| 1. |
- Askmyr, Maria, et al.
(författare)
-
Low-dose busulphan conditioning and neonatal stem cell transplantation preserves vision and restores hematopoiesis in severe murine osteopetrosis.
- 2009
-
Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 37, s. 302-308
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Infantile malignant osteopetrosis is a fatal disease caused by lack of functional osteoclasts. In most of patients, TCIRG1, encoding a subunit of a proton pump essential for bone resorption, is mutated. Osteopetrosis leads to bone marrow failure and blindness due to optic nerve compression. Oc/oc mice have a deletion in Tcirg1 and die around 3 to 4 weeks, but can be rescued by neonatal stem cell transplantation (SCT) after irradiation conditioning. However, as irradiation of neonatal mice results in retinal degeneration, we wanted to investigate whether conditioning with busulphan prior to SCT can lead to preservation of vision and reversal of osteopetrosis in the oc/oc mouse model. MATERIALS AND METHODS: Pregnant dams were conditioned with busulphan and their litters transplanted with 1 x 10(6) normal lineage-depleted bone marrow cells intravenously or intraperitoneally. Mice were followed in terms of survival and engraftment level, as well as with peripheral blood lineage analysis, bone and eye histopathology and a visual-tracking drum test to assess vision. RESULTS: Busulphan at 15 mg/kg was toxic to oc/oc mice. However, six of seven oc/oc mice conditioned with busulphan 7.5 mg/kg survived past the normal lifespan with 10% engraftment, correction of the skeletal phenotype, and normalization of peripheral blood lineages. Busulphan, in contrast to irradiation, did not have adverse effects on the retina as determined by histopathology, and 8 weeks after transplantation control and oc/oc mice retained their vision. CONCLUSION: Low-dose busulphan conditioning and neonatal SCT leads to prolonged survival of oc/oc mice, reverses osteopetrosis and prevents blindness even at low engraftment levels.
|
|
| 2. |
- Grasselli, Robert K., et al.
(författare)
-
Active centers, catalytic behavior, symbiosis and redox properties of MoV(Nb,Ta)TeO ammoxidation catalysts
- 2006
-
Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 38:1-3, s. 7-16
-
Tidskriftsartikel (refereegranskat)abstract
- Selective as well as waste forming active centers were defined for MoVNbTeO and MoVTaTeO catalysts in the ammoxidation of propane to acrylonitrile and all catalytic functionalities were assigned to specific elements at the respective active centers. Symbiosis between M1 and M2 phases of these catalysts was observed, with phase cooperation being more extensive in the Nb than Ta containing compositions. The difference in catalytic effectiveness arises most likely because contact and surface area exposure of the two respective, cooperating phase pairs are not equal. The M1 phase of the catalysts is reducible by propane and ammonia in the absence of dioxygen and is regenerable to its original, fully oxidized state by dioxygen (air). No structural collapse is observed even after 120 C3H8 + NH3 reduction pulses. The so induced reduction of the catalyst extends up to 70 layers deep. The product distribution over the first few pulses is very similar to that under catalytic conditions, supporting the concept that lattice oxygen is involved in the catalytic ammoxidation process. Therefore, the ammoxidation of paraffins is a redox process, as is of course the well-known olefin ammoxidation process.
|
|
| 3. |
- Holmberg, Johan K
(författare)
-
Gain-of-function induced defects by PITX2 in eye and limb development
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- My research has been focused on eye and limb development with regard to the transcription factor PITX2. In the first paper we present an Axenfeld-Rieger syndrome PITX2 gain-of-function eye mouse model. Axenfeld-Rieger syndrome is a rare autosomal disorder affecting the development of eyes, teeth and abdomen. The eye defects consist of anomalies in the anterior segment. In addition, almost 50% of Axenfeld-Rieger syndrome patients develop glaucoma, the leading cause of vision loss worldwide. The mouse model faithfully recapitulated these eye symptoms. The next paper describes a forelimb phenotype due to a brief pulse of PITX2 overexpression in the forelimbs during embryogenesis. This overexpression interferes with tendon morphogenesis resulting in severe bone malformations, which in turn twist the forelimb and makes it non-supportable. The mechanisms behind limb tendon development and positioning are largely unknown, which makes this study a valuable resource for further studies on the development of the musculoskeletal system. In the third paper we compare the phenotypic outcome of PITX2 overexpression between three different mouse strains to study the effect of strain specific modifier genes. We observe both gain-of- and loss-of-function phenotypes, which indicate existence of strain specific genes working in concert with PITX2 during eye and limb development. To put these papers in a context I have aimed at gaining a deeper insight into the role of PITX2 in the development of eye and limb, and to increase the understanding of the pathophysiology of the eye defects associated with Axenfeld-Rieger syndrome.
|
|
| 4. |
- Holmberg, Johan K, et al.
(författare)
-
PITX2 gain-of-function induced defects in mouse forelimb development.
- 2008
-
Ingår i: BMC Developmental Biology. - 1471-213X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle. RESULTS: To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis. CONCLUSION: Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis.
|
|
| 5. |
- Häger, Mattias, et al.
(författare)
-
Cib2 binds integrin a7Bb1D and is reduced in laminin a2 chain deficient muscular dystrophy
- 2008
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:36, s. 24760-24769
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding laminin alpha 2 chain cause congenital muscular dystrophy type 1A. In skeletal muscle, laminin alpha 2 chain binds at least two receptor complexes: the dystrophin-glycoprotein complex and integrin alpha 7 beta 1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin alpha 2 chain-deficient mouse limb muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium-and integrin-binding protein 2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin alpha IIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin alpha 7 beta 1-binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle, Cib2 colocalizes with the integrin alpha 7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium-binding protein that interacts with integrin alpha 7B beta 1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin alpha 7B beta 1D signaling in skeletal muscle.
|
|
| 6. |
- Häggblad, Robert, et al.
(författare)
-
Substituted Mo-V(Ti)-Te(Ce)-oxide M2 catalysts for propene ammoxidation
- 2008
-
Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 50:1-4, s. 52-65
-
Tidskriftsartikel (refereegranskat)abstract
- One of the most effective propane to acrylonitrile ammoxidation catalyst is comprised of the two phases M1 (orthorhombic) Mo7.5V1.5NbTeO29 and M2 (pseudo-hexagonal) Mo4V2Te2O20. Under reaction conditions, the two phases work in symbiosis with each other where M1 is the paraffin activating component and M2 is the olefin activating component. Since the catalytic improvement of either phase should result in an enhancement of the overall acrylonitrile yield, controlled substitution of certain elements in either or both phases might result in the desired improvement. Our current study concentrates on the partial substitutions of V with Ti and Te with Ce in the M2 phase. Ti substitution results in a considerable propene activity improvement, whereas the selectivity to acrylonitrile is unaffected. Substitution with Ce, on the contrary, substantially improves the selectivity to acrylonitrile. Also, a minor improvement of the activity is notable. The acrylonitrile selectivity improvement is a result of better NH3 utilization and comes at the expense of reduced acrolein make. XRD reveals that all of the substituted compositions retain the M2 structure and essentially are monophasic. XANES recordings show for the bulk that the Mo is 6+, the V is 4+, or 4+ and 5+ when Ce is present, the Ti is 4+, the Ce is 3+, and the Te 4+ with some 6+ also present. According to the ESR data, in the M2 with Ce (7Te/3Ce) only 21% of the V is 4+, the remainder being 5+, which tentatively can be explained by the existence of some cation vacancies in the hexagonal channels. HRTEM imaging reveals little if any differences between the materials, all have the typical pseudo-hexagonal habit of the M2 phase and expose a 1-2 nm thick surface layer without any apparent long-range ordering. XPS data show that all catalysts, including the base, are highly enriched at the surface with Te at the expense of other metals. The 7Te/3Ce composition exhibits also substantial Ce surface enrichment. Moreover, the valences of the cations at the surface differ from the bulk in that for all fresh catalysts V is 5+ and Te is 6+ on the surface. Characterization by XPS of catalysts used in propene ammoxidation, reveals reduction of Te and, except when Ce is present, also Mo. Therefore, it might be inferred that the surfaces of the catalysts studied here are comprised essentially of one or a few monolayers of TeMoO or TeCeMoO on an interacting M2 crystalline base.
|
|
