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Medical Sciences	50%

Selected Abstracts

Signalling events involved in interferon-,-inducible macrophage nitric oxide generation

IMMUNOLOGY, Issue 4 2003
Julie Blanchette
Summary Nitric oxide (NO) produced by macrophages (M,) in response to interferon-, (IFN-,) plays a pivotal role in the control of intracellular pathogens. Current knowledge of the specific biochemical cascades involved in this IFN-,-inducible M, function is still limited. In the present study, we evaluated the participation of various second messengers , Janus kinase 2 (JAK2), signal transducer and activator of transcription (STAT) 1,, MAP kinase kinase (MEK1/2), extracellular signal-regulated kinases 1 and 2 (Erk1/Erk2) and nuclear factor kappa B (NF-,B) , in the regulation of NO production by IFN-,-stimulated J774 murine M,. The use of specific signalling inhibitors permitted us to establish that JAK2/STAT1,- and Erk1/Erk2-dependent pathways are the main players in IFN-,-inducible M, NO generation. To determine whether the inhibitory effect was taking place at the pre- and/or post-transcriptional level, we evaluated the effect of each antagonist on inducible nitric oxide synthase (iNOS) gene and protein expression, and on the capacity of IFN-, to induce JAK2, Erk1/Erk2 and STAT1, phosphorylation. All downregulatory effects occurred at the pretranscriptional level, except for NF-,B, which seems to exert its role in NO production through an iNOS-independent event. In addition, electrophoretic mobility shift assay (EMSA) analysis revealed that STAT1, is essential for IFN-,-inducible iNOS expression and NO production, whereas the contribution of NF-,B to this cellular regulation seems to be minimal. Moreover, our data suggest that Erk1/Erk2 are responsible for STAT1, Ser727 residue phosphorylation in IFN-,-stimulated M,, thus contributing to the full activation of STAT1,. Taken together, our results indicate that JAK2, MEK1/2, Erk1/Erk2 and STAT1, are key players in the IFN-,-inducible generation of NO by M,. [source]

The NHS forensic mental health R&D programme: Developing new talent or maintaining a stage army?

PERSONALITY AND MENTAL HEALTH, Issue 3 2008
Keith Soothill
This paper considers the successful recipients of the 79 project awards made during the 12-year ,life' (1996,2007) of the NHS Forensic Mental Health (FMH) R&D programme. The focus is on whether the 213 persons (principal investigators (PIs) and/or co-investigators (CIs)) represent new talent or existing academic entrepreneurs in the FMH field. Amongst PIs, awards were almost without exception given to researchers with an established research track record. Forensic psychiatrists continue to be the main players, but other research groupings are emerging as PIs. In contrast, CIs range more widely in terms of previous research experience and professional background. 38.5 percent had no apparent experience of previous funded research projects apart from grants funded by the FMH programme. Hence, CIs are the source of new talent amongst the programme's project awards. The authors warn of the dangers of losing the benefits of this investment as policy priorities shift. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Gründungen an der Schnittstelle zwischen Wissenschaft und Wirtschaft , die Rolle der Hochschulen

PERSPEKTIVEN DER WIRTSCHAFTSPOLITIK, Issue 3 2002
Frieder Mayer, Krahmer
In national innovation systems, universities are not only essential elements of the research infrastructure, but also main players in the field of education and further education. Their specific role in the interplay between knowledge production and market implementation of knowledge via start,ups derives from this fact. This article takes as its theme the university environment which supports and stimulates the start,up processes. It also shows the progress achieved in the German university landscape in recent years on the path towards a culture of entrepreneurship in teaching and research. This is manifested, for example, in the number of start,up chairs, the development of networks to exploit the start,up potential of universities together with regional partners, and in the numbers of spin,offs established. [source]

Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability,

THE JOURNAL OF PATHOLOGY, Issue 5 2009
Mi Ran Kang
Abstract Mounting evidence indicates that alterations of autophagy processes are directly involved in the development of many human diseases, including cancers. Autophagy-related gene (ATG) products are main players in the autophagy process. In humans there are 16 known ATG genes, of which four (ATG2B, ATG5, ATG9B and ATG12) have mononucleotide repeats with seven or more nucleotides. Frameshift mutations of genes with mononucleotide repeats are features of cancers with microsatellite instability (MSI). It is not known whether ATG genes with mononucleotide repeats are altered by frameshift mutations in gastric and colorectal carcinomas with MSI. For this, we analysed the mononecleotide repeats in ATG2B, ATG5, ATG9B and ATG12 in 32 gastric carcinomas with high MSI (MSI-H), 13 gastric carcinomas with low MSI (MSI-L), 43 colorectal carcinomas with MSI-H and 15 colorectal carcinomas with MSI-L by a single-strand conformation polymorphism (SSCP) analysis. We found ATG2B, ATG5, ATG9B and ATG12 mutations in 10, 2, 13 and 0 cancers, respectively. The mutations were detected in MSI-H cancers but not in MSI-L cancers. Gastric and colorectal cancers with MSI-H harboured one or more ATG mutations in 28.1% and 27.9%, respectively. Our data indicate that frameshift mutations in ATG genes with mononucleotide repeats are common in gastric and colorectal carcinomas with MSI-H, and suggest that these mutations may contribute to cancer development by deregulating the autophagy process. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]