RESUMO
Allergic rhinitis is the most common chronic disease in Sweden, with impact on quality of life and with a heavy economic burden for the society. More than 20 years have passed since national recommendations were launched, and meanwhile both ARIA (Allergic rhinitis and its impact of asthma) and EUFOREA (The European Forum for Research and Education in Allergy and Airway Diseases) have presented international guidelines which in this article have been adapted to the clinical situation in Sweden. Visual analogue scale (VAS) is recommended for symptom evaluation, and the importance of correct allergen analysis and examination for coexisting asthma is emphasized. Treatment is recommended according to EUFOREA. Follow-up is important, and if VAS is ≥5 the disease is regarded as uncontrolled and must lead to a change of treatment. Since self-treatment is common in allergic rhinitis the importance of patient cooperation and information is underlined.
Assuntos
Asma , Rinite Alérgica Perene , Rinite Alérgica , Humanos , Criança , Adulto , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/tratamento farmacológico , Qualidade de Vida , Suécia/epidemiologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapia , Asma/tratamento farmacológicoRESUMO
TAF4 is crucial for the activity of many transcription factors, including CREB, RAR and CSL/RBP-Jkappa, but the role for TAF4 in neural development is unknown. Embryonic cortical neural stem cells (NSC) showed strong expression of TAF4 that decreased during neuronal but not glial differentiation. In a protein-protein interaction screen, we identified the intracellular signaling factor RanBPM as a co-factor of TAF4. RanBPM co-localized with TAF4 in a subset of mitotic progenitors in vivo and endogenous TAF4 and RanBPM could be co-immunoprecipitated from NSC extracts. Interestingly, co-transfections of TAF4 and RanBPM led to a significant increase in the number of primary neurite processes but no increase in total neurite length, whereas RanBPM and a TAF4 isoform lacking the RanBPM-interacting domain exerted no significant effect. Our results demonstrate that temporally high expression levels of two factors considered to be relatively general in function can influence very specific events in neuronal differentiation.
Assuntos
Diferenciação Celular/fisiologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Proteínas Nucleares/metabolismo , Células-Tronco/metabolismo , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fator de Transcrição TFIID/metabolismo , Proteína ran de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Células Cultivadas , Córtex Cerebral/citologia , Proteínas do Citoesqueleto , Neuritos/metabolismo , Neuritos/ultraestrutura , Neurônios/citologia , Proteínas Nucleares/genética , Estrutura Terciária de Proteína/fisiologia , Ratos , Células-Tronco/citologia , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Transfecção , Proteína ran de Ligação ao GTP/genéticaRESUMO
The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF(II)135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo.