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

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

Scattering theory of interface resistance in magnetic multilayers

The scattering theory of transport has to be applied with care in a diffuse environment. Here we discuss how the scattering matrices of heterointerfaces can be used to compute interface resistances of dirty magnetic multilayers. First principles calculations of these interface resistances agree well with experiments in the CPP (current perpendicular to the interface plane) configuration.Comment: submitted to J. Phys. D (special issue at the occasion of Prof. T. Shinjo's 60th birthday

Report on the evaluation of the IMD programme in Guatemala 2002 - 2003

An external evaluation was carried out in July-August 2003 to assess the results and the implementation process of the first 15 months of IMD’s programme in Guatemala. The central objective of this programme is to strengthen political parties and the party system in a sustainable way. Several unfavourable conditions limit the realisation of this ambition: (i) the political party system in Guatemala has been unstable, fragmented, polarised and discredited, (ii) political parties were often not more than electoral machines, lacking a programmatic and ideological base, and generally figured among the weakest actors in society, (iii) political participation by citizens has been very low, especially among the indigenous majority of the population. Against this background, since March 2002 IMD developed in a joint venture with UNDP an ambitious project for a multiparty dialogue process, trying to generate consensus on a shared National Agenda that reflects the basic principles of the Peace Agreements. The basic idea was that collaboration and dialogue among the parties is a prerequisite for future democratic stability, as none of the individual parties is able to sustain such a national project. Moreover, the national Congress does not function as a forum for dialogue given the polarized political climate in the country...