perturbação depressiva major. No pós terapia, melhoria de sintomas depressivos (d=1,36) e proporção de clientes que alcançam melhoria válida (74%), movimento para a população funcional (61%) e melhoria clinicamente significativa (53%) foram comparáveis com os resultados da investigação reportados. As melhorias pós terapia nos resultados interpessoais relacionados (d=.62) foi menos substancial do que para os sintomas. Aos três meses de seguimento houve a manutenção dos sintomas mas não dos ganhos interpessoais. As análises de benchemarking e de melhoria clinicamente significativas atenuam as limitações de um design de medidas repetidas, fornecendo evidência empírica para a terapia narrativa para adultos com perturbação depressiva major. Questo lavoro ha valutato i sintomi depressivi e gli outcome nella capacità di relazionarsi a livello interpersonale in 8 sedute di psicoterapia narrativa manualizzata in un gruppo di 47 adulti con depressione maggiore. I risultati ottenuti relativamente a: post terapy, miglioramento dei sintomi depressivi (d_1.36), proporzione di pazienti che hanno raggiunto un miglioramento affidabile e consistente (74%), movimento verso il funzionamento atteso nella popolazione (61%) e miglioramento clinicamente significativo (53%) sono paragonabili ai valori di riferimento della ricerca sull'outcome. I miglioramento della capacità di relazionarsi valutata alla fine del trattamento (d_.62) si è rivelata meno sostanziale rispetto ai sintomi. Un follow-up dopo 3 mesi ha dimostrato che il miglioramento sintomatologico è stato mantenuto, ma non quello degli obiettivi interpersonali. Valori di riferimento e analisi della significatività clinica hanno fatto fronte ai limiti del disegno a misure ripetute, offrendo prove empiriche sulla rilevanza della terapia narrativa in pazienti adulti con depressione maggiore