| 1. |
|
|
| 2. |
- Clausen, Niels, et al.
(författare)
-
Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
-
Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
|
|
| 3. |
|
|
| 4. |
- Ljung, R., et al.
(författare)
-
Treatment of children with haemophilia in Europe: A survey of 20 centres in 16 countries
- 2000
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 6, s. 619-624
-
Tidskriftsartikel (refereegranskat)abstract
- A survey was made of the current status of treatment of haemophilic boys at 20 centres in 16 European countries and includes approximately 1500 of the estimated 6500 haemophiliacs in the participating countries. Many mild haemophiliacs are not seen, or seen infrequently, at haemophilia centres and this requires study. Nine of 18 centres provide continuous prophylaxis to 80-100% of their patients, five centres provide it to 55-80% and the remaining four centres to 15-40% of the boys. The median dose given was 6240 U kg-1 year-1 (range 3120-7800). Four centres administered only recombinant concentrates to children with severe haemophilia A, while seven centres administered recombinant concentrates to 75-90% and the remaining centres to less than 50% of the boys (two centres <10%). When asked for the choice of concentrate for a newly diagnosed boy with severe haemophilia A, all but one centre preferred recombinant concentrate. Most boys below 6 years received concentrates via a peripheral vein but three centres preferred a central venous line for 80-100% of the boys. Thirteen of 18 centres applied home treatment to 84-100% of the boys and the remaining five centres to 57-77% of the boys.
|
|
| 5. |
|
|
| 6. |
- Becker, D., et al.
(författare)
-
Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum : the pH behaviour of Trichoderma reesei CeI7A and its E223S/A224H/L225V/T226A/D262G mutant
- 2001
-
Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 356, s. 19-30
-
Tidskriftsartikel (refereegranskat)abstract
- The crystal structures of Family 7 glycohydrolases suggest that a histidine residue near the acid/base catalyst could account for the higher pH optimum of the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma reesei enzymes. Modelling studies indicated that introduction of histidine at the homologous position in T. reesei Cel7A (Ala(224)) required additional changes to accommodate the bulkier histidine side chain. X-ray crystallography of the catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major differences from the wild-type are confined to the mutations themselves, The introduced histidine residue is in plane with its counterpart in H. insolens Cel7B, but is 1.0 Angstrom (= 0.1 nm) closer to the acid/base Glu(217) residue, with a 3.1 Angstrom contact between N-2 and O'(1). The pH variation of k(cat)/K-m for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped for both wildtype and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild-type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/-0.02. With this poor substrate, the ionizations probably represent those of the free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed similar behaviour. The shift in the mutant pH optimum was associated with lower k(cat)/K-m values for both lactosides and cellobiosides, and a marginally lower stability. However, k(cat) values for cellobiosides are higher for the mutant. This we attribute to reduced nonproductive binding in the +1 and +2 subsites; inhibition by cellobiose is certainly relieved in the mutant. The weaker binding of cellobiose is due to the loss of two water-mediated hydrogen bonds.
|
|
| 7. |
- Becker, D, et al.
(författare)
-
Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum: the pH behaviour of Trichoderma reesei CeI7A and its E223S/A224H/L225V/T226A/D262G mutant
- 2001
-
Ingår i: Biochemical Journal. ; 356, s. 19-30
-
Tidskriftsartikel (refereegranskat)abstract
- The crystal structures of Family 7 glycohydrolases suggest that a histidine residue near the acid/base catalyst could account for the higher pH optimum of the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma reesei enzymes. Modelling studies indicated that introduction of histidine at the homologous position in T. reesei Cel7A (Ala(224)) required additional changes to accommodate the bulkier histidine side chain. X-ray crystallography of the catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major differences from the wild-type are confined to the mutations themselves. The introduced histidine residue is in plane with its counterpart in H. insolens Cel7B, but is 1.0 A (=0.1 nm) closer to the acid/base Glu(217) residue, with a 3.1 A contact between N(epsilon2) and O(epsilon1). The pH variation of k(cat)/K(m) for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped for both wild-type and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild-type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/-0.02. With this poor substrate, the ionizations probably represent those of the free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed similar behaviour. The shift in the mutant pH optimum was associated with lower k(cat)/K(m) values for both lactosides and cellobiosides, and a marginally lower stability. However, k(cat) values for cellobiosides are higher for the mutant. This we attribute to reduced non-productive binding in the +1 and +2 subsites; inhibition by cellobiose is certainly relieved in the mutant. The weaker binding of cellobiose is due to the loss of two water-mediated hydrogen bonds.
|
|
| 8. |
- Claeyssens, A., et al.
(författare)
-
Spectral variations of Lyman alpha emission within strongly lensed sources observed with MUSE
- 2019
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:4, s. 5022-5029
-
Tidskriftsartikel (refereegranskat)abstract
- We present an analysis of HI Lyman alpha emission in deep VLT/MUSE observations of two highly magnified and extended galaxies at z = 3.5 and 4.03, including a newly discovered, almost complete Einstein ring. While these Lyman a haloes are intrinsically similar to the ones typically seen in other MUSE deep fields, the benefits of gravitational lensing allow us to construct exceptionally detailed maps of Lyman alpha line properties at sub-kpc scales. By combining all multiple images, we are able to observe complex structures in the Lyman a emission and uncover small (similar to 120 km s(-1) in Lyman alpha peak shift), but significant at >4 sigma, systematic variations in the shape of the Lyman a line profile within each halo. Indeed, we observe a global trend for the line peak shift to become redder at large radii, together with a strong correlation between the peak wavelength and line width. This systematic intrahalo variation is markedly similar to the object-to-object variations obtained from the integrated properties of recent large samples. Regions of high surface brightness correspond to relatively small line shifts, which could indicate that Lyman alpha emission escapes preferentially from regions where the line profile has been less severely affected by scattering of Lyman alpha photons.
|
|
| 9. |
- Fischer, K., et al.
(författare)
-
Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry
- 2014
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:4, s. 280-286
-
Tidskriftsartikel (refereegranskat)abstract
- Haemophilia is a rare disease. To improve knowledge, prospective studies of large numbers of subjects are needed. To establish a large well-documented birth cohort of patients with haemophilia enabling studies on early presentation, side effects and outcome of treatment. Twenty-one haemophilia treatment centres have been collecting data on all children with haemophilia with FVIII/IX levels up to 25% born from 2000 onwards. Another eight centres collected data on severe haemophilia A only. At baseline, details on delivery and diagnosis, gene mutation, family history of haemophilia and inhibitors are collected. For the first 75 exposure days, date, reason, dose and product are recorded for each infusion. Clinically relevant inhibitors are defined as follows: at least two positive inhibitor titres and a FVIII/IX recovery <66% of expected. For inhibitor patients, results of all inhibitor- and recovery tests are collected. For continued treatment, data on bleeding, surgery, prophylaxis and clotting factor consumption are collected annually. Data are downloaded for analysis annually. In May 2013, a total of 1094 patients were included: 701 with severe, 146 with moderate and 247 with mild haemophilia. Gene defect data were available for 87.6% of patients with severe haemophilia A. The first analysis, performed in May 2011, lead to two landmark publications. The outcome of this large collaborative research confirms its value for the improvement of haemophilia care. High-quality prospective observational cohorts form an ideal source to study natural history and treatment in rare diseases such as haemophilia.
|
|
| 10. |
- Vanzella, Eros, et al.
(författare)
-
JWST/NIRCam Probes Young Star Clusters in the Reionization Era Sunrise Arc
- 2023
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 945:1
-
Tidskriftsartikel (refereegranskat)abstract
- Star cluster formation in the early universe and its contribution to reionization remains largely unconstrained to date. Here we present JWST/NIRCam imaging of the most highly magnified galaxy known at z ∼ 6, the Sunrise arc. We identify six young massive star clusters (YMCs) with measured radii spanning from ∼20 down to ∼1 pc (corrected for lensing magnification), estimated stellar masses of ∼106–7 M⊙, and ages of 1–30 Myr based on SED fitting to photometry measured in eight filters extending to rest frame 7000 Å. The resulting stellar mass surface densities are higher than 1000 M⊙ pc−2 (up to a few 105 M⊙ pc−2), and their inferred dynamical ages qualify the majority of these systems as gravitationally bound stellar clusters. The star cluster ages map the progression of star formation along the arc, with two evolved systems (≳10 Myr old) followed by very young clusters. The youngest stellar clusters (<5 Myr) show evidence of prominent Hβ+[O ııı] emission based on photometry with equivalent widths larger than >1000 Å rest frame and are hosted in a 200 pc sized star-forming complex. Such a region dominates the ionizing photon production with a high efficiency log(ξion [Hz erg-1]~25.7 . A significant fraction of the recently formed stellar mass of the galaxy (10%–30%) occurred in these YMCs. We speculate that such sources of ionizing radiation boost the ionizing photon production efficiency, which eventually carves ionized channels that might favor the escape of Lyman continuum radiation. The survival of some of the clusters would make them the progenitors of massive and relatively metal-poor globular clusters in the local universe.
|
|
| 11. |
- von Ossowski, I., et al.
(författare)
-
Engineering the exo-loop of Trichoderma reesei cellobiohydrolase, Ce17A. A comparison with Phanerochaete chrysosporium Cel7D
- 2003
-
Ingår i: Journal of Molecular Biology. - 0022-2836 .- 1089-8638. ; 333:4, s. 817-829
-
Tidskriftsartikel (refereegranskat)abstract
- The exo-loop of Trichoderma reesei cellobiohydrolase Cel7A forms the roof of the active site tunnel at the catalytic centre. Mutants were designed to study the role of this loop in crystalline cellulose degradation. A hydrogen bond to substrate made by a tyrosine at the tip of the loop was removed by the Y247F mutation. The mobility of the loop was reduced by introducing a new disulphide bridge in the mutant D241C/D249C. The tip of the loop was deleted in mutant Delta(G245-Y252). No major structural disturbances were observed in the mutant enzymes, nor was the thermostability of the enzyme affected by the mutations. The Y247F mutation caused a slight k(cat) reduction on 4-nitrophenyl lactoside, but only a small effect on cellulose hydrolysis. Deletion of the tip of the loop increased both k(cat) and K-M and gave reduced product inhibition. Increased activity was observed on amorphous cellulose, while only half the original activity remained on crystalline cellulose. Stabilisation of the exo-loop by the disulphide bridge enhanced the activity on both amorphous and crystalline cellulose. The ratio Glc(2)/(Glc(3) + Glc(1)) released from cellulose, which is indicative of processive action, was highest with Tr Cel7A wild-type enzyme and smallest with the deletion mutant on both substrates. Based on these data it seems that the exo-loop of Tr Cel7A has evolved to facilitate processive crystalline cellulose degradation, which does not require significant conformational changes of this loop.
|
|
