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- Greiner, Birgit, et al.
(författare)
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Anatomical and physiological evidence for polarisation vision in the nocturnal bee Megalopta genalis
- 2007
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Ingår i: Journal of Comparative Physiology A. - : Springer Science and Business Media LLC. - 1432-1351 .- 0340-7594. ; 193:6, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- The presence of a specialised dorsal rim area with an ability to detect the e-vector orientation of polarised light is shown for the first time in a nocturnal hymenopteran. The dorsal rim area of the halictid bee Megalopta genalis features a number of characteristic anatomical specialisations including an increased rhabdom diameter and a lack of primary screening pigments. Optically, these specialisations result in wide spatial receptive fields (Delta rho = 14 degrees), a common adaptation found in the dorsal rim areas of insects used to filter out interfering effects (i.e. clouds) from the sky. In this specialised eye region all nine photoreceptors contribute their microvilli to the entire length of the ommatidia. These orthogonally directed microvilli are anatomically arranged in an almost linear, anterior-posterior orientation. Intracellular recordings within the dorsal rim area show very high polarisation sensitivity and a sensitivity peak within the ultraviolet part of the spectrum.
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- Reetz, Manfred T., et al.
(författare)
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Directed Evolution of an Enantioselective Epoxide Hydrolase : Uncovering the Source of Enantioselectivity at Each Evolutionary Stage
- 2009
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Ingår i: Journal of the American Chemical Society. - : ACS. - 0002-7863 .- 1520-5126. ; 131:21, s. 7334-7343
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Forskningsöversikt (refereegranskat)abstract
- Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic kinetic resolution of racemic glycidyl phenyl ether. Kinetic data, molecular dynamics calculations, molecular modeling, inhibition experiments, and X-ray structural work for the wild-type (WT) enzyme and the best mutant reveal the basis of the large increase in enantioselectivity (E = 4.6 versus E = 115). The overall structures of the WT and the mutant are essentially identical, but dramatic differences are observed in the active site as revealed by the X-ray structures. All of the experimental and computational results support a model in which productive positioning of the preferred (S)-glycidyl phenyl ether, but not the (R)-enantiomer, forms the basis of enhanced enantioselectivity. Predictions regarding substrate scope and enantioselectivity of the best mutant are shown to be possible.
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- Ulmert, David, et al.
(författare)
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Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study
- 2008
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Based on a large, representative unscreened cohort from Malmo, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis. Methods: In 1974-1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer. Results: Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer ( area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher). Conclusion: A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
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- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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- Vickers, Andrew J., et al.
(författare)
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Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large, Representative, Population-based Cohort
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:5, s. 753-760
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that changes in prostate-specific antigen (PSA) over time (ie, PSA velocity [PSAV]) aid prostate cancer detection. Some guidelines do incorporate PSAV cut points as an indication for biopsy. Objective: To evaluate whether PSAV enhances prediction of biopsy outcome in a large, representative, population-based cohort. Design, setting, and participants: There were 2742 screening-arm participants with PSA < 3 ng/ml at initial screening in the European Randomized Study of Screening for Prostate Cancer in Rotterdam, Netherlands, or Goteborg, Sweden, and who were subsequently biopsied during rounds 2-6 due to elevated PSA. Measurements: Total, free, and intact PSA and human kallikrein 2 were measured for 16 screening rounds at intervals of 2 or 4 yr. We created logistic regression models to predict prostate cancer based on age and PSA, with or without free-to-total PSA ratio (%fPSA). PSAV was added to each model and any enhancement in predictive accuracy assessed by area under the curve (AUC). Results and limitations: PSAV led to small enhancements in predictive accuracy (AUC of 0.569 vs 0.531; 0.626 vs 0.609 if %fPSA was included), although not for high-grade disease. The enhancement depended on modeling a nonlinear relationship between PSAV and cancer. There was no benefit if we excluded men with higher velocities, which were associated with lower risk. These results apply to men in a screening program with elevated PSA; men with prior negative biopsy were not evaluated in this study. Conclusions: In men with PSA of about >= 3 ng/ml, we found little justification for formal calculation of PSAV or for use of PSAV cut points to determine biopsy. Informal assessment of PSAV will likely aid clinical judgment, such as a sudden rise in PSA suggesting prostatitis, which could be further evaluated before biopsy. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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