433 research outputs found
Le changement climatique : conséquences pour les végétaux
Le changement climatique va profondément affecter les productions agricoles et sylvicoles. Les effets en termes de potentialité de production seront très variables suivant les régions et les couvets végétaux. Ils peuvent se traduire par une tendance globale à une stimulation modérée en climat tempéré et pour un réchauffement limité à 2°-3° C. Au-delà , comme pour les basses latitudes, des températures excessives et la fréquence accrue des sécheresses conduiront à des effets négatifs. Ces impacts vont amener à des adaptations, qui combineront des modifications locales des systèmes de culture ou de gestion, ainsi que déplacements géographiques des systèmes de production. Les acteurs de terrain, qui ont déjà pu observer des évolutions notables en conséquence du réchauffement récent, y sont assez bien préparésClimatic change will deeply impact agricultural and forest productions. The effects in terms of production potentialities will be largely variable between regions and productions. They may result in a global tendency to slightly increase in temperate climates as far as the warming is limited to 2°C-3°C. Above, as for low latitudes, the overall effect will be negative due to excessive temperatures and increased drought frequencies. These impacts will induce adaptive actions. They will combine changes in cropping or forestry systems on a local scale, together with geographical shifts in production systems. Field actors have been already able to observe significant changes due to the recent warming and seem to be well prepared for this adaptatio
Developmental and Regional Studies of the Metabolism of Inositol 1,4,5-Trisphosphate in Rat Brain
Coupling of CNS receptors to phosphoinositide turnover has previously been found to vary with both age and brain region. To determine whether the metabolism of the second messenger inositol 1,4,5-trisphosphate also displays such variations, activities of inositol 1,4,5-trisphosphate 5′-phosphatase and 3′-kinase were measured in developing rat cerebral cortex and adult rat brain regions. The 5′-phosphatase activity was relatively high at birth (∼50% of adult values) and increased to adult levels by 2 weeks postnatal. In contrast, the 3′-kinase activity was low at birth and reached ∼50% of adult levels by 2 weeks postnatal. In the adult rat, activities of the 3′-kinase were comparable in the cerebral cortex, hippocampus, and cerebellum, whereas much lower activities were found in hypothalamus and pons/medulla. The 5′-phosphatase activities were similar in cerebral cortex, hippocampus, hypothalamus, and pons/medulla, whereas 5-to 10-fold higher activity was present in the cerebellum. The cerebellum is estimated to contain 50–60% of the total inositol 1,4,5-trisphosphate 5′-phosphatase activity present in whole adult rat brain. The localization of the enriched 5′-phosphatase activity within the cerebellum was examined. Application of a histochemical lead-trapping technique for phosphatase indicated a concentration of inositol 1,4,5-trisphosphate 5′-phosphatase activity in the cerebellar molecular layer. Further support for this conclusion was obtained from studies of Purkinje cell-deficient mutant mice, in which a marked decrement of cerebellar 5′-phosphatase was observed. These results suggest that the metabolic fate of inositol 1,4,5-trisphosphate depends on both brain region and stage of development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65545/1/j.1471-4159.1990.tb01976.x.pd
Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and has Therapeutic Potential in Affected Dogs
AbstractBACKGROUND: This investigation sought to elucidate the relationship between hepatocyte growth factor (HGF)–induced metastatic behavior and the tyrosine kinase inhibitors (TKIs) crizotinib and dasatinib in canine osteosarcoma (OS). Preliminary evidence of an apparent clinical benefit from adjuvant therapy with dasatinib in four dogs is described. METHODS: The inhibitors were assessed for their ability to block phosphorylation of MET; reduce HGF-induced production of matrix metalloproteinase (MMP); and prevent invasion, migration, and cell viability in canine OS cell lines. Oral dasatinib (0.75 mg/kg) was tested as an adjuvant therapy in four dogs with OS. RESULTS: Constitutive phosphorylation of MET was detected in two cell lines, and this was unaffected by 20-nM incubation with either dasatinib or crizotinib. Incubation of cell lines with HGF (MET ligand) increased cell migration and invasion in both cell lines and increased MMP-9 activity in one. Dasatinib suppressed OS cell viability and HGF-induced invasion and migration, whereas crizotinib reduced migration and MMP-9 production but did not inhibit invasion or viability. CONCLUSIONS: Invasion, migration, and viability of canine OS cell lines are increased by exogenous HGF. HGF induces secretion of different forms of MMP in different cell lines. The HGF-driven increase in viability and metastatic behaviors we observed are more uniformly inhibited by dasatinib. These observations suggest a potential clinical benefit of adjuvant dasatinib treatment for dogs with OS
Cholesterol Synthesis and Nerve Regeneration
In this report, we examine the requirement of cholesterol biosynthesis and its axonal transport for goldfish optic nerve regeneration. Cholesterol, labeled by intraocular injection of [ 3 H]mevalonolactone. exhibited a delayed appearance in the optic tectum. Squalene and other minor components were labeled but not transported. Following optic nerve crush, the amount of labeled cholesterol transport was elevated, while retinal labeling was not altered relative to control fish. A requirement for cholesterol biosynthesis is inferred from the inhibition of neurite outgrowth in retinal explants caused by the cholesterol synthesis inhibitor, 20, 25-diazacholes-terol. The inhibition of growth could be overcome by addition of mevalonolactone, but not cholesterol, to the medium. Intraperitoneal administration of 200 nmol of dia-zacholesterol resulted in 92-98% inhibition of retinal cholesterol synthesis and accumulation of labeled des-mosterol and other lipids in fish retina and brain which persisted for 2 weeks. Diazacholesterol-treated fish showed no reduction in the amount of lipid-soluble radioactivity transported following intraocular injection of [ 3 H]mevalonolactone, but there were alterations in the chromatographic pattern of the transported labeled lipids. In contrast to its effects on neurite outgrowth in vitro , diazacholesterol did not inhibit optic nerve regeneration in vivo , as measured both by arrival of labeled rapidly transported protein at the tectum and by time required for the return of visual function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65710/1/j.1471-4159.1984.tb12701.x.pd
Properties of a CDP-Diglyceride Hydrolase from Guinea Pig Brain
Enzymatic hydrolysis of the pyrophosphate bond of CDP-diglyceride (CDP-DG), previously shown to occur in bacteria, is demonstrable in mammalian tissues. Activity was enriched in a lysosomal fraction obtained from guinea pig cerebral cortex and was purified 92-fold relative to the homogenate by a combination of XM-300 ultrafiltration and DEAE-cellulose column chromatography. When incubated with CDP-dipalmitin, the purified enzyme produced stoichiometric amounts of CMP and phosphatidate. dCDP-DG served as a substrate, while ADP-DG was an inhibitor, as were 5′-AMP and 5′-dAMP. CDP-DG hydrolysis was not affected by the presence of excess amounts of CDP-choline, CDP-glycerol, sodium pyrophosphate, or cyclic 3′,5′-AMP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65407/1/j.1471-4159.1981.tb01691.x.pd
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Osteoprotegerin activates osteosarcoma cells that co-express RANK and RANKL
Background:
Osteosarcoma (OS) is an aggressive and often fatal cancer that afflicts over 1000 humans and 10,000 dogs per year in the United States. Recent evidence suggests deregulation in the signaling triad, receptor activator of nuclear factor kappa B (RANK), its activating ligand (RANKL), and the RANKL inhibitor, osteoprotegerin (OPG) plays a key role in the pathogenesis of OS. This study investigated the expression of RANK and RANKL in osteosarcoma tumors and cell lines and describes an activating effect of OPG on OS cells in vitro.
Results:
Canine OS tumors and cell lines co-express mRNA for both RANK and RANKL. Expression of these proteins in OS cell lines was confirmed by Western blot and immunofluorescence microscopy. Expression of the soluble form of RANKL was not detected in media from OS cells. OPG-Fc incubation increased the phosphorylation status of ERK, AKT and the p65 subunit of nuclear factor kappa B (NFκB) and induced NFκB translocation from the cytoplasm to the nucleus in canine OS cells. OPG increased proliferation in both canine and human derived OS cell lines.
Conclusion:
RANKL is produced by OS tumors and cell lines that also express RANK. This data provides preliminary evidence for a potential autocrine and or paracrine activation pathway in canine OS. An activating effect of exogenous OPG on signal transduction proteins, NFκB and proliferation in OS is described. These data provide new information concerning aberrant signaling in OS and could be important to those considering OPG as a therapeutic agent for osteosarcoma.KEYWORDS: Invasion, Cancer, Osteolytic, RANKL, RANK-L, Metastatic, Bone tumorsThis is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Elsevier. The published article can be found at: http://www.journals.elsevier.com/experimental-cell-research
Retrospective Multi-Center Analysis of Canine Socket Prostheses for Partial Limbs
Introduction: Socket prostheses for treatment of distal limb pathology are becoming increasingly prevalent in veterinary medicine, however, limited objective data is available. Objectives of the present study were to retrospectively evaluate owner satisfaction, clinical outcomes, and prognostic factors associated with dogs receiving socket prostheses for partial limbs in a larger patient population.Materials and Methods: Client databases of a single prosthesis provider were reviewed to identify owners whose dogs had received a prosthetic device within the last 10 years. An online survey was developed to evaluate owner-reported outcomes. The survey inquired about anatomy of the residuum, concurrent disease, prosthesis use, rehabilitation, activity, complications, and owner satisfaction. Medical records and radiographs were requested from all participants. Radiographs were used to confirm level of amputation and evaluate for osseous complications. Survey responses were analyzed by assigning author-defined numeric scores defining clinical outcome and owner satisfaction.Results: One-hundred thirty-seven owners were contacted. The response rate was 50/137 (37%); 47 responses were analyzed. Forty-six of 47 owners reported positive satisfaction; 1/47 was displeased. Forty-two of 47 dogs were scored to have acceptable to full function; 5/47 had unacceptable clinical function using the author-defined scoring system. A 62% short-term complication rate and a 19% long-term complication rate were reported. Skin sores were the most common short and long-term complication. There was a significant correlation between both clinical outcome scores and owner satisfaction with days per week spent in the prosthesis. Additionally, clinical outcome scores and owner satisfaction significantly varied between dogs with different durations of prosthesis wear with a trend toward better outcomes associated with longer prosthesis wear. Radiographs were obtained for 23/47 dogs to further define level of defect. The most proximal level of defect was mid-radius for the forelimb and mid-tibia for the hind limb. There was no correlation between level of defect and either owner satisfaction or clinical outcome.Discussion/Conclusion: Results of this survey suggest a high degree of owner satisfaction despite substantial complication rates. Based on preliminary data, further evaluation of socket prostheses as a limb-sparing option for treatment of distal limb pathology should be considered. Prospective clinical trials with objective outcome measures are required to draw firm conclusions
Comparative analysis of the surface exposed proteome of two canine osteosarcoma cell lines and normal canine osteoblasts
BACKGROUND: Osteosarcoma (OSA) is the most common primary bone tumor of dogs and carries a poor prognosis despite aggressive treatment. An improved understanding of the biology of OSA is critically needed to allow for development of novel diagnostic, prognostic, and therapeutic tools. The surface-exposed proteome (SEP) of a cancerous cell includes a multifarious array of proteins critical to cellular processes such as proliferation, migration, adhesion, and inter-cellular communication. The specific aim of this study was to define a SEP profile of two validated canine OSA cell lines and a normal canine osteoblast cell line utilizing a biotinylation/streptavidin system to selectively label, purify, and identify surface-exposed proteins by mass spectrometry (MS) analysis. Additionally, we sought to validate a subset of our MS-based observations via quantitative real-time PCR, Western blot and semi-quantitative immunocytochemistry. Our hypothesis was that MS would detect differences in the SEP composition between the OSA and the normal osteoblast cells. RESULTS: Shotgun MS identified 133 putative surface proteins when output from all samples were combined, with good consistency between biological replicates. Eleven of the MS-detected proteins underwent analysis of gene expression by PCR, all of which were actively transcribed, but varied in expression level. Western blot of whole cell lysates from all three cell lines was effective for Thrombospondin-1, CYR61 and CD44, and indicated that all three proteins were present in each cell line. Semi-quantitative immunofluorescence indicated that CD44 was expressed at much higher levels on the surface of the OSA than the normal osteoblast cell lines. CONCLUSIONS: The results of the present study identified numerous differences, and similarities, in the SEP of canine OSA cell lines and normal canine osteoblasts. The PCR, Western blot, and immunocytochemistry results, for the subset of proteins evaluated, were generally supportive of the mass spectrometry data. These methods may be applied to other cell lines, or other biological materials, to highlight unique and previously unrecognized differences between samples. While this study yielded data that may prove useful for OSA researchers and clinicians, further refinements of the described techniques are expected to yield greater accuracy and produce a more thorough SEP analysis
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