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- Lehmann, O. J., et al.
(author)
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Novel anterior segment phenotypes resulting from forkhead gene alterations: Evidence for cross-species conservation of function
- 2003
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In: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:6, s. 2627-2633
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Journal article (peer-reviewed)abstract
- PURPOSE. Mutations in murine and human Versions of an ancestrally related gene usually result in similar phenotypes. However, interspecics differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS. A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS. Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.
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| 2. |
- Fazey, Ioan, et al.
(author)
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Ten essentials for action-oriented and second order energy transitions, transformations and climate change research
- 2018
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In: Energy Research and Social Science. - : Elsevier BV. - 2214-6296 .- 2214-6326. ; 40, s. 54-70
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Research review (peer-reviewed)abstract
- The most critical question for climate research is no longer about the problem, but about how to facilitate the transformative changes necessary to avoid catastrophic climate-induced change. Addressing this question, however, will require massive upscaling of research that can rapidly enhance learning about transformations. Ten essentials for guiding action-oriented transformation and energy research are therefore presented, framed in relation to second-order science. They include: (1) Focus on transformations to low-carbon, resilient living; (2) Focus on solution processes; (3) Focus on ‘how to’ practical knowledge; (4) Approach research as occurring from within the system being intervened; (5) Work with normative aspects; (6) Seek to transcend current thinking; (7) Take a multi-faceted approach to understand and shape change; (8) Acknowledge the value of alternative roles of researchers; (9) Encourage second-order experimentation; and (10) Be reflexive. Joint application of the essentials would create highly adaptive, reflexive, collaborative and impact-oriented research able to enhance capacity to respond to the climate challenge. At present, however, the practice of such approaches is limited and constrained by dominance of other approaches. For wider transformations to low carbon living and energy systems to occur, transformations will therefore also be needed in the way in which knowledge is produced and used.
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