| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
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| 3. |
- Koivula, Anu, et al.
(författare)
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The active site of cellobiohydrolase Cel6A from Trichoderma reesei: the roles of aspartic acids D221 and D175.
- 2002
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Ingår i: J Am Chem Soc. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 124:34, s. 10015-24
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Tidskriftsartikel (refereegranskat)abstract
- Trichoderma reesei cellobiohydrolase Cel6A is an inverting glycosidase. Structural studies have established that the tunnel-shaped active site of Cel6A contains two aspartic acids, D221 and D175, that are close to the glycosidic oxygen of the scissile bond and at hydrogen-bonding distance from each other. Here, site-directed mutagenesis, X-ray crystallography, and enzyme kinetic studies have been used to confirm the role of residue D221 as the catalytic acid. D175 is shown to affect protonation of D221 and to contribute to the electrostatic stabilization of the partial positive charge in the transition state. Structural and modeling studies suggest that the single-displacement mechanism of Cel6A may not directly involve a catalytic base. The value of (D2O)(V) of 1.16 +/- 0.14 for hydrolysis of cellotriose suggests that the large direct effect expected for proton transfer from the nucleophilic water through a water chain (Grotthus mechanism) is offset by an inverse effect arising from reversibly breaking the short, tight hydrogen bond between D221 and D175 before catalysis.
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| 4. |
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| 5. |
- Li, Jian-Liang, et al.
(författare)
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A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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| 6. |
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| 7. |
- Billker, Oliver, et al.
(författare)
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Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei
- 2002
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Ingår i: Journal of Eukaryotic Microbiology. - : Wiley. - 1066-5234 .- 1550-7408. ; 49:6, s. 489-497
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Tidskriftsartikel (refereegranskat)abstract
- Transmission of malaria parasites from vertebrate blood to the mosquito vector depends critically on the differentiation of the gametocytes into gametes. This occurs in response to environmental stimuli encountered by the parasite in the mosquito bloodmeal. Male gametogenesis involves three rounds of DNA replication and endomitosis, and the assembly de novo of 8 motile axonemes. Azadirachtin, a plant limnoid and insecticide with an unkown mode of action, specifically inhibits the release of motile gametes from activated microgametocytes but does not inhibit growth and replication of a sexual blood stages. We have combined confocal laser scanning microscopy and transmission electron microscopy to examine the effect of azadirachtin on the complex reorganisation of the microtubule cytoskeleton during gametogenesis in Plasmodium berghei. Neither the replication of the genome nor the ability of tubulin monomers to assemble into microtubules upon gametocyte activation were prevented by azadirachtin. However, the drug interfered with the formation of mitotic spindles and with the assembly of microtubules into typical axonemes. Our observations suggest that azadarachtin specifically disrupts the patterning of microtubules into more complex structures, such as mitotic spindles and axonemes.
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| 8. |
- Böhlmark, Johan, et al.
(författare)
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Measurement of the magnetic field change in a pulsed high current magnetron discharge
- 2004
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Ingår i: Plasma Sources Science and Technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 13:4, s. 654-661
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we present a study of how the magnetic field of a circular planar magnetron is affected when it is exposed to a pulsed high current discharge. Spatially resolved magnetic field measurements are presented and the magnetic disturbance is quantified for different process parameters. The magnetic field is severely deformed by the discharge and we record changes of several millitesla, depending on the spatial location of the measurement. The shape of the deformation reveals the presence of azimuthally drifting electrons close to the target surface. Time resolved measurements show a transition between two types of magnetic perturbations. There is an early stage that is in phase with the axial discharge current and a late stage that is not in phase with the discharge current. The later part of the magnetic field deformation is seen as a travelling magnetic wave. We explain the magnetic perturbations by a combination of E × B drifting electrons and currents driven by plasma pressure gradients and the shape of the magnetic field. A plasma pressure wave is also recorded by a single tip Langmuir probe and the velocity (~103 m s−1) of the expanding plasma agrees well with the observed velocity of the magnetic wave. We note that the axial (discharge) current density is much too high compared to the azimuthal current density to be explained by classical collision terms, and an anomalous charge transport mechanism is required.
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| 9. |
- Djoussé, Luc, et al.
(författare)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 10. |
- Dunagan, John, et al.
(författare)
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FUSE:Lightweight Guaranteed Distributed Failure Notification
- 2004
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Ingår i: Proceedings of the 6th Symposium on Operating Systems Design and Implementation (OSDI). - : Association for Computing Machinery (ACM).
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Konferensbidrag (refereegranskat)abstract
- FUSE is a lightweight failure notification service for building distributed systems. Distributed systems built with FUSE are guaranteed that failure notifications never fail. Whenever a failure notification is triggered, all live members of the FUSE group will hear a notification within a bounded period of time, irrespective of node or communication failures. In contrast to previous work on failure detection, the responsibility for deciding that afailure has occurred is shared between the FUSE service and the distributed application. This allows applications to implement their own definitions of failure. Our experience building a scalable distributed event delivery system on an overlay network has convinced us of the usefulness of this service. Our results demonstrate that the network costs of each FUSE group can be small; in particular, our overlay network implementation requires no additional liveness-verifying ping traffic beyond that already needed to maintain the overlay, making the steady state network load independent of the number of active FUSE groups.
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