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111.
Introduction
Both canine cutaneous mast cell tumor (MCT) and human systemic mastocytosis (SM) are characterized by abnormal proliferation and accumulation of mast cells in tissues and, frequently, by the presence of activating mutations in the receptor tyrosine kinase V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (c-KIT), albeit at different incidence (>80% in SM and 10–30% in MCT). In the last few years, it has been discovered that additional mutations in other genes belonging to the methylation system, the splicing machinery and cell signaling, contribute, with c-KIT, to SM pathogenesis and/or phenotype. In the present study, the mutational profile of the Tet methylcytosine dioxygenase 2 (TET2), the isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2), the serine/arginine-rich splicing factor 2 (SRSF2), the splicing factor 3b subunit 1 (SF3B1), the Kirsten rat sarcoma viral oncogene homolog (KRAS) and the neuroblastoma RAS viral oncogene homolog (NRAS), commonly mutated in human myeloid malignancies and mastocytosis, was investigated in canine MCTs.Methods
Using the Sanger sequencing method, a cohort of 75 DNA samples extracted from MCT biopsies already investigated for c-KIT mutations were screened for the “human-like” hot spot mutations of listed genes.Results
No mutations were ever identified except for TET2 even if with low frequency (2.7%). In contrast to what is observed in human TET2 no frame-shift mutations were found in MCT samples.Conclusion
Results obtained in this preliminary study are suggestive of a substantial difference between human SM and canine MCT if we consider some target genes known to be involved in the pathogenesis of human SM. 相似文献112.
alpha- and beta-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins. Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation. Here, we demonstrate that beta-Spectrin is required in neurons for proper midline axon guidance in the Drosophila embryonic CNS. In beta-spectrin mutants many axons inappropriately cross the CNS midline, suggesting a role for beta-Spectrin in midline repulsion. Surprisingly, neither the Ankyrin-binding nor the pleckstrin homology (PH) domains of beta-Spectrin are required for accurate guidance decisions. alpha-Spectrin is dependent upon beta-Spectrin for its normal subcellular localization and/or maintenance, whereas alpha-spectrin mutants exhibit a redistribution of beta-Spectrin to the axon scaffold. beta-spectrin mutants show specific dose-dependent genetic interactions with the midline repellent slit and its neuronal receptor roundabout (robo), but not with other guidance molecules. The results suggest that beta-Spectrin contributes to midline repulsion through the regulation of Slit-Robo pathway components. We propose that the Spectrin network is playing a role independently of Ankyrin in the establishment and/or maintenance of specialized membrane domains containing guidance molecules that ensure the fidelity of axon repulsion at the midline. 相似文献
113.
Cloning and characterization of the eae gene from a dog attaching and effacing Escherichia coli strain 4221 总被引:1,自引:0,他引:1
Hongyan An John M Fairbrother J.Daniel Dubreuil Josée Harel 《FEMS microbiology letters》1997,148(2):239-245
We have cloned and determined the nucleotide sequence of the eae gene from a dog attaching and effacing (A/E) Escherichia coli (DEPEC) strain 4221. When comparing the predicted amino acid sequence of the eaeDEPEC to that of the Eae proteins from enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli O157:H7 (EHEC), Citrobacter freundii biotype 4280, and a swine A/E E. coli strain O45 (PEPEC), the overall sequence identity was 84, 81, 83 and 83%, respectively, with the greatest divergence at the C-terminal end, the putative receptor-binding portion. Interestingly, the DEPEC Eae shares the greatest identity at the C-terminal region with the Citrobacter freundii Eae protein. We have constructed and purified a maltose-binding fusion protein (MBP) containing the product of the entire eae gene of the DEPEC strain 4221. Binding of MBP-EaeDEPEC fusion protein to HEp-2 cells was demonstrated by immunofluorescence microscopy. In addition, the Eae protein of DEPEC (4221) demonstrated a strong serological relationship with that of EPEC (E2348/69) as observed using a polyclonal antiserum against MBP-EaeDEPEC fusion protein. 相似文献
114.
Ronald R. Dubreuil Tatyana Grushko 《BioEssays : news and reviews in molecular, cellular and developmental biology》1998,20(11):875-878
Spectrin, together with actin and a number of other accessory proteins, forms a submembrane cytoskeletal network in the human erythrocyte ghost. Through an elegant combination of structural, biochemical, and genetic studies, spectrin was shown to be an important determinant of erythrocyte shape and membrane stability. Genetic studies of a novel nonerythroid spectrin (βH) in Drosophila and Caenorhabditis elegans now reveal that spectrin can influence the shape and stability of whole organisms.(1,2) Nonerythroid spectrins are proposed to have roles in cell adhesion, establishment of cell polarity, and attachment of other cytoskeletal structures to the plasma membrane. The phenotypes of the βH spectrin mutations provide an exciting biological context in which to evaluate these roles and perhaps to uncover new ones. BioEssays 20:875–878, 1998. © 1998 John Wiley & Sons, Inc. 相似文献
115.
Laure I. Dudet Pierre Chailler J. Daniel Dubreuil Beatrice Martineau-Doize 《Journal of cellular physiology》1996,168(1):173-182
Pasteurella multocida toxin (PMT) causes cytoplasmic retraction in epithelial cells, activates osteoclast neoformation, and is a potent mitogen for Swiss 3T3 fibroblasts. In the present study designed to further investigate the effects of PMT on cell shape and proliferation, we report that the mitogenic effect of affinity-purified PMT on quiescent 3T3 cells was even superior at 5 ng/ml to that of fetal bovine serum or bombesin. This positive effect was inhibited by heat denaturation and methylamine treatment (this agent blocks internalization). Preincubation of PMT with gangliosides GM1, GM2, or GM3 counteracted its effect on DNA synthesis, suggesting that the toxin binds to GM-type ceramides on target cells. The distribution of F-actin was analyzed in control/treated cells using FITC-conjugated phalloidin. In comparison with FBS and bombesin, PMT triggered a more rapid and profound reorganization of cortical actin into prominent stress fibers after only 5–10 min. This event lead to the retraction of cells after only 30 min and ultimately to the induction of mitotic figures. Interestingly, methylamine blocked the effects of PMT on stress fiber formation and cell retraction but not the ruffling response, suggesting that some early events may not require toxin internalization. In summary, these findings indicate that PMT concomitantly exerts a strong mitogenic activity and a rapid stimulation of cytoskeletal rearrangements, possibly after binding to membrane gangliosides and subsequent internalization. We propose that this toxin could be used in the future as a defined inducer of transduction signals involved in cellular proliferation and control of cell shape. © 1996 Wiley-Liss, Inc. 相似文献
116.
Natural Infection of a Household Pet Red-Capped Mangabey (Cercocebus torquatus torquatus) with a New Simian Immunodeficiency Virus
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Marie Claude Georges-Courbot Chong Yang Lu Maria Makuwa Paul Telfer Richard Onanga Guy Dubreuil Zhiwei Chen Stephen M. Smith Alain Georges Feng Gao Beatrice H. Hahn Preston A. Marx 《Journal of virology》1998,72(1):600-608
A seroprevalence survey was conducted for simian immunodeficiency virus (SIV) antibody in household pet monkeys in Gabon. Twenty-nine monkeys representing seven species were analyzed. By using human immunodeficiency virus type 2 (HIV-2)/SIVsm, SIVmnd, and SIVagm antigens, one red-capped mangabey (RCM) (Cercocebus torquatus torquatus) was identified as harboring SIV-cross-reactive antibodies. A virus isolate, termed SIVrcm, was subsequently established from this seropositive RCM by cocultivation of its peripheral blood mononuclear cells (PBMC) with PBMC from seronegative humans or RCMs. SIVrcm was also isolated by cocultivation of CD8-depleted RCM PBMC with Molt 4 clone 8 cells but not with CEMx174 cells. The lack of growth in CEMx174 cells distinguished this new SIV from all previously reported sooty mangabey-derived viruses (SIVsm), which grow well in this cell line. SIVrcm was also successfully transmitted (cell free) to human and rhesus PBMC as well as to Molt 4 clone 8 cells. To determine the evolutionary origins of this newly identified virus, subgenomic pol (475 bp) and gag (954 bp) gene fragments were amplified from infected cell culture DNA and sequenced. The position of SIVrcm relative to those of members of the other primate lentivirus lineages was then examined in evolutionary trees constructed from deduced protein sequences. This analysis revealed significantly discordant phylogenetic positions of SIVrcm in the two genomic regions. In trees derived from partial gag sequences, SIVrcm clustered independently from all other HIV and SIV strains, consistent with a new primate lentivirus lineage. However, in trees derived from pol sequences, SIVrcm grouped with the HIV-1/SIVcpz lineage. These findings suggest that the SIVrcm genome is mosaic and possibly is the result of a recombination event involving divergent lentiviruses in the distant past. Further analysis of this and other SIVrcm isolates may shed new light on the origin of HIV-1. 相似文献
117.
Genetic diversity within and among maize populations: a comparison between isozyme and nuclear RFLP loci 总被引:7,自引:0,他引:7
P. Dubreuil A. Charcosset 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1998,96(5):577-587
In order to compare the potential of enzyme and DNA markers to investigate genetic diversity within and among populations,
ten maize populations were characterized for (1) 20 isozyme loci and (2) restriction fragment length polymorphism (RFLP) for
35 probe-enzyme combinations. Each population was represented by a sample of at least 30 individuals. The average number of
alleles detected per locus was clearly higher for RFLPs (6.3) than for isozymes (2.4). Similarly, total diversity was higher
for RFLPs (0.60) than for isozymes (0.23). This difference is consistent with observations on inbred-line collections and
can be related to the fact that many variations at the DNA level do not change the amino-acid composition or the global charge
of proteins. By contrast, the magnitude of population differentiation, relative to the total diversity, was similar for isozymes
(23%) and RFLPs (22%). This suggests that the isozyme and RFLP loci considered in this study are subject to similar evolutionary
forces, and that both are mostly neutral. However, RFLPs proved clearly superior to isozymes both to (1) identify the origin
of a given individual and (2) reveal a relevant genetic structure among populations. The higher polymorphism observed for
RFLP loci and the greater number of these loci contributed to the superior discriminative ability of the RFLP data.
Received: 1 June 1997 / Accepted: 3 November 1997 相似文献
118.
Diane D'allard Julie Gay Clotilde Descarpentries Emilie Frisan Kevin Adam Frederique Verdier Célia Floquet Patrice Dubreuil Catherine Lacombe Michaela Fontenay Patrick Mayeux Olivier Kosmider 《PloS one》2013,8(4)
The stem cell factor receptor (SCF) c-Kit plays a pivotal role in regulating cell proliferation and survival in many cell types. In particular, c-Kit is required for early amplification of erythroid progenitors, while it must disappear from cell surface for the cell entering the final steps of maturation in an erythropoietin-dependent manner. We initially observed that imatinib (IM), an inhibitor targeting the tyrosine kinase activity of c-Kit concomitantly down-regulated the expression of c-Kit and accelerated the Epo-driven differentiation of erythroblasts in the absence of SCF. We investigated the mechanism by which IM or related masitinib (MA) induce c-Kit down-regulation in the human UT-7/Epo cell line. We found that the down-regulation of c-Kit in the presence of IM or MA was inhibited by a pre-incubation with methyl-β-cyclodextrin suggesting that c-Kit was internalized in the absence of ligand. By contrast to SCF, the internalization induced by TKI was independent of the E3 ubiquitin ligase c-Cbl. Furthermore, c-Kit was degraded through lysosomal, but not proteasomal pathway. In pulse-chase experiments, IM did not modulate c-Kit synthesis or maturation. Analysis of phosphotyrosine peptides in UT-7/Epo cells treated or not with IM show that IM did not modify overall tyrosine phosphorylation in these cells. Furthermore, we showed that a T670I mutation preventing the full access of IM to the ATP binding pocket, did not allow the internalization process in the presence of IM. Altogether these data show that TKI-induced internalization of c-Kit is linked to a modification of the integrity of ATP binding pocket. 相似文献
119.
A. Mimet V. Pellissier H. Quénol R. Aguejdad V. Dubreuil F. Rozé 《International journal of biometeorology》2009,53(3):287-298
The effect of towns on plant phenology, i.e. advancement of spring development compared with a rural environment, via the
urban heat island (UHI) phenomenon, has been shown for many towns in many countries. This work combines experimental and observational
methodology to provide a better and deeper view of climatic habitat in an urban context with a view to understanding the relationship
between plant development and urban climate on the intra-urban scale (by taking into account town structure). A dense network
of 17 meteorological stations was set up in Rennes, France, enabling us to identify and quantify climatic changes associated
with the UHI. Meanwhile, phenological observations were made during early spring (March and April) in 2005 on Platanus acerifolia and Prunus cerasus to study the relationship between climatic and phenological data. The results show that there is both a climatic gradient
and a developmental gradient corresponding to the type of urbanisation in the town of Rennes. The town influences plant phenology
by reducing the diurnal temperature range and by increasing the minimum temperature as one approaches the town centre. The
influence of ground cover type (plants or buildings) on development is also shown. The developmental phases of preflowering
and flowering are influenced to differing extents by climatic variables. The period during which climatic variables are effective
before a given developmental phase varies considerably. The preflowering phases are best correlated with the mean of the minimum
air temperature for the 15-day period before the observation, whereas flowering appears to be more dependent on the mean of
the daily diurnal temperature range for the 8 days preceding the observation. 相似文献
120.