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Miller KA Barrow J Collinson JM Davidson S Lear M Hill RE Mackenzie A 《Developmental biology》2007,311(2):665-678
The product of the Msx1 gene is a potent inhibitor of muscle differentiation. Msx1 is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msx1 may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msx1 in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msx1 gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and immunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msx1 gene proximal enhancer element that supports the expression of the Msx1 gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells. 相似文献
74.
Lucas KA Filley JR Erb JM Graybill ER Hawes JW 《The Journal of biological chemistry》2007,282(34):24980-24989
The subcellular sites of branched-chain amino acid metabolism in plants have been controversial, particularly with respect to valine catabolism. Potential enzymes for some steps in the valine catabolic pathway are clearly present in both mitochondria and peroxisomes, but the metabolic functions of these isoforms are not clear. The present study examined the possible function of these enzymes in metabolism of isobutyryl-CoA and propionyl-CoA, intermediates in the metabolism of valine and of odd-chain and branched-chain fatty acids. Using (13)C NMR, accumulation of beta-hydroxypropionate from [2-(13)C]propionate was observed in seedlings of Arabidopsis thaliana and a range of other plants, including both monocots and dicots. Examination of coding sequences and subcellular targeting elements indicated that the completed genome of A. thaliana likely codes for all the enzymes necessary to convert valine to propionyl-CoA in mitochondria. However, Arabidopsis mitochondria may lack some of the key enzymes for metabolism of propionyl-CoA. Known peroxisomal enzymes may convert propionyl-CoA to beta-hydroxypropionate by a modified beta-oxidation pathway. The chy1-3 mutation, creating a defect in a peroxisomal hydroxyacyl-CoA hydrolase, abolished the accumulation of beta-hydroxyisobutyrate from exogenous isobutyrate, but not the accumulation of beta-hydroxypropionate from exogenous propionate. The chy1-3 mutant also displayed a dramatically increased sensitivity to the toxic effects of excess propionate and isobutyrate but not of valine. (13)C NMR analysis of Arabidopsis seedlings exposed to [U-(13)C]valine did not show an accumulation of beta-hydroxypropionate. No evidence was observed for a modified beta-oxidation of valine. (13)C NMR analysis showed that valine was converted to leucine through the production of alpha-ketoisovalerate and isopropylmalate. These data suggest that peroxisomal enzymes for a modified beta-oxidation of isobutyryl-CoA and propionyl-CoA could function for metabolism of substrates other than valine. 相似文献
75.
Manton KJ Haupt LM Vengadasalam K Nurcombe V Cool SM 《Journal of molecular histology》2007,38(5):415-424
Summary Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans
(GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development.
The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems.
Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 μg/ml) resulted
in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When
we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2
(BMP2) and transforming growth factor-β1 (TGFβ1) and the isolated cell surface GAGs, differences between the two model systems
emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFβ1
actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGβ1 effects. These results emphasise
the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the
GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.
Kerry J. Manton and Larisa M. Haupt—Co-first authors. 相似文献
76.
Grünert M Dombrowski C Sadasivam M Manton K Cool SM Nurcombe V 《Journal of molecular histology》2007,38(5):393-404
During their commitment and differentiation toward the osteoblast lineage, mesenchymal stem cells secrete a unique extracellular
matrix (ECM) that contains large quantities of glycosaminoglycans (GAGs). Proteoglycans (PGs) are major structural and functional
components of the ECM and are composed of a core protein to which one or more glycosaminoglycan sugar chains (GAGs) attach.
The association of BMP2, a member of the TGF-β super-family of growth factors, and a known heparin-binding protein, with GAGs
has been implicated as playing a significant role in modulating the growth factor’s in vitro bioactivity. Here we have characterised
an osteoblast-derived matrix (MX) obtained from decellularised MC3T3-E1 cell monolayers for its structural attributes, using
SEM and histology, and for its functional ability to maintain cell growth and viability. Using a combination of histology
and anion exchange chromatography, we first confirmed the retention of GAGs within MX following the decellularisation process.
Then the binding specificity of the retained GAG species within the MX for BMP2 was examined using a BMP2-HBP/EGFP (BMP2 Heparin-Binding
Peptide/Enhanced Green Fluorescent Protein) fusion protein. The results of this study provide further evidence for a central
role of the ECM in the regulation of BMP2 bioactivity, hence on mesenchymal stem cell commitment to the osteoblast lineage. 相似文献
77.
Andrea Swei Kerry E. OConnor Lisa I. Couper Jose Thekkiniath Patricia A. Conrad Kerry A. Padgett Joseph Burns Melissa H. Yoshimizu Ben Gonzales Brandon Munk Nicholas Shirkey Lora Konde Choukri Ben Mamoun Robert S. Lane Anne Kjemtrup 《International journal for parasitology》2019,49(2):95-103
Babesiosis is a potentially fatal tick-borne zoonotic disease caused by a species complex of blood parasites that can infect a variety of vertebrates, particularly dogs, cattle, and humans. In the United States, human babesiosis is caused by two distinct parasites, Babesia microti and Babesia duncani. The enzootic cycle of B. microti, endemic in the northeastern and upper midwestern regions, has been well characterised. In the western United States, however, the natural reservoir host and tick vector have not been identified for B. duncani, greatly impeding efforts to understand and manage this zoonotic disease. Two and a half decades after B. duncani was first described in a human patient in Washington State, USA, we provide evidence that the enzootic tick vector is the winter tick, Dermacentor albipictus, and the reservoir host is likely the mule deer, Odocoileus hemionus. The broad, overlapping ranges of these two species covers a large portion of far-western North America, and is consistent with confirmed cases of B. duncani in the far-western United States. 相似文献
78.
Plant and Soil - Trade-offs between slow and fast nutrient turnover rates among plants may affect soil properties and biomass production. We examined how plant traits interact with abiotic... 相似文献
79.
Kerry A. Broom Richard Findlay Darren S. Addison Cristian Goiceanu Zenon Sienkiewicz 《Bioelectromagnetics》2019,40(7):498-511
Despite much research, gaps remain in knowledge about the potential health effects of exposure to radiofrequency (RF) fields. This study investigated the effects of early‐life exposure to pulsed long term evolution (LTE) 1,846 MHz downlink signals on innate mouse behavior. Animals were exposed for 30 min/day, 5 days/week at a whole‐body average specific energy absorption rate (SAR) of 0.5 or 1 W/kg from late pregnancy (gestation day 13.5) to weaning (postnatal day 21). A behavioral tracking system measured locomotor, drinking, and feeding behavior in the home cage from 12 to 28 weeks of age. The exposure caused significant effects on both appetitive behaviors and activity of offspring that depended on the SAR. Compared with sham‐exposed controls, exposure at 0.5 W/kg significantly decreased drinking frequency (P ≤ 0.000) and significantly decreased distance moved (P ≤ 0.001). In contrast, exposure at 1 W/kg significantly increased drinking frequency (P ≤ 0.001) and significantly increased moving duration (P ≤ 0.005). In the absence of other plausible explanations, it is concluded that repeated exposure to low‐level RF fields in early life may have a persistent and long‐term effect on adult behavior. Bioelectromagnetics. 2019;40:498–511. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc. 相似文献
80.