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- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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- Kips, J. C., et al.
(författare)
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Murine models of asthma
- 2003
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Ingår i: Eur Respir J. ; 22:2
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Tidskriftsartikel (refereegranskat)abstract
- In vivo animal models can offer valuable information on several aspects of asthma pathogenesis and treatment. The mouse is increasingly used in these models, mainly because this species allows for the application in vivo of a broad range of immunological tools, including gene deletion technology. Mice, therefore, seem particularly useful to further elucidate factors influencing the response to inhaled allergens. Examples include: the role of immunoregulatory mechanisms that protect against T-helper cell type 2 cell development; the trafficking of T-cells; and the contribution of the innate immunity. However, as for other animal species, murine models also have limitations. Mice do not spontaneously develop asthma and no model mimics the entire asthma phenotype. Instead, mice should be used to model specific traits of the human disease. The present task force report draws attention to specific aspects of lung structure and function that need to be borne in mind when developing such models and interpreting the results. In particular, efforts should be made to develop models that mimic the lung function changes characteristic of asthma as closely as possible. A large section of this report is therefore devoted to an overview of airway function and its measurement in mice.
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- Joos, G. F., et al.
(författare)
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Indirect airway challenges
- 2003
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Ingår i: Eur Respir J. ; 21:6
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Tidskriftsartikel (refereegranskat)abstract
- Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.
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- Piponiot, Camille, et al.
(författare)
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Distribution of biomass dynamics in relation to tree size in forests across the world
- 2022
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 234, s. 1664-1677
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Tidskriftsartikel (refereegranskat)abstract
- Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4–52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1–10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.
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