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- Weber, H., et al.
(författare)
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The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis
- 2014
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 24:1, s. 65-85
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Tidskriftsartikel (refereegranskat)abstract
- NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.
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- Beech, Jason P., et al.
(författare)
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Cell morphology and deformability in deterministic lateral displacement devices
- 2011
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Ingår i: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011. - 9781618395955 ; 2, s. 1355-1357
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Konferensbidrag (refereegranskat)abstract
- Deterministic Lateral Displacement (DLD) devices have been used to separate particles based on size [1] and shape [2]. Here we show how DLD devices can also be used to separate particles based on their ability to deform under shear forces. Varying experimental conditions allows us to vary the relative contributions of size, morphology and deformability. The ability to distinguish between cells based on deformability with high resolution and throughput, in cheap and simple devices, could find highly interesting and relevant applications, for example in the detection of circulating tumor cells or malaria-infected blood cells.
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- Beech, Jason P., et al.
(författare)
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Sample preparation for single-cell whole chromosome analysis
- 2012
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Ingår i: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012. - 9780979806452 ; , s. 998-999
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Konferensbidrag (refereegranskat)abstract
- In this work we present an integrated system for whole chromosome analysis of single bacterium. Using whole genome barcoding techniques, which offer direct and rapid microscopic visualization of the entire genome in one field-of-view, we aim to rapidly identify individual bacterium. We are developing our device to achieve the crucial, and difficult process of isolating a bacterium, removing the DNA in one piece and transferring it to a nano-channel for visualisation. In order to achieve control over the bacteria we encapsulate them in agarose, using flow focusing. The encapsulated bacteria can then be transported in microchannels to proximity with the nanochannels and then chemically lysis can be performed. Following lysis the intact genome can be extracted and transferred to the meandering nanochannel for analysis. We believe this device holds the potential to significantly decrease analysis times for single cell, whole genome analysis with the potential of opening up for automated, high-throughput genome analysis in microfluidic systems.
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- Coleman, M P, et al.
(författare)
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Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership) : an analysis of population-based cancer registry data
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9760, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.
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