| 1. |
- Buitenhuis, M, et al.
(författare)
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Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 105:11, s. 4272-4281
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitor of DNA binding (Id) proteins function as inhibitors of members of the basic helix-loop-helix family of transcription factors and have been demonstrated to play an important role in regulating lymphopoiesis. However, the role of these proteins in regulation of myelopoiesis is currently unclear. In this study, we have investigated the role of Id1 and Id2 in the regulation of granulopoiesis. Id1 expression was initially upregulated during early granulopoiesis, which was then followed by a decrease in expression during final maturation. In contrast, Id2 expression was up-regulated in terminally differentiated granulocytes. In order to determine whether Id expression plays a critical role in regulating granulopoiesis, Id1 and Id2 were ectopically expressed in CD34(+) cells by retroviral transduction. Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced. Constitutive Id2 expression accelerates final maturation of both eosinophils and neutrophils, whereas inhibition of Id2 expression blocks differentiation of both lineages. Transplantation of beta 2-microglobulin(-/-) nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34(+) cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development. These data demonstrate that both Id1 and Id2 play a critical, although differential role in granulopolesis.
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| 2. |
- Andrén, Anders, et al.
(författare)
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The occurrence of noncoagulating milk and the association of bovine milk coagulation properties with genetic variants of the caseins in 3 Scandinavian dairy breeds
- 2013
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 96:8, s. 4830-4842
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Tidskriftsartikel (refereegranskat)abstract
- Substantial variation in milk coagulation properties has been observed among dairy cows. Consequently, raw milk from individual cows and breeds exhibits distinct coagulation capacities that potentially affect the technological properties and milk processing into cheese. This variation is largely influenced by protein composition, which is in turn affected by underlying genetic polymorphisms in the major milk proteins. In this study, we conducted a large screening on 3 major Scandinavian breeds to resolve the variation in milk coagulation traits and the frequency of milk with impaired coagulation properties (noncoagulation). In total, individual coagulation properties were measured on morning milk collected from 1,299 Danish Holstein (DH), Danish Jersey (DJ), and Swedish Red (SR) cows. The 3 breeds demonstrated notable interbreed differences in coagulation properties, with DJ cows exhibiting superior coagulation compared with the other 2 breeds. In addition, milk samples from 2% of DH and 16% of SR cows were classified as noncoagulating. Furthermore, the cows were genotyped for major genetic variants in the alpha(S1)- (CSN1S1), beta- (CSN2), and kappa-casein (CSN3) genes, revealing distinct differences in variant frequencies among breeds. Allele I of CSN2, which had not formerly been screened in such a high number of cows in these Scandinavian breeds, showed a frequency around 7% in DH and DJ, but was not detected in SR. Genetic polymorphisms were significantly associated with curd firming rate and rennet coagulation time. Thus, CSN1S1 C, CSN2 B, and CSN3 B positively affected milk coagulation, whereas CSN2 A(2), in particular, had a negative effect. In addition to the influence of individual casein genes, the effects of CSN1S1-CSN2-CSN3 composite genotypes were also examined, and revealed strong associations in all breeds, which more or less reflected the single gene results. Overall, milk coagulation is under the influence of additive genetic variation. Optimal milk for future cheese production can be ensured by monitoring the frequency of unfavorable variants and thus preventing an increase in the number of cows producing milk with impaired coagulation. Selective breeding for variants associated with superior milk coagulation can potentially increase raw milk quality and cheese yield in all 3 Scandinavian breeds.
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| 3. |
- Buitenhuis, Miranda, et al.
(författare)
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Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:1, s. 112-121
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is a highly regulated process resulting in the formation of all blood lineages. Aberrant regulation of phosphatidylinositol-3-kinase (PI3K) signaling has been observed in hematopoietic malignancies, suggesting that regulated PI3K signaling is critical for regulation of blood cell production. An ex vivo differentiation system was used to investigate the role of PI3K and its downstream effector, protein kinase B (PKB/c-akt) in myelopoiesis. PI3K activity was essential for hematopoietic progenitor survival. High PKB activity was found to promote neutrophil and monocyte development, while, conversely, reduction of PKB activity was required to induce optimal eosinophil differentiation. In addition, transplantation of beta2-microglobulin (-/-) NOD/SCID mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in enhanced neutrophil and monocyte development, whereas ectopic expression of dominant-negative PKB induced eosinophil development in vivo. Inhibitory phosphorylation of C/EBPalpha on Thr222/226 was abrogated upon PKB activation in hematopoietic progenitors. Ectopic expression of a nonphosphorylatable C/EBPalpha mutant inhibited eosinophil differentiation ex vivo, whereas neutrophil development was induced, demonstrating the importance of PKB-mediated C/EBPalpha phosphorylation in regulation of granulopoiesis. These results identify an important novel role for PKB in regulation of cell fate choices during hematopoietic lineage commitment.
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| 4. |
- Nygård, Kim, 1978, et al.
(författare)
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Anisotropic hydrodynamic function of dense confined colloids
- 2017
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Ingår i: Physical Review E. - 2470-0045 .- 2470-0053. ; 95:6
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Tidskriftsartikel (refereegranskat)abstract
- Dense colloidal dispersions exhibit complex wave-vector-dependent diffusion, which is controlled by both direct particle interactions and indirect nonadditive hydrodynamic interactions mediated by the solvent. In bulk the hydrodynamic interactions are probed routinely, but in confined geometries their studies have been hitherto hindered by additional complications due to confining walls. Here we solve this issue by combining high-energy x-ray photon correlation spectroscopy and small-angle x-ray-scattering experiments on colloid-filledmicrofluidic channels to yield the confined fluid's hydrodynamic function in the short-time limit. Most importantly, we find the confined fluid to exhibit a strongly anisotropic hydrodynamic function, similar to its anisotropic structure factor. This observation is important in order to guide future theoretical research.
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