| 1. |
- Birney, Ewan, et al.
(author)
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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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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)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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| 2. |
- Galluzzi, L, et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Research review (peer-reviewed)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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| 5. |
- Adewumi, Oluseun, et al.
(author)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Journal article (peer-reviewed)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 6. |
- Prescott, D R, et al.
(author)
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A reliability analysis method using binary decision diagrams in phased mission planning
- 2009
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In: Proceedings of the Institution of Mechanical Engineers. Part O, Journal of risk and reliability. - : Sage Publications. - 1748-006X .- 1748-0078. ; 223:2, s. 133-143
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Journal article (peer-reviewed)abstract
- The use of autonomous systems is becoming increasingly common in many fields. A significant example of this is the ambition to deploy unmanned aerial vehicles (UAVs) for both civil and military applications. In order for autonomous systems such as these to operate effectively, they must be capable of making decisions regarding the appropriate future course of their mission responding to changes in circumstance in as short a time as possible. The systems will typically perform phased missions and, owing to the uncertain nature of the environments in which the systems operate, the mission objectives may be subject to change at short notice. The ability to evaluate the different possible mission configurations is crucial in making the right decision about the mission tasks that should be performed in order to give the highest possible probability of mission success.Because binary decision diagrams (BDDs) may be quickly and accurately quantified to give measures of the system reliability it is anticipated that they are the most appropriate analysis tools to form the basis of a reliability-based prognostics methodology. The current paper presents a new BDD-based approach for phased mission analysis, which seeks to take advantage of the proven fast analysis characteristics of the BDD and enhance it in ways that are suited to the demands of a decision-making capability for autonomous systems. The BDD approach presented allows BDDs representing the failure causes in the different phases of a mission to be constructed quickly by treating component failures in different phases of the mission as separate variables. This allows flexibility when building mission phase failure BDDs because a global variable ordering scheme is not required. An alternative representation of component states in time intervals allows the dependencies to be efficiently dealt with during the quantification process. Nodes in the BDD can represent components with any number of failure modes or factors external to the system that could affect its behaviour, such as the weather. Path simplification rules and quantification rules are developed that allow the calculation of phase failure probabilities for this new BDD approach. The proposed method provides a phased mission analysis technique that allows the rapid construction of reliability models for phased missions and, with the use of BDDs, rapid quantification.
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| 8. |
- Olsson, Catharina, 1968, et al.
(author)
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Identification of genes for the ghrelin and motilin receptors and a novel related gene in fish, and stimulation of intestinal motility in zebrafish (Danio rerio) by ghrelin and motilin.
- 2008
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In: General and comparative endocrinology. - : Elsevier BV. - 0016-6480. ; 155:1, s. 217-26
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Journal article (peer-reviewed)abstract
- In mammals ghrelin has a diverse range of effects including stimulation of gut motility but although present in teleost fish its effects on motility have not been investigated. The present study used bioinformatics to search for fish paralogues of the ghrelin receptor and the closely related motilin receptor, and investigated the effects of ghrelin and motilin on gut motility in zebrafish, Danio rerio. Fish paralogues of the human ghrelin and motilin receptor genes were identified, including those from the zebrafish. In addition, a third gene was identified in three species of pufferfish (the only fish genome completely sequenced), which is distinct from the ghrelin and motilin receptors but more closely aligned to these receptors relative to other G-protein coupled receptors. Immunohistochemistry demonstrated strong ghrelin receptor-like reactivity in the muscle of the zebrafish intestine. In isolated intestinal bulb and mid/distal intestine preparations, ghrelin, motilin, and the motilin receptor agonist erythromycin all evoked contraction; these responses ranged between 9% and 51% of the contractions evoked by carbachol (10(-6) M). There were some variations in the concentrations found to be active in the different tissues, e.g., whereas motilin and rat ghrelin caused contraction of the intestinal bulb circular muscle at concentrations as low as 10(-8) M, human ghrelin (10(-8) to 10(-6) M) was without activity. Neither ghrelin (10(-7) M) nor erythromycin (10(-5) M) affected the contractions evoked by electrical field stimulation. The results suggest that both ghrelin and motilin can regulate intestinal motility in zebrafish and most likely other teleosts, and are discussed in relation to the evolution of these regulatory peptides.
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