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- Brun, Ann, et al.
(författare)
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Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 103:11, s. 4126-4133
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Tidskriftsartikel (refereegranskat)abstract
- Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in adult BM and fetal liver, whereas lineage distribution was normal. Although the cell cycle kinetics of primitive progenitors was normal during endogenous hematopoiesis, defects in proliferative responses of BM Lin(-) Sca1(+) c-kit(+) stem and progenitor cells were observed in culture and in vivo after the transplantation of BM and fetal liver HSCs. Quantitative analysis of mRNA from fetal liver revealed that a deficiency of Hoxb4 alone changed the expression levels of several other Hox genes and of genes involved in cell cycle regulation. In summary, the deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs and impaired proliferative capacity. However, Hoxb4 is not required for the generation of HSCs or the maintenance of steady state hematopoiesis.
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- Falk, Sven, et al.
(författare)
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Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion
- 2008
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 2:5, s. 472-483
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Tidskriftsartikel (refereegranskat)abstract
- Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the presence of FGF and requires Wnt signaling. Moreover, TGF-beta signal activation counteracts Wnt-incluced proliferation of midbrain neuroepithelial cells. Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells.
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- Frutkin, Andrew D., et al.
(författare)
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A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre
- 2006
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 41:4, s. 724-731
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Tidskriftsartikel (refereegranskat)abstract
- Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type 11 TGF-beta receptor (tgfbr2(flox)) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2(flox). Surprisingly, SMMHC-Cre rnice recombined tglbr2(flox) at low levels in SMC and at high levels in the testis. Recombination of tgfbr2(flox) in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2(null). In contrast, mice expressing Cre from a SM22 alpha promoter (SM22-Cre) efficiently recombined tgfbr2(flox) in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2(flox) zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2(flox) and would have conversion of tgfbr2(flox/flox) to tgfbr2(null/null) in SMC-produced no live SM22-Cre : tgfbr2(flox/flox) pups (P < 0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22 alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge. (c) 2006 Elsevier Inc. All rights reserved.
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- Grönlund, Christer, et al.
(författare)
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Spatio-temporal processing of surface EMG signals from the sternocleidomastoideus muscle to assess effects of radiotherapy on motor unit conduction velocity and firing rate : a pilot study
- 2008
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Ingår i: Biomedical Signal Processing and Control. - : Elsevier. - 1746-8094. ; 3:2, s. 163-168
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Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy causes both muscle and nerve tissue damage. However, the evolution and mechanisms of these damages are not fully understood. Information on the state of active muscle fibres and motoneurons can be obtained by measuring sEMG signals and calculating the conduction velocity (CV) and firing rate of individual motor units, respectively. The aim of this pilot study was to evaluate if the multi-channel surface EMG (sEMG) technique could be applied to the sternocleidomastoideus muscle (SCM) of radiotherapy patients, and to assess if the CV and firing rate are altered as a consequence of the radiation. Surface EMG signals were recorded from the radiated and healthy SCM muscles of 10 subjects, while subjects performed isometric rotation of the head. CV and firing rate were calculated using two recently proposed methods based on spatio-temporal processing of the sEMG signals. The multi-channel sEMG technique was successfully applied to the SCM muscle and CV and firing rates were obtained. The measurements were fast and simple and comfortable for the patients. Sufficient data quality was obtained from both sides of seven and four subjects for the CV and firing rate analysis, respectively. No differences in CV or firing rate were found between the radiated and non-radiated sides (p = 0.13 and p = 0.20, respectively). Firing rate and CV were also obtained from a myokymic discharge pattern. It was found that the CV decreased significantly (p = 0.01) during the bursts.
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- Ittner, Lars M, et al.
(författare)
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Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells
- 2005
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Ingår i: Journal of Biology. - : Springer Science and Business Media LLC. - 1475-4924. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood. RESULTS: Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFbeta signaling in these cells is crucial for normal eye development. In the anterior eye, TGFbeta2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice. CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.
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| 10. |
- Kalezic, Nebojsa, et al.
(författare)
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Cardiovascular and muscle activity during chewing in whiplash-associated disorders (WAD)
- 2010
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Ingår i: Archives of Oral Biology. - : Elsevier BV. - 0003-9969 .- 1879-1506. ; 55:6, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The present study aimed to elucidate possible physiological mechanisms behind impaired endurance during chewing as previously reported in WAD. We tested the hypothesis of a stronger autonomic reaction in WAD than in healthy subjects in response to dynamic loading of the jaw-neck motor system. Design. Cardiovascular reactivity, muscle fatigue indicies of EMG, and perceptions of fatigue, exhaustion and pain were assessed during standardised chewing. Twenty-one WAD subjects and a gender/age matched control group participated. Baseline recordings were followed by two sessions of alternating unilateral chewing of a bolus of gum with each session followed by a rest period. Results. More than half of the WAD subjects terminated the test prematurely due to exhaustion and pain. In line with our hypothesis the chewing evoked an increased autonomic response in WAD exhibited as a higher increase in heart rate as compared to controls. Furthermore, we saw consistently higher values of arterial blood pressure for WAD than for controls across all stages of the experiment. Masseter EMG did not indicate muscle fatigue nor were there group differences in amplitude and mean power frequency. Pain in the WAD group increased during the first session and remained increased, whereas no pain was reported for the controls. Conclusion. More intense response to chewing in WAD might indicate pronounced vulnerability to dynamic loading of the jaw-neck motor system with increased autonomic reactivity to the test. Premature termination and autonomic involvement without EMG signs of muscle fatigue may indicate central mechanisms behind insufficient endurance during chewing.
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