A Defined, Feeder-Free, Serum-Free System to Generate In Vitro Hematopoietic Progenitors and Differentiated Blood Cells from hESCs and hiPSCs

Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimentional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments

Post-Translational Inhibition of IP-10 Secretion in IEC by Probiotic Bacteria: Impact on Chronic Inflammation

Peer reviewedPublisher PD

Reflexivity, the picturing of selves, the forging of methods

This paper addresses alternative models for a reflexive methodology and examines the ways in which doctoral students have appropriated these texts in their theses. It then considers the indeterminate qualities of those appropriations. The paper offers a new account of reflexivity as 'picturing', drawing analogies from the interpretation of two very different pictures, by Velázquez and Tshibumba. It concludes with a more open and fluid account of reflexivity, offering the notion of 'signature', and drawing on the work of Gell and also Deleuze and Guattari in relation to the inherently specific nature of 'concepts' situated in space and time

The significance of genome-wide transcriptional regulation in the evolution of stress tolerance.

It is widely recognized that stress plays an important role in directing the adaptive adjustment of an organism to changing environments. However, very little is known about the evolution of mechanisms that promote stress-induced variation. Adaptive transcriptional responses have been implicated in the evolution of tolerance to natural and anthropogenic stressors in the environment. Recent technological advances in transcriptomics provide a mechanistic understanding of biological pathways or processes involved in stress-induced phenotypic change. Furthermore, these studies are (semi) quantitative and provide insight into the reaction norms of identified target genes in response to specific stressors. We argue that plasticity in gene expression reaction norms may be important in the evolution of stress tolerance and adaptation to environmental stress. This review highlights the consequences of transcriptional plasticity of stress responses within a single generation and concludes that gene promoters containing a TATA box are more capable of rapid and variable responses than TATA-less genes. In addition, the consequences of plastic transcriptional responses to stress over multiple generations are discussed. Based on examples from the literature, we show that constitutive over expression of specific stress response genes results in stress adapted phenotypes. However, organisms with an innate capacity to buffer stress display plastic transcriptional responses. Finally, we call for an improved integration of the concept of phenotypic plasticity with studies that focus on the regulation of transcription. © Springer Science+Business Media B.V. 2010

Persoonsgerichte continuïteit: Een verkennende studie

Patient-centered continuity involves the development and use of a patient image in the successive contacts of a general practitioner with a patient. In the patient image the common history of doctor and patient is condensed. In this study two questions were examined: • Which components can be recognized in the patient image? • How do general practitioners use these components in their patient management? In an exploring study seven general practitioners applicating Kolb's model of experimental learning passed six empirical cycles. In each cycle a hypothesis was developed and tested in practice: the participating doctors executed an instruction in five to ten contacts. Two major components could be recognized: the cognitive component, and the feeling component. Within the latter two categories appeared to be relevant: feelings about the relation with the patient and feelings about the patient as a person. We compared these feelings on four moments: immediately before a consultation, as soon as the patient had entered the consultation room, immediately after the consultation and one to two weeks after the consultation. We found that general practitioners reported more tension evoked by the patient if contact with the patient was near. If they reported such a feeling, they mentioned relatively few feelings about this patient as a person, at that moment. In tincognitive component a distinction could be made between the easily transferable knowledge of the patients disease or illness history, and knowledge about the patients way of coping with health problems which cannot easily be transferred to another doctor. The patient image almost always influenced patient management in general practice. A continuing relationship leads up to less action rather than more