University of Zurich

About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.

A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes.

Abstract: We have developed a simple non-radioactive in situ hybridization procedure for tissue sections and cultured cells using digoxigenin-labelled cRNA probes. This protocol can be applied for the detection of various transcripts present at a wide range of expression levels in the central nervous system. Cerebellar hybridization signals for transcripts estimated to be expressed at high (MBP, myelin basic protein), moderate (GluR1, subunit of AMPA/kainate sensitive glutamate receptors) and low (inositol polyphosphate-5-phosphatase) levels of abundance are demonstrated as examples. The sensitivity and cellular resolution were significantly improved by avoiding any ethanol treatment commonly used in other procedures. The localization of a labelled cell with respect to its environment is shown to be more easily assessed by counterstaining of the tissue with the nuclear dye Hoechst 33258. The present protocol can be combined with immunocytochemistry as demonstrated for glial fibrillary acidic protein (GFAP). All steps of the procedure, including preparation and labelling of the cRNA probes, pretreatment of tissue, hybridization and visualization of the labelled transcripts, are described in detail.

Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.

Abstract: Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91(phox). We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.

Perception of hazards: the role of social trust and knowledge

Abstract: Recent research indicates that social trust of those who manage a hazard is strongly correlated to judgments about the hazard's risk and benefits. The present study investigates the more specific question of “For which hazards is this?” It was postulated that when an individual lacks knowledge about a hazard, social trust of authorities managing the hazard determines perceived risks and benefits. On the other hand, when an individual has personal knowledge about a hazard and therefore does not need to rely on managing authorities, social trust is unrelated to judged risks and benefits. Participants (N = 91) assessed risks, benefits, and trust in managing authorities and personal knowledge associated with 25 hazardous technologies and activities. As expected, strong correlations between social trust and judged risks and benefits were observed for hazards about which people did not possess much knowledge. No significant correlations between social trust and judged risks and benefits were found for hazards about which people were knowledgeable. Results suggest that the lay public relies on social trust when making judgments of risks and benefits when personal knowledge about a hazard is lacking. Replicating findings of other studies, the present study also found negative correlations between perceived risks and perceived benefits. When social trust was controlled for, correlations between perceived risks and benefits diminished. Implications of the results for risk management are discussed.