| 1. |
- 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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| 2. |
- Birney, Ewan, et al.
(författare)
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Prepublication data sharing
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
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Tidskriftsartikel (refereegranskat)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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| 3. |
- Conrad, Chris, et al.
(författare)
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Single molecule profiling of tau gene expression in Alzheimer's disease
- 2007
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:3, s. 1228-1236
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Tidskriftsartikel (refereegranskat)abstract
- Tau is a microtubule-associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer's disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single-molecule-based technology, polymerase colony or polony, to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2-beta-1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging-related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing-based therapeutics is an emerging area of drug development, and a well-defined and quantitative assay for monitoring single-gene transcriptome will be relevant for such development.
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| 4. |
- Frith, Martin C., et al.
(författare)
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Pseudo-messenger RNA : Phantoms of the transcriptome
- 2006
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 2:4, s. 504-514
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo-messenger RNA to be RNA molecules that resemble protein- coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo - messenger RNAs ( approximately half of which are transposonassociated) among the 102,801 FANTOM3 mouse cDNAs: just over 10% of the FANTOM3 transcriptome. These comprise not only transcribed pseudogenes, but also disrupted splice variants of otherwise protein- coding genes. Some may encode truncated proteins, only a minority of which appear subject to nonsense- mediated decay. The presence of an excess of transcripts whose only disruptions are opal stop codons suggests that there are more selenoproteins than currently estimated. We also describe compensatory frameshifts, where a segment of the gene has changed frame but remains translatable. In summary, we survey a large class of non- standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways. Many of these transcripts do not correspond cleanly to any identifiable object in the genome, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level.
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| 5. |
- Moon, Soo-Jin, et al.
(författare)
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Highly Efficient Organic Sensitizers for Solid-State Dye-Sensitized Solar Cells
- 2009
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:38, s. 16816-16820
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Tidskriftsartikel (refereegranskat)abstract
- Org. sensitizers comprising of donor, electron-conducting, and anchoring groups are designed and developed for dye-sensitized solar cell applications. A solar cell employing 3-(5'-{4-[bis-(4-hexyloxy-phenyl)-amino]-phenyl}-[2,2']bithiophenyl-5-yl)-2-cyano-acrylic acid dye spiro-OMeTAD as a hole-transporting material exhibits a short circuit photocurrent d. of 9.64 mA/cm2, an open-circuit voltage of 798 mV, and a fill factor of 0.57, corresponding to an overall conversion efficiency of 4.4% at std. AM 1.5 sunlight. Photoinduced absorption spectroscopy probes an efficient hole-transfer from dyes to the spiro-OMeTAD.
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| 6. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 7. |
- Slotte, Tanja, et al.
(författare)
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Splicing variation at a FLOWERING LOCUS C homeolog is associated with flowering time variation in the tetraploid Capsella bursa-pastoris
- 2009
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 183:1, s. 337-345
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Tidskriftsartikel (refereegranskat)abstract
- The long-term fates of duplicate genes are well studied both empirically and theoretically, but how the short-term evolution of duplicate genes contributes to phenotypic variation is less well known. Here, we have studied the genetic basis of flowering time variation in the disomic tetraploid Capsella bursa-pastoris. We sequenced four duplicate candidate genes for flowering time and 10 background loci in samples from western Eurasia and China. Using a mixed-model approach that accounts for population structure, we found that polymorphisms at one homeolog of two candidate genes, FLOWERING LOCUS C (FLC) and CRYPTOCHROME1 (CRY1), were associated with natural flowering time variation. No potentially causative polymorphisms were found in the coding region of CRY1; however, at FLC two splice site polymorphisms were associated with early flowering. Accessions harboring nonconsensus splice sites expressed an alternatively spliced transcript or did not express this FLC homeolog. Our results are consistent with the function of FLC as a major repressor of flowering in Arabidopsis thaliana and imply that nonfunctionalization of duplicate genes could provide an important source of phenotypic variation.
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| 8. |
- Vallin, Örjan, et al.
(författare)
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Thermal characterization of Silicon-on-SiC substrates
- 2008
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Ingår i: Proceedings of IEEE International SOI Conference. ; , s. 69-70
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Konferensbidrag (refereegranskat)abstract
- Thermal characterization of the new Si-on-SiC hybrid substrate has shown thermal properties superior in comparison with SOI. The thermal resistivity was shown to be a factor of four lower, and the lateral thermal spread was much more efficient, as is explained by the excellent heat conductivity of the SiC substrate. These results correspond well to the absence of MOSFET self-heating effects for the BaSiC. Transmission electron microscopy reveals a defect free bond and recrystallization of the amorphous silicon, which improves the heat conductivity.
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| 9. |
- Wang, Conan, et al.
(författare)
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Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold
- 2009
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:16, s. 10672-10683
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are a family of plant defense proteins that are highly resistant to adverse chemical, thermal, and enzymatic treatment. Here, we present the first crystal structure of a cyclotide, varv F, from the European field pansy, Viola arvensis, determined at a resolution of 1.8 angstrom. The solution state NMR structure was also determined and, combined with measurements of biophysical parameters for several cyclotides, provided an insight into the structural features that account for the remarkable stability of the cyclotide family. The x-ray data confirm the cystine knot topology and the circular backbone, and delineate a conserved network of hydrogen bonds that contribute to the stability of the cyclotide fold. The structural role of a highly conserved Glu residue that has been shown to regulate cyclotide function was also determined, verifying its involvement in a stabilizing hydrogen bond network. We also demonstrate that varv F binds to dodecylphosphocholine micelles, defining the binding orientation and showing that its structure remains unchanged upon binding, further demonstrating that the cyclotide fold is rigid. This study provides a biological insight into the mechanism by which cyclotides maintain their native activity in the unfavorable environment of predator insect guts. It also provides a structural basis for explaining how a cluster of residues important for bioactivity may be involved in self-association interactions in membranes. As well as being important for their bioactivity, the structural rigidity of cyclotides makes them very suitable as a stable template for peptide-based drug design.
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