| 1. |
- Erickson, Alison R, et al.
(author)
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Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease
- 2012
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In: PLOS ONE. - San Francisco : Public Library Science. - 1932-6203. ; 7:11
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Journal article (peer-reviewed)abstract
- Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.
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| 2. |
- Heap, Graham A., et al.
(author)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Journal article (peer-reviewed)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 3. |
- Kyrpides, Nikos C, et al.
(author)
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Genomic encyclopedia of bacteria and archaea: sequencing a myriad of type strains.
- 2014
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In: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 12:8
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Journal article (peer-reviewed)abstract
- Microbes hold the key to life. They hold the secrets to our past (as the descendants of the earliest forms of life) and the prospects for our future (as we mine their genes for solutions to some of the planet's most pressing problems, from global warming to antibiotic resistance). However, the piecemeal approach that has defined efforts to study microbial genetic diversity for over 20 years and in over 30,000 genome projects risks squandering that promise. These efforts have covered less than 20% of the diversity of the cultured archaeal and bacterial species, which represent just 15% of the overall known prokaryotic diversity. Here we call for the funding of a systematic effort to produce a comprehensive genomic catalog of all cultured Bacteria and Archaea by sequencing, where available, the type strain of each species with a validly published name (currently∼11,000). This effort will provide an unprecedented level of coverage of our planet's genetic diversity, allow for the large-scale discovery of novel genes and functions, and lead to an improved understanding of microbial evolution and function in the environment.
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| 4. |
- Simelton, Elisabeth, 1967, et al.
(author)
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African farmers’ perceptions of erratic rainfall
- 2011
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In: Centre for Climate change economics and policy. ; :73
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Journal article (other academic/artistic)abstract
- Farmers’ perceptions of how rainfall is changing is crucial in anticipating the effects of climate change, as only farmers who perceive a problem will adapt to it. However, even within the same location, people may perceive rainfall changes differently. Therefore, how can scientists, practitioners, and farmers ensure that they talk about the same rainfall changes? The overall aim of this paper is to improve the understanding of what people mean when they say rainfall is becoming more erratic. To do this we used interviews to identify farmers’ perceptions of rainfall changes from four semi-arid regions in four African countries: Botswana, Ethiopia, Ghana and Malawi, and integrated this with (daily or monthly) meteorological data to assess the perceived and actual rainfall. A conceptual rainfall matrix was designed to organise the data in terms of perceptions of onset, duration or cessation. Semi-structured interviews were used to identify factors that may confound perceptions of changes in rainfall. The matrix helped to clarify ways in which rainfall was becoming “more erratic”, in particular in identifying that increasing frequency of dry days and reduced amounts of rainfall (i.e. a meteorological definition) were behind perceptions that rainy seasons started later and finished earlier. A common perception that could not be found within meteorological data was that “rainfall used to start earlier than now”. Also, the timings of the perceived changes diverged. Perceptions that could be reproduced across datasets include “it is difficult to know when the rainy season starts”. Here, “more erratic rainfall” may refer to increasing inter-annual variability in the timing of onsets (using an agronomic definition), which resulted in less predictable rainy seasons. Factors confounding perceptions of rainfall include (lack of and existing) institutional support that prevent farmers from responding at the onset of the rainy season, as well as a lack of words to express variability and change. We introduce “access droughts” to denote crop failures that result from institutional support that leads to maladaptation strategies and increased sensitivity of the agricultural system. Access droughts are sometimes mistaken (by farmers, scientists, extension, policy makers etc.) for agronomic or meteorological droughts. The research suggests that top-down climate impact scenarios need to be grounded with farmers’ and extension workers’ understandings of how weather is changing more carefully in order to improve policy implementation. The graphs presented
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