Transcriptional regulation of the human ALDH1A1 promoter by the oncogenic homeoprotein TLX1/HOX11

The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity

Maatschappelijk organisaties, de weg kwijt?

__Abstract__ Dit paper over Nederlandse maatschappelijke organisaties beperkt zich tot de gesubsidieerde particuliere organisaties binnen de internationale samenwerking voor ontwikkeling (OS). De rol van het ministerie van Buitenlandse Zaken (Buza) is van grote invloed geweest op de professionalisering en de beleidskeuzes van de particuliere OS-sector. Nu subsidiering steeds meer onder vuur ligt, zoeken ontwikkelingsorganisaties hun heil op de charimarkt dan wel op de zakelijke markt. Dit lijkt ons de weg van de minste weerstand; het leidt bovendien af van de kern en de meerwaarde van hun mandaat. Ontwikkelingsorganisaties doen er beter aan anticyclisch te denken en hun oorspronkelijke politieke opdracht te hervinden: weerwerk bieden, misstanden aan de kaak stellen en oplossingen zoeken in de verbinding tussen mondiale problemen en de Nederlandse samenleving. Dat kun je niet aan de markt overlaten. Wij zijn dan ook van mening dat de overheid dit ruimhartig moet subsidieren, en dat ontwikkelingsorganisaties daarvoor moeten gaan vechten

Identification clouds: aspects of the implementation

This note is concerned with the automatic assignment of keyphrases to (short) documents, for instance abstracts. The assumption is that there is a standardized list of keyphrases that can be used. The emphasis is on implementation issue

Modeling and experimental verification of the dynamic interaction of an AFM-tip with a photonic crystal microcavity

We present a transmission model for estimating the effect of the atomic-force microscopy tapping tip height on a photonic crystal microcavity (MC). This model uses a fit of the measured tip-height-dependent transmission above a “hot spot” in the MC. The predicted transmission versus average tapping height is in good agreement with the values obtained from tapping mode experiments. Furthermore, we show that for the existing, nonoptimized structure, the transmission coefficient can be tuned between 0.32 and 0.8 by varying the average tapping height from 26 to 265 nm. A transmission larger than that of the undisturbed cavity at resonance was observed at specific tip locations just outside the cavity-terminating holes

Estrés Abiótico y Homeostasis Iónica

Master Universitario en Biología Agraria y Acuicultura.-- 75 horas, 3 Créditos ECTS.Peer reviewe