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- Liu, Qiyong P., et al.
(författare)
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Bacterial glycosidases for the production of universal red blood cells
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 25:4, s. 454-464
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Tidskriftsartikel (refereegranskat)abstract
- Enzymatic removal of blood group ABO antigens to develop universal red blood cells ( RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes. The crystal structure of a member of the alpha-N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD(+). The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions.
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| 3. |
- Liu, Qiyong P, et al.
(författare)
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Identification of a GH110 subfamily of alpha 1,3-galactosidases - Novel enzymes for removal of the alpha 3Gal xenotransplantation antigen
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:13, s. 8545-8554
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Tidskriftsartikel (refereegranskat)abstract
- In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha 1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-galactosidases (CAZy GH110) with highly restricted substrate specificity and neutral pH optimum (Liu, Q. P., Sulzenbacher, G., Yuan, H., Bennett, E. P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S. B., White, T., Neveu, J. M., Lane, W. S., Bourne, Y., Olsson, M. L., Henrissat, B., and Clausen, H. (2007) Nat. Biotechnol. 25, 454-464). One member of this family from Bacteroides fragilis had exquisite substrate specificity for the branched blood group B structure Gal alpha 1-3(Fuc alpha 1-2) Gal, whereas linear oligosaccharides terminated by alpha 1,3-linked galactose such as the immunodominant xenotransplantation epitope Gal alpha 1-3Gal beta 1-4GlcNAc did not serve as substrates. Here we demonstrate the existence of two distinct subfamilies of GH110 in B. fragilis and thetaiotaomicron strains. Members of one subfamily have exclusive specificity for the branched blood group B structures, whereas members of a newly identified subfamily represent linkage specific alpha 1,3-galactosidases that act equally well on both branched blood group B and linear alpha 1,3Gal structures. We determined by one-dimensional H-1 NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known alpha-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha 3Gal xenotransplantation epitope.
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- Cooke, S.J., et al.
(författare)
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Developing a mechanistic understanding of fish migrations by linking telemetry with physiology, behavior, genomics and experimental biology: an interdisciplinary case study on adult fraser river sockeys salmon
- 2008
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Ingår i: Fisheries. ; 33:7, s. 321-338
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Tidskriftsartikel (refereegranskat)abstract
- Fish migration represents one of the most complex and intriguing biological phenomena in the animal kingdom. How do fish migrate such vast distances? What are the costs and benefits of migration? Some of these fundamental questions have been addressed through the use of telemetry. However, telemetry alone has not and will not yield a complete understanding of the migration biology of fish or provide solutions to problems such as identifying physical barriers to migration or understanding potential impacts of climate change. Telemetry can be coupled with other tools and techniques to yield new insights into animal biology. Using Fraser River sockeye salmon (Oncorhynchus nerka) as a model, we summarize the advances that we have made in understanding salmonid migration biology through the integration of disciplines (i.e., interdisciplinary research) including physiology, behavior, functional genomics, and experimental biology. We also discuss opportunities for using large-scale telemetry arrays and taking a more experimental approach to studies of fish migration that use telemetry (i.e., intervention studies involving endocrine implants, simulated migration studies) rather than simply focusing on descriptive or correlational techniques. Only through integrative and interdisciplinary research will it be possible to understand the mechanistic basis of fish migrations and to predict and possibly mitigate the consequences of anthropogenic impacts. Telemetry is a tool that has the potential to integrate research across disciplines and between the lab and the field to advance the science of fish migration biology. The techniques that we have applied to the study of Pacific salmon are equally relevant to other fish taxa in both marine and freshwater systems as well as migratory animals beyond ichthyofauna. The interdisciplinary approach used here was essential to address a pressing and complex conservation problem association with sockeye salmon migration.
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- Horsley, A R, et al.
(författare)
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Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis.
- 2008
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 63:2, s. 135-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lung clearance index (LCI) is a sensitive marker of early lung disease in children but has not been assessed in adults. Measurement is hindered by the complexity of the equipment required. The aims of this study were to assess performance of a novel gas analyser (Innocor) and to use it as a clinical tool for the measurement of LCI in cystic fibrosis (CF). METHODS: LCI was measured in 48 healthy adults, 12 healthy school-age children and 33 adults with CF by performing an inert gas washout from 0.2% sulfur hexafluoride (SF6). SF6 signal:noise ratio and 10-90% rise time of Innocor were compared with a mass spectrometer used in similar studies in children. RESULTS: Compared with the mass spectrometer, Innocor had a superior signal:noise ratio but a slower rise time (150 ms vs 60 ms) which may limit its use in very young children. Mean (SD) LCI in healthy adults was significantly different from that in patients with CF: 6.7 (0.4) vs 13.1 (3.8), p<0.001. Ten of the patients with CF had forced expiratory volume in 1 s > or = 80% predicted but only one had a normal LCI. LCI repeats were reproducible in all three groups of subjects (mean intra-visit coefficient of variation ranged from 3.6% to 5.4%). CONCLUSIONS: Innocor can be adapted to measure LCI and affords a simpler alternative to a mass spectrometer. LCI is raised in adults with CF with normal spirometry, and may prove to be a more sensitive marker of the effects of treatment in this group.
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| 7. |
- Ruschin, Mark, et al.
(författare)
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Dose dependence of mass and microcalcification detection in digital mammography: free response human observer studies.
- 2007
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Ingår i: Medical physics. - : Wiley. - 0094-2405. ; 34:2, s. 400-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the effect of dose reduction in digital mammography on the detection of two lesion types-malignant masses and clusters of microcalcifications. Two free-response observer studies were performed-one for each lesion type. Ninety screening images were retrospectively selected; each image was originally acquired under automatic exposure conditions, corresponding to an average glandular dose of 1.3 mGy for a standard breast (50 mm compressed breast thickness with 50% glandularity). For each study, one to three simulated lesions were added to each of 40 images (abnormals) while 50 were kept without lesions (normals). Two levels of simulated system noise were added to the images yielding two new image sets, corresponding to simulated dose levels of 50% and 30% of the original images (100%). The manufacturer's standard display processing was subsequently applied to all images. Four radiologists experienced in mammography evaluated the images by searching for lesions and marking and assigning confidence levels to suspicious regions. The search data were analyzed using jackknife free-response (JA-FROC) methodology. For the detection of masses, the mean figure-of-merit (FOM) averaged over all readers was 0.74, 0.71, and 0.68 corresponding to dose levels of 100%, 50%, and 30%, respectively. These values were not statistically different from each other (F= 1.67, p=0.19) but showed a decreasing trend. In contrast, in the microcalcification study the mean FOM was 0.93, 0.67, and 0.38 for the same dose levels and these values were all significantly different from each other (F = 109.84, p < 0.0001). The results indicate that lowering the present dose level by a factor of two compromised the detection of microcalcifications but had a weaker effect on mass detection.
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