| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 3. |
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| 4. |
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| 5. |
- Carlegrim, Elin, et al.
(författare)
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Near-edge x-ray absorption studies of Na-doped tetracyanoethylene films : A model system for the V(TCNE)x room-temperature molecular magnet
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : Institutionen för teknik och naturvetenskap. - 1098-0121 .- 1550-235X. ; 77:5, s. 054420-1-054420-8
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Tidskriftsartikel (refereegranskat)abstract
- V(TCNE)(x), with TCNE=tetracyanoethylene and x similar to 2, is an organic-based molecular magnet with potential to be used in spintronic devices. With the aim of shedding light on the unoccupied frontier electronic structure of V(TCNE)(x) we have studied pristine TCNE and sodium-intercalated TCNE by near edge x-ray absorption fine structure (NEXAFS) spectroscopy as well as with theoretical calculations. Sodium-intercalated TCNE was used as a model system of the more complex V(TCNE)(x) and both experimental and theoretical results of the model compound have been used to interpret the NEXAFS spectra of V(TCNE)(x). By comparing the experimental and theoretical C K-edge of pristine TCNE, the contributions from the various carbon species (cyano and vinyl) could be disentangled. Upon fully sodium intercalation, TCNE is n doped with one electron per molecule and the features in the C and N K-edge spectra of pristine TCNE undergo strong modification caused by partially filling the TCNE lowest unoccupied molecular orbital (LUMO). When comparing the C and N K-edge NEXAFS spectra of fully sodium-doped TCNE with V(TCNE)(x), the spectra are similar except for broadening of the features which originates from structural disorder of the V(TCNE)(x) films. The combined results from the model system and V(TCNE)(x) suggest that the lowest unoccupied molecular orbital with density on the nitrogen atoms in V(TCNE)(x) has no significant hybridization with vanadium and is similar to the so-called singly occupied molecular orbital of the TCNE anion. This suggests that the LUMO of V(TCNE)(x) is TCNE- or vanadiumlike, in contrast to the frontier occupied electronic structure where the highest occupied molecular orbital is a hybridization between V(3d) and cyano carbons. The completely different nature of the unoccupied and occupied frontier electronic structure of the material will most likely affect both charge injection and transport properties of a spintronic device featuring V(TCNE)(x).
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| 7. |
- Klug, Stefanie J, et al.
(författare)
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TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
- 2009
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
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| 8. |
- Matsumoto, Taro, et al.
(författare)
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VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis.
- 2005
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Ingår i: EMBO J. - 0261-4189. ; 24:13, s. 2342-53
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is essential in vasculogenesis and angiogenesis. We have generated a pan-phosphorylation site map of VEGFR-2 and identified one major tyrosine phosphorylation site in the kinase insert (Y951), in addition to two major sites in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells, whereas phosphorylation of Y951 was identified in a subset of vessels. Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951 peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress fibers and migration, but not mitogenesis. Tumor vascularization and growth was reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling in pathological angiogenesis.
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| 9. |
- Wu, Mousheng, et al.
(författare)
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Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease
- 2009
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 17:2, s. 276-286
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Tidskriftsartikel (refereegranskat)abstract
- Poly(A)-specific ribonuclease (PARN) is a homodimeric, processive, and cap-interacting 3' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. The crystal structure of a C-terminally truncated PARN in complex with m(7)GpppG reveals that, in one subunit, m(7)GpppG binds to a cavity formed by the RRM domain and the nuclease domain, whereas in the other subunit, it binds almost exclusively to the RRM domain. Importantly, our structural and competition data show that the cap-binding site overlaps with the active site in the nuclease domain. Mutational analysis demonstrates that residues involved in m(7)G recognition are crucial for cap-stimulated deadenylation activity, and those involved in both cap and poly(A) binding are important for catalysis. A modeled PARN, which shows that the RRM domain from one subunit and the R3H domain from the other subunit enclose the active site, provides a structural foundation for further studies to elucidate the mechanism of PARN-mediated deadenylation.
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| 10. |
- Örbom, Anders, et al.
(författare)
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Serial digital autoradiography with a silicon strip detector as a high resolution imaging modality for TRT Dosimetry
- 2007
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Ingår i: 2007 IEEE Nuclear Science Symposium Conference Record, vols 1-11. - 1082-3654. - 9781424409228 ; , s. 4054-4056
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Konferensbidrag (refereegranskat)abstract
- This study aims to investigate the possibility of implementing serial autoradiography using a silicon strip detector as an imaging modality in pre-clinical radionuclide therapy research, in order to study the effect of non-uniform uptake on absorbed dose distribution and biological response. Tumor tissues expressing CD20 (B-cell lymphoma) or carcinoembryonic antigen (CEA; colorectal cancer) were excised from animals injected with I-131-labelled anti-CD20 or anti-CEA antibodies and antibody fragments. The tumors were cryosectioned at 100 mu m and imaged using a real-time silicon- strip imager with a pixel-size of 50 mu m. Software was developed to correct for image artifacts and to realign the image sections into a volume by a two-step process with least square error and mutual information registration measures. The realigned volumes were convolved with beta dose point kernels to provide the dose rate distribution for I-131 and Y-90 at the time of sacrifice. Using these volumes, comparisons can be made between uptake and penetration of different antibodies and the dose rate uniformity of different radionuclides. Simulations performed using measured I-131 and I-125 energy spectra showed that energy separation with less than 5% error could be performed with 100 counts per pixel. Imaging and subsequent separation of a sample containing both I-131 and I-125 proved the possibility of simultaneous imaging of two targeting agents in the same tissue. Thinner tissue sections were also set aside and successfully used for H&E staining and immunohistochemistry to enable future comparison of uptake and dose rate in different cell-type populations in the tissue. This method successfully provides high-resolution activity and dose rate volumes and has potential for multi-labeling imaging and co-registration with histology. As a complimentary imaging modality it can aid in investigating the effect of non-uniform uptake. Optimization is still needed in both the sectioning protocol and realignment software.
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