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| 2. |
- Watanabe, A., et al.
(författare)
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Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:20, s. 2319-2333
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Tidskriftsartikel (refereegranskat)abstract
- Karyotype is an important prognostic factor in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but the underlying pharmacogenomics remain unknown. Asparaginase is an integral component in current chemotherapy for childhood BCP-ALL. Asparaginase therapy depletes serum asparagine. Normal hematopoietic cells can produce asparagine by asparagine synthetase (ASNS) activity, but ALL cells are unable to synthesize adequate amounts of asparagine. The ASNS gene has a typical CpG island in its promoter. Thus, methylation of the ASNS CpG island could be one of the epigenetic mechanisms for ASNS gene silencing in BCP-ALL. To gain deep insights into the pharmacogenomics of asparaginase therapy, we investigated the association of ASNS methylation status with asparaginase sensitivity. The ASNS CpG island is largely unmethylated in normal hematopoietic cells, but it is allele-specifically methylated in BCP-ALL cells. The ASNS gene is located at 7q21, an evolutionally conserved imprinted gene cluster. ASNS methylation in childhood BCP-ALL is associated with an aberrant methylation of the imprinted gene cluster at 7q21. Aberrant methylation of mouse Asns and a syntenic imprinted gene cluster is also confirmed in leukemic spleen samples from ETV6-RUNX1 knockin mice. In 3 childhood BCP-ALL cohorts, ASNS is highly methylated in BCP-ALL patients with favorable karyotypes but is mostly unmethylated in BCP-ALL patients with poor prognostic karyotypes. Higher ASNS methylation is associated with higher L-asparaginase sensitivity in BCP-ALL through lower ASNS gene and protein expression levels. These observations demonstrate that silencing of the ASNS gene as a result of aberrant imprinting is a pharmacogenetic mechanism for the leukemia-specific activity of asparaginase therapy in BCP-ALL.
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| 3. |
- dos Reis, Fabio Bueno, Jr., et al.
(författare)
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Nodulation and nitrogen fixation by Mimosa spp. in the Cerrado and Caatinga biomes of Brazil
- 2010
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 186:4, s. 934-946
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Tidskriftsartikel (refereegranskat)abstract
- P>An extensive survey of nodulation in the legume genus Mimosa was undertaken in two major biomes in Brazil, the Cerrado and the Caatinga, in both of which there are high degrees of endemicity of the genus. Nodules were collected from 67 of the 70 Mimosa spp. found. Thirteen of the species were newly reported as nodulating. Nodules were examined by light and electron microscopy, and all except for M. gatesiae had a structure typical of effective Mimosa nodules. The endosymbiotic bacteria in nodules from all of the Mimosa spp. were identified as Burkholderia via immunolabelling with an antibody against Burkholderia phymatum STM815. Twenty of the 23 Mimosa nodules tested were shown to contain nitrogenase by immunolabelling with an antibody to the nitrogenase Fe- (nifH) protein, and using the delta 15N (15N natural abundance) technique, contributions by biological N-2 fixation of up to 60% of total plant N were calculated for Caatinga Mimosa spp. It is concluded that nodulation in Mimosa is a generic character, and that the preferred symbionts of Brazilian species are Burkholderia. This is the first study to demonstrate N-2 fixation by beta-rhizobial symbioses in the field.
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| 4. |
- Goi, K. L. S., et al.
(författare)
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Elastic modulus of sintered porous Ti-Si-Zr, using activation by Ti-Si mechanically alloyed powder and TiH2 powder
- 2008
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Ingår i: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 475:1-2, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- A novel biomaterial based on Ti-Si-Zr was developed using the sintering process with a composition targeting at a bulk modulus in the same range as that of human bone, i.e. 10-30 GPa. Control of porosity should also be possible to allow for the promotion osseointegration. The sintering procedure involves the use of mechanically alloyed Ti-Si-powder, and TiH2, to promote bonding, but not consolidation. The effect of porosity on the bulk modulus using compression testing is investigated. The influence of sintering temperature, heating rate, and amount and size of the TiH2-activator on porosity are also investigated. The achievable bulk modulus was in the range of 20-55 GPa at porosity levels ranging from 16% to 54%. Porosity had a profound influence on the bulk modulus, and the choice of appropriate processing conditions enables the creation of an engineered porosity and bulk modulus primarily by varying the sintering temperature and the size of the TiH2-powder particles. © 2007.
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| 5. |
- Jarfors, A. E. W., et al.
(författare)
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Microstructure formation of porous sintered Ti-Si-Zr compacts with mechanically alloyed-activated Ti-Si and TiH2 powders
- 2014
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 594, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- Metallic implants are widely used in applications associated with bone. A major drawback of using metals is their elastic modulus which is higher than that of bone resulting in stress shielding and premature failure of the implant. The employment of biomaterials with a porous structure has the potential to lower the modulus and promote osseointegration. The present work investigates the microstructure formation and the resulting elastic modulus of a new Ti-Si-Zr alloy. The sintering procedure involves the use of both mechanically alloyed Ti-Si powder and TiH2 to activate sintering with the TiH2 also serving as a pore precursor. The procedure is designed to promote bonding but not consolidation. The influence of sintering temperature, heating rate, as well as the amount and size of the TiH2 on the phases formed and porosity was investigated. It was observed that the use of TiH2 increased the degree of porosity whilst the size of TiH2 particles could be used to control the pore size. The results showed that when using small TiH2 particles, the elastic modulus was strongly dependent on the fraction of TiH2. When large TiH2 particles were used, the porosity had no significant influence on the elastic modulus. The variation in behavior could be attributed to differences in microstructure. To control the bulk modulus it is essential to understand the differences in the microstructure formation mechanisms between these two cases. (C) 2014 Elsevier B.V. All rights reserved.
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